Movement Disorders

TOPLINE:

A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.

METHODOLOGY:

• Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
• At baseline, 7321 women (18.6%) had migraine.
• The mean follow-up duration was 22 years.
• The primary outcome was a self-reported, physician-confirmed diagnosis of PD.

TAKEAWAY:

• During the study period, 685 women self-reported a diagnosis of PD.
• Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
• No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
• Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.

IN PRACTICE:

“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.

SOURCE:

The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.

LIMITATIONS:

The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.

DISCLOSURES:

The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.

METHODOLOGY:

• Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
• At baseline, 7321 women (18.6%) had migraine.
• The mean follow-up duration was 22 years.
• The primary outcome was a self-reported, physician-confirmed diagnosis of PD.

TAKEAWAY:

• During the study period, 685 women self-reported a diagnosis of PD.
• Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
• No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
• Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.

IN PRACTICE:

“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.

SOURCE:

The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.

LIMITATIONS:

The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.

DISCLOSURES:

The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

TOPLINE:

A history of migraine is not associated with an elevated risk for Parkinson’s disease (PD) in women, regardless of headache frequency or migraine subtype, a new study suggests.

METHODOLOGY:

• Researchers analyzed data on 39,312 women health professionals aged ≥ 45 years and having no history of PD who enrolled in the Women’s Health Study between 1992 and 1995 and were followed until 2021.
• At baseline, 7321 women (18.6%) had migraine.
• The mean follow-up duration was 22 years.
• The primary outcome was a self-reported, physician-confirmed diagnosis of PD.

TAKEAWAY:

• During the study period, 685 women self-reported a diagnosis of PD.
• Of these, 18.7% of reported cases were in women with any migraine and 81.3% in women without migraine.
• No significant association was found between PD risk and a history of migraine, migraine subtypes (with or without aura), or migraine frequency.
• Migraine was not associated with a higher risk for PD than that of nonmigraine headaches.

IN PRACTICE:

“These results are reassuring for women who have migraine, which itself causes many burdens, that they don’t have to worry about an increased risk of Parkinson’s disease in the future,” study author Tobias Kurth, Charité - Universitätsmedizin Berlin, Germany, said in a press release.

SOURCE:

The study was led by Ricarda S. Schulz, MSc, Charité - Universitätsmedizin Berlin. It was published online in Neurology.

LIMITATIONS:

The study’s findings may not be generalizable to other populations, such as men and non-White individuals. The self-reported data on migraine and PD may be subject to inaccuracies. PD is often not diagnosed until symptoms have reached an advanced stage, potentially leading to cases being underreported. Changes in the status and frequency of migraine over the study period were not accounted for, which may have affected the results.

DISCLOSURES:

The authors did not disclose any specific funding for this work. The Women’s Health Study was supported by the National Cancer Institute and National Heart, Lung, and Blood Institute. Two authors reported having financial ties outside this work. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Edema in the feet and legs is a common complaint in our practices. It can cause pain, weakness, heaviness, discomfort, limited movement, and a negative body image. Medications can contribute to edema, either alone or in combination with other health issues.

Edema is also associated with advanced age, female sex, obesity, diabetes, hypertension, pain, lack of physical activity, and mobility limitations. These factors often necessitate medication prescriptions, which can aggravate the problem. Therefore, it is important to know how to treat or prevent medication-induced edema.

There are four main causes of edema, and all can facilitate medication-induced edema.

• Increased capillary pressure. Conditions such as heart failure, renal dysfunction, venous insufficiency, deep vein thrombosis, and cirrhosis can increase capillary pressure, leading to edema.
• Decreased oncotic pressure. Hypoalbuminemia, a primary cause of reduced colloid oncotic pressure, can result from nephrotic syndrome, diabetic nephropathy, lupus nephropathy, amyloidosis, nephropathies, cirrhosis, chronic liver disease, and malabsorption or malnutrition.
• Increased capillary permeability. Vascular injury, often associated with diabetes, can increase capillary permeability and contribute to edema.
• Impaired lymphatic drainage. Lymphatic obstruction is common in patients with lymphedema, tumors, inflammation, fibrosis, certain infections, surgery, and congenital anomalies. Conditions such as thyroid disorders can also cause an increase in interstitial albumin and other proteins without a corresponding increase in lymphatic flow, leading to lymphedema.

Medications That Can Cause Edema

• Calcium channel blockers (CCBs). Drugs such as nifedipine and amlodipine can increase hydrostatic pressure by causing selective vasodilation of precapillary vessels, leading to increased intracapillary pressures. Newer lipophilic CCBs (eg, levamlodipine) exhibit lower rates of edema. Reducing the dose is often effective. Diuretics are not very effective for vasodilation-induced edema. Combining CCBs with angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), which induce postcapillary dilation and normalize intracapillary pressure, may reduce fluid leakage into the interstitial space. This combination may be more beneficial than high-dose CCB monotherapy.
• Thiazolidinedione (eg, pioglitazone). These increase vascular permeability and hydrostatic pressure. They work by stimulating the peroxisome proliferator–activated gamma receptor, increasing vascular endothelial permeability, vascular endothelial growth factor secretion, and renal retention of sodium and fluids. Because of other adverse effects, their use is now limited.
• Agents for neuropathic pain (gabapentin and pregabalin). These drugs can induce selective vasodilation of arterioles through a mechanism similar to that of CCBs, causing increased intracapillary pressures. Edema usually begins within the first month of treatment or dose increase and often regresses after dose reduction or drug discontinuation.
• Antiparkinsonian dopamine agonists. These increase hydrostatic pressure by reducing sympathetic tone and dilating arterioles through alpha-2 adrenergic receptor activity.
• New antipsychotics. Drugs like clozapine, iloperidone, lurasidone, olanzapine, quetiapine, risperidone, and ziprasidone can increase hydrostatic pressure through antagonistic effects on alpha-1 adrenergic receptors, causing vasodilation.
• Nitrates. These drugs increase hydrostatic pressure by causing preferential venous dilation, leading to increased venous pooling.
• Nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs can increase hydrostatic pressure by inhibiting vasodilation of afferent renal arterioles, decreasing the glomerular filtration rate, and stimulating the renin-angiotensin-aldosterone system, which leads to sodium and water retention. These adverse effects warrant cautious use of these agents.
• ACE inhibitors. Drugs such as enalapril and ramipril can increase vascular permeability. They reduce the metabolism and accumulation of bradykinin, which increases vascular permeability and fluid leakage. These effects are rare and are usually related to allergic responses.
• Insulin. Insulin decreases capillary oncotic pressure and increases vascular permeability. Rapid correction of hyperglycemia can cause a loss of oncotic pressure, while chronic hyperglycemia can damage vascular membranes, increasing permeability. These effects are generally benign and can be managed with careful dose titration, sodium restriction, or diuretics.
• Steroids. Steroids with mineralocorticoid activity can increase renal sodium and water retention, leading to increased blood volume. Fludrocortisone has the highest mineralocorticoid activity, while dexamethasone and methylprednisolone have negligible activity.

Implications

Understanding how these medications cause edema is important for effective management. For example, in the case of those causing edema due to reduced oncotic pressure, like insulin, slow dose titrations can help adapt to osmolarity changes. For drugs causing edema due to increased hydrostatic pressure, diuretics are more effective in acute management.

The key takeaways from this review are:

• Awareness of drug-induced edema. Many drugs besides CCBs can cause edema.
• Combination therapy. Combining ACE inhibitors or ARBs with CCBs can prevent or reduce CCB-induced edema.
• Edema management strategies. Strategies to manage or prevent edema should include dose reductions or replacement of the problematic medication, especially in severe or refractory cases.

Dr. Wajngarten, professor of cardiology, University of São Paulo, Brazil, has disclosed no relevant financial relationships.

This story was translated from the Medscape Portuguese edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Peter Grinspoon, MD, has some advice for clinicians when patients ask questions about microdosing of psychedelics: Keep the lines of communication open — and don’t be judgmental.

“If you’re dismissive or critical or sound like you’re judging them, then the patients just clam up,” said Dr. Grinspoon, a professor of medicine at Harvard Medical School and a primary care physician at Massachusetts General Hospital, both in Boston.

Psychedelic drugs are still illegal in the majority of states despite the growth of public interest in and use of these substances. That growth is evidenced by a flurry of workshops, reports, law enforcement seizures, and pressure by Congressional members for the Food and Drug Administration to approve new psychedelic drugs, just in the past year.

A recent study in JAMA Health Forum showed a nearly 14-fold increase in Google searches — from 7.9 to 105.6 per 10 million nationwide — for the term “microdosing” and related wording, between 2015 and 2023.

Two states — Oregon and Colorado — have decriminalized certain psychedelic drugs and are in various stages of establishing regulations and centers for prospective clients. Almost two dozen localities, like Ann Arbor, Michigan, have decriminalized psychedelic drugs. A handful of states have active legislation to decriminalize use, while others have bills that never made it out of committee.

But no definitive studies have reported that microdosing produces positive mental effects at a higher rate than placebo, according to Dr. Grinspoon. So responding to patient inquiries about microdosing can be complicated, and clinicians must provide counsel on issues of legality and therapeutic appropriateness.

“We’re in this renaissance where everybody is idealizing these medications, as opposed to 20 years ago when we were in the war on drugs and everybody was dismissing them,” Dr. Grinspoon said. “The truth is somewhere in between.”
 

The Science

Microdosing is defined as taking doses of 1/5 to 1/20 of the conventional recreational amount, which might include a dried psilocybin mushroom, lysergic acid diethylamide, or 3,4-methylenedioxymethamphetamine. But even that much may be neither effective nor safe.

Dr. Grinspoon said clinicians should tell patients that psychedelics may cause harm, although the drugs are relatively nontoxic and are not addictive. An illegally obtained psilocybin could cause negative reactions, especially if the drug has been adulterated with other substances and if the actual dose is higher than what was indicated by the seller.

He noted that people have different reactions to psychedelics, just as they have to prescription medications. He cited one example of a woman who microdosed and could not sleep for 2 weeks afterward. Only recently have randomized, double-blinded studies begun on benefits and harms.

Researchers have also begun investigating whether long-term microdosing of psilocybin could lead to valvular heart disease (VHD), said Kevin Yang, MD, a psychiatry resident at the University of California San Diego School of Medicine. A recent review of evidence concluded that microdosing various psychedelics over a period of months can lead to drug-induced VHD.

“It’s extremely important to emphasize with patients that not only do we not know if it works or not, we also don’t really know how safe it is,” Dr. Yang said.

Dr. Yang also said clinicians should consider referring patients to a mental health professional, and especially those that may have expertise in psychedelic therapies.

One of those experts is Rachel Yehuda, PhD, director of the Center for Psychedelic Psychotherapy and Trauma Research at Icahn School of Medicine at Mount Sinai in New York City. She said therapists should be able to assess the patient’s perceived need for microdosing and “invite reflections about why current approaches are falling short.”

“I would also not actively discourage it either but remain curious until both of you have a better understanding of the reasons for seeking this out and potential alternative strategies for obtaining more therapeutic benefits,” she said. “I think it is really important to study the effects of both micro- and macrodosing of psychedelics but not move in advance of the data.”
 

Navigating Legality

Recent ballot measures in Oregon and Colorado directed the states to develop regulated and licensed psilocybin-assisted therapy centers for legal “trips.” Oregon’s first center was opened in 2023, and Colorado is now developing its own licensing model.

According to the Oregon Health Authority, the centers are not medical facilities, and prescription or referral from a medical professional is not required.

The Oregon Academy of Family Physicians (OAFP) has yet to release guidance to clinicians on how to talk to their patients about these drugs or potential interest in visiting a licensed therapy center.

However, Betsy Boyd-Flynn, executive director of OAFP, said the organization is working on continuing medical education for what the average family physician needs to know if a patient asks about use.

“We suspect that many of our members have interest and want to learn more,” she said.

Dr. Grinspoon said clinicians should talk with patients about legality during these conversations.

“The big question I get is: ‘I really want to try microdosing, but how do I obtain the mushrooms?’ ” he said. “You can’t really as a physician tell them to do anything illegal. So you tell them to be safe, be careful, and to use their judgment.”

Patients who want to pursue microdosing who do not live in Oregon have two legal and safe options, Dr. Grinspoon said: Enroll in a clinical study or find a facility in a state or country — such as Oregon or Jamaica — that offers microdosing with psilocybin.

Clinicians also should warn their patients that the consequences of obtaining illicit psilocybin could exacerbate the mental health stresses they are seeking to alleviate.

“It’s going to get worse if they get tangled up with law enforcement or take something that’s contaminated and they get real sick,” he said.

Lisa Gillespie contributed reporting to this story. A version of this article appeared on Medscape.com.

Peter Grinspoon, MD, has some advice for clinicians when patients ask questions about microdosing of psychedelics: Keep the lines of communication open — and don’t be judgmental.

“If you’re dismissive or critical or sound like you’re judging them, then the patients just clam up,” said Dr. Grinspoon, a professor of medicine at Harvard Medical School and a primary care physician at Massachusetts General Hospital, both in Boston.

Psychedelic drugs are still illegal in the majority of states despite the growth of public interest in and use of these substances. That growth is evidenced by a flurry of workshops, reports, law enforcement seizures, and pressure by Congressional members for the Food and Drug Administration to approve new psychedelic drugs, just in the past year.

A recent study in JAMA Health Forum showed a nearly 14-fold increase in Google searches — from 7.9 to 105.6 per 10 million nationwide — for the term “microdosing” and related wording, between 2015 and 2023.

Two states — Oregon and Colorado — have decriminalized certain psychedelic drugs and are in various stages of establishing regulations and centers for prospective clients. Almost two dozen localities, like Ann Arbor, Michigan, have decriminalized psychedelic drugs. A handful of states have active legislation to decriminalize use, while others have bills that never made it out of committee.

But no definitive studies have reported that microdosing produces positive mental effects at a higher rate than placebo, according to Dr. Grinspoon. So responding to patient inquiries about microdosing can be complicated, and clinicians must provide counsel on issues of legality and therapeutic appropriateness.

“We’re in this renaissance where everybody is idealizing these medications, as opposed to 20 years ago when we were in the war on drugs and everybody was dismissing them,” Dr. Grinspoon said. “The truth is somewhere in between.”
 

The Science

Microdosing is defined as taking doses of 1/5 to 1/20 of the conventional recreational amount, which might include a dried psilocybin mushroom, lysergic acid diethylamide, or 3,4-methylenedioxymethamphetamine. But even that much may be neither effective nor safe.

Dr. Grinspoon said clinicians should tell patients that psychedelics may cause harm, although the drugs are relatively nontoxic and are not addictive. An illegally obtained psilocybin could cause negative reactions, especially if the drug has been adulterated with other substances and if the actual dose is higher than what was indicated by the seller.

He noted that people have different reactions to psychedelics, just as they have to prescription medications. He cited one example of a woman who microdosed and could not sleep for 2 weeks afterward. Only recently have randomized, double-blinded studies begun on benefits and harms.

Researchers have also begun investigating whether long-term microdosing of psilocybin could lead to valvular heart disease (VHD), said Kevin Yang, MD, a psychiatry resident at the University of California San Diego School of Medicine. A recent review of evidence concluded that microdosing various psychedelics over a period of months can lead to drug-induced VHD.

“It’s extremely important to emphasize with patients that not only do we not know if it works or not, we also don’t really know how safe it is,” Dr. Yang said.

Dr. Yang also said clinicians should consider referring patients to a mental health professional, and especially those that may have expertise in psychedelic therapies.

One of those experts is Rachel Yehuda, PhD, director of the Center for Psychedelic Psychotherapy and Trauma Research at Icahn School of Medicine at Mount Sinai in New York City. She said therapists should be able to assess the patient’s perceived need for microdosing and “invite reflections about why current approaches are falling short.”

“I would also not actively discourage it either but remain curious until both of you have a better understanding of the reasons for seeking this out and potential alternative strategies for obtaining more therapeutic benefits,” she said. “I think it is really important to study the effects of both micro- and macrodosing of psychedelics but not move in advance of the data.”
 

Navigating Legality

Recent ballot measures in Oregon and Colorado directed the states to develop regulated and licensed psilocybin-assisted therapy centers for legal “trips.” Oregon’s first center was opened in 2023, and Colorado is now developing its own licensing model.

According to the Oregon Health Authority, the centers are not medical facilities, and prescription or referral from a medical professional is not required.

The Oregon Academy of Family Physicians (OAFP) has yet to release guidance to clinicians on how to talk to their patients about these drugs or potential interest in visiting a licensed therapy center.

However, Betsy Boyd-Flynn, executive director of OAFP, said the organization is working on continuing medical education for what the average family physician needs to know if a patient asks about use.

“We suspect that many of our members have interest and want to learn more,” she said.

Dr. Grinspoon said clinicians should talk with patients about legality during these conversations.

“The big question I get is: ‘I really want to try microdosing, but how do I obtain the mushrooms?’ ” he said. “You can’t really as a physician tell them to do anything illegal. So you tell them to be safe, be careful, and to use their judgment.”

Patients who want to pursue microdosing who do not live in Oregon have two legal and safe options, Dr. Grinspoon said: Enroll in a clinical study or find a facility in a state or country — such as Oregon or Jamaica — that offers microdosing with psilocybin.

Clinicians also should warn their patients that the consequences of obtaining illicit psilocybin could exacerbate the mental health stresses they are seeking to alleviate.

“It’s going to get worse if they get tangled up with law enforcement or take something that’s contaminated and they get real sick,” he said.

Lisa Gillespie contributed reporting to this story. A version of this article appeared on Medscape.com.

Peter Grinspoon, MD, has some advice for clinicians when patients ask questions about microdosing of psychedelics: Keep the lines of communication open — and don’t be judgmental.

“If you’re dismissive or critical or sound like you’re judging them, then the patients just clam up,” said Dr. Grinspoon, a professor of medicine at Harvard Medical School and a primary care physician at Massachusetts General Hospital, both in Boston.

Psychedelic drugs are still illegal in the majority of states despite the growth of public interest in and use of these substances. That growth is evidenced by a flurry of workshops, reports, law enforcement seizures, and pressure by Congressional members for the Food and Drug Administration to approve new psychedelic drugs, just in the past year.

A recent study in JAMA Health Forum showed a nearly 14-fold increase in Google searches — from 7.9 to 105.6 per 10 million nationwide — for the term “microdosing” and related wording, between 2015 and 2023.

Two states — Oregon and Colorado — have decriminalized certain psychedelic drugs and are in various stages of establishing regulations and centers for prospective clients. Almost two dozen localities, like Ann Arbor, Michigan, have decriminalized psychedelic drugs. A handful of states have active legislation to decriminalize use, while others have bills that never made it out of committee.

But no definitive studies have reported that microdosing produces positive mental effects at a higher rate than placebo, according to Dr. Grinspoon. So responding to patient inquiries about microdosing can be complicated, and clinicians must provide counsel on issues of legality and therapeutic appropriateness.

“We’re in this renaissance where everybody is idealizing these medications, as opposed to 20 years ago when we were in the war on drugs and everybody was dismissing them,” Dr. Grinspoon said. “The truth is somewhere in between.”
 

The Science

Microdosing is defined as taking doses of 1/5 to 1/20 of the conventional recreational amount, which might include a dried psilocybin mushroom, lysergic acid diethylamide, or 3,4-methylenedioxymethamphetamine. But even that much may be neither effective nor safe.

Dr. Grinspoon said clinicians should tell patients that psychedelics may cause harm, although the drugs are relatively nontoxic and are not addictive. An illegally obtained psilocybin could cause negative reactions, especially if the drug has been adulterated with other substances and if the actual dose is higher than what was indicated by the seller.

He noted that people have different reactions to psychedelics, just as they have to prescription medications. He cited one example of a woman who microdosed and could not sleep for 2 weeks afterward. Only recently have randomized, double-blinded studies begun on benefits and harms.

Researchers have also begun investigating whether long-term microdosing of psilocybin could lead to valvular heart disease (VHD), said Kevin Yang, MD, a psychiatry resident at the University of California San Diego School of Medicine. A recent review of evidence concluded that microdosing various psychedelics over a period of months can lead to drug-induced VHD.

“It’s extremely important to emphasize with patients that not only do we not know if it works or not, we also don’t really know how safe it is,” Dr. Yang said.

Dr. Yang also said clinicians should consider referring patients to a mental health professional, and especially those that may have expertise in psychedelic therapies.

One of those experts is Rachel Yehuda, PhD, director of the Center for Psychedelic Psychotherapy and Trauma Research at Icahn School of Medicine at Mount Sinai in New York City. She said therapists should be able to assess the patient’s perceived need for microdosing and “invite reflections about why current approaches are falling short.”

“I would also not actively discourage it either but remain curious until both of you have a better understanding of the reasons for seeking this out and potential alternative strategies for obtaining more therapeutic benefits,” she said. “I think it is really important to study the effects of both micro- and macrodosing of psychedelics but not move in advance of the data.”
 

Navigating Legality

Recent ballot measures in Oregon and Colorado directed the states to develop regulated and licensed psilocybin-assisted therapy centers for legal “trips.” Oregon’s first center was opened in 2023, and Colorado is now developing its own licensing model.

According to the Oregon Health Authority, the centers are not medical facilities, and prescription or referral from a medical professional is not required.

The Oregon Academy of Family Physicians (OAFP) has yet to release guidance to clinicians on how to talk to their patients about these drugs or potential interest in visiting a licensed therapy center.

However, Betsy Boyd-Flynn, executive director of OAFP, said the organization is working on continuing medical education for what the average family physician needs to know if a patient asks about use.

“We suspect that many of our members have interest and want to learn more,” she said.

Dr. Grinspoon said clinicians should talk with patients about legality during these conversations.

“The big question I get is: ‘I really want to try microdosing, but how do I obtain the mushrooms?’ ” he said. “You can’t really as a physician tell them to do anything illegal. So you tell them to be safe, be careful, and to use their judgment.”

Patients who want to pursue microdosing who do not live in Oregon have two legal and safe options, Dr. Grinspoon said: Enroll in a clinical study or find a facility in a state or country — such as Oregon or Jamaica — that offers microdosing with psilocybin.

Clinicians also should warn their patients that the consequences of obtaining illicit psilocybin could exacerbate the mental health stresses they are seeking to alleviate.

“It’s going to get worse if they get tangled up with law enforcement or take something that’s contaminated and they get real sick,” he said.

Lisa Gillespie contributed reporting to this story. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

Tardive dyskinesia is a chronic, potentially irreversible, hyperkinetic movement disorder. And the challenge with tardive dyskinesia is that it’s underdiagnosed and undertreated. With the expanded use of dopamine receptor–blocking agents, there are about 7.5 million Americans who are now exposed and at risk for tardive dyskinesia.

It’s thought that about 500,000-750,000 of these patients may in fact have tardive dyskinesia, but only 15% are treated. So why are people not being treated for tardive dyskinesia? Well, there are a number of possible answers.

Until a few years ago, there were no Food and Drug Administration (FDA)–approved treatments for tardive dyskinesia, and these antipsychotic medications that the patients were taking, in many cases, were potentially lifesaving drugs, so they couldn’t simply be stopped. As a result of that, I think physicians developed a certain psychic blindness to identifying tardive dyskinesia, because it was their drugs that were causing the disease and yet they couldn’t be stopped. So, there really wasn’t much they could do in terms of making the diagnosis.

In addition, they were trained that tardive dyskinesia doesn’t have much impact on patients. But we now know, through surveys and other studies, that tardive dyskinesia can have a tremendous impact on patients and on your ability to treat the patient’s underlying mental health issues. It’s estimated that 50% of patients with tardive dyskinesia actually reduce the amount of antipsychotic medication they’re taking on their own, and about 40% may in fact stop their antipsychotic medication altogether.

Thirty-five percent of patients stopped seeing their doctor after they developed tardive dyskinesia, and about 20% of patients actually told other patients not to take their antipsychotic medication. So, tardive dyskinesia is impacting your ability to treat patients. In addition, it impacts the patients themselves. Nearly three out of four patients with tardive dyskinesia said, in surveys, that it caused severe impact on their psychosocial functioning.

It also impacted caregivers, with 70% of caregivers saying that the patients with tardive dyskinesia made them more anxious and limited them socially. So, we have this tremendous impact from tardive dyskinesia.

In addition, physicians sometimes don’t identify tardive dyskinesia correctly. They mistake it for another movement disorder: drug-induced parkinsonism. Or it falls under the rubric of extrapyramidal symptoms (EPS), and they were trained that you treat EPS with benztropine. The challenge with that is that benztropine is only indicated for acute dystonia or for drug-induced parkinsonism. It actually makes tardive dyskinesia worse. And, in the product insert for benztropine, it’s recommended that it should not be used in tardive dyskinesia. So if you have a patient whom you suspect has tardive dyskinesia, you have to discontinue the benztropine. That’s a really important first step.

And then, what else should you do? There are now two FDA-approved treatments for tardive dyskinesia. These are valbenazine and deutetrabenazine. Both of these drugs have been demonstrated in large double-blind, placebo-controlled studies to reduce tardive dyskinesia, as measured by the Abnormal Involuntary Movement Scale, by about 30%. These drugs have been demonstrated to be safe and well tolerated, with the main side effect being somnolence.

Some people can also develop parkinsonism. Why could there be Parkinsonism? This is because vesicular monoamine transporter 2 (VMAT2) inhibitors work by reducing the amount of dopamine that can be packaged in the presynaptic neuron. That means that less dopamine is available to the synapse, and this reduces movement. The American Psychiatric Association has issued guidelines for the treatment of tardive dyskinesia and has said that moderate to severe tardive dyskinesia should be treated first-line with VMAT2 inhibitors and that mild tardive dyskinesia should also be treated with VMAT2 inhibitors if the tardive dyskinesia is impacting the patient.

Given the impact that tardive dyskinesia has on patients and caregivers, and the physician’s ability to treat these patients’ mental health issues, we need to become aggressive and treat the tardive dyskinesia so that patients can improve and be able to have their movements treated without impacting their underlying mental health issues.

Daniel Kremens, professor, Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, codirector, Parkinson’s Disease and Movement Disorders Division, Jack and Vickie Farber Center for Neuroscience, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, has disclosed relevant financial relationships with Teva Pharmaceuticals, AbbVie, Merz, Allergan, Bial, Cerevel, Amneal, Acadia, Supernus, Adamas, Acorda, Kyowa Kirin, and Neurocrine.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Tardive dyskinesia is a chronic, potentially irreversible, hyperkinetic movement disorder. And the challenge with tardive dyskinesia is that it’s underdiagnosed and undertreated. With the expanded use of dopamine receptor–blocking agents, there are about 7.5 million Americans who are now exposed and at risk for tardive dyskinesia.

It’s thought that about 500,000-750,000 of these patients may in fact have tardive dyskinesia, but only 15% are treated. So why are people not being treated for tardive dyskinesia? Well, there are a number of possible answers.

Until a few years ago, there were no Food and Drug Administration (FDA)–approved treatments for tardive dyskinesia, and these antipsychotic medications that the patients were taking, in many cases, were potentially lifesaving drugs, so they couldn’t simply be stopped. As a result of that, I think physicians developed a certain psychic blindness to identifying tardive dyskinesia, because it was their drugs that were causing the disease and yet they couldn’t be stopped. So, there really wasn’t much they could do in terms of making the diagnosis.

In addition, they were trained that tardive dyskinesia doesn’t have much impact on patients. But we now know, through surveys and other studies, that tardive dyskinesia can have a tremendous impact on patients and on your ability to treat the patient’s underlying mental health issues. It’s estimated that 50% of patients with tardive dyskinesia actually reduce the amount of antipsychotic medication they’re taking on their own, and about 40% may in fact stop their antipsychotic medication altogether.

Thirty-five percent of patients stopped seeing their doctor after they developed tardive dyskinesia, and about 20% of patients actually told other patients not to take their antipsychotic medication. So, tardive dyskinesia is impacting your ability to treat patients. In addition, it impacts the patients themselves. Nearly three out of four patients with tardive dyskinesia said, in surveys, that it caused severe impact on their psychosocial functioning.

It also impacted caregivers, with 70% of caregivers saying that the patients with tardive dyskinesia made them more anxious and limited them socially. So, we have this tremendous impact from tardive dyskinesia.

In addition, physicians sometimes don’t identify tardive dyskinesia correctly. They mistake it for another movement disorder: drug-induced parkinsonism. Or it falls under the rubric of extrapyramidal symptoms (EPS), and they were trained that you treat EPS with benztropine. The challenge with that is that benztropine is only indicated for acute dystonia or for drug-induced parkinsonism. It actually makes tardive dyskinesia worse. And, in the product insert for benztropine, it’s recommended that it should not be used in tardive dyskinesia. So if you have a patient whom you suspect has tardive dyskinesia, you have to discontinue the benztropine. That’s a really important first step.

And then, what else should you do? There are now two FDA-approved treatments for tardive dyskinesia. These are valbenazine and deutetrabenazine. Both of these drugs have been demonstrated in large double-blind, placebo-controlled studies to reduce tardive dyskinesia, as measured by the Abnormal Involuntary Movement Scale, by about 30%. These drugs have been demonstrated to be safe and well tolerated, with the main side effect being somnolence.

Some people can also develop parkinsonism. Why could there be Parkinsonism? This is because vesicular monoamine transporter 2 (VMAT2) inhibitors work by reducing the amount of dopamine that can be packaged in the presynaptic neuron. That means that less dopamine is available to the synapse, and this reduces movement. The American Psychiatric Association has issued guidelines for the treatment of tardive dyskinesia and has said that moderate to severe tardive dyskinesia should be treated first-line with VMAT2 inhibitors and that mild tardive dyskinesia should also be treated with VMAT2 inhibitors if the tardive dyskinesia is impacting the patient.

Given the impact that tardive dyskinesia has on patients and caregivers, and the physician’s ability to treat these patients’ mental health issues, we need to become aggressive and treat the tardive dyskinesia so that patients can improve and be able to have their movements treated without impacting their underlying mental health issues.

Daniel Kremens, professor, Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, codirector, Parkinson’s Disease and Movement Disorders Division, Jack and Vickie Farber Center for Neuroscience, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, has disclosed relevant financial relationships with Teva Pharmaceuticals, AbbVie, Merz, Allergan, Bial, Cerevel, Amneal, Acadia, Supernus, Adamas, Acorda, Kyowa Kirin, and Neurocrine.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

Tardive dyskinesia is a chronic, potentially irreversible, hyperkinetic movement disorder. And the challenge with tardive dyskinesia is that it’s underdiagnosed and undertreated. With the expanded use of dopamine receptor–blocking agents, there are about 7.5 million Americans who are now exposed and at risk for tardive dyskinesia.

