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Progressive cognitive decline
Individuals with DS are at significantly increased risk of developing Alzheimer’s disease (AD) because of the overexpression of the amyloid precursor protein (APP) gene on chromosome 21.
The patient exhibits hallmark symptoms of AD, including progressive memory loss, disorientation, difficulty performing daily tasks, and behavioral changes such as irritability and social withdrawal. The MRI findings of ventricular enlargement and cortical atrophy are consistent with brain changes commonly seen in AD, particularly in individuals with DS who often develop these changes earlier in life (typically in their thirties or forties).
Frontotemporal dementia primarily causes behavioral and language changes with relative memory sparing early on, making it inconsistent with this patient's prominent memory loss, disorientation, and generalized cortical atrophy — features more typical of AD.
Vascular dementia often presents with stepwise decline and focal neurologic deficits; it is unlikely in this patient, given the absence of cerebrovascular events or risk factors like hypertension or diabetes.
While normal pressure hydrocephalus can cause ventricular enlargement, its classic triad of gait disturbance, urinary incontinence, and dementia is incomplete here, making this answer unlikely.
DS is the most common genetic cause of intellectual disability, occurring in approximately 1 in 700 live births worldwide. Nearly all adults with DS develop neuropathologic changes associated with AD by age 40, and the lifetime risk of developing dementia exceeds 90%; by the age of 55-60, at least 70% of individuals with DS exhibit clinical signs of dementia.
The link between DS and neurodegeneration is largely attributed to the triplication of chromosome 21, which includes the APP gene. Overexpression of APP leads to excessive production and accumulation of amyloid-β (Aβ), which forms the hallmark plaques seen in AD. In DS, amyloid plaques begin to form as early as the teenage years, and by the fourth decade, neurofibrillary tangles (tau protein aggregates) and widespread neurodegeneration are nearly universal.
Initial symptoms of AD often include memory impairment, particularly short-term memory deficits, and executive dysfunction, difficulty with planning and problem-solving, and visuospatial deficits. Behavioral and personality changes, such as irritability, withdrawal, or apathy, are also commonly reported. Compared with sporadic AD, individuals with DS often show earlier behavioral symptoms, including impulsivity and changes in social interactions, which may precede noticeable memory deficits. Additionally, late-onset myoclonic epilepsy is common in individuals with DS and dementia, further complicating diagnosis and care.
The diagnosis of dementia in DS is challenging because of baseline intellectual disability, which makes it difficult to assess cognitive decline using standard neuropsychological tests. However, a combination of clinical history, caregiver reports, neuroimaging, and biomarker analysis can aid in early detection. Structural MRI of the brain often reveals ventricular enlargement and cortical atrophy, while PET imaging can detect early amyloid and tau accumulation.
Because AD is now the leading cause of death in individuals with DS, the lack of effective disease-modifying treatments highlights an important need for clinical trials focused on this population. Current research aims to explore the role of anti-amyloid monoclonal antibodies, neuroprotective agents, and lifestyle interventions to delay or prevent neurodegeneration.
Shaheen E. Lakhan, MD, PhD, MS, MEd, Chief of Pain Management, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
Disclosure: Shaheen E. Lakhan, MD, PhD, MS, MEd, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Individuals with DS are at significantly increased risk of developing Alzheimer’s disease (AD) because of the overexpression of the amyloid precursor protein (APP) gene on chromosome 21.
The patient exhibits hallmark symptoms of AD, including progressive memory loss, disorientation, difficulty performing daily tasks, and behavioral changes such as irritability and social withdrawal. The MRI findings of ventricular enlargement and cortical atrophy are consistent with brain changes commonly seen in AD, particularly in individuals with DS who often develop these changes earlier in life (typically in their thirties or forties).
Frontotemporal dementia primarily causes behavioral and language changes with relative memory sparing early on, making it inconsistent with this patient's prominent memory loss, disorientation, and generalized cortical atrophy — features more typical of AD.
Vascular dementia often presents with stepwise decline and focal neurologic deficits; it is unlikely in this patient, given the absence of cerebrovascular events or risk factors like hypertension or diabetes.
While normal pressure hydrocephalus can cause ventricular enlargement, its classic triad of gait disturbance, urinary incontinence, and dementia is incomplete here, making this answer unlikely.
