News Roundup

The net benefit of IV t-PA treatment in patients with ischemic stroke was greater in patients also using antiplatelet drugs, despite an increased risk of symptomatic intracerebral hemorrhage, reported researchers in the March 10 online Archives of Neurology. Of 301 consecutive ischemic stroke patients treated with IV t-PA at a single university hospital, 89 also used antiplatelet drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 13.5% of patients who received antiplatelet drugs and in 2.8% of those who did not, and was independently predicted by antiplatelet drug use (odds ratio, 6.0). However, prior antiplatelet therapy was also independently associated with a favorable outcome, defined as a modified Rankin Scale score of 2 or less at three months (odds ratio, 2.0).

The prevalence of cerebral microbleeds is high, increases with age, and may be indicative of an increased risk of cerebrovascular problems, reported researchers in the April 1 Neurology. Among 1,062 study participants 60 and older (mean age, 69.6), the MRI-detected prevalence of cerebral microbleeds increased from 17.8% in those ages 60 to 69 to 38.3% in those older than 80. “APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers,” said the authors, while cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location.

Pesticide exposure may increase the risk of Parkinson’s disease, according to the results of a family-based case-control study reported in the March 28 BMC Neurology. The 319 patients with Parkinson’s disease were significantly more likely to report direct pesticide application than were their unaffected relatives (odds ratio, 1.61). There was also a dose-response pattern between frequency, duration, and cumulative exposure and Parkinson’s disease. Additional analyses found that insecticides and herbicides increased the risk of Parkinson’s disease, and that two insecticide classes—organochlorines and organophosphorus compounds—were significantly associated with Parkinson’s disease. Consuming well water and living or working on a farm did not appear to increase risk of disease, however.

There may be an association between the severity of age-related white matter changes and the severity of gait and motor compromise, researchers reported in the March 18 Neurology. In the Leukoaraiosis and Disability Study, 639 nondisabled individuals older than 65 were followed for three years. Mean scores on the Short Physical Performance Battery and walking speeds decreased with severity of age-related white matter changes, and balance was best among those with mild age-related white matter changes compared with moderate or severe changes. A history of falls was also twice as likely in those participants with severe versus mild age-related white matter changes, and 1.5 times as likely in those with moderate changes. “Physical activity might have the potential to reduce the risk of limitations in mobility,” noted the authors, as physically inactive individuals had a higher risk of pathologic Short Physical Performance Battery scores.

High intake of magnesium—but not calcium, potassium, or sodium—appeared to reduce the risk of cerebral infarction in male smokers, reported researchers in the March 10 Archives of Internal Medicine. In a study of 26,556 Finnish male smokers ages 50 to 69 at baseline, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages occurred during a mean follow-up of 13.6 years. Men in the highest quintile of magnesium intake had a 0.85 relative risk of cerebral infarction compared with those in the lowest quintile; the inverse association was stronger in men younger than 60 (relative risk, 0.76). No other minerals were significantly associated with risk of any subtype of stroke. The researchers suggested that high magnesium intake may play a role in the primary prevention of cerebral infarction.

Disclosure of a dementia diagnosis resulted in relief rather than a “catastrophic emotional reaction” among 90 individuals with suspected Alzheimer’s disease and their companions. As reported in the March Journal of the American Geriatrics Society, 69% of the participants were diagnosed with dementia; however, Geriatric Depression Scale scores did not change significantly compared with prediagnosis scores. Instead, a substantial decrease in State-Trait Anxiety Inventory was observed, even among those patients who were only mildly cognitively impaired. The authors suggested that patients and their families may appreciate the explanation of symptoms and the development of a treatment plan that comes with a diagnosis.

Overexpression of the cdk5 activator p25 led to increased amyloidogenic processing of amyloid precursor protein, which may have implications for Alzheimer’s disease pathogenesis, reported researchers in the March 13 Neuron. Mice that overexpressed p25 showed elevated levels of BACE1 mRNA and protein pSTAT3, whereas cdk5-deficient mice had reduced levels; a targeted mutation to the STAT3 cdk5 responsive site also led to lower levels of BACE1. The authors noted that transcriptional control of BACE1 could have implications for Alzheimer’s disease. As a cdk5 inhibitor reversed BACE-driven amyloidgenic processing, it may provide a therapeutic candidate for Alzheimer’s disease.