It’s thought that about 500,000-750,000 of these patients may in fact have tardive dyskinesia, but only 15% are treated. So why are people not being treated for tardive dyskinesia? Well, there are a number of possible answers.

Until a few years ago, there were no Food and Drug Administration (FDA)–approved treatments for tardive dyskinesia, and these antipsychotic medications that the patients were taking, in many cases, were potentially lifesaving drugs, so they couldn’t simply be stopped. As a result of that, I think physicians developed a certain psychic blindness to identifying tardive dyskinesia, because it was their drugs that were causing the disease and yet they couldn’t be stopped. So, there really wasn’t much they could do in terms of making the diagnosis.

In addition, they were trained that tardive dyskinesia doesn’t have much impact on patients. But we now know, through surveys and other studies, that tardive dyskinesia can have a tremendous impact on patients and on your ability to treat the patient’s underlying mental health issues. It’s estimated that 50% of patients with tardive dyskinesia actually reduce the amount of antipsychotic medication they’re taking on their own, and about 40% may in fact stop their antipsychotic medication altogether.

Thirty-five percent of patients stopped seeing their doctor after they developed tardive dyskinesia, and about 20% of patients actually told other patients not to take their antipsychotic medication. So, tardive dyskinesia is impacting your ability to treat patients. In addition, it impacts the patients themselves. Nearly three out of four patients with tardive dyskinesia said, in surveys, that it caused severe impact on their psychosocial functioning.

It also impacted caregivers, with 70% of caregivers saying that the patients with tardive dyskinesia made them more anxious and limited them socially. So, we have this tremendous impact from tardive dyskinesia.

In addition, physicians sometimes don’t identify tardive dyskinesia correctly. They mistake it for another movement disorder: drug-induced parkinsonism. Or it falls under the rubric of extrapyramidal symptoms (EPS), and they were trained that you treat EPS with benztropine. The challenge with that is that benztropine is only indicated for acute dystonia or for drug-induced parkinsonism. It actually makes tardive dyskinesia worse. And, in the product insert for benztropine, it’s recommended that it should not be used in tardive dyskinesia. So if you have a patient whom you suspect has tardive dyskinesia, you have to discontinue the benztropine. That’s a really important first step.

And then, what else should you do? There are now two FDA-approved treatments for tardive dyskinesia. These are valbenazine and deutetrabenazine. Both of these drugs have been demonstrated in large double-blind, placebo-controlled studies to reduce tardive dyskinesia, as measured by the Abnormal Involuntary Movement Scale, by about 30%. These drugs have been demonstrated to be safe and well tolerated, with the main side effect being somnolence.

Some people can also develop parkinsonism. Why could there be Parkinsonism? This is because vesicular monoamine transporter 2 (VMAT2) inhibitors work by reducing the amount of dopamine that can be packaged in the presynaptic neuron. That means that less dopamine is available to the synapse, and this reduces movement. The American Psychiatric Association has issued guidelines for the treatment of tardive dyskinesia and has said that moderate to severe tardive dyskinesia should be treated first-line with VMAT2 inhibitors and that mild tardive dyskinesia should also be treated with VMAT2 inhibitors if the tardive dyskinesia is impacting the patient.

Given the impact that tardive dyskinesia has on patients and caregivers, and the physician’s ability to treat these patients’ mental health issues, we need to become aggressive and treat the tardive dyskinesia so that patients can improve and be able to have their movements treated without impacting their underlying mental health issues.

Daniel Kremens, professor, Department of Neurology, Sidney Kimmel Medical College, Thomas Jefferson University, codirector, Parkinson’s Disease and Movement Disorders Division, Jack and Vickie Farber Center for Neuroscience, Thomas Jefferson University Hospital, Philadelphia, Pennsylvania, has disclosed relevant financial relationships with Teva Pharmaceuticals, AbbVie, Merz, Allergan, Bial, Cerevel, Amneal, Acadia, Supernus, Adamas, Acorda, Kyowa Kirin, and Neurocrine.

A version of this article first appeared on Medscape.com.

As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.

Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
 

‘Tap the Brakes’

However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.

Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”

A Holistic Approach to Shared Decision-Making

To avoid needlessly scaring patients, Dr. Hoy suggested broaching the topic of Parkinson’s disease biomarkers during advance care planning. “In the same conversation that you might talk about establishing surrogate decision-makers or potential do-not-resuscitate/intubate orders, you can talk about the potential of predictive testing, which is becoming more prevalent across domains of clinical practice.”

Understanding each patient’s values, preferences, and priorities requires a holistic approach, he said. “In the context of prodromal Parkinson’s disease, the benefits of enrolling in a new clinical trial or implementing lifestyle changes might vary depending on the person. Do you think this person would be likely to enroll in a clinical trial or implement those lifestyle changes?” Additionally, he recommended considering how a patient might react to a false diagnosis.

Whereas a diagnosis of mild cognitive impairment might not lead to Alzheimer’s disease or dementia, wrote Dr. Rees and colleagues, growing evidence including a review published in Neurology in 2022 supports the accuracy of alpha-synuclein seed amplification assays in detecting both established and prodromal Parkinson’s disease. For people thusly diagnosed, Dr. Rees and colleagues wrote, the psychosocial burden of inevitable progression could create feelings of helplessness, possibly undermining benefits of early knowledge.

Beyond patients’ reactions, said Dr. Hoy, a diagnosis of prodromal Parkinson’s disease could result in social stigma, changes to interpersonal relationships, or discrimination. “Understanding the implications and uncertainties of potential disclosure, relative to what a person would want to know or might be able to do about it, will be the key for deciding when is the right time,” he said.
 

Supporting Primary Care

As the shared decision-making burden likely will fall to primary care providers, Dr. Hoy added, neurologists should prioritize increasing these providers’ capacity to advise and refer patients appropriately. Although it is too soon to develop clinical guidelines, he said, neurologists could help educate such providers about pPD and the growing availability of promising biomarkers.

“Parkinson’s is thought of as a movement disorder first and foremost,” said Dr. Hoy. However, various non-motor symptoms including sleep problems, depression, anxiety, apathy, constipation, and gastrointestinal issues often appear before movement-related symptoms during the prodromal phase.

As potentially the first line of defense against prodromal Parkinson’s disease, primary care providers also should know the distinction between early and timely diagnosis, added Dr. Hoy. Introduced by Dr. Rees and colleagues in a 2018 review published in F1000Research, timely diagnosis balances patient preferences, the availability and efficacy of DMT, and health systems’ ability to support and manage individuals at every stage of disease.

The current study was funded by a Parkinson’s UK grant (which paid Dr. Rees’s salary). The editorial was supported by a National Institute of Mental Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative award, a grant from the National Institute on Aging, and a Wellcome Discovery Award. Dr. Hoy reported no relevant disclosures.

As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.

Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
 

‘Tap the Brakes’

However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.

Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”

A Holistic Approach to Shared Decision-Making

To avoid needlessly scaring patients, Dr. Hoy suggested broaching the topic of Parkinson’s disease biomarkers during advance care planning. “In the same conversation that you might talk about establishing surrogate decision-makers or potential do-not-resuscitate/intubate orders, you can talk about the potential of predictive testing, which is becoming more prevalent across domains of clinical practice.”

Understanding each patient’s values, preferences, and priorities requires a holistic approach, he said. “In the context of prodromal Parkinson’s disease, the benefits of enrolling in a new clinical trial or implementing lifestyle changes might vary depending on the person. Do you think this person would be likely to enroll in a clinical trial or implement those lifestyle changes?” Additionally, he recommended considering how a patient might react to a false diagnosis.

Whereas a diagnosis of mild cognitive impairment might not lead to Alzheimer’s disease or dementia, wrote Dr. Rees and colleagues, growing evidence including a review published in Neurology in 2022 supports the accuracy of alpha-synuclein seed amplification assays in detecting both established and prodromal Parkinson’s disease. For people thusly diagnosed, Dr. Rees and colleagues wrote, the psychosocial burden of inevitable progression could create feelings of helplessness, possibly undermining benefits of early knowledge.

Beyond patients’ reactions, said Dr. Hoy, a diagnosis of prodromal Parkinson’s disease could result in social stigma, changes to interpersonal relationships, or discrimination. “Understanding the implications and uncertainties of potential disclosure, relative to what a person would want to know or might be able to do about it, will be the key for deciding when is the right time,” he said.
 

Supporting Primary Care

As the shared decision-making burden likely will fall to primary care providers, Dr. Hoy added, neurologists should prioritize increasing these providers’ capacity to advise and refer patients appropriately. Although it is too soon to develop clinical guidelines, he said, neurologists could help educate such providers about pPD and the growing availability of promising biomarkers.

“Parkinson’s is thought of as a movement disorder first and foremost,” said Dr. Hoy. However, various non-motor symptoms including sleep problems, depression, anxiety, apathy, constipation, and gastrointestinal issues often appear before movement-related symptoms during the prodromal phase.

As potentially the first line of defense against prodromal Parkinson’s disease, primary care providers also should know the distinction between early and timely diagnosis, added Dr. Hoy. Introduced by Dr. Rees and colleagues in a 2018 review published in F1000Research, timely diagnosis balances patient preferences, the availability and efficacy of DMT, and health systems’ ability to support and manage individuals at every stage of disease.

The current study was funded by a Parkinson’s UK grant (which paid Dr. Rees’s salary). The editorial was supported by a National Institute of Mental Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative award, a grant from the National Institute on Aging, and a Wellcome Discovery Award. Dr. Hoy reported no relevant disclosures.

As the availability of potential biomarkers for Parkinson’s disease drives the debate around diagnosing prodromal Parkinson’s disease (pPD) from theory to practice, said authors of a recent study, clinicians should weigh each patient’s preferences, circumstances, and goals against the potential benefits and harms of disclosure. The study and an accompanying editorial appeared online in Neurology.

Because markers such as SNCA, LRRK2, and GBA mutations impact small subgroups of patients at risk of developing monogenic forms of Parkinson’s disease, wrote Richard N. Rees, MBChB, MD, from the Department of Clinical and Movement Neurosciences at University College London Queen Square Institute of Neurology, and colleagues, researchers are working to identify people at risk of idiopathic Parkinson’s disease using models based on known risk and protective factors. The recent development of highly accurate cerebrospinal fluid (and potentially serum) alpha-synuclein seed amplification assays, which may show Parkinson’s disease’s signature before overt symptoms appear, will reinforce these efforts, authors added.
 

‘Tap the Brakes’

However, sources interviewed by Neurology Reviews counseled caution with potential prodromal Parkinson’s disease biomarkers. “As the science advances in Parkinson’s disease and related disorders,” said Michael S. Okun, MD, “our ability to predict who will and will not be diagnosed will improve. We should, however, tap the brakes and consider the consequences of making a diagnosis in someone at risk — especially someone without symptoms.” Dr. Okun is National Medical Advisor to the Parkinson’s Foundation and director of the Norman Fixel Institute for Neurological Diseases at University of Florida Health in Gainesville, Florida. He was not involved with the study.

Neurologists should ask themselves why they are testing for Parkinson’s disease biomarkers, said Dr. Okun, and what counseling and shared decision-making they provided beforehand. “This already complex scenario becomes even more complicated when we consider that many people with GBA gene mutations and some with LRRK2 mutations may never actually manifest Parkinson’s disease.”

A Holistic Approach to Shared Decision-Making

To avoid needlessly scaring patients, Dr. Hoy suggested broaching the topic of Parkinson’s disease biomarkers during advance care planning. “In the same conversation that you might talk about establishing surrogate decision-makers or potential do-not-resuscitate/intubate orders, you can talk about the potential of predictive testing, which is becoming more prevalent across domains of clinical practice.”

Understanding each patient’s values, preferences, and priorities requires a holistic approach, he said. “In the context of prodromal Parkinson’s disease, the benefits of enrolling in a new clinical trial or implementing lifestyle changes might vary depending on the person. Do you think this person would be likely to enroll in a clinical trial or implement those lifestyle changes?” Additionally, he recommended considering how a patient might react to a false diagnosis.

Whereas a diagnosis of mild cognitive impairment might not lead to Alzheimer’s disease or dementia, wrote Dr. Rees and colleagues, growing evidence including a review published in Neurology in 2022 supports the accuracy of alpha-synuclein seed amplification assays in detecting both established and prodromal Parkinson’s disease. For people thusly diagnosed, Dr. Rees and colleagues wrote, the psychosocial burden of inevitable progression could create feelings of helplessness, possibly undermining benefits of early knowledge.

Beyond patients’ reactions, said Dr. Hoy, a diagnosis of prodromal Parkinson’s disease could result in social stigma, changes to interpersonal relationships, or discrimination. “Understanding the implications and uncertainties of potential disclosure, relative to what a person would want to know or might be able to do about it, will be the key for deciding when is the right time,” he said.
 

Supporting Primary Care

As the shared decision-making burden likely will fall to primary care providers, Dr. Hoy added, neurologists should prioritize increasing these providers’ capacity to advise and refer patients appropriately. Although it is too soon to develop clinical guidelines, he said, neurologists could help educate such providers about pPD and the growing availability of promising biomarkers.

“Parkinson’s is thought of as a movement disorder first and foremost,” said Dr. Hoy. However, various non-motor symptoms including sleep problems, depression, anxiety, apathy, constipation, and gastrointestinal issues often appear before movement-related symptoms during the prodromal phase.

As potentially the first line of defense against prodromal Parkinson’s disease, primary care providers also should know the distinction between early and timely diagnosis, added Dr. Hoy. Introduced by Dr. Rees and colleagues in a 2018 review published in F1000Research, timely diagnosis balances patient preferences, the availability and efficacy of DMT, and health systems’ ability to support and manage individuals at every stage of disease.

The current study was funded by a Parkinson’s UK grant (which paid Dr. Rees’s salary). The editorial was supported by a National Institute of Mental Health Brain Research Through Advancing Innovative Neurotechnologies (BRAIN) Initiative award, a grant from the National Institute on Aging, and a Wellcome Discovery Award. Dr. Hoy reported no relevant disclosures.

DENVER — Among patients with major depressive disorder, transcranial magnetic stimulation (TMS) had similar efficacy to electroconvulsive therapy (ECT), according to results from a retrospective study of patients treated in the past 20 years.

“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
 

Study Findings Lead to More Questions

The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.

Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.

The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”

Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
 

Comparing Treatment Options

Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.

Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.

“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai

Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.

DENVER — Among patients with major depressive disorder, transcranial magnetic stimulation (TMS) had similar efficacy to electroconvulsive therapy (ECT), according to results from a retrospective study of patients treated in the past 20 years.

“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
 

Study Findings Lead to More Questions

The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.

Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.

The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”

Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
 

Comparing Treatment Options

Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.

Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.

“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai

Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.

DENVER — Among patients with major depressive disorder, transcranial magnetic stimulation (TMS) had similar efficacy to electroconvulsive therapy (ECT), according to results from a retrospective study of patients treated in the past 20 years.

“We always learn in our textbooks that after about two or three medication trials is when you can start exploring more serious treatment protocols, such as ECT or TMS, but a lot of these patients weren’t going forward with it, and I was curious about it. I figured that TMS, which is a less expensive, less scary procedure that patients would more likely be open to, that is also approved for treatment resistant depression, would be a good alternative to ECT,” said Anuttham Kandhadai, a third-year medical student at University of Texas Medical Branch at Galveston, who presented the study at the 2024 annual meeting of the American Academy of Neurology.
 

Study Findings Lead to More Questions

The researchers found lower rates of depressive episodes, suicidal attempts, and suicidal ideation among patients treated with TMS, but an important limitation was that the researchers did not know the severity of the depression in the two patient groups, according to Branch Coslett, MD, who attended the session and has performed research with TMS to treat aphasia in stroke patients. “I think it’s a very interesting study, and certainly something worth pursuing, but given that ECT is only used as a last resort, whereas TMS is often used as a second-line therapy, I think you’re really talking about very different populations that have had these treatments,” said Dr. Coslett.

Mr. Kandhadai recognized the limitations of the study and looks forward to expanding the research. “I’d love to explore cost effectiveness of the treatments. I’d love to explore patient familiarity and patient comfort with different treatments. And I’d also love to explore a more controlled study that can determine how severe someone’s depression is, and then be able to control for that and explore the outcomes based on the treatment protocol,” he said.

The ideal comparative study would be prospective, “but that will never be done. One Flew Over the Cuckoo’s Nest and similar sources of information have really poisoned the well,” said Dr. Coslett. However, he noted that advances have been made in ECT, and that targeting the right hemisphere produces fewer side effects: “The outcomes from unilateral right hemisphere stimulation are said to be every bit as good or maybe better, and you don’t get the confusion, you don’t get the memory loss, you don’t get all that sort of stuff that you’d expect when somebody has a prolonged, generalized tonic-clonic seizure.”

Still, people are naturally reluctant to undergo ECT. “I’ve seen it. It’s pretty barbaric. It’s better now and at my institution, people do get it, but they really, really have to be intractable,” he said.
 

Comparing Treatment Options

Mr. Kandhadai and his co-authors used the TriNetX database to identify patients with treatment-resistant major depressive disorder who received TMS or ECT in the past 20 years. There were 2,916 patients in both cohorts, who were matched by age, sex, ethnicity, mood and behavioral disorders, endocrine disorders, intellectual disabilities, cerebrovascular disease, and other nervous system disorders. The mean age at treatment was 48.2 years, 38.5% were male, and 3.1% were Black or African American.

Short-term outcomes favored TMS, including the frequency of disorientation (0.41% vs 2.81%), retrograde amnesia (0.34% vs 0.65%), and headache (4.36% vs 7.20%). Long-term outcomes from 1 month to 5 years post treatment were also better in the TMS group, including depressive episodes (44.99% vs 53.77%), suicide attempts (3.98% vs 6.86%), and suicidal ideation (12.38% vs 23.49%). Kaplan-Meier curve analysis between 1 month and 5 years showed a benefit to TMS in probability of not experiencing a depressive episode, and not experiencing suicidal ideation.

“ECT has been the gold standard of treatment resistant depression for a long time, and it deserves to be. I think it’s something you should offer your patients. Not everyone might be comfortable with it, and if they’re not, I think it’s important to not stop the conversation there, but to offer something like TMS because TMS is something that might be more accessible to patients. It might be more affordable, and it might be less scary,” said Mr. Kandhadai

Mr. Kandhadai and Dr. Coslett have no relevant financial disclosures.

DENVER – Real-world, US claims-based data show major gaps in the care and management of three major neurologic disorders: Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS).

Investigators led by Nikki Win, PhD, medical manager/team lead, OMNI Scientific Strategy and Collaborations, US Medical Affairs, Genentech/Roche, found that patients with Parkinson’s disease were referred to a specialist most often, followed by those with MS and those with AD. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

National Neurologist Shortage

The national neurologist shortage, coupled with the growing incidence of Alzheimer’s disease, Parkinson’s disease, MS, and other conditions has led the AAN and other organizations to call for expanding the role of primary care physicians in the diagnosis and management of neurologic disorders, the leading global cause of disability.

“These neurological conditions are increasing in prevalence and there’s a limited number of neurologists, so we wanted to understand what this looks like in the US,” Dr. Win said.

“There is a need to understand the patient journey from primary care to neurology care, from presentation of a suspected neurological disorder to diagnosis, referral to a specialist, and the time elapsed before the specialist visit for Alzheimer’s disease, MS, and Parkinson’s disease in the US,” Dr. Win added. 

Timely and accurate diagnoses of neurologic disorders can optimize treatment outcomes. Because many of these diseases are first detected during a visit with a primary care physician, it is important to understand the timeline from the initial visit to a specialist referral, the investigators noted. 
 

Analyzing Trends in Specialist Referrals

Using claims data from the Optum Normative Health Information database, researchers identified 48,525 adults with Alzheimer’s disease, 26,431 with Parkinson’s disease, and 8169 with MS who received a diagnosis from a primary care physician between 2016 and 2021.

They examined the proportion, timing, and demographic factors associated with referrals from primary care clinicians or other healthcare providers to specialists including neurologists, neurosurgeons, psychiatrists, and geriatric medicine specialists.

Results showed that patients with Parkinson’s disease were referred to a specialist most often (53%), followed by those with MS (42%) and those with Alzheimer’s disease (27%).

Individuals with Alzheimer’s disease waited the longest for a specialist referral, with a median of 10 months between the time of referral and the first specialist visit compared with 5.7 months for patients with Parkinson’s disease and 2.6 months for MS patients.