DS is the most common genetic cause of intellectual disability, occurring in approximately 1 in 700 live births worldwide. Nearly all adults with DS develop neuropathologic changes associated with AD by age 40, and the lifetime risk of developing dementia exceeds 90%; by the age of 55-60, at least 70% of individuals with DS exhibit clinical signs of dementia.
The link between DS and neurodegeneration is largely attributed to the triplication of chromosome 21, which includes the APP gene. Overexpression of APP leads to excessive production and accumulation of amyloid-β (Aβ), which forms the hallmark plaques seen in AD. In DS, amyloid plaques begin to form as early as the teenage years, and by the fourth decade, neurofibrillary tangles (tau protein aggregates) and widespread neurodegeneration are nearly universal.
Initial symptoms of AD often include memory impairment, particularly short-term memory deficits, and executive dysfunction, difficulty with planning and problem-solving, and visuospatial deficits. Behavioral and personality changes, such as irritability, withdrawal, or apathy, are also commonly reported. Compared with sporadic AD, individuals with DS often show earlier behavioral symptoms, including impulsivity and changes in social interactions, which may precede noticeable memory deficits. Additionally, late-onset myoclonic epilepsy is common in individuals with DS and dementia, further complicating diagnosis and care.
The diagnosis of dementia in DS is challenging because of baseline intellectual disability, which makes it difficult to assess cognitive decline using standard neuropsychological tests. However, a combination of clinical history, caregiver reports, neuroimaging, and biomarker analysis can aid in early detection. Structural MRI of the brain often reveals ventricular enlargement and cortical atrophy, while PET imaging can detect early amyloid and tau accumulation.
Because AD is now the leading cause of death in individuals with DS, the lack of effective disease-modifying treatments highlights an important need for clinical trials focused on this population. Current research aims to explore the role of anti-amyloid monoclonal antibodies, neuroprotective agents, and lifestyle interventions to delay or prevent neurodegeneration.
Shaheen E. Lakhan, MD, PhD, MS, MEd, Chief of Pain Management, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
Disclosure: Shaheen E. Lakhan, MD, PhD, MS, MEd, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Individuals with DS are at significantly increased risk of developing Alzheimer’s disease (AD) because of the overexpression of the amyloid precursor protein (APP) gene on chromosome 21.
The patient exhibits hallmark symptoms of AD, including progressive memory loss, disorientation, difficulty performing daily tasks, and behavioral changes such as irritability and social withdrawal. The MRI findings of ventricular enlargement and cortical atrophy are consistent with brain changes commonly seen in AD, particularly in individuals with DS who often develop these changes earlier in life (typically in their thirties or forties).
Frontotemporal dementia primarily causes behavioral and language changes with relative memory sparing early on, making it inconsistent with this patient's prominent memory loss, disorientation, and generalized cortical atrophy — features more typical of AD.
Vascular dementia often presents with stepwise decline and focal neurologic deficits; it is unlikely in this patient, given the absence of cerebrovascular events or risk factors like hypertension or diabetes.
While normal pressure hydrocephalus can cause ventricular enlargement, its classic triad of gait disturbance, urinary incontinence, and dementia is incomplete here, making this answer unlikely.
DS is the most common genetic cause of intellectual disability, occurring in approximately 1 in 700 live births worldwide. Nearly all adults with DS develop neuropathologic changes associated with AD by age 40, and the lifetime risk of developing dementia exceeds 90%; by the age of 55-60, at least 70% of individuals with DS exhibit clinical signs of dementia.
The link between DS and neurodegeneration is largely attributed to the triplication of chromosome 21, which includes the APP gene. Overexpression of APP leads to excessive production and accumulation of amyloid-β (Aβ), which forms the hallmark plaques seen in AD. In DS, amyloid plaques begin to form as early as the teenage years, and by the fourth decade, neurofibrillary tangles (tau protein aggregates) and widespread neurodegeneration are nearly universal.
Initial symptoms of AD often include memory impairment, particularly short-term memory deficits, and executive dysfunction, difficulty with planning and problem-solving, and visuospatial deficits. Behavioral and personality changes, such as irritability, withdrawal, or apathy, are also commonly reported. Compared with sporadic AD, individuals with DS often show earlier behavioral symptoms, including impulsivity and changes in social interactions, which may precede noticeable memory deficits. Additionally, late-onset myoclonic epilepsy is common in individuals with DS and dementia, further complicating diagnosis and care.