Maximum carotid plaque thickness was associated with an increased risk of vascular outcomes, especially among Hispanics, in an analysis of 2,189 subjects in a population-based cohort, as reported in the April 1 Neurology. Carotid plaque was present in 58% of the participants. During the mean 6.9 years of follow-up, vascular events occurred among 319 subjects: 121 had ischemic strokes, 118 had myocardial infarctions, and 166 died of vascular causes. Although there was a 2.8-fold increased risk of combined vascular events among those with carotid plaque thickness greater than the prespecified cutoff of 1.9 mm compared with those with no carotid plaque, the association was only significant among Hispanics after full adjustment. “Approximately 44% of the low-risk individuals … had a 10-year vascular risk of 18.3% if having carotid plaque,” said the researchers. They concluded that maximum carotid plaque thickness may be a useful risk stratification tool and a surrogate end point in clinical trials.

Parenchymal volumetric loss dose-dependently correlated with severity of traumatic brain injury (TBI), according to the results of a study of 69 chronic-phase TBI patients reported in the March 4 Neurology. A minimum of one year after TBI, high-resolution structural MRI also detected a spatially extensive pattern of volume loss that covaried with TBI severity, “with particularly widespread effects in white matter volume and sulcal/subdural CSF.” Of the 38 brain regions imaged, the most reliable effects were observed in the frontal, temporal, and cingulate regions, stated the researchers. They noted that the pattern of volume loss was independent of contributions of focal and diffuse injury, as focal lesions were associated with greater frontal and temporal volume loss, but the loss remained marked when analyses were restricted to patients with diffuse injury.

Researchers have proposed a mechanism for the brain’s conversion to epilepsy following injury. As reported in the March 28 online Proceedings of the National Academy of Sciences, the researchers used a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network. Although the investigators noted that network activity in the dentate gyrus was robust after a number of major changes, “the incorporation of a small number of highly interconnected granule cell hubs greatly increase[d] network activity, resulting in a hyperexcitable, potentially seizure-prone circuit.” They suggested that these neural hub cells may be a therapeutic target for epilepsy.

Impaired olfaction may predate clinical Parkinson’s disease in men by at least four years, reported researchers in the February Annals of Neurology. Olfaction was tested in 2,267 Parkinson’s disease– and dementia-free men ages 71 to 95 for up to eight years. Thirty-five men were diagnosed with Parkinson’s disease at an average age of 82.9. During the first four years of follow-up, age-adjusted incidence of Parkinson’s disease declined from the lowest to the highest quartiles of odor identification; the odds ratio for Parkinson’s disease in the lowest quartile compared with the two highest quartiles was 5.2. The researchers suggested that tests of olfaction may be a useful screening tool for risk of Parkinson’s disease in men.

The net benefit of IV t-PA treatment in patients with ischemic stroke was greater in patients also using antiplatelet drugs, despite an increased risk of symptomatic intracerebral hemorrhage, reported researchers in the March 10 online Archives of Neurology. Of 301 consecutive ischemic stroke patients treated with IV t-PA at a single university hospital, 89 also used antiplatelet drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 13.5% of patients who received antiplatelet drugs and in 2.8% of those who did not, and was independently predicted by antiplatelet drug use (odds ratio, 6.0). However, prior antiplatelet therapy was also independently associated with a favorable outcome, defined as a modified Rankin Scale score of 2 or less at three months (odds ratio, 2.0).

The prevalence of cerebral microbleeds is high, increases with age, and may be indicative of an increased risk of cerebrovascular problems, reported researchers in the April 1 Neurology. Among 1,062 study participants 60 and older (mean age, 69.6), the MRI-detected prevalence of cerebral microbleeds increased from 17.8% in those ages 60 to 69 to 38.3% in those older than 80. “APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers,” said the authors, while cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location.

Pesticide exposure may increase the risk of Parkinson’s disease, according to the results of a family-based case-control study reported in the March 28 BMC Neurology. The 319 patients with Parkinson’s disease were significantly more likely to report direct pesticide application than were their unaffected relatives (odds ratio, 1.61). There was also a dose-response pattern between frequency, duration, and cumulative exposure and Parkinson’s disease. Additional analyses found that insecticides and herbicides increased the risk of Parkinson’s disease, and that two insecticide classes—organochlorines and organophosphorus compounds—were significantly associated with Parkinson’s disease. Consuming well water and living or working on a farm did not appear to increase risk of disease, however.

