Pathophysiology
An 80-year-old woman is concerned about her risk of Alzheimer’s disease. She has no family history, no cognitive symptoms, and genetic testing reveals APOE ε3/ε3 genotype. She asks how much her age alone affects her risk.
Which of the following best describes how the risk of developing Alzheimer’s disease changes with increasing age?
A. Risk increases linearly after age 50, doubling every decade
B. Risk decreases slightly after age 75 due to neuronal adaptation
C. Risk remains stable after age 65 in the absence of genetic mutations
D. Risk increases exponentially with age, doubling approximately every 5 years after 65
Answer: D. Risk increases exponentially with age, doubling approximately every 5 years after 65
Explanation:
Age is the strongest non-modifiable risk factor for sporadic Alzheimer’s disease. Starting around age 65, the risk roughly doubles every 5 years. By age 85, the lifetime risk exceeds 30%, even in individuals without a genetic predisposition. Aging is associated with reduced protein clearance, oxidative stress and cumulative amyloid accumulation that contribute to the development of Alzheimer's.
A 70-year-old male is brought to his physician by his son due to increasing forgetfulness, irritability, and recent changes in hygiene. The son reports that his father has begun repeating conversations, stopped playing cards with friends, and has food stains on his suit jacket. On physical examination, the patient appears confused, agitated, and has a slowed, shuffling gait with unsteadiness in turning. He is oriented to his name and city but cannot recall the current day or year. He also denies feeling anxious but reports waking early and feeling tired.
Which of the following symptoms is most characteristic of early Alzheimer's disease in this patient's presentation?
A. Shuffling gait with unsteadiness in turning
B. Blunted affect and irritability
C. Anterograde amnesia
D. Significant weight loss despite good appetite
E. Visual hallucinations
C
Anterograde amnesia (difficulty learning new information and recalling recent events) is the most characteristic and often earliest cognitive symptom of Alzheimer's disease.
A) Shuffling gait can be seen in Lewy Body or vascular dementia.
B) Blunted affect/irritability and weight loss can be seen with depression or other medical issues.
D) Visual hallucinations are characteristic of Lewy Body dementia.
A 70-year-old male with a history of hypertension and recent cognitive decline undergoes initial laboratory testing. His results show elevated BUN (22 mg/dL) and creatinine (1.3 mg/dL), but normal thyroid-stimulating hormone (TSH) and vitamin B12 levels. A urinalysis is ordered. The primary purpose of ordering a urinalysis in the initial workup of this patient's cognitive decline is to:
A. Screen for diabetic nephropathy contributing to renal dysfunction.
B. Detect evidence of chronic kidney disease as a direct cause of dementia.
C. Rule out a UTI causing acute delirium or exacerbating cognitive symptoms.
D. Assess for electrolyte imbalances that can lead to confusion.
E. Identify protein markers indicative of early Alzheimer's pathology.
C
In elderly patients presenting with cognitive decline, one of the first steps is to distinguish between dementia (chronic) and delirium (acute and reversible).
UTIs are one of the most common causes of delirium in older adults—even in the absence of classic UTI symptoms like dysuria or frequency.
A) UA might detect proteinuria, but diagnosing diabetic nephropathy involves other tests (e.g., albumin/creatinine ratio, A1c). This is not an acute concern in dementia workup.
Mr Roberts, a 70-year-old man is diagnosed with mild dementia and comorbid mild depression. He lives alone and has become withdrawn from his usual social activities. In addition to considering medication, the physician wants to recommend lifestyle changes. Which of the following non-pharmacologic interventions would be most appropriate to suggest for this patient?
A) Beginning a strenuous, high-intensity weightlifting program
B) Encouraging renewed participation in social activities like a senior center or card games
C) Strict adherence to a ketogenic diet to improve neuronal function
D) Requiring a minimum of two hours per day of computer-based memory game
E) Immediately moving him to a skilled nursing facility to ensure safety
Correct Answer: B)
Encouraging renewed participation in social activities like a senior center or card games.
For Mr. Roberts, who had stopped playing cards with friends, Dr. Webb suggested more social interactions. Social engagement is a key non-pharmacologic intervention that can improve mood, provide cognitive stimulation, and enhance the quality of life in patients with mild dementia and depression.