“Some patients with common conditions like Alzheimer’s disease, MS, and Parkinson’s disease don’t see a neurologist, and when they do, it can take as long as 10 months,” said Dr. Win.

Using zip code heatmaps, researchers found that the proportion of referrals for all neurologic disorders was higher in the Midwest and Northeast, whereas patients in the South and West were less likely to receive a referral. 

Referrals for Alzheimer’s disease were low nationwide, except for some areas of Michigan and New England. California had the lowest referral rate for MS, followed by regions in the South and Northeast. Patients with Parkinson’s disease living in the Midwest and Northeast were more likely than those in the West to receive a specialist referral. 

Previous studies have reported regional shortages of neurologists, said Dr. Win. “Our data seem to correlate that in terms of the areas with lower referral patterns, but as to whether that is causative or correlative, we don’t know.” 

Odds of referral were also influenced by demographic characteristics such as sex, age, race, and ethnicity, investigators found. 

For example, there were fewer referrals with increasing age across all three neurologic disorders, and men were more likely than women to be referred for Alzheimer’s disease and Parkinson’s disease. Compared with White patients, Parkinson’s disease referrals were less likely among African American, Asian, and Hispanic patients and Alzheimer’s disease referrals were less common among Asian and Hispanic patients.

Insurance status also affected referrals. People with MS and Parkinson’s disease who had commercial insurance were referred more often than were those with Medicare Advantage, said Dr. Win.

She also noted, “Additional research is needed to understand how being referred or not being referred to a neurologist actually impacts patient treatment, care and outcomes.”
 

Neurology Challenges

Commenting on the research, Thomas Vidic, MD, a community neurologist in Elkhart, Indiana, and clinical professor of neurology at Indiana University School of Medicine at South Bend, said that he was surprised by the variation in wait times for patients.

This, he said, could reflect a study limitation or a higher comfort level among primary care doctors in treating dementia.

With respect to MS, Dr. Vidic said that he believes primary care physicians may not be uncertain about prescribing the approved medications for the disease because there are so many of them.

In addition, patients with Alzheimer’s disease are older and perhaps less accepting of being referred to a specialist that may be hours away.

The bottom line for Dr. Vidic, though, is the lack of specialists. “It comes back to the fact we’re not doing a good job of having community neurologists available to take care of these problems,” he said.

The issue of community neurologist shortages was underlined by the study’s findings about geographic gaps in specialist referrals across the country, he said.

Neurologists make up about 2% of the medical workforce and this has remained static for some time, Dr. Vidic noted. Meanwhile, people are living longer and developing more neurologic diseases.

Dr. Vidic also pointed to the lack of neurology training programs. “There has not been a significant change in the number of programs in the last 10-15 years,” he said.

Study funding was not disclosed. Dr. Win reports receiving personal compensation for serving as an employee of Genentech and has stock in Genentech. Dr. Vidic reports no relevant financial disclosures.

A version of this article appeared on Medscape.com.

DENVER – Real-world, US claims-based data show major gaps in the care and management of three major neurologic disorders: Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS).

Investigators led by Nikki Win, PhD, medical manager/team lead, OMNI Scientific Strategy and Collaborations, US Medical Affairs, Genentech/Roche, found that patients with Parkinson’s disease were referred to a specialist most often, followed by those with MS and those with AD. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

National Neurologist Shortage

The national neurologist shortage, coupled with the growing incidence of Alzheimer’s disease, Parkinson’s disease, MS, and other conditions has led the AAN and other organizations to call for expanding the role of primary care physicians in the diagnosis and management of neurologic disorders, the leading global cause of disability.

“These neurological conditions are increasing in prevalence and there’s a limited number of neurologists, so we wanted to understand what this looks like in the US,” Dr. Win said.

“There is a need to understand the patient journey from primary care to neurology care, from presentation of a suspected neurological disorder to diagnosis, referral to a specialist, and the time elapsed before the specialist visit for Alzheimer’s disease, MS, and Parkinson’s disease in the US,” Dr. Win added. 

Timely and accurate diagnoses of neurologic disorders can optimize treatment outcomes. Because many of these diseases are first detected during a visit with a primary care physician, it is important to understand the timeline from the initial visit to a specialist referral, the investigators noted. 
 

Analyzing Trends in Specialist Referrals

Using claims data from the Optum Normative Health Information database, researchers identified 48,525 adults with Alzheimer’s disease, 26,431 with Parkinson’s disease, and 8169 with MS who received a diagnosis from a primary care physician between 2016 and 2021.

They examined the proportion, timing, and demographic factors associated with referrals from primary care clinicians or other healthcare providers to specialists including neurologists, neurosurgeons, psychiatrists, and geriatric medicine specialists.

Results showed that patients with Parkinson’s disease were referred to a specialist most often (53%), followed by those with MS (42%) and those with Alzheimer’s disease (27%).

Individuals with Alzheimer’s disease waited the longest for a specialist referral, with a median of 10 months between the time of referral and the first specialist visit compared with 5.7 months for patients with Parkinson’s disease and 2.6 months for MS patients.

“Some patients with common conditions like Alzheimer’s disease, MS, and Parkinson’s disease don’t see a neurologist, and when they do, it can take as long as 10 months,” said Dr. Win.

Using zip code heatmaps, researchers found that the proportion of referrals for all neurologic disorders was higher in the Midwest and Northeast, whereas patients in the South and West were less likely to receive a referral. 

Referrals for Alzheimer’s disease were low nationwide, except for some areas of Michigan and New England. California had the lowest referral rate for MS, followed by regions in the South and Northeast. Patients with Parkinson’s disease living in the Midwest and Northeast were more likely than those in the West to receive a specialist referral. 

Previous studies have reported regional shortages of neurologists, said Dr. Win. “Our data seem to correlate that in terms of the areas with lower referral patterns, but as to whether that is causative or correlative, we don’t know.” 

Odds of referral were also influenced by demographic characteristics such as sex, age, race, and ethnicity, investigators found. 

For example, there were fewer referrals with increasing age across all three neurologic disorders, and men were more likely than women to be referred for Alzheimer’s disease and Parkinson’s disease. Compared with White patients, Parkinson’s disease referrals were less likely among African American, Asian, and Hispanic patients and Alzheimer’s disease referrals were less common among Asian and Hispanic patients.

Insurance status also affected referrals. People with MS and Parkinson’s disease who had commercial insurance were referred more often than were those with Medicare Advantage, said Dr. Win.

She also noted, “Additional research is needed to understand how being referred or not being referred to a neurologist actually impacts patient treatment, care and outcomes.”
 

Neurology Challenges

Commenting on the research, Thomas Vidic, MD, a community neurologist in Elkhart, Indiana, and clinical professor of neurology at Indiana University School of Medicine at South Bend, said that he was surprised by the variation in wait times for patients.

This, he said, could reflect a study limitation or a higher comfort level among primary care doctors in treating dementia.

With respect to MS, Dr. Vidic said that he believes primary care physicians may not be uncertain about prescribing the approved medications for the disease because there are so many of them.

In addition, patients with Alzheimer’s disease are older and perhaps less accepting of being referred to a specialist that may be hours away.

The bottom line for Dr. Vidic, though, is the lack of specialists. “It comes back to the fact we’re not doing a good job of having community neurologists available to take care of these problems,” he said.

The issue of community neurologist shortages was underlined by the study’s findings about geographic gaps in specialist referrals across the country, he said.

Neurologists make up about 2% of the medical workforce and this has remained static for some time, Dr. Vidic noted. Meanwhile, people are living longer and developing more neurologic diseases.

Dr. Vidic also pointed to the lack of neurology training programs. “There has not been a significant change in the number of programs in the last 10-15 years,” he said.

Study funding was not disclosed. Dr. Win reports receiving personal compensation for serving as an employee of Genentech and has stock in Genentech. Dr. Vidic reports no relevant financial disclosures.

A version of this article appeared on Medscape.com.

DENVER – Real-world, US claims-based data show major gaps in the care and management of three major neurologic disorders: Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis (MS).

Investigators led by Nikki Win, PhD, medical manager/team lead, OMNI Scientific Strategy and Collaborations, US Medical Affairs, Genentech/Roche, found that patients with Parkinson’s disease were referred to a specialist most often, followed by those with MS and those with AD. 

The findings were presented at the 2024 annual meeting of the American Academy of Neurology (AAN).
 

National Neurologist Shortage

The national neurologist shortage, coupled with the growing incidence of Alzheimer’s disease, Parkinson’s disease, MS, and other conditions has led the AAN and other organizations to call for expanding the role of primary care physicians in the diagnosis and management of neurologic disorders, the leading global cause of disability.

“These neurological conditions are increasing in prevalence and there’s a limited number of neurologists, so we wanted to understand what this looks like in the US,” Dr. Win said.

“There is a need to understand the patient journey from primary care to neurology care, from presentation of a suspected neurological disorder to diagnosis, referral to a specialist, and the time elapsed before the specialist visit for Alzheimer’s disease, MS, and Parkinson’s disease in the US,” Dr. Win added. 

Timely and accurate diagnoses of neurologic disorders can optimize treatment outcomes. Because many of these diseases are first detected during a visit with a primary care physician, it is important to understand the timeline from the initial visit to a specialist referral, the investigators noted. 
 

Analyzing Trends in Specialist Referrals

Using claims data from the Optum Normative Health Information database, researchers identified 48,525 adults with Alzheimer’s disease, 26,431 with Parkinson’s disease, and 8169 with MS who received a diagnosis from a primary care physician between 2016 and 2021.

They examined the proportion, timing, and demographic factors associated with referrals from primary care clinicians or other healthcare providers to specialists including neurologists, neurosurgeons, psychiatrists, and geriatric medicine specialists.

Results showed that patients with Parkinson’s disease were referred to a specialist most often (53%), followed by those with MS (42%) and those with Alzheimer’s disease (27%).

Individuals with Alzheimer’s disease waited the longest for a specialist referral, with a median of 10 months between the time of referral and the first specialist visit compared with 5.7 months for patients with Parkinson’s disease and 2.6 months for MS patients.

“Some patients with common conditions like Alzheimer’s disease, MS, and Parkinson’s disease don’t see a neurologist, and when they do, it can take as long as 10 months,” said Dr. Win.

