Alzheimer Disease vs Frontotemporal Dementia

Why Lecanemab is correct

• The picture is early Alzheimer disease (AD): amnestic decline with an MMSE of 23/30 (mild dementia range) plus a confirmatory CSF biomarker profile of low Abeta42 and elevated total-tau and phospho-tau
• Lecanemab is an anti-amyloid-beta monoclonal antibody directed at soluble protofibrils and is FDA-approved for mild cognitive impairment or mild dementia due to AD with confirmed amyloid pathology
• In the CLARITY-AD trial it slowed clinical decline by roughly 27% versus placebo over 18 months, making it disease-modifying rather than purely symptomatic
• Eligibility requires confirmed amyloid pathology (CSF or amyloid PET) and a baseline MRI; donanemab is a similarly disease-modifying alternative

Why the others are wrong

• Donepezil — a cholinesterase inhibitor that improves symptoms by raising synaptic acetylcholine but does not alter amyloid pathology or the disease trajectory (right-concept-wrong-mechanism)
• Solanezumab — also an anti-amyloid monoclonal antibody, but it binds monomeric soluble Abeta rather than the protofibrils and deposited plaque that have to be cleared; it failed to slow decline in the EXPEDITION program and in the A4 trial and was never approved, so it does not modify the disease (right-class-wrong-target)
• Memantine — an NMDA-receptor antagonist used in moderate-to-severe AD for symptom control, not to slow underlying pathology (anchoring on AD label without matching mechanism)

Additional high-yield points

• Amyloid-related imaging abnormalities (ARIA-E edema, ARIA-H microhemorrhage) require serial MRI monitoring during anti-amyloid therapy
• APOE4 carriers (especially homozygotes) have higher ARIA risk, and concurrent anticoagulation raises ARIA-H/hemorrhage risk, so genotype and bleeding risk should be assessed before starting

Why Asymmetric frontal and anterior temporal atrophy is correct

• Disinhibition, loss of empathy, hyperorality with a new sweet tooth, lack of insight, and preserved memