Alzheimer's Disease Challenge Center

The history and findings in this case are suggestive of Alzheimer's disease (AD). 

AD is the most common type of dementia. It is characterized by cognitive and behavioral impairment that significantly impairs a patient's social and occupational functioning. The predominant AD pathogenesis hypothesis suggests that AD is largely caused by the accumulation of insoluble amyloid beta deposits and neurofibrillary tangles induced by highly phosphorylated tau proteins in the neocortex, hippocampus, and amygdala, as well as significant loss of neurons and synapses, which leads to brain atrophy. Estimates suggest that approximately 6.2 million people ≥ 65 years of age have AD and that by 2060, the number of Americans with AD may increase to 13.8 million, the result of an aging population and the lack of effective prevention and treatment strategies. AD is a chronic disease that confers tremendous emotional and economic burdens to individuals, families, and society. 

Insidiously progressive memory loss is commonly seen in patients presenting with AD. As the disease progresses over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes are also observed in many individuals with AD.

Criteria for the clinical diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are frequently employed. Among individuals who meet the core clinical criteria for probable AD dementia, biomarker evidence may help to increase the certainty that AD is the basis of the clinical dementia syndrome. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid beta for AD. Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD as it enables accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT may be used when MRI is not possible, such as in a patient with a pacemaker. 

PET is increasingly being used as a noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, the US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, a significant achievement in improving AD diagnosis. 

Currently, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-d-aspartate antagonist are the standard medical treatment for AD. Recently approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021; and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents are often used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, which can be problematic. Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.

Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD). 

AD is the most common type of dementia. It is characterized by cognitive and behavioral impairment that significantly impairs a patient's social and occupational functioning. The predominant AD pathogenesis hypothesis suggests that AD is largely caused by the accumulation of insoluble amyloid beta deposits and neurofibrillary tangles induced by highly phosphorylated tau proteins in the neocortex, hippocampus, and amygdala, as well as significant loss of neurons and synapses, which leads to brain atrophy. Estimates suggest that approximately 6.2 million people ≥ 65 years of age have AD and that by 2060, the number of Americans with AD may increase to 13.8 million, the result of an aging population and the lack of effective prevention and treatment strategies. AD is a chronic disease that confers tremendous emotional and economic burdens to individuals, families, and society. 

Insidiously progressive memory loss is commonly seen in patients presenting with AD. As the disease progresses over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes are also observed in many individuals with AD.

Criteria for the clinical diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are frequently employed. Among individuals who meet the core clinical criteria for probable AD dementia, biomarker evidence may help to increase the certainty that AD is the basis of the clinical dementia syndrome. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid beta for AD. Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD as it enables accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT may be used when MRI is not possible, such as in a patient with a pacemaker. 

PET is increasingly being used as a noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, the US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, a significant achievement in improving AD diagnosis. 

Currently, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-d-aspartate antagonist are the standard medical treatment for AD. Recently approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021; and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents are often used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, which can be problematic. Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.

Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD). 

AD is the most common type of dementia. It is characterized by cognitive and behavioral impairment that significantly impairs a patient's social and occupational functioning. The predominant AD pathogenesis hypothesis suggests that AD is largely caused by the accumulation of insoluble amyloid beta deposits and neurofibrillary tangles induced by highly phosphorylated tau proteins in the neocortex, hippocampus, and amygdala, as well as significant loss of neurons and synapses, which leads to brain atrophy. Estimates suggest that approximately 6.2 million people ≥ 65 years of age have AD and that by 2060, the number of Americans with AD may increase to 13.8 million, the result of an aging population and the lack of effective prevention and treatment strategies. AD is a chronic disease that confers tremendous emotional and economic burdens to individuals, families, and society. 

Insidiously progressive memory loss is commonly seen in patients presenting with AD. As the disease progresses over the course of several years, other areas of cognition are impaired. Patients may develop language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes are also observed in many individuals with AD.

Criteria for the clinical diagnosis of AD (eg, insidious onset of cognitive impairment, clear history of worsening symptoms) have been developed and are frequently employed. Among individuals who meet the core clinical criteria for probable AD dementia, biomarker evidence may help to increase the certainty that AD is the basis of the clinical dementia syndrome. Several cerebrospinal fluid and blood biomarkers have shown excellent diagnostic ability by identifying tau pathology and cerebral amyloid beta for AD. Neuroimaging is becoming increasingly important for identifying the underlying causes of cognitive impairment. Currently, MRI is considered the preferred neuroimaging modality for AD as it enables accurate measurement of the three-dimensional volume of brain structures, particularly the size of the hippocampus and related regions. CT may be used when MRI is not possible, such as in a patient with a pacemaker. 

PET is increasingly being used as a noninvasive method for depicting tau pathology deposition and distribution in patients with cognitive impairment. In 2020, the US Food and Drug Administration approved the first tau PET tracer, ¹⁸F-flortaucipir, a significant achievement in improving AD diagnosis. 

Currently, the only therapies available for AD are symptomatic therapies. Cholinesterase inhibitors and a partial N-methyl-d-aspartate antagonist are the standard medical treatment for AD. Recently approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021; and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents are often used to treat the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and/or sleep disorders, which can be problematic. Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.

Behavioral interventions, including patient-centered approaches and caregiver training, may also be beneficial for managing the cognitive and behavioral manifestations of AD. These modalities are often used in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Regular physical activity and exercise is also emerging as a potential strategy for delaying AD progression and possibly conferring a protective effect on brain health.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).

AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.

CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD. 

Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials. 

Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).

AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.

CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD. 

Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials. 

Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of Alzheimer's disease (AD), which probably was preceded by chronic traumatic encephalopathy (CTE).

AD is the most prevalent cause of cognitive impairment and dementia worldwide. Presently, approximately 50 million individuals are affected by AD; by 2050, the number of affected individuals globally is expected to reach 152 million. AD has a prolonged and progressive disease course that begins with neuropathologic changes in the brain years before onset of clinical manifestations. These changes include the accumulation of beta-amyloid plaques, neurofibrillary tangles, and neuroinflammation. Neuroimaging studies have shown that beta-amyloid plaques begin to deposit in the brain ≥ 10 years before the start of cognitive decline. Patients with AD normally present with slowly progressive memory loss; as the disease progresses, other areas of cognition are affected. Patients may experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. Slowly progressive behavioral changes may also occur.

CTE is a neurodegenerative disorder that is believed to be the long-term consequence of repetitive head trauma. Its incidence is highest among athletes of high-impact sports, such as boxing or American football, and victims of domestic violence. Clinically, CTE can be indistinguishable from AD. Although neuropathologic differences exist, they can be confirmed only on postmortem examination. Patients with CTE may present with behavioral symptoms, such as aggression, depression, emotional lability, apathy, and suicidal feelings, as well as motor symptoms, including tremor, ataxia, incoordination, and dysarthria. Cognitive symptoms, including attention and concentration deficits and memory impairment, also occur. CTE is also associated with the development of dementia and may predispose patients to early-onset AD. 

Curative therapies do not exist for AD; thus, management centers on symptomatic treatment for neuropsychiatric or cognitive symptoms. Cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist are the standard medical therapies used in patients with AD. For patients with mild cognitive impairment or mild dementia, several newly approved antiamyloid therapies are also available. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Presently, both aducanumab and lecanemab are recommended only for the treatment of patients with mild cognitive impairment or mild dementia, the population in which their safety and efficacy were demonstrated in clinical trials. 

Psychotropic agents may be used to treat symptoms, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders, which can be problematic. Behavioral interventions may also be used, normally in combination with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations). Regular physical activity and exercise may help to delay disease progression and are recommended as an adjunct to the medical management of AD.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of late-onset Alzheimer's disease (AD). 

AD is a neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. At least two thirds of cases of dementia in people ≥ 65 years of age are due to AD, making it the most common type of dementia. At present, there is no cure for AD, which is associated with a long preclinical stage and a progressive disease course. In the United States, AD is the sixth leading cause of death.

Individuals with AD develop amyloid plaques in the hippocampus and in other areas of the cerebral cortex. The symptoms of AD vary depending on the stage of the disease; however, in most patients with late-onset AD (≥ 65 years of age), the most common presenting symptom is episodic short-term memory loss, with relative sparing of long-term memory. Subsequently, patients may experience impairments in problem-solving, judgment, executive functioning, motivation, and organization. It is not uncommon for individuals with AD to lack insight into the impairments they are experiences, or even to deny deficits. 