Incorrect answers:
A) Beginning a strenuous, high-intensity weightlifting program: While physical activity is beneficial, a strenuous, high-intensity program may not be safe or appropriate without a full physical assessment and gradual introduction.
C) Strict adherence to a ketogenic diet to improve neuronal function: This is not a standard, evidence-based recommendation for dementia management.
D) Requiring a minimum of two hours per day of computer-based memory games: While cognitive stimulation is good, there is no evidence for a specific "dose," and this may cause frustration.
E) Immediately moving him to a skilled nursing facility to ensure safety: This is overly aggressive for mild dementia and does not respect patient autonomy.
Which of the following best explains what the finding of mild, symmetric atrophy suggests about the underlying disease process?
A. A vascular pathology such as multi-infarct dementia
B. An asymmetric neurodegenerative process, such as frontotemporal dementia
C. A diffuse, progressive neurodegenerative condition like Alzheimer’s disease
D. An acute inflammatory disorder involving the hippocampus
Correct Answer: C. A diffuse, progressive neurodegenerative condition like Alzheimer’s disease
Explanation:
Symmetric, mild atrophy of the medial temporal lobes (particularly the hippocampus and entorhinal cortex) is a classic early imaging finding in Alzheimer’s disease. It reflects a slowly progressive, diffuse neurodegenerative process that typically affects both hemispheres in a relatively uniform pattern in the early stages. Symmetry and gradual progression help distinguish Alzheimer’s from other causes of cognitive decline.
A 66-year-old woman with a strong family history of Alzheimer’s disease undergoes genetic testing. She is found to be homozygous for the APOE ε2 allele. She is cognitively intact and curious about her risk.
Which of the following best explains the effect of the APOE ε2 allele in Alzheimer’s disease?
A. APOE ε2 enhances tau phosphorylation and clearance from neurons
B. APOE ε2 promotes aggregation of Aβ into dense-core plaques
C. APOE ε2 reduces amyloid-beta deposition and enhances its clearance
D. APOE ε2 increases acetylcholine release from the basal forebrain
Answer: C. APOE ε2 reduces amyloid-beta deposition and enhances its clearance
The APOE gene encodes apolipoprotein E, involved in lipid transport and amyloid-beta metabolism. The ε4 allele increases Alzheimer’s risk by promoting Aβ aggregation and impairing clearance, while ε2 is protective. APOE ε2 has a lower lifetime risk of Alzheimer’s disease, even in those with a family history.
A 70-year-old male presents with progressive cognitive decline, including repeating conversations and difficulty with time orientation. His son reports that his father has become more moody and socially withdrawn. Physical examination reveals a shuffling gait and diminished deep tendon reflexes in the lower extremities. His blood pressure is 178/80 mmHg. Laboratory studies reveal elevated BUN and creatinine, but normal B12 and thyroid function.
Considering the patient's symptoms, which of the following is the most likely reason for his elevated blood pressure and what type of dementia might this suggest?
A. Medication side effect; Lewy Body dementia
B. Uncontrolled hypertension; Vascular dementia
C. Hypothyroidism; Alzheimer's disease
D. Vitamin deficiency; Frontotemporal dementia
E. Normal aging; Parkinson's disease dementia
B
The patient has a history of hypertension, and his son reports non-adherence to medication (half-full bottle). Therefore, his elevated blood pressure is most likely due to uncontrolled hypertension.
Vascular dementia is caused by chronic cerebrovascular disease, often from uncontrolled hypertension, diabetes, and hyperlipidemia.
Stepwise decline in cognition (often fluctuating), executive dysfunction, gait issues, and urinary incontinence can occur.
E) Normal aging does not cause significant memory loss or executive dysfunction. Parkinson’s disease dementia requires prior motor symptoms for at least 1 year before cognitive decline (which we don’t have).
A 70-year-old male with new-onset cognitive symptoms and a GDS-15 score of 5/15 is being evaluated. During the workup, the physician aims to differentiate between true dementia and "pseudodementia" caused by depression. Which of the following is most likely to be observed in a patient whose cognitive impairment is primarily due to severe depression (pseudodementia), rather than a primary neurodegenerative dementia?
A. A tendency to confabulate when unable to recall information.
B. Consistent "don't know" answers on cognitive tests, with a strong emphasis on memory complaints.
C. Preservation of insight into their memory deficits, but denial of mood symptoms.
D. Significant improvement in cognitive performance after initiation of cholinesterase inhibitors.
E. Rapid progression to severe functional impairment within a few weeks.
B
Patients with pseudodementia (depression-related cognitive impairment):
Patients with true dementia often:
Minimize or are unaware of their memory problems (poor insight).
May try to cover up deficits, confabulate (make up answers), or get answers wrong while still trying.
Show a more generalized cognitive decline that is less responsive to antidepressant treatment in terms of cognitive improvement (though depression symptoms themselves might improve).
A 76-year-old woman with moderate AD develops mild, non-psychotic agitation in the evenings. Her family asks what should be tried first to manage this new behavior. According to the principles of managing behavioral symptoms in dementia, which approach should be prioritized?
A) Immediately starting a low-dose second-generation antipsychotic
B) Implementing behavioral and environmental interventions like reassurance and a structured routine
C) Requesting a neurology consult to consider adding memantine to her regimen
D) Prescribing a benzodiazepine for short-term anxiety relief
E) Discontinuing her current acetylcholinesterase inhibitor
Correct answer: B) Non-pharmacologic strategies are the first-line approach for mild behavioral symptoms. This includes providing a familiar and structured environment, using reassurance, and removing hazards to ensure safety.
Incorrect answers:
A: Antipsychotics are reserved for severe agitation or psychosis that poses a safety risk and are not the first step for mild symptoms.
D: Benzodiazepines should be avoided because they increase the risk of delirium and falls in elderly patients.
C, E: These pharmacologic changes would not be the first step in managing mild behavioral symptoms.
An 80-year-old man with a 4-year history of Alzheimer’s disease presents for routine follow-up. His caregiver reports gradual worsening of memory, disorientation, and occasional word-finding difficulty. Neurologic exam shows no gait disturbance or incontinence. MRI of the brain shows generalized cortical atrophy, prominent sulci, ventricular enlargement, and hippocampal volume loss.
Which of the following best explains the cause of the ventricular enlargement in this patient?
A. Increased cerebrospinal fluid production due to choroid plexus hyperplasia
B. Obstruction of cerebrospinal fluid outflow at the cerebral aqueduct
C. Decreased CSF absorption at the arachnoid villi causing communicating hydrocephalus
D. Compensatory ventricular expansion due to cortical atrophy
Correct Answer: D. Compensatory ventricular expansion due to cortical atrophy
Explanation:
Hydrocephalus ex vacuo refers to ventricular enlargement secondary to loss of brain tissue—not due to CSF overproduction or obstruction. In Alzheimer’s disease, progressive neuronal loss and cortical atrophy lead to expansion of the ventricles and sulci as the brain shrinks.
Which feature best distinguishes Alzheimer’s disease from vascular dementia in terms of disease progression?
A. Absence of cerebellar symptoms
B. Early presence of visual hallucinations
C. Gradual and continuous progression of cognitive symptoms
D. Sudden onset of confusion
Answer: C. Gradual and continuous progression of cognitive symptoms
Explanation:
Alzheimer’s disease typically presents with a gradual, insidious decline in cognition. In contrast, vascular dementia often shows a stepwise decline, with sudden drops in function following cerebrovascular events such as strokes.
A 70-year-old male with a history of hypertension is experiencing cognitive decline. His son notes that he struggles with paying bills, has a generally dirtier apartment, and has become more disheveled. On examination, he has decreased vibratory sensation and diminished reflexes in his lower extremities, along with a slowed, shuffling gait. He scored 21/30 on the MMSE.
While memory loss is a prominent symptom in many dementias, which of the following types of dementia is least likely to present with memory loss as the initial or most prominent symptom?
A. Alzheimer's disease
B. Vascular dementia
C. Lewy Body dementia
D. Frontotemporal dementia
D
Frontotemporal dementia (FTD).
Key early symptoms: Personality changes, disinhibition, compulsive behaviors, emotional blunting, and language dysfunction (aphasia).
Memory is relatively preserved early on, unlike Alzheimer's.
Behavioral variant FTD (bvFTD): impulsivity, apathy, poor judgment.