The diagnosis of dementia in DS is challenging because of baseline intellectual disability, which makes it difficult to assess cognitive decline using standard neuropsychological tests. However, a combination of clinical history, caregiver reports, neuroimaging, and biomarker analysis can aid in early detection. Structural MRI of the brain often reveals ventricular enlargement and cortical atrophy, while PET imaging can detect early amyloid and tau accumulation.
Because AD is now the leading cause of death in individuals with DS, the lack of effective disease-modifying treatments highlights an important need for clinical trials focused on this population. Current research aims to explore the role of anti-amyloid monoclonal antibodies, neuroprotective agents, and lifestyle interventions to delay or prevent neurodegeneration.
Shaheen E. Lakhan, MD, PhD, MS, MEd, Chief of Pain Management, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
Disclosure: Shaheen E. Lakhan, MD, PhD, MS, MEd, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
A 40-year-old man with Down syndrome (DS) presented with progressive cognitive decline over 2 years, characterized by memory impairment, difficulty performing familiar tasks, and increasing disorientation. His caregivers noted mood changes, including irritability and withdrawal, and occasional episodes of agitation. Clinical history revealed congenital heart disease (surgically repaired in childhood) and hypothyroidism, which was well controlled with levothyroxine. Physical examination showed no focal neurologic deficits, but he exhibited mild hypotonia, a characteristic feature of DS, and a shuffling gait. Routine blood tests revealed normal thyroid function, no evidence of vitamin B12 deficiency, and unremarkable metabolic panels. An MRI scan (as shown in the image) demonstrated marked ventricular enlargement and generalized cortical atrophy.
Alzheimer's Disease & Down Syndrome
Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Editor's Note: This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
Loss of appetite and mood fluctuations
Given the patient's results on the genetic panel and MRI, as well as the noted cognitive decline and increased aggression, this patient is suspected of having limbic-predominant age-related TDP-43 encephalopathy (LATE) secondary to AD and is referred to the neurologist on her multidisciplinary care team for further consultation and testing.
AD is one of the most common forms of dementia. More than 6 million people in the United States have clinical AD or mild cognitive impairment because of AD. LATE is a new classification of dementia, identified in 2019, that mimics AD but is a unique disease entity driven by the misfolding of the protein TDP-43, which regulates gene expression in the brain. Misfolded TDP-43 protein is common among older adults aged ≥ 85 years, and about a quarter of this population has enough misfolded TDP-43 protein to affect their memory and cognition.
Diagnosing AD currently relies on a clinical approach. A complete physical examination, with a detailed neurologic examination and a mental status examination, is used to evaluate disease stage. Initial mental status testing evaluates attention and concentration, recent and remote memory, language, praxis, executive function, and visuospatial function. Because LATE is a newly discovered form of dementia, there are no set guidelines on diagnosing LATE and no robust biomarker for TDP-43. What is known about LATE has been gleaned mostly from retrospective clinicopathologic studies.
The LATE consensus working group reports that the clinical course of disease, as studied by autopsy-proven LATE neuropathologic change (LATE-NC), is described as an "amnestic cognitive syndrome that can evolve to incorporate multiple cognitive domains and ultimately to impair activities of daily living." Researchers are currently analyzing different clinical assessments and neuroimaging with MRI to characterize LATE. A group of international researchers recently published a set of clinical criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS), which is associated with LATE-NC. Their criteria include "core, standard and advanced features that are measurable in vivo, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degenerative patterns and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate, low)." Other neuroimaging studies of autopsy-confirmed LATE-NC have shown that atrophy is mostly focused in the medial temporal lobe with marked reduced hippocampal volume.
The group reports that LATE and AD probably share pathophysiologic mechanisms. One of the universally accepted hallmarks of AD is the formation of beta-amyloid plaques, which are dense, mostly insoluble deposits of beta-amyloid protein that develop around neurons in the hippocampus and other regions in the cerebral cortex used for decision-making. These plaques disrupt brain function and lead to brain atrophy. The LATE group also reports that this same pathology has been noted with LATE: "Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy." That said, genetic studies have helped identify five genes with risk alleles for LATE (GRN, TMEM106B, ABCC9, KCNMB2, and APOE), suggesting disease-specific underlying mechanisms compared to AD.
Patient and caregiver education and guidance is vital with a dementia diagnosis. If LATE and/or AD are suspected, physicians should encourage the involvement of family and friends who agree to become more involved in the patient's care as the disease progresses. These individuals need to understand the patient's wishes around care, especially for the future when the patient is no longer able to make decisions. The patient may also consider establishing medical advance directives and durable power of attorney for medical and financial decision-making. Caregivers supporting the patient are encouraged to help balance the physical needs of the patient while maintaining respect for them as a competent adult to the extent allowed by the progression of their disease.
Because LATE is a new classification of dementia, there are no known effective treatments. One ongoing study is testing the use of autologous bone marrow–derived stem cells to help improve cognitive impairment among patients with LATE, AD, and other dementias. Current AD treatments are focused on symptomatic therapies that modulate neurotransmitters — either acetylcholine or glutamate. The standard medical treatment includes cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist. Two amyloid-directed antibodies (aducanumab, lecanemab) are currently available in the United States for individuals with AD exhibiting mild cognitive impairment or mild dementia. A third agent currently in clinical trials (donanemab) has shown significantly slowed clinical progression after 1.5 years among clinical trial participants with early symptomatic AD and amyloid and tau pathology.
Shaheen E. Lakhan, MD, PhD, MS, MEd, Chief of Pain Management, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
Disclosure: Shaheen E. Lakhan, MD, PhD, MS, MEd, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Given the patient's results on the genetic panel and MRI, as well as the noted cognitive decline and increased aggression, this patient is suspected of having limbic-predominant age-related TDP-43 encephalopathy (LATE) secondary to AD and is referred to the neurologist on her multidisciplinary care team for further consultation and testing.
AD is one of the most common forms of dementia. More than 6 million people in the United States have clinical AD or mild cognitive impairment because of AD. LATE is a new classification of dementia, identified in 2019, that mimics AD but is a unique disease entity driven by the misfolding of the protein TDP-43, which regulates gene expression in the brain. Misfolded TDP-43 protein is common among older adults aged ≥ 85 years, and about a quarter of this population has enough misfolded TDP-43 protein to affect their memory and cognition.
Diagnosing AD currently relies on a clinical approach. A complete physical examination, with a detailed neurologic examination and a mental status examination, is used to evaluate disease stage. Initial mental status testing evaluates attention and concentration, recent and remote memory, language, praxis, executive function, and visuospatial function. Because LATE is a newly discovered form of dementia, there are no set guidelines on diagnosing LATE and no robust biomarker for TDP-43. What is known about LATE has been gleaned mostly from retrospective clinicopathologic studies.
The LATE consensus working group reports that the clinical course of disease, as studied by autopsy-proven LATE neuropathologic change (LATE-NC), is described as an "amnestic cognitive syndrome that can evolve to incorporate multiple cognitive domains and ultimately to impair activities of daily living." Researchers are currently analyzing different clinical assessments and neuroimaging with MRI to characterize LATE. A group of international researchers recently published a set of clinical criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS), which is associated with LATE-NC. Their criteria include "core, standard and advanced features that are measurable in vivo, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degenerative patterns and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate, low)." Other neuroimaging studies of autopsy-confirmed LATE-NC have shown that atrophy is mostly focused in the medial temporal lobe with marked reduced hippocampal volume.
The group reports that LATE and AD probably share pathophysiologic mechanisms. One of the universally accepted hallmarks of AD is the formation of beta-amyloid plaques, which are dense, mostly insoluble deposits of beta-amyloid protein that develop around neurons in the hippocampus and other regions in the cerebral cortex used for decision-making. These plaques disrupt brain function and lead to brain atrophy. The LATE group also reports that this same pathology has been noted with LATE: "Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy." That said, genetic studies have helped identify five genes with risk alleles for LATE (GRN, TMEM106B, ABCC9, KCNMB2, and APOE), suggesting disease-specific underlying mechanisms compared to AD.
Patient and caregiver education and guidance is vital with a dementia diagnosis. If LATE and/or AD are suspected, physicians should encourage the involvement of family and friends who agree to become more involved in the patient's care as the disease progresses. These individuals need to understand the patient's wishes around care, especially for the future when the patient is no longer able to make decisions. The patient may also consider establishing medical advance directives and durable power of attorney for medical and financial decision-making. Caregivers supporting the patient are encouraged to help balance the physical needs of the patient while maintaining respect for them as a competent adult to the extent allowed by the progression of their disease.