Neuropsychiatric symptoms, such as apathy, social withdrawal, disinhibition, agitation, psychosis, and wandering are common in the mid- to late stages of the disease. Patients may also experience difficulty performing learned motor tasks (dyspraxia), olfactory dysfunction, and sleep disturbances; develop extrapyramidal motor signs (eg, dystonia, akathisia, and parkinsonian symptoms) followed by difficulties with primitive reflexes and incontinence, and may ultimately become totally dependent on caregivers.

A thorough history and physical examination are essential for the diagnosis of AD. Because some patients may lack insight into their disease, it is vital to elicit a history from the patient's family and caregivers as well. Onset and early symptoms are important to note to aid in differentiating AD from other types of dementia. In most patients with late-onset AD, comprehensive clinical assessment can provide reasonable diagnostic certainty. This should include a detailed neurologic examination to rule out other conditions; most patients with AD will have a normal neurologic exam.

A mental status examination to evaluate concentration, attention, recent and remote memory, language, visuospatial functioning, praxis, and executive functioning should also be conducted. Brief standard examinations, such the Mini-Mental State Examination, can be used for initial screening purposes, although they are less sensitive and specific than more comprehensive tests. Follow-up visits for patients diagnosed with AD should therefore include a full mental status examination to gauge disease progression as well as the development of neuropsychiatric symptoms.

Brain imaging can be beneficial both for diagnosing AD and monitoring the disease's clinical course. MRI or CT of the brain can help eliminate alternate causes of dementia, such as stroke or tumors, from consideration. Dilated lateral ventricles and widened cortical sulci, particularly in the temporal area, are typical findings in AD.

The standard medical treatment for AD includes cholinesterase inhibitors (ChEIs) and a partial N-methyl-D-aspartate (NMDA) antagonist. Both US and European guidelines list ChEIs (donepezil, rivastigmine, galantamine, tacrine) as first-line pharmacotherapies for mild to moderate AD; however, these agents only show modest efficacy on cognitive deficits and nonsignificant efficacy on functional capacity in mild to moderate AD. Memantine, a partial NMDA antagonist, shows very limited efficacy on cognitive symptoms, with no improvement in functional domains. Newly approved anti-amyloid therapies include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents may help to mitigate the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders. Behavioral interventions (eg, patient-centered approaches and caregiver training) may be beneficial for managing the cognitive and behavioral manifestations of AD and are often combined with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise also be beneficial for brain health and delaying disease progression.

Numerous novel agents are under investigation for AD, including anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents (such as NMDA receptor modulators), and brain stimulation.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of late-onset Alzheimer's disease (AD). 

AD is a neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. At least two thirds of cases of dementia in people ≥ 65 years of age are due to AD, making it the most common type of dementia. At present, there is no cure for AD, which is associated with a long preclinical stage and a progressive disease course. In the United States, AD is the sixth leading cause of death.

Individuals with AD develop amyloid plaques in the hippocampus and in other areas of the cerebral cortex. The symptoms of AD vary depending on the stage of the disease; however, in most patients with late-onset AD (≥ 65 years of age), the most common presenting symptom is episodic short-term memory loss, with relative sparing of long-term memory. Subsequently, patients may experience impairments in problem-solving, judgment, executive functioning, motivation, and organization. It is not uncommon for individuals with AD to lack insight into the impairments they are experiences, or even to deny deficits. 

Neuropsychiatric symptoms, such as apathy, social withdrawal, disinhibition, agitation, psychosis, and wandering are common in the mid- to late stages of the disease. Patients may also experience difficulty performing learned motor tasks (dyspraxia), olfactory dysfunction, and sleep disturbances; develop extrapyramidal motor signs (eg, dystonia, akathisia, and parkinsonian symptoms) followed by difficulties with primitive reflexes and incontinence, and may ultimately become totally dependent on caregivers.