Using zip code heatmaps, researchers found that the proportion of referrals for all neurologic disorders was higher in the Midwest and Northeast, whereas patients in the South and West were less likely to receive a referral. 

Referrals for Alzheimer’s disease were low nationwide, except for some areas of Michigan and New England. California had the lowest referral rate for MS, followed by regions in the South and Northeast. Patients with Parkinson’s disease living in the Midwest and Northeast were more likely than those in the West to receive a specialist referral. 

Previous studies have reported regional shortages of neurologists, said Dr. Win. “Our data seem to correlate that in terms of the areas with lower referral patterns, but as to whether that is causative or correlative, we don’t know.” 

Odds of referral were also influenced by demographic characteristics such as sex, age, race, and ethnicity, investigators found. 

For example, there were fewer referrals with increasing age across all three neurologic disorders, and men were more likely than women to be referred for Alzheimer’s disease and Parkinson’s disease. Compared with White patients, Parkinson’s disease referrals were less likely among African American, Asian, and Hispanic patients and Alzheimer’s disease referrals were less common among Asian and Hispanic patients.

Insurance status also affected referrals. People with MS and Parkinson’s disease who had commercial insurance were referred more often than were those with Medicare Advantage, said Dr. Win.

She also noted, “Additional research is needed to understand how being referred or not being referred to a neurologist actually impacts patient treatment, care and outcomes.”
 

Neurology Challenges

Commenting on the research, Thomas Vidic, MD, a community neurologist in Elkhart, Indiana, and clinical professor of neurology at Indiana University School of Medicine at South Bend, said that he was surprised by the variation in wait times for patients.

This, he said, could reflect a study limitation or a higher comfort level among primary care doctors in treating dementia.

With respect to MS, Dr. Vidic said that he believes primary care physicians may not be uncertain about prescribing the approved medications for the disease because there are so many of them.

In addition, patients with Alzheimer’s disease are older and perhaps less accepting of being referred to a specialist that may be hours away.

The bottom line for Dr. Vidic, though, is the lack of specialists. “It comes back to the fact we’re not doing a good job of having community neurologists available to take care of these problems,” he said.

The issue of community neurologist shortages was underlined by the study’s findings about geographic gaps in specialist referrals across the country, he said.

Neurologists make up about 2% of the medical workforce and this has remained static for some time, Dr. Vidic noted. Meanwhile, people are living longer and developing more neurologic diseases.

Dr. Vidic also pointed to the lack of neurology training programs. “There has not been a significant change in the number of programs in the last 10-15 years,” he said.

Study funding was not disclosed. Dr. Win reports receiving personal compensation for serving as an employee of Genentech and has stock in Genentech. Dr. Vidic reports no relevant financial disclosures.

A version of this article appeared on Medscape.com.

DENVER — Among residents of urban environments, the highest levels of exposure to environmental trichloroethylene (TCE) is associated with a 24% increase in risk of Parkinson’s disease, according to results from a new nationwide analysis of a Medicare population.

TCE has long been used as an industrial solvent, and it is a component of several household cleaning products. Case reports have suggested that workers exposed to it have increased risk of Parkinson’s disease, with risk increases as high as 500%.

Exposure can come through air or water, but 97% of environmental TCE is found in the air, according to Brittany Krzyzanowski, PhD, who presented the study at the 2024 annual meeting of the American Academy of Neurology.

Previous studies of TCE had looked primarily at occupational exposure, such as workers at TCE-emitting facilities, or soldiers stationed at Camp Lejeune in North Carolina, where levels of TCE were more than 70-fold higher than EPA-permissible levels. A recent study found a 70% increase in risk of Parkinson’s disease associated with individuals who were stationed there.
 

From Population Data to Individual Risk

In an interview, Dr. Krzyzanowski pointed out that the Camp Lejeune studies didn’t assign TCE exposure to individuals — instead, researchers noted whether an individual was stationed at that base or another. “Our study adds to the previous work by investigating environmental exposure using TCE estimates that we are able to assign to individuals. [It shows that] you don’t have to work in a facility with TCE, you don’t have to be stationed on a military base with tainted water, you just have to live in a census tract with higher levels of TCE to have increased risk,” said Dr. Krzyzanowski, a research assistant professor at Barrow Neurological Institute in Phoenix.

In the new study, Dr. Krzyzanowski and her colleagues analyzed data from 1,559,135 Medicare beneficiaries with no other health coverage, who had a valid US ZIP code. There were 252,700 incident cases of Parkinson’s disease who were initially diagnosed between 2016 and 2018. These individuals were matched 1:5 with 1,306,435 healthy controls.

Airborne TCE exposure data was drawn the Environmental Protection Agency’s National Air Toxics Assessment data from 2005, about 12 years prior to the start of the study and in line with the expected latency between exposure and development of Parkinson’s disease.

“We found a nationwide association between airborne TCE exposure and Parkinson’s disease risks, but this was only true for the metropolitan areas. Within these metro areas, there was a dose-response effect, where increasing levels of TCE were associated with increasing risk of Parkinson’s disease. In particular, those living in the metros with the highest levels of TCE had a 24% greater risk of Parkinson’s compared with those in metros with the lowest levels of TCE,” Dr. Krzyzanowski said during her presentation. The P-value for the trend was less than .0001.

The census tracts in metropolitan areas are smaller than those in rural areas because of differences in population density, and this leads to greater precision of TCE exposure estimates in urban environments, according to Dr. Krzyzanowski, and this could explain the lack of a statistically significant association seen among rural populations.

‘More Substantial’ Data Adds to Previous Evidence

The new study is an important addition to the literature examining TCE exposure and Parkinson’s disease, according to session moderator Jeff Bronstein, MD, PhD, who was asked for comment. “It’s more substantial data making that association between TCE and Parkinson’s. It’s been growing over the past decade, and this is a more objective, big data association, so it adds more strength to the body of knowledge that we already have. It’s unbiased, which is nice,” said Dr. Bronstein, professor of neurology and director of movement disorders at UCLA.

It remains uncertain whether TCE is a direct cause of Parkinson’s disease, but “a lot of us believe it’s causal. There’s a lot of evidence now. There are some very good studies with inhalation models that show it affects autophagy, or the way we break down proteins, and that it also involves LRRK2 [leucine-rich repeat kinase 2], which is one of the proteins involved in some of the genetic forms [of Parkinson’s disease], and it might affect mitochondria. They’re all linked in network and right now the animal studies point to that network,” said Dr. Bronstein.

Dr. Krzyzanowski has no relevant financial disclosures. Dr. Bronstein consults for a legal firm involved in the Camp Lejeune litigation.

DENVER — Among residents of urban environments, the highest levels of exposure to environmental trichloroethylene (TCE) is associated with a 24% increase in risk of Parkinson’s disease, according to results from a new nationwide analysis of a Medicare population.

TCE has long been used as an industrial solvent, and it is a component of several household cleaning products. Case reports have suggested that workers exposed to it have increased risk of Parkinson’s disease, with risk increases as high as 500%.

Exposure can come through air or water, but 97% of environmental TCE is found in the air, according to Brittany Krzyzanowski, PhD, who presented the study at the 2024 annual meeting of the American Academy of Neurology.

Previous studies of TCE had looked primarily at occupational exposure, such as workers at TCE-emitting facilities, or soldiers stationed at Camp Lejeune in North Carolina, where levels of TCE were more than 70-fold higher than EPA-permissible levels. A recent study found a 70% increase in risk of Parkinson’s disease associated with individuals who were stationed there.
 

From Population Data to Individual Risk

In an interview, Dr. Krzyzanowski pointed out that the Camp Lejeune studies didn’t assign TCE exposure to individuals — instead, researchers noted whether an individual was stationed at that base or another. “Our study adds to the previous work by investigating environmental exposure using TCE estimates that we are able to assign to individuals. [It shows that] you don’t have to work in a facility with TCE, you don’t have to be stationed on a military base with tainted water, you just have to live in a census tract with higher levels of TCE to have increased risk,” said Dr. Krzyzanowski, a research assistant professor at Barrow Neurological Institute in Phoenix.

In the new study, Dr. Krzyzanowski and her colleagues analyzed data from 1,559,135 Medicare beneficiaries with no other health coverage, who had a valid US ZIP code. There were 252,700 incident cases of Parkinson’s disease who were initially diagnosed between 2016 and 2018. These individuals were matched 1:5 with 1,306,435 healthy controls.

Airborne TCE exposure data was drawn the Environmental Protection Agency’s National Air Toxics Assessment data from 2005, about 12 years prior to the start of the study and in line with the expected latency between exposure and development of Parkinson’s disease.

“We found a nationwide association between airborne TCE exposure and Parkinson’s disease risks, but this was only true for the metropolitan areas. Within these metro areas, there was a dose-response effect, where increasing levels of TCE were associated with increasing risk of Parkinson’s disease. In particular, those living in the metros with the highest levels of TCE had a 24% greater risk of Parkinson’s compared with those in metros with the lowest levels of TCE,” Dr. Krzyzanowski said during her presentation. The P-value for the trend was less than .0001.

The census tracts in metropolitan areas are smaller than those in rural areas because of differences in population density, and this leads to greater precision of TCE exposure estimates in urban environments, according to Dr. Krzyzanowski, and this could explain the lack of a statistically significant association seen among rural populations.

‘More Substantial’ Data Adds to Previous Evidence

The new study is an important addition to the literature examining TCE exposure and Parkinson’s disease, according to session moderator Jeff Bronstein, MD, PhD, who was asked for comment. “It’s more substantial data making that association between TCE and Parkinson’s. It’s been growing over the past decade, and this is a more objective, big data association, so it adds more strength to the body of knowledge that we already have. It’s unbiased, which is nice,” said Dr. Bronstein, professor of neurology and director of movement disorders at UCLA.

It remains uncertain whether TCE is a direct cause of Parkinson’s disease, but “a lot of us believe it’s causal. There’s a lot of evidence now. There are some very good studies with inhalation models that show it affects autophagy, or the way we break down proteins, and that it also involves LRRK2 [leucine-rich repeat kinase 2], which is one of the proteins involved in some of the genetic forms [of Parkinson’s disease], and it might affect mitochondria. They’re all linked in network and right now the animal studies point to that network,” said Dr. Bronstein.

Dr. Krzyzanowski has no relevant financial disclosures. Dr. Bronstein consults for a legal firm involved in the Camp Lejeune litigation.