Because LATE is a new classification of dementia, there are no known effective treatments. One ongoing study is testing the use of autologous bone marrow–derived stem cells to help improve cognitive impairment among patients with LATE, AD, and other dementias. Current AD treatments are focused on symptomatic therapies that modulate neurotransmitters — either acetylcholine or glutamate. The standard medical treatment includes cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist. Two amyloid-directed antibodies (aducanumab, lecanemab) are currently available in the United States for individuals with AD exhibiting mild cognitive impairment or mild dementia. A third agent currently in clinical trials (donanemab) has shown significantly slowed clinical progression after 1.5 years among clinical trial participants with early symptomatic AD and amyloid and tau pathology.
Shaheen E. Lakhan, MD, PhD, MS, MEd, Chief of Pain Management, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
Disclosure: Shaheen E. Lakhan, MD, PhD, MS, MEd, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
Given the patient's results on the genetic panel and MRI, as well as the noted cognitive decline and increased aggression, this patient is suspected of having limbic-predominant age-related TDP-43 encephalopathy (LATE) secondary to AD and is referred to the neurologist on her multidisciplinary care team for further consultation and testing.
AD is one of the most common forms of dementia. More than 6 million people in the United States have clinical AD or mild cognitive impairment because of AD. LATE is a new classification of dementia, identified in 2019, that mimics AD but is a unique disease entity driven by the misfolding of the protein TDP-43, which regulates gene expression in the brain. Misfolded TDP-43 protein is common among older adults aged ≥ 85 years, and about a quarter of this population has enough misfolded TDP-43 protein to affect their memory and cognition.
Diagnosing AD currently relies on a clinical approach. A complete physical examination, with a detailed neurologic examination and a mental status examination, is used to evaluate disease stage. Initial mental status testing evaluates attention and concentration, recent and remote memory, language, praxis, executive function, and visuospatial function. Because LATE is a newly discovered form of dementia, there are no set guidelines on diagnosing LATE and no robust biomarker for TDP-43. What is known about LATE has been gleaned mostly from retrospective clinicopathologic studies.
The LATE consensus working group reports that the clinical course of disease, as studied by autopsy-proven LATE neuropathologic change (LATE-NC), is described as an "amnestic cognitive syndrome that can evolve to incorporate multiple cognitive domains and ultimately to impair activities of daily living." Researchers are currently analyzing different clinical assessments and neuroimaging with MRI to characterize LATE. A group of international researchers recently published a set of clinical criteria for limbic-predominant amnestic neurodegenerative syndrome (LANS), which is associated with LATE-NC. Their criteria include "core, standard and advanced features that are measurable in vivo, including older age at evaluation, mild clinical syndrome, disproportionate hippocampal atrophy, impaired semantic memory, limbic hypometabolism, absence of neocortical degenerative patterns and low likelihood of neocortical tau, with degrees of certainty (highest, high, moderate, low)." Other neuroimaging studies of autopsy-confirmed LATE-NC have shown that atrophy is mostly focused in the medial temporal lobe with marked reduced hippocampal volume.
The group reports that LATE and AD probably share pathophysiologic mechanisms. One of the universally accepted hallmarks of AD is the formation of beta-amyloid plaques, which are dense, mostly insoluble deposits of beta-amyloid protein that develop around neurons in the hippocampus and other regions in the cerebral cortex used for decision-making. These plaques disrupt brain function and lead to brain atrophy. The LATE group also reports that this same pathology has been noted with LATE: "Many subjects with LATE-NC have comorbid brain pathologies, often including amyloid-beta plaques and tauopathy." That said, genetic studies have helped identify five genes with risk alleles for LATE (GRN, TMEM106B, ABCC9, KCNMB2, and APOE), suggesting disease-specific underlying mechanisms compared to AD.
Patient and caregiver education and guidance is vital with a dementia diagnosis. If LATE and/or AD are suspected, physicians should encourage the involvement of family and friends who agree to become more involved in the patient's care as the disease progresses. These individuals need to understand the patient's wishes around care, especially for the future when the patient is no longer able to make decisions. The patient may also consider establishing medical advance directives and durable power of attorney for medical and financial decision-making. Caregivers supporting the patient are encouraged to help balance the physical needs of the patient while maintaining respect for them as a competent adult to the extent allowed by the progression of their disease.
Because LATE is a new classification of dementia, there are no known effective treatments. One ongoing study is testing the use of autologous bone marrow–derived stem cells to help improve cognitive impairment among patients with LATE, AD, and other dementias. Current AD treatments are focused on symptomatic therapies that modulate neurotransmitters — either acetylcholine or glutamate. The standard medical treatment includes cholinesterase inhibitors and a partial N-methyl-D-aspartate antagonist. Two amyloid-directed antibodies (aducanumab, lecanemab) are currently available in the United States for individuals with AD exhibiting mild cognitive impairment or mild dementia. A third agent currently in clinical trials (donanemab) has shown significantly slowed clinical progression after 1.5 years among clinical trial participants with early symptomatic AD and amyloid and tau pathology.
Shaheen E. Lakhan, MD, PhD, MS, MEd, Chief of Pain Management, Carilion Clinic and Virginia Tech Carilion School of Medicine, Roanoke, Virginia.
Disclosure: Shaheen E. Lakhan, MD, PhD, MS, MEd, has disclosed no relevant financial relationships.
Image Quizzes are fictional or fictionalized clinical scenarios intended to provide evidence-based educational takeaways.
An 85-year-old woman presents to her geriatrician with her daughter, who is her primary caregiver. Seven years ago, the patient was diagnosed with mild Alzheimer's disease (AD). Her symptoms at diagnosis were irritability, forgetfulness, and panic attacks. Cognitive, behavioral, and functional assessments showed levels of decline; neurologic examination revealed mild hyposmia. The patient has been living with her daughter ever since her AD diagnosis.
At today's visit, the daughter reports that her mother has been experiencing loss of appetite and wide mood fluctuations with moments of unusual agitation. In addition, she tells the geriatrician that her mother has had trouble maintaining her balance and seems to have lost her sense of time. The patient has difficulty remembering what month and day it is, and how long it's been since her brother came to visit — which has been every Sunday like clockwork since the patient moved in with her daughter. The daughter also notes that her mother loses track of the story line when she is watching movie and TV shows lately.
The physician orders a brain MRI and genetic panel. MRI reveals atrophy in the frontal cortex as well as the medial temporal lobe, with hippocampal sclerosis. The genetic panel shows APOE and TMEM106 mutations.
Alzheimer’s Disease: Differential Diagnosis
Forgetfulness and mood fluctuations
This patient's symptoms go beyond just memory problems: She has difficulty with daily tasks, shows behavioral changes, and has significant communication difficulties — symptoms not found in mild cognitive impairment. While the patient has some behavioral changes, she does not exhibit the pronounced personality changes typical of frontotemporal dementia. Finally, the patient's cognitive decline is gradual and consistent without the stepwise progression typical of vascular dementia. Given the comprehensive presentation of the patient's symptoms and the results of her clinical investigations, middle-stage Alzheimer's disease is the most fitting diagnosis.
Alzheimer's disease is a progressive and irreversible brain disorder that affects memory, behavior, and cognitive skills. This condition causes the degeneration and death of brain cells, leading to various cognitive issues. Alzheimer's disease is the most common cause of dementia and accounts for 60%-80% of dementia cases. Although the exact cause is unknown, it is believed to result from genetic, lifestyle, and environmental factors. Alzheimer's disease progresses through stages — mild (early stage), moderate (middle stage), and severe (late stage) — and each stage has different signs and symptoms.
Alzheimer's disease is commonly observed in individuals 65 years or older, as age is the most significant risk factor. Another risk factor for Alzheimer's disease is family history; individuals who have parents or siblings with Alzheimer's disease are more likely to develop the disease. The risk increases with the number of family members diagnosed with the disease. Genetics also contribute to the development of Alzheimer's disease. Genes for developing Alzheimer's disease have been classified as deterministic and risk genes, which imply that they can cause the disease or increase the risk of developing it; however, the deterministic gene, which almost guarantees the occurrence of Alzheimer's, is rare and is found in less than 1% of cases. Experiencing a head injury is also a possible risk factor for Alzheimer's disease.
Accurate diagnosis of Alzheimer's disease requires a thorough history and physical examination. Gathering information from the patient's family and caregivers is important because some patients may not be aware of their condition. It is common for Alzheimer's disease patients to experience "sundowning," which causes confusion, agitation, and behavioral issues in the evening. A comprehensive physical examination, including a detailed neurologic and mental status exam, is necessary to determine the stage of the disease and rule out other conditions. Typically, the neurologic exam of Alzheimer's disease patients is normal.