Primary progressive aphasia: word-finding difficulty, speech production issues.
A) Alzheimer’s disease. Classic presentation: early and prominent memory loss, especially of new information. Later involves language and visuospatial deficits.
B) Vascular dementia. Can vary depending on lesion locations, but memory loss is still prominent, especially with medial temporal or thalamic infarcts. Often shows stepwise decline and executive dysfunction.
C) Lewy Body dementia. Memory loss can be early but is usually accompanied or preceded by: visual hallucinations, Parkinsonian features, fluctuating cognition, and REM sleep behavior disorder.
A physician notes that a patient's MMSE score of 25/30 might still be concerning despite falling in the "None to minimal Cognitive Impairment" range. This concern is most justified if the patient has which of the following characteristics?
A) A history of untreated depression
B) A low level of educational attainment
C) A high level of educational attainment (e.g., a PhD)
D) A primary language other than English
E) Concurrent use of a benzodiazepine
Correct answer: C) The interpretation of the MMSE must be adjusted for the patient's background, as demographic variables like education can have a significant effect on scores. For a patient with a high educational attainment, a score of 25 may represent a significant drop from their personal baseline, potentially masking an early but true cognitive deficit.
Incorrect answers:
A, E: Depression and benzodiazepine use would be expected to lower the score, making a normal score less concerning, not more.
B, D: A lower educational attainment or language barrier would be reasons to suspect a score of 25 is an underestimation of the patient's true cognitive ability.
An 80-year-old man with severe AD develops debilitating agitation and psychosis, posing a safety risk. His medical history is significant for a prior stroke. When counseling the family about initiating a second-generation antipsychotic, the physician must discuss which specific black box warning?
A) An increased risk of both stroke and all-cause mortality
B) A high likelihood of severe anticholinergic effects worsening cognition
C) The potential for renal failure and hepatic toxicity with long-term use
D) A significant risk of inducing serotonin syndrome
E) A high risk of dependency and paradoxical agitation
Correct answer: A) The use of antipsychotics in elderly patients with dementia carries significant risks, specifically an increased incidence of stroke and higher all-cause mortality. This is a critical counseling point, especially for a patient with a history of stroke.
Incorrect answers:
B: This is the primary concern with Tricyclic antidepressants (TCAs), which should be avoided because their anticholinergic effects worsen cognition.
C: This is not the specific black box warning for this class in this population.
D: This risk is associated with serotonergic agents like SSRIs.
E: This profile is more characteristic of benzodiazepines.
An 82-year-old woman with a 5-year history of Alzheimer’s disease is brought to clinic because of recent difficulty walking. She has a shuffling gait, reduced arm swing, and occasional freezing when turning. There is no resting tremor. Her cognitive symptoms include disorientation, word-finding difficulty, and poor short-term memory. MRI shows diffuse cortical atrophy with no evidence of infarcts.
Which of the following best explains the development of Parkinsonian gait in this patient with Alzheimer’s disease?
A. Early involvement of the substantia nigra due to alpha-synuclein deposition
B. Frontal-subcortical circuit dysfunction and possible overlapping Lewy body pathology
C. Autoimmune-mediated demyelination of motor tracts
D. Primary cerebellar degeneration related to Alzheimer's disease
Correct Answer: B. Frontal-subcortical circuit dysfunction and possible overlapping Lewy body pathology
Explanation:
In late-stage Alzheimer’s disease, degeneration can extend into frontal motor cortex circuits, impairing motor planning and gait control, leading to parkinsonian features. In some older adults, coexisting Lewy body pathology, as seen in mixed dementia, may contribute by affecting the dopaminergic pathways of the basal ganglia. These changes can cause a shuffling gait and reduced arm swing even without classic Parkinson’s disease.
The cerebellum is the main site of atrophy in Alzheimer’s disease. Cerebellar degeneration causes ataxic gait (wide-based and unsteady, not parkinsonian gait (shuffling and slow).
Which of the following genetic changes is most strongly associated with increased risk for late-onset (sporadic) Alzheimer’s disease?
A. Presenilin-1 mutation on chromosome 14
B. Trisomy 21 leading to APP gene overexpression
C. Mutation in the MAPT gene encoding tau protein
D. APOE ε4 allele inheritance
Answer: D. APOE ε4 allele inheritance
Explanation:
The APOE ε4 allele is the most significant genetic risk factor for late-onset Alzheimer’s disease by impairing amyloid clearance and promoting its aggregation. Presenilin and APP mutations are associated with early-onset familial Alzheimer’s disease.
A 70-year-old male presents with a history of hypertension and increasing cognitive and functional decline. His son reports that the patient's blood pressure medications are "still half full" despite being due for refills. The patient appears disheveled, has food stains on his clothing, and scored 21/30 on the Mini-Mental State Examination (MMSE), indicating mild cognitive impairment. His Geriatric Depression Scale (GDS-15) score is 5/15, suggesting mild depression.
The co-occurrence of depression with dementia, as seen in this patient, is often associated with which of the following clinical features in older adults?
A. An immediate and complete resolution of cognitive symptoms upon antidepressant initiation.
B. A more overt expression of sadness, guilt, and suicidal ideation.
C. Exacerbation of cognitive deficits and functional decline.
D. Decreased need for social interaction and stimulation.
E. Preservation of recent memory with decline in remote memory.
C
Depression and dementia often co-occur and can create a negative feedback loop where each condition exacerbates the other. Depression can impair attention, motivation, and executive function, leading to an apparent worsening of cognitive impairment and functional decline. This can result in greater difficulty with activities of daily living, medication adherence, and social functioning.
A) This is characteristic of pseudodementia (depression mimicking dementia), but not when true dementia is also present. In cases with underlying dementia, cognitive symptoms may partially improve but do not fully resolve.
E) This is the opposite of most dementia patterns. In typical Alzheimer’s, recent memory is impaired first. Remote memory is relatively preserved until later.
A 68-year-old woman presents with a 9-month history of progressive memory loss and cognitive slowing. Her physician initiates a standard laboratory workup to rule out common, reversible causes of dementia. Which of the following sets of laboratory tests is most appropriate for the initial screening in this patient?
A) ApoE genotyping, CSF amyloid/tau levels, and a heavy metal screen
B) Complete blood count, liver function tests, and an EEG
C) Serum electrolytes, blood urea nitrogen (BUN), and creatinine
D) TSH, Vitamin B12 level, and RPR
E) Homocysteine level, erythrocyte sedimentation rate, and blood alcohol level
Correct answer: D) TSH, Vitamin B12 level, and RPR. A key part of the workup is to order laboratory studies to rule out reversible causes of dementia. The core, universally recommended screening panel includes a TSH to rule out hypothyroidism, a Vitamin B12 level to rule out deficiency, and an RPR or other treponemal test to rule out neurosyphilis. Mr. Roberts had these tests performed, and all were normal.
Incorrect answers:
A) ApoE genotyping, CSF amyloid/tau levels, and a heavy metal screen: These are advanced or specialized tests, not part of the initial routine screening.
B) Complete blood count, liver function tests, and an EEG: While often included in a comprehensive workup, they are not considered the core three screening tests for the most common reversible dementias.
C) Serum electrolytes, blood urea nitrogen (BUN), and creatinine: This is a basic metabolic panel. While electrolyte and renal issues can cause confusion, they are not the primary screening panel for the classic reversible dementias.
E) Homocysteine level, erythrocyte sedimentation rate, and blood alcohol level: These are specialized tests ordered only if specific conditions are suspected.
A patient who was recently started on donepezil for Alzheimer's disease calls the clinic complaining of new symptoms. His wife reports he has had several episodes of diarrhea and feels lightheaded, and his heart rate is 50 bpm. These symptoms are most likely caused by which of the following effects of his new medication?
A) Potent anticholinergic effects
B) Serotonin syndrome
C) Increased parasympathetic activity
D) Dopaminergic blockade
E) Adrenergic stimulation
Correct answer: C) Increased parasympathetic activity. As an acetylcholinesterase inhibitor, donepezil increases cholinergic activity throughout the body. This leads to common parasympathetic (cholinomimetic) side effects, including GI upset (diarrhea), bradycardia (slow heart rate), and lightheadedness.
Incorrect answers:
A) Potent anticholinergic effects: This is the opposite of the drug's effect; it would cause dry mouth and constipation.
B) Serotonin syndrome: This is associated with serotonergic drugs, not donepezil.
D) Dopaminergic blockade: This is the mechanism of antipsychotic medications.
E) Adrenergic stimulation: This would cause tachycardia and hypertension.
An 81-year-old man with mild cognitive impairment is brought in by his daughter for evaluation. He has become withdrawn and lost interest in activities over the past few months. He denies feeling "depressed" but appears apathetic. His speech is slow, and he often pauses when asked about his mood. The clinician considers screening for depression.
Which of the following best explains why the Geriatric Depression Scale (GDS) may be more appropriate than the PHQ-9 in this patient?
A. The GDS includes questions that focus on cognitive functioning rather than emotional state
B. The GDS eliminates somatic symptoms that may be misleading in older adults
C. The PHQ-9 requires clinician administration, while the GDS is designed for caregiver input
D. The GDS uses clinical observation rather than self-report, which is better for cognitively impaired individuals
Correct Answer: B. The GDS eliminates somatic symptoms that may be misleading in older adults
Explanation:
The Geriatric Depression Scale (GDS) was specifically developed for older adults, recognizing that somatic symptoms such as fatigue, sleep disturbances, or changes in appetite may reflect aging or chronic illness. The GDS focuses more on mood and affective symptoms, using simple yes/no questions that reduce confusion. This makes it more sensitive and specific in older populations, especially when physical symptoms are nonspecific.
Which of the following steps is considered an early initiating event in the amyloid cascade hypothesis of Alzheimer’s disease?
A. Tau hyperphosphorylation leading to microtubule destabilization
B. Aggregation of alpha-synuclein into Lewy bodies
C. Accumulation of soluble Aβ oligomers derived from APP cleavage
D. Synaptic loss secondary to hippocampal atrophy
Answer: C. Accumulation of soluble Aβ oligomers derived from APP cleavage
Explanation:
The amyloid cascade hypothesis proposes that Alzheimer’s disease begins with abnormal cleavage of AP by β- and γ-secretase, producing a highly aggregation-prone peptide. These soluble Aβ oligomers are thought to be neurotoxic, preceding plaque deposition and triggering downstream tau pathology and neuroinflammation.
A 70-year-old male with a known history of hypertension is brought to the clinic by his son, who expresses concern about the patient's increasing confusion, poor hygiene, and forgetfulness regarding medication adherence. On examination, the patient exhibits a blunted affect, appears agitated, and has difficulty recalling the current day and year. His physical exam is notable for a BMI of 18.3 kg/m2 and a shuffling gait with unsteadiness. He scores 21/30 on the MMSE and 5/15 on the Geriatric Depression Scale.
Considering the patient's presentation, the co-occurrence of a shuffling gait and significant cognitive decline raises a strong suspicion for which of the following types of dementia?
A. Frontotemporal dementia (Behavioral Variant)
B. Vascular dementia
C. Alzheimer's disease
D. Lewy Body dementia
E. Normal Pressure Hydrocephalus
D
The patient's presentation combines two key features that, when occurring together, strongly point towards Lewy Body Dementia (LBD):
Significant cognitive decline: Indicated by the son's concerns about forgetfulness and confusion, the patient's difficulty recalling time, and his MMSE score of 21/30 (suggesting mild cognitive impairment/dementia).
Parkinsonian motor features: The description of a "shuffling gait with unsteadiness" is highly characteristic of parkinsonism (bradykinesia, rigidity, and gait instability).
A) Frontotemporal: Earlier onset (usually <65 years). Presents with personality change, disinhibition, compulsions, not primarily gait changes or memory loss early on.
B) Vascular Dementia: While uncontrolled hypertension is a risk factor for vascular dementia, and motor symptoms can occur depending on the location of brain damage (e.g., after a stroke), the characteristic "shuffling gait" directly points to parkinsonism. Cognitive decline in vascular dementia is often more "patchy" or stepwise.
C) Alzheimer's Disease: While Alzheimer's is the most common cause of dementia and involves significant memory loss, it does not typically present with prominent motor symptoms like a shuffling gait until very late stages of the disease, if at all.
E) Classically presents with the triad: gait disturbance (often described as "magnetic" or shuffling), urinary incontinence, and dementia. While the shuffling gait fits, NPH's cognitive deficits are often more characterized by executive dysfunction and apathy rather than prominent memory loss initially. More importantly, in the context of common dementia types, LBD offers a more comprehensive fit for the combination of significant cognitive and Parkinsonian motor symptoms in the early-to-mid stages of the disease.
A 65-year-old man presents with significant personality changes, including apathy and disinhibition. A brain MRI is ordered. In contrast to the typical findings of Alzheimer's disease, which includes atrophy of the temporal lobes, which of the following MRI findings would be most expected in this patient?
A) Widespread white matter ischemic changes
B) Enlarged ventricles out of proportion to sulcal widening
C) A large, ring-enhancing lesion in the parietal lobe
D) Pronounced and disproportionate atrophy of the frontal and temporal lobes
E) No significant atrophy, but with decreased metabolism in the parieto-occipital regions on PET scan
Correct answer: D) Pronounced and disproportionate atrophy of the frontal and temporal lobes. The patient's presentation with primary personality and behavioral changes is classic for the behavioral variant of Frontotemporal Dementia (bvFTD). This clinical syndrome is caused by progressive degeneration of the frontal and/or temporal lobes, which would be visible as disproportionate atrophy in those regions on an MRI.
Incorrect answers:
A) Widespread white matter ischemic changes: This finding is characteristic of vascular dementia.
B) Enlarged ventricles out of proportion to sulcal widening: This is the characteristic imaging finding for Normal Pressure Hydrocephalus.
C) A large, ring-enhancing lesion in the parietal lobe: This would suggest a brain tumor or abscess, not a neurodegenerative dementia.
E) No significant atrophy, but with decreased metabolism in the parieto-occipital regions on PET scan: This pattern of hypometabolism is more characteristic of Dementia with Lewy Bodies.
A neurologist is screening patients for eligibility to receive the new amyloid-targeting therapy, lecanemab (monoclonal ab that helps clear amyloid beta plaques). Which of the following patients would be the most appropriate candidate for this disease-modifying treatment?
A) A 75-year-old with an MMSE of 15/30 and a history of multiple strokes.
B) A 68-year-old with an MMSE of 26/30 and a positive amyloid PET scan.
C) A 72-year-old with prominent visual hallucinations and parkinsonism.
D) An 80-year-old with severe dementia (MMSE 8/30) on hospice care.
E) A 65-year-old with suspected frontotemporal dementia based on personality changes.
Correct answer: B) These novel therapies have strict selection criteria. They are reserved for patients with early-stage or mild cognitive impairment and require confirmation of amyloid pathology through a PET scan or CSF analysis. This patient, with a high MMSE score and a positive PET scan, is the only one who meets both of these essential criteria.
Incorrect answers:
A, D: The dementia in these patients is too advanced (moderate to severe) and they are outside the treatment window for this therapy.
C: This patient's symptoms are classic for Lewy Body Dementia, which is not treated with amyloid-targeting antibodies.
E: This therapy targets amyloid, which is not the primary pathology in Frontotemporal Dementia.
A 78-year-old woman with a diagnosis of mild Alzheimer’s disease is brought to the clinic by her son, who reports that she has become more withdrawn, stopped attending her weekly church group, and often says things like, “I don’t see the point in doing anything.” Her Mini-Mental State Exam (MMSE) score has declined from 25 to 21 in the past 3 months. The clinician suspects comorbid depression and starts her on a low-dose SSRI.
Which of the following best explains how treating depression in this patient may impact her cognitive symptoms?
A. Antidepressants reverse hippocampal atrophy associated with Alzheimer’s disease
B. Treatment of depression may improve attention, motivation, and memory performance
C. SSRIs stimulate new cholinergic neuron growth in the basal forebrain
D. Depression treatment prevents further beta-amyloid accumulation
Correct Answer: B. Treatment of depression may improve attention, motivation, and memory performance
Explanation:
Depression in older adults can mimic or worsen cognitive symptoms such as inattention, poor memory, slowed processing, and apathy, especially in the context of dementia. This is known as pseudodementia or depression-related cognitive impairment. Treating the depression often results in improvement in cognitive performance, particularly in domains related to attention, executive function, and motivation.