There may be an association between the severity of age-related white matter changes and the severity of gait and motor compromise, researchers reported in the March 18 Neurology. In the Leukoaraiosis and Disability Study, 639 nondisabled individuals older than 65 were followed for three years. Mean scores on the Short Physical Performance Battery and walking speeds decreased with severity of age-related white matter changes, and balance was best among those with mild age-related white matter changes compared with moderate or severe changes. A history of falls was also twice as likely in those participants with severe versus mild age-related white matter changes, and 1.5 times as likely in those with moderate changes. “Physical activity might have the potential to reduce the risk of limitations in mobility,” noted the authors, as physically inactive individuals had a higher risk of pathologic Short Physical Performance Battery scores.

High intake of magnesium—but not calcium, potassium, or sodium—appeared to reduce the risk of cerebral infarction in male smokers, reported researchers in the March 10 Archives of Internal Medicine. In a study of 26,556 Finnish male smokers ages 50 to 69 at baseline, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages occurred during a mean follow-up of 13.6 years. Men in the highest quintile of magnesium intake had a 0.85 relative risk of cerebral infarction compared with those in the lowest quintile; the inverse association was stronger in men younger than 60 (relative risk, 0.76). No other minerals were significantly associated with risk of any subtype of stroke. The researchers suggested that high magnesium intake may play a role in the primary prevention of cerebral infarction.

Disclosure of a dementia diagnosis resulted in relief rather than a “catastrophic emotional reaction” among 90 individuals with suspected Alzheimer’s disease and their companions. As reported in the March Journal of the American Geriatrics Society, 69% of the participants were diagnosed with dementia; however, Geriatric Depression Scale scores did not change significantly compared with prediagnosis scores. Instead, a substantial decrease in State-Trait Anxiety Inventory was observed, even among those patients who were only mildly cognitively impaired. The authors suggested that patients and their families may appreciate the explanation of symptoms and the development of a treatment plan that comes with a diagnosis.

Overexpression of the cdk5 activator p25 led to increased amyloidogenic processing of amyloid precursor protein, which may have implications for Alzheimer’s disease pathogenesis, reported researchers in the March 13 Neuron. Mice that overexpressed p25 showed elevated levels of BACE1 mRNA and protein pSTAT3, whereas cdk5-deficient mice had reduced levels; a targeted mutation to the STAT3 cdk5 responsive site also led to lower levels of BACE1. The authors noted that transcriptional control of BACE1 could have implications for Alzheimer’s disease. As a cdk5 inhibitor reversed BACE-driven amyloidgenic processing, it may provide a therapeutic candidate for Alzheimer’s disease.

Maximum carotid plaque thickness was associated with an increased risk of vascular outcomes, especially among Hispanics, in an analysis of 2,189 subjects in a population-based cohort, as reported in the April 1 Neurology. Carotid plaque was present in 58% of the participants. During the mean 6.9 years of follow-up, vascular events occurred among 319 subjects: 121 had ischemic strokes, 118 had myocardial infarctions, and 166 died of vascular causes. Although there was a 2.8-fold increased risk of combined vascular events among those with carotid plaque thickness greater than the prespecified cutoff of 1.9 mm compared with those with no carotid plaque, the association was only significant among Hispanics after full adjustment. “Approximately 44% of the low-risk individuals … had a 10-year vascular risk of 18.3% if having carotid plaque,” said the researchers. They concluded that maximum carotid plaque thickness may be a useful risk stratification tool and a surrogate end point in clinical trials.

Parenchymal volumetric loss dose-dependently correlated with severity of traumatic brain injury (TBI), according to the results of a study of 69 chronic-phase TBI patients reported in the March 4 Neurology. A minimum of one year after TBI, high-resolution structural MRI also detected a spatially extensive pattern of volume loss that covaried with TBI severity, “with particularly widespread effects in white matter volume and sulcal/subdural CSF.” Of the 38 brain regions imaged, the most reliable effects were observed in the frontal, temporal, and cingulate regions, stated the researchers. They noted that the pattern of volume loss was independent of contributions of focal and diffuse injury, as focal lesions were associated with greater frontal and temporal volume loss, but the loss remained marked when analyses were restricted to patients with diffuse injury.