Volumetric MRI is a recent technique that allows precise measurement of changes in brain volume. In Alzheimer's disease, shrinkage in the medial temporal lobe is visible through volumetric MRI. However, hippocampal atrophy is also a normal part of age-related memory decline, which raises doubts about the appropriateness of using volumetric MRI for early detection of Alzheimer's disease. The full potential of volumetric MRI in aiding the diagnosis of Alzheimer's disease is yet to be fully established.
Alzheimer's disease has no known cure, and treatment options are limited to addressing symptoms. Currently, three types of drugs are approved for treating the moderate or severe stages of the disease: cholinesterase inhibitors, partial N-methyl D-aspartate (NMDA) antagonists, and amyloid-directed antibodies. Cholinesterase inhibitors increase acetylcholine levels, a chemical crucial for cognitive functions such as memory and learning. NMDA antagonists (memantine) blocks NMDA receptors whose overactivation is implicated in Alzheimer's disease and related to synaptic dysfunction. Antiamyloid monoclonal antibodies bind to and promote the clearance of amyloid-beta peptides, thereby reducing amyloid plaques in the brain, which are associated with Alzheimer's disease.
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.
This patient's symptoms go beyond just memory problems: She has difficulty with daily tasks, shows behavioral changes, and has significant communication difficulties — symptoms not found in mild cognitive impairment. While the patient has some behavioral changes, she does not exhibit the pronounced personality changes typical of frontotemporal dementia. Finally, the patient's cognitive decline is gradual and consistent without the stepwise progression typical of vascular dementia. Given the comprehensive presentation of the patient's symptoms and the results of her clinical investigations, middle-stage Alzheimer's disease is the most fitting diagnosis.
Alzheimer's disease is a progressive and irreversible brain disorder that affects memory, behavior, and cognitive skills. This condition causes the degeneration and death of brain cells, leading to various cognitive issues. Alzheimer's disease is the most common cause of dementia and accounts for 60%-80% of dementia cases. Although the exact cause is unknown, it is believed to result from genetic, lifestyle, and environmental factors. Alzheimer's disease progresses through stages — mild (early stage), moderate (middle stage), and severe (late stage) — and each stage has different signs and symptoms.
Alzheimer's disease is commonly observed in individuals 65 years or older, as age is the most significant risk factor. Another risk factor for Alzheimer's disease is family history; individuals who have parents or siblings with Alzheimer's disease are more likely to develop the disease. The risk increases with the number of family members diagnosed with the disease. Genetics also contribute to the development of Alzheimer's disease. Genes for developing Alzheimer's disease have been classified as deterministic and risk genes, which imply that they can cause the disease or increase the risk of developing it; however, the deterministic gene, which almost guarantees the occurrence of Alzheimer's, is rare and is found in less than 1% of cases. Experiencing a head injury is also a possible risk factor for Alzheimer's disease.
Accurate diagnosis of Alzheimer's disease requires a thorough history and physical examination. Gathering information from the patient's family and caregivers is important because some patients may not be aware of their condition. It is common for Alzheimer's disease patients to experience "sundowning," which causes confusion, agitation, and behavioral issues in the evening. A comprehensive physical examination, including a detailed neurologic and mental status exam, is necessary to determine the stage of the disease and rule out other conditions. Typically, the neurologic exam of Alzheimer's disease patients is normal.
Volumetric MRI is a recent technique that allows precise measurement of changes in brain volume. In Alzheimer's disease, shrinkage in the medial temporal lobe is visible through volumetric MRI. However, hippocampal atrophy is also a normal part of age-related memory decline, which raises doubts about the appropriateness of using volumetric MRI for early detection of Alzheimer's disease. The full potential of volumetric MRI in aiding the diagnosis of Alzheimer's disease is yet to be fully established.
Alzheimer's disease has no known cure, and treatment options are limited to addressing symptoms. Currently, three types of drugs are approved for treating the moderate or severe stages of the disease: cholinesterase inhibitors, partial N-methyl D-aspartate (NMDA) antagonists, and amyloid-directed antibodies. Cholinesterase inhibitors increase acetylcholine levels, a chemical crucial for cognitive functions such as memory and learning. NMDA antagonists (memantine) blocks NMDA receptors whose overactivation is implicated in Alzheimer's disease and related to synaptic dysfunction. Antiamyloid monoclonal antibodies bind to and promote the clearance of amyloid-beta peptides, thereby reducing amyloid plaques in the brain, which are associated with Alzheimer's disease.