A thorough history and physical examination are essential for the diagnosis of AD. Because some patients may lack insight into their disease, it is vital to elicit a history from the patient's family and caregivers as well. Onset and early symptoms are important to note to aid in differentiating AD from other types of dementia. In most patients with late-onset AD, comprehensive clinical assessment can provide reasonable diagnostic certainty. This should include a detailed neurologic examination to rule out other conditions; most patients with AD will have a normal neurologic exam.

A mental status examination to evaluate concentration, attention, recent and remote memory, language, visuospatial functioning, praxis, and executive functioning should also be conducted. Brief standard examinations, such the Mini-Mental State Examination, can be used for initial screening purposes, although they are less sensitive and specific than more comprehensive tests. Follow-up visits for patients diagnosed with AD should therefore include a full mental status examination to gauge disease progression as well as the development of neuropsychiatric symptoms.

Brain imaging can be beneficial both for diagnosing AD and monitoring the disease's clinical course. MRI or CT of the brain can help eliminate alternate causes of dementia, such as stroke or tumors, from consideration. Dilated lateral ventricles and widened cortical sulci, particularly in the temporal area, are typical findings in AD.

The standard medical treatment for AD includes cholinesterase inhibitors (ChEIs) and a partial N-methyl-D-aspartate (NMDA) antagonist. Both US and European guidelines list ChEIs (donepezil, rivastigmine, galantamine, tacrine) as first-line pharmacotherapies for mild to moderate AD; however, these agents only show modest efficacy on cognitive deficits and nonsignificant efficacy on functional capacity in mild to moderate AD. Memantine, a partial NMDA antagonist, shows very limited efficacy on cognitive symptoms, with no improvement in functional domains. Newly approved anti-amyloid therapies include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents may help to mitigate the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders. Behavioral interventions (eg, patient-centered approaches and caregiver training) may be beneficial for managing the cognitive and behavioral manifestations of AD and are often combined with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise also be beneficial for brain health and delaying disease progression.

Numerous novel agents are under investigation for AD, including anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents (such as NMDA receptor modulators), and brain stimulation.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of late-onset Alzheimer's disease (AD). 

AD is a neurodegenerative disease associated with progressive impairment of behavioral and cognitive functions, including memory, comprehension, language, attention, reasoning, and judgment. At least two thirds of cases of dementia in people ≥ 65 years of age are due to AD, making it the most common type of dementia. At present, there is no cure for AD, which is associated with a long preclinical stage and a progressive disease course. In the United States, AD is the sixth leading cause of death.

Individuals with AD develop amyloid plaques in the hippocampus and in other areas of the cerebral cortex. The symptoms of AD vary depending on the stage of the disease; however, in most patients with late-onset AD (≥ 65 years of age), the most common presenting symptom is episodic short-term memory loss, with relative sparing of long-term memory. Subsequently, patients may experience impairments in problem-solving, judgment, executive functioning, motivation, and organization. It is not uncommon for individuals with AD to lack insight into the impairments they are experiences, or even to deny deficits. 

Neuropsychiatric symptoms, such as apathy, social withdrawal, disinhibition, agitation, psychosis, and wandering are common in the mid- to late stages of the disease. Patients may also experience difficulty performing learned motor tasks (dyspraxia), olfactory dysfunction, and sleep disturbances; develop extrapyramidal motor signs (eg, dystonia, akathisia, and parkinsonian symptoms) followed by difficulties with primitive reflexes and incontinence, and may ultimately become totally dependent on caregivers.

A thorough history and physical examination are essential for the diagnosis of AD. Because some patients may lack insight into their disease, it is vital to elicit a history from the patient's family and caregivers as well. Onset and early symptoms are important to note to aid in differentiating AD from other types of dementia. In most patients with late-onset AD, comprehensive clinical assessment can provide reasonable diagnostic certainty. This should include a detailed neurologic examination to rule out other conditions; most patients with AD will have a normal neurologic exam.

A mental status examination to evaluate concentration, attention, recent and remote memory, language, visuospatial functioning, praxis, and executive functioning should also be conducted. Brief standard examinations, such the Mini-Mental State Examination, can be used for initial screening purposes, although they are less sensitive and specific than more comprehensive tests. Follow-up visits for patients diagnosed with AD should therefore include a full mental status examination to gauge disease progression as well as the development of neuropsychiatric symptoms.