Researchers have proposed a mechanism for the brain’s conversion to epilepsy following injury. As reported in the March 28 online Proceedings of the National Academy of Sciences, the researchers used a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network. Although the investigators noted that network activity in the dentate gyrus was robust after a number of major changes, “the incorporation of a small number of highly interconnected granule cell hubs greatly increase[d] network activity, resulting in a hyperexcitable, potentially seizure-prone circuit.” They suggested that these neural hub cells may be a therapeutic target for epilepsy.

Impaired olfaction may predate clinical Parkinson’s disease in men by at least four years, reported researchers in the February Annals of Neurology. Olfaction was tested in 2,267 Parkinson’s disease– and dementia-free men ages 71 to 95 for up to eight years. Thirty-five men were diagnosed with Parkinson’s disease at an average age of 82.9. During the first four years of follow-up, age-adjusted incidence of Parkinson’s disease declined from the lowest to the highest quartiles of odor identification; the odds ratio for Parkinson’s disease in the lowest quartile compared with the two highest quartiles was 5.2. The researchers suggested that tests of olfaction may be a useful screening tool for risk of Parkinson’s disease in men.

The net benefit of IV t-PA treatment in patients with ischemic stroke was greater in patients also using antiplatelet drugs, despite an increased risk of symptomatic intracerebral hemorrhage, reported researchers in the March 10 online Archives of Neurology. Of 301 consecutive ischemic stroke patients treated with IV t-PA at a single university hospital, 89 also used antiplatelet drugs prior to thrombolysis. Symptomatic intracerebral hemorrhage occurred in 13.5% of patients who received antiplatelet drugs and in 2.8% of those who did not, and was independently predicted by antiplatelet drug use (odds ratio, 6.0). However, prior antiplatelet therapy was also independently associated with a favorable outcome, defined as a modified Rankin Scale score of 2 or less at three months (odds ratio, 2.0).

The prevalence of cerebral microbleeds is high, increases with age, and may be indicative of an increased risk of cerebrovascular problems, reported researchers in the April 1 Neurology. Among 1,062 study participants 60 and older (mean age, 69.6), the MRI-detected prevalence of cerebral microbleeds increased from 17.8% in those ages 60 to 69 to 38.3% in those older than 80. “APOE ε4 carriers had significantly more often strictly lobar microbleeds than noncarriers,” said the authors, while cardiovascular risk factors and presence of lacunar infarcts and white matter lesions were associated with microbleeds in a deep or infratentorial location.

Pesticide exposure may increase the risk of Parkinson’s disease, according to the results of a family-based case-control study reported in the March 28 BMC Neurology. The 319 patients with Parkinson’s disease were significantly more likely to report direct pesticide application than were their unaffected relatives (odds ratio, 1.61). There was also a dose-response pattern between frequency, duration, and cumulative exposure and Parkinson’s disease. Additional analyses found that insecticides and herbicides increased the risk of Parkinson’s disease, and that two insecticide classes—organochlorines and organophosphorus compounds—were significantly associated with Parkinson’s disease. Consuming well water and living or working on a farm did not appear to increase risk of disease, however.

There may be an association between the severity of age-related white matter changes and the severity of gait and motor compromise, researchers reported in the March 18 Neurology. In the Leukoaraiosis and Disability Study, 639 nondisabled individuals older than 65 were followed for three years. Mean scores on the Short Physical Performance Battery and walking speeds decreased with severity of age-related white matter changes, and balance was best among those with mild age-related white matter changes compared with moderate or severe changes. A history of falls was also twice as likely in those participants with severe versus mild age-related white matter changes, and 1.5 times as likely in those with moderate changes. “Physical activity might have the potential to reduce the risk of limitations in mobility,” noted the authors, as physically inactive individuals had a higher risk of pathologic Short Physical Performance Battery scores.

High intake of magnesium—but not calcium, potassium, or sodium—appeared to reduce the risk of cerebral infarction in male smokers, reported researchers in the March 10 Archives of Internal Medicine. In a study of 26,556 Finnish male smokers ages 50 to 69 at baseline, 2,702 cerebral infarctions, 383 intracerebral hemorrhages, and 196 subarachnoid hemorrhages occurred during a mean follow-up of 13.6 years. Men in the highest quintile of magnesium intake had a 0.85 relative risk of cerebral infarction compared with those in the lowest quintile; the inverse association was stronger in men younger than 60 (relative risk, 0.76). No other minerals were significantly associated with risk of any subtype of stroke. The researchers suggested that high magnesium intake may play a role in the primary prevention of cerebral infarction.