DENVER — Among residents of urban environments, the highest levels of exposure to environmental trichloroethylene (TCE) is associated with a 24% increase in risk of Parkinson’s disease, according to results from a new nationwide analysis of a Medicare population.

TCE has long been used as an industrial solvent, and it is a component of several household cleaning products. Case reports have suggested that workers exposed to it have increased risk of Parkinson’s disease, with risk increases as high as 500%.

Exposure can come through air or water, but 97% of environmental TCE is found in the air, according to Brittany Krzyzanowski, PhD, who presented the study at the 2024 annual meeting of the American Academy of Neurology.

Previous studies of TCE had looked primarily at occupational exposure, such as workers at TCE-emitting facilities, or soldiers stationed at Camp Lejeune in North Carolina, where levels of TCE were more than 70-fold higher than EPA-permissible levels. A recent study found a 70% increase in risk of Parkinson’s disease associated with individuals who were stationed there.
 

From Population Data to Individual Risk

In an interview, Dr. Krzyzanowski pointed out that the Camp Lejeune studies didn’t assign TCE exposure to individuals — instead, researchers noted whether an individual was stationed at that base or another. “Our study adds to the previous work by investigating environmental exposure using TCE estimates that we are able to assign to individuals. [It shows that] you don’t have to work in a facility with TCE, you don’t have to be stationed on a military base with tainted water, you just have to live in a census tract with higher levels of TCE to have increased risk,” said Dr. Krzyzanowski, a research assistant professor at Barrow Neurological Institute in Phoenix.

In the new study, Dr. Krzyzanowski and her colleagues analyzed data from 1,559,135 Medicare beneficiaries with no other health coverage, who had a valid US ZIP code. There were 252,700 incident cases of Parkinson’s disease who were initially diagnosed between 2016 and 2018. These individuals were matched 1:5 with 1,306,435 healthy controls.

Airborne TCE exposure data was drawn the Environmental Protection Agency’s National Air Toxics Assessment data from 2005, about 12 years prior to the start of the study and in line with the expected latency between exposure and development of Parkinson’s disease.

“We found a nationwide association between airborne TCE exposure and Parkinson’s disease risks, but this was only true for the metropolitan areas. Within these metro areas, there was a dose-response effect, where increasing levels of TCE were associated with increasing risk of Parkinson’s disease. In particular, those living in the metros with the highest levels of TCE had a 24% greater risk of Parkinson’s compared with those in metros with the lowest levels of TCE,” Dr. Krzyzanowski said during her presentation. The P-value for the trend was less than .0001.

The census tracts in metropolitan areas are smaller than those in rural areas because of differences in population density, and this leads to greater precision of TCE exposure estimates in urban environments, according to Dr. Krzyzanowski, and this could explain the lack of a statistically significant association seen among rural populations.

‘More Substantial’ Data Adds to Previous Evidence

The new study is an important addition to the literature examining TCE exposure and Parkinson’s disease, according to session moderator Jeff Bronstein, MD, PhD, who was asked for comment. “It’s more substantial data making that association between TCE and Parkinson’s. It’s been growing over the past decade, and this is a more objective, big data association, so it adds more strength to the body of knowledge that we already have. It’s unbiased, which is nice,” said Dr. Bronstein, professor of neurology and director of movement disorders at UCLA.

It remains uncertain whether TCE is a direct cause of Parkinson’s disease, but “a lot of us believe it’s causal. There’s a lot of evidence now. There are some very good studies with inhalation models that show it affects autophagy, or the way we break down proteins, and that it also involves LRRK2 [leucine-rich repeat kinase 2], which is one of the proteins involved in some of the genetic forms [of Parkinson’s disease], and it might affect mitochondria. They’re all linked in network and right now the animal studies point to that network,” said Dr. Bronstein.

Dr. Krzyzanowski has no relevant financial disclosures. Dr. Bronstein consults for a legal firm involved in the Camp Lejeune litigation.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Recently, Acadia Pharmaceuticals announced it was stopping trials on Nuplazid for indications outside of Parkinson’s disease psychosis.

I was impressed with what I saw in my office. Although I know there’s some controversy over the drug, the majority of studies do show efficacy, and in my little practice I clearly noticed improvements in patients with Parkinson’s disease who’d previously failed the more standard agents (note - I have no financial affiliation with Acadia Pharmaceuticals).

So, as a lay-neurologist, I expected the drug to work for other kinds of psychosis, particularly Alzheimer’s disease. All of us in practice know how much we need new options for that.

But when the clinical trials came, the drug didn’t work. It didn’t work for schizophrenia, either, Finally, Acadia threw in the towel and gave up.

I have no idea what happened. I’m sure others are wondering the same thing. On paper, I’d have thought it would work for Alzheimer’s psychosis, but in the real world it didn’t.

Is psychosis between the two disorders that different, with different neurotransmitter causes? Are the benefits in my patients with Parkinson’s disease really just from my own selection bias? Or is there just a lot we still don’t know?

Medicine, unfortunately, is littered with ideas that should have worked, but either didn’t, or at least aren’t as good as we thought they should have been. Look at the graveyard full of amyloid-targeting drugs. Yeah, I know Leqembi is out there, and donanemab is in the wings, but are they anywhere near as good as we thought they’d be? Not at all.

At the same time, we’ve been waiting for the BTK drugs (not to be confused with a Korean pop band) for multiple sclerosis. They sounded like they were the Next Big Thing.

They may be, but recent data on one of them, evobrutinib, was less than encouraging. Of course, that shouldn’t extrapolate to the group as a whole, but it does leave you wondering why.

Medicine is always improving, but it’s also still a trial-and-error process. Just because something should work doesn’t mean it will, and it may be years before we know why.

It’s just a reminder that, here in 2024, we still have a lot to learn.
 

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.

Stroke, Alzheimer’s disease, and other neurological conditions are now the leading cause of health loss and disability around the world, affecting nearly half of the world’s population, a new comprehensive analysis showed.

In 2021, neurological conditions were responsible for 443 million years of healthy life lost due to illness, disability, and premature death — a measurement known as disability-adjusted life years (DALY) — making them the top contributor to the global disease burden, ahead of cardiovascular diseases.

Some 3.4 billion people — 43% of the entire global population — had a neurological illness in 2021, the report noted.

“As the world’s leading cause of overall disease burden, and with case numbers rising 59% globally since 1990, nervous system conditions must be addressed through effective, culturally acceptable, and affordable prevention, treatment, rehabilitation, and long-term care strategies,” lead author Jaimie Steinmetz, PhD, from the Institute of Health Metrics and Evaluation (IHME), University of Washington, Seattle, said in a news release. 

The findings, from the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2021, “have important health service and policy implications and serve as evidence that global neurological heath loss has been under-recognized and is increasing and unevenly distributed geographically and socioeconomically,” the authors noted.

The study was published online in The Lancet: Neurology.
 

The Top 10

The top 10 contributors to neurological health loss in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer’s disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications from preterm birth, autistic spectrum disorders, and nervous system cancers.

Neurological consequences of COVID-19 ranked 20th out of 37 unique conditions assessed.

In 2021, there were more than 23 million global cases of COVID-19 with long-term cognitive symptoms or Guillain-Barré syndrome, accounting for 57% of all infectious neurological disease cases and contributing to 2.48 million years of healthy life lost, the study found.

The most prevalent neurological disorders were tension-type headache (about 2 billion cases) and migraine (about 1.1 billion cases), while diabetic neuropathy is the fastest-growing of all neurological conditions.

“The number of people with diabetic neuropathy has more than tripled globally since 1990, rising to 206 million in 2021. This is in line with the increase in the global prevalence of diabetes,” co-senior author Liane Ong, PhD, from IHME, said in the release.

The data showed striking differences in the burden of neurological conditions between world regions and national income levels, with over 80% of neurological deaths and health loss occurring in low- and middle-income countries.

Regions with the highest burden of neurological conditions were central and western sub-Saharan Africa, while high-income Asia Pacific and Australasia had the lowest burden.

“Nervous system health loss disproportionately impacts many of the poorest countries partly due to the higher prevalence of conditions affecting neonates and children under 5, especially birth-related complications and infections,” co-senior author Tarun Dua, MD, with the World Health Organization (WHO) brain health unit, noted in the news release.

“Improved infant survival has led to an increase in long-term disability, while limited access to treatment and rehabilitation services is contributing to the much higher proportion of deaths in these countries,” Dr. Dua said.
 

Prioritize Prevention

The analysis also provides estimates of the proportion of neurological conditions that are potentially preventable by eliminating known risk factors for stroke, dementia, multiple sclerosis, Parkinson’s disease, encephalitis, meningitis, and intellectual disability.

It shows that modifying 18 risk factors over a person’s lifetime — most importantly high systolic blood pressure — could prevent 84% of global DALYs from stroke. Controlling lead exposure could lower intellectual disability cases by 63% and reducing high fasting plasma glucose to normal levels could cut dementia by roughly 15%.

“Because many neurological conditions lack cures, and access to medical care is often limited, understanding modifiable risk factors and the potentially avoidable neurological condition burden is essential to help curb this global health crisis,” co-lead author Katrin Seeher, PhD, mental health specialist with WHO’s brain health unit, said in the release.

It’s important to note that nervous system conditions include infectious and vector-borne diseases and injuries as well as noncommunicable diseases and injuries, Dr. Steinmetz said, “demanding different strategies for prevention and treatment throughout life.”

“We hope that our findings can help policymakers more comprehensively understand the impact of neurological conditions on both adults and children to inform more targeted interventions in individual countries, as well as guide ongoing awareness and advocacy efforts around the world,” Dr. Steinmetz added.

In an accompanying editorial, Wolfgang Grisold, MD, president of the World Federation of Neurology, London, noted that the study builds on previous findings and expands the number of neurological conditions studied from 15 to 37.

“This important new GBD report highlights that the burden of neurological conditions is greater than previously thought,” wrote Dr. Grisold, who was not a part of the study. “In the next iteration, more attention should be given to neuromuscular diseases, the effects of cancer in the nervous system, and neuropathic pain. Comparing the disability caused by conditions with episodic occurrence versus those that cause permanent and progressive disease will remain challenging because the effects on the individuals vary substantially.”

The study was funded by the Bill and Melinda Gates Foundation. Full disclosures are included in the original article.

A version of this article appeared on Medscape.com.