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.
This patient's symptoms go beyond just memory problems: She has difficulty with daily tasks, shows behavioral changes, and has significant communication difficulties — symptoms not found in mild cognitive impairment. While the patient has some behavioral changes, she does not exhibit the pronounced personality changes typical of frontotemporal dementia. Finally, the patient's cognitive decline is gradual and consistent without the stepwise progression typical of vascular dementia. Given the comprehensive presentation of the patient's symptoms and the results of her clinical investigations, middle-stage Alzheimer's disease is the most fitting diagnosis.
Alzheimer's disease is a progressive and irreversible brain disorder that affects memory, behavior, and cognitive skills. This condition causes the degeneration and death of brain cells, leading to various cognitive issues. Alzheimer's disease is the most common cause of dementia and accounts for 60%-80% of dementia cases. Although the exact cause is unknown, it is believed to result from genetic, lifestyle, and environmental factors. Alzheimer's disease progresses through stages — mild (early stage), moderate (middle stage), and severe (late stage) — and each stage has different signs and symptoms.
Alzheimer's disease is commonly observed in individuals 65 years or older, as age is the most significant risk factor. Another risk factor for Alzheimer's disease is family history; individuals who have parents or siblings with Alzheimer's disease are more likely to develop the disease. The risk increases with the number of family members diagnosed with the disease. Genetics also contribute to the development of Alzheimer's disease. Genes for developing Alzheimer's disease have been classified as deterministic and risk genes, which imply that they can cause the disease or increase the risk of developing it; however, the deterministic gene, which almost guarantees the occurrence of Alzheimer's, is rare and is found in less than 1% of cases. Experiencing a head injury is also a possible risk factor for Alzheimer's disease.
Accurate diagnosis of Alzheimer's disease requires a thorough history and physical examination. Gathering information from the patient's family and caregivers is important because some patients may not be aware of their condition. It is common for Alzheimer's disease patients to experience "sundowning," which causes confusion, agitation, and behavioral issues in the evening. A comprehensive physical examination, including a detailed neurologic and mental status exam, is necessary to determine the stage of the disease and rule out other conditions. Typically, the neurologic exam of Alzheimer's disease patients is normal.
Volumetric MRI is a recent technique that allows precise measurement of changes in brain volume. In Alzheimer's disease, shrinkage in the medial temporal lobe is visible through volumetric MRI. However, hippocampal atrophy is also a normal part of age-related memory decline, which raises doubts about the appropriateness of using volumetric MRI for early detection of Alzheimer's disease. The full potential of volumetric MRI in aiding the diagnosis of Alzheimer's disease is yet to be fully established.
Alzheimer's disease has no known cure, and treatment options are limited to addressing symptoms. Currently, three types of drugs are approved for treating the moderate or severe stages of the disease: cholinesterase inhibitors, partial N-methyl D-aspartate (NMDA) antagonists, and amyloid-directed antibodies. Cholinesterase inhibitors increase acetylcholine levels, a chemical crucial for cognitive functions such as memory and learning. NMDA antagonists (memantine) blocks NMDA receptors whose overactivation is implicated in Alzheimer's disease and related to synaptic dysfunction. Antiamyloid monoclonal antibodies bind to and promote the clearance of amyloid-beta peptides, thereby reducing amyloid plaques in the brain, which are associated with Alzheimer's disease.
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 patient is a 72-year-old retired schoolteacher accompanied by her daughter. Over the past year, her family has become increasingly concerned about her forgetfulness, mood fluctuations, and challenges in performing daily activities. The patient often forgets her grandchildren's names and struggles to recall significant recent events. She frequently misplaces household items and has missed several appointments. During her consultation, she has difficulty finding the right words, often repeats herself, and seems to lose track of the conversation. Her daughter shared concerning incidents, such as the patient wearing heavy sweaters during hot summer days and falling victim to a phone scam, which was uncharacteristic of her previous discerning nature. Additionally, the patient has become more reclusive, avoiding the social gatherings she once loved. She occasionally exhibits signs of agitation, especially in the evening. She has also stopped cooking as a result of instances of forgetting to turn off the stove and has had challenges managing her finances, leading to unpaid bills. A thorough neurologic exam is performed and is normal. Coronal T1-weighted MRI reveals hippocampal atrophy, particularly on the right side.