Disclosure of a dementia diagnosis resulted in relief rather than a “catastrophic emotional reaction” among 90 individuals with suspected Alzheimer’s disease and their companions. As reported in the March Journal of the American Geriatrics Society, 69% of the participants were diagnosed with dementia; however, Geriatric Depression Scale scores did not change significantly compared with prediagnosis scores. Instead, a substantial decrease in State-Trait Anxiety Inventory was observed, even among those patients who were only mildly cognitively impaired. The authors suggested that patients and their families may appreciate the explanation of symptoms and the development of a treatment plan that comes with a diagnosis.

Overexpression of the cdk5 activator p25 led to increased amyloidogenic processing of amyloid precursor protein, which may have implications for Alzheimer’s disease pathogenesis, reported researchers in the March 13 Neuron. Mice that overexpressed p25 showed elevated levels of BACE1 mRNA and protein pSTAT3, whereas cdk5-deficient mice had reduced levels; a targeted mutation to the STAT3 cdk5 responsive site also led to lower levels of BACE1. The authors noted that transcriptional control of BACE1 could have implications for Alzheimer’s disease. As a cdk5 inhibitor reversed BACE-driven amyloidgenic processing, it may provide a therapeutic candidate for Alzheimer’s disease.

Maximum carotid plaque thickness was associated with an increased risk of vascular outcomes, especially among Hispanics, in an analysis of 2,189 subjects in a population-based cohort, as reported in the April 1 Neurology. Carotid plaque was present in 58% of the participants. During the mean 6.9 years of follow-up, vascular events occurred among 319 subjects: 121 had ischemic strokes, 118 had myocardial infarctions, and 166 died of vascular causes. Although there was a 2.8-fold increased risk of combined vascular events among those with carotid plaque thickness greater than the prespecified cutoff of 1.9 mm compared with those with no carotid plaque, the association was only significant among Hispanics after full adjustment. “Approximately 44% of the low-risk individuals … had a 10-year vascular risk of 18.3% if having carotid plaque,” said the researchers. They concluded that maximum carotid plaque thickness may be a useful risk stratification tool and a surrogate end point in clinical trials.

Parenchymal volumetric loss dose-dependently correlated with severity of traumatic brain injury (TBI), according to the results of a study of 69 chronic-phase TBI patients reported in the March 4 Neurology. A minimum of one year after TBI, high-resolution structural MRI also detected a spatially extensive pattern of volume loss that covaried with TBI severity, “with particularly widespread effects in white matter volume and sulcal/subdural CSF.” Of the 38 brain regions imaged, the most reliable effects were observed in the frontal, temporal, and cingulate regions, stated the researchers. They noted that the pattern of volume loss was independent of contributions of focal and diffuse injury, as focal lesions were associated with greater frontal and temporal volume loss, but the loss remained marked when analyses were restricted to patients with diffuse injury.

Researchers have proposed a mechanism for the brain’s conversion to epilepsy following injury. As reported in the March 28 online Proceedings of the National Academy of Sciences, the researchers used a large-scale, biophysically realistic model of the epileptic rat dentate gyrus to reconnect the aberrant recurrent granule cell network. Although the investigators noted that network activity in the dentate gyrus was robust after a number of major changes, “the incorporation of a small number of highly interconnected granule cell hubs greatly increase[d] network activity, resulting in a hyperexcitable, potentially seizure-prone circuit.” They suggested that these neural hub cells may be a therapeutic target for epilepsy.

Impaired olfaction may predate clinical Parkinson’s disease in men by at least four years, reported researchers in the February Annals of Neurology. Olfaction was tested in 2,267 Parkinson’s disease– and dementia-free men ages 71 to 95 for up to eight years. Thirty-five men were diagnosed with Parkinson’s disease at an average age of 82.9. During the first four years of follow-up, age-adjusted incidence of Parkinson’s disease declined from the lowest to the highest quartiles of odor identification; the odds ratio for Parkinson’s disease in the lowest quartile compared with the two highest quartiles was 5.2. The researchers suggested that tests of olfaction may be a useful screening tool for risk of Parkinson’s disease in men.