Brain imaging can be beneficial both for diagnosing AD and monitoring the disease's clinical course. MRI or CT of the brain can help eliminate alternate causes of dementia, such as stroke or tumors, from consideration. Dilated lateral ventricles and widened cortical sulci, particularly in the temporal area, are typical findings in AD.

The standard medical treatment for AD includes cholinesterase inhibitors (ChEIs) and a partial N-methyl-D-aspartate (NMDA) antagonist. Both US and European guidelines list ChEIs (donepezil, rivastigmine, galantamine, tacrine) as first-line pharmacotherapies for mild to moderate AD; however, these agents only show modest efficacy on cognitive deficits and nonsignificant efficacy on functional capacity in mild to moderate AD. Memantine, a partial NMDA antagonist, shows very limited efficacy on cognitive symptoms, with no improvement in functional domains. Newly approved anti-amyloid therapies include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents may help to mitigate the secondary symptoms of AD, such as depression, agitation, aggression, hallucinations, delusions, and sleep disorders. Behavioral interventions (eg, patient-centered approaches and caregiver training) may be beneficial for managing the cognitive and behavioral manifestations of AD and are often combined with pharmacologic interventions (eg, anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, antidepressants or mood stabilizers for mood disorders). Regular physical activity and exercise also be beneficial for brain health and delaying disease progression.

Numerous novel agents are under investigation for AD, including anti-tau therapy, anti-neuroinflammatory therapy, neuroprotective agents (such as NMDA receptor modulators), and brain stimulation.

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of early-onset Alzheimer's disease (AD) with aphasia. 

AD is a neurodegenerative disorder characterized by cognitive and behavioral impairment that significantly interferes with a patient's social and occupational functioning. There is currently no cure for AD, which has a long preclinical period and a progressive course. Individuals with AD develop amyloid plaques in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are involved in thinking and making decisions.

Patients with AD typically present with insidiously progressive memory loss; over the course of several years, other areas of cognition are impaired. Subsequent to memory loss, patients may also experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. In many patients, slowly progressive behavioral changes are also observed.

AD is most prevalent in individuals older than 65 years; however, early‐onset AD (in individuals aged 60 years or older) can also occur. Early-onset AD shares the same essential neuropathological characteristics (ie, amyloid plaques and neurofibrillary tangles) as late-onset (65 years or older) AD, but it differs in several ways. For example, memory loss is an extremely common presenting symptom in late-onset AD, whereas nonamnestic presentation (ie, language, visuospatial, or executive impairment) is very rare, occurring in only about 5% of cases. Conversely, nonamnestic presentations may occur in 30%-40% of patients with early-onset AD. Frequent nonamnestic cognitive manifestations in patients with early-onset AD are those seen in mild to moderate AD, including visual agnosia (55.1%), aphasia (57.9%), and behavioral changes (61.7%). In addition, several studies have suggested that early-onset AD may have a more aggressive course than late-onset AD does, including faster cognitive and functional decline.

Presently, only symptomatic therapies are available for AD. The standard medical treatment for AD includes cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist. Newly approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents may be used to treat the secondary symptoms of AD (eg, depression, agitation, aggression, hallucinations, delusions, sleep disorders), which can be problematic. Behavioral interventions ranging from patient-centered approaches to caregiver training may also be used to help manage cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Routine physical activity and exercise may affect AD progression and may possibly exert a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of early-onset Alzheimer's disease (AD) with aphasia. 

AD is a neurodegenerative disorder characterized by cognitive and behavioral impairment that significantly interferes with a patient's social and occupational functioning. There is currently no cure for AD, which has a long preclinical period and a progressive course. Individuals with AD develop amyloid plaques in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are involved in thinking and making decisions.

Patients with AD typically present with insidiously progressive memory loss; over the course of several years, other areas of cognition are impaired. Subsequent to memory loss, patients may also experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. In many patients, slowly progressive behavioral changes are also observed.

AD is most prevalent in individuals older than 65 years; however, early‐onset AD (in individuals aged 60 years or older) can also occur. Early-onset AD shares the same essential neuropathological characteristics (ie, amyloid plaques and neurofibrillary tangles) as late-onset (65 years or older) AD, but it differs in several ways. For example, memory loss is an extremely common presenting symptom in late-onset AD, whereas nonamnestic presentation (ie, language, visuospatial, or executive impairment) is very rare, occurring in only about 5% of cases. Conversely, nonamnestic presentations may occur in 30%-40% of patients with early-onset AD. Frequent nonamnestic cognitive manifestations in patients with early-onset AD are those seen in mild to moderate AD, including visual agnosia (55.1%), aphasia (57.9%), and behavioral changes (61.7%). In addition, several studies have suggested that early-onset AD may have a more aggressive course than late-onset AD does, including faster cognitive and functional decline.

Presently, only symptomatic therapies are available for AD. The standard medical treatment for AD includes cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist. Newly approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents may be used to treat the secondary symptoms of AD (eg, depression, agitation, aggression, hallucinations, delusions, sleep disorders), which can be problematic. Behavioral interventions ranging from patient-centered approaches to caregiver training may also be used to help manage cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Routine physical activity and exercise may affect AD progression and may possibly exert a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.

The history and findings in this case are suggestive of early-onset Alzheimer's disease (AD) with aphasia. 

AD is a neurodegenerative disorder characterized by cognitive and behavioral impairment that significantly interferes with a patient's social and occupational functioning. There is currently no cure for AD, which has a long preclinical period and a progressive course. Individuals with AD develop amyloid plaques in the hippocampus, a structure deep in the brain that helps to encode memories, and in other areas of the cerebral cortex that are involved in thinking and making decisions.

Patients with AD typically present with insidiously progressive memory loss; over the course of several years, other areas of cognition are impaired. Subsequent to memory loss, patients may also experience language disorders (eg, anomic aphasia or anomia) and impairment in visuospatial skills and executive functions. In many patients, slowly progressive behavioral changes are also observed.

AD is most prevalent in individuals older than 65 years; however, early‐onset AD (in individuals aged 60 years or older) can also occur. Early-onset AD shares the same essential neuropathological characteristics (ie, amyloid plaques and neurofibrillary tangles) as late-onset (65 years or older) AD, but it differs in several ways. For example, memory loss is an extremely common presenting symptom in late-onset AD, whereas nonamnestic presentation (ie, language, visuospatial, or executive impairment) is very rare, occurring in only about 5% of cases. Conversely, nonamnestic presentations may occur in 30%-40% of patients with early-onset AD. Frequent nonamnestic cognitive manifestations in patients with early-onset AD are those seen in mild to moderate AD, including visual agnosia (55.1%), aphasia (57.9%), and behavioral changes (61.7%). In addition, several studies have suggested that early-onset AD may have a more aggressive course than late-onset AD does, including faster cognitive and functional decline.

Presently, only symptomatic therapies are available for AD. The standard medical treatment for AD includes cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist. Newly approved antiamyloid therapies are also available for patients with mild cognitive impairment or mild dementia. These include aducanumab, a first-in-class amyloid beta–directed antibody that was approved in 2021, and lecanemab, another amyloid beta–directed antibody that was approved in 2023. Both aducanumab and lecanemab are recommended for the treatment of patients with mild cognitive impairment or mild dementia stage of disease, the population in which the safety and efficacy of these newer agents were demonstrated in clinical trials. 

Psychotropic agents may be used to treat the secondary symptoms of AD (eg, depression, agitation, aggression, hallucinations, delusions, sleep disorders), which can be problematic. Behavioral interventions ranging from patient-centered approaches to caregiver training may also be used to help manage cognitive and behavioral manifestations of AD, often in combination with pharmacologic interventions, such as anxiolytics for anxiety and agitation, neuroleptics for delusions or hallucinations, and antidepressants or mood stabilizers for mood disorders and specific manifestations (eg, episodes of anger or rage). Routine physical activity and exercise may affect AD progression and may possibly exert a protective effect on brain health. 

Jasvinder Chawla, MD, Professor of Neurology, Loyola University Medical Center, Maywood; Director, Clinical Neurophysiology Lab, Department of Neurology, Hines VA Hospital, Hines, IL.

Jasvinder Chawla, MD, has disclosed no relevant financial relationships.

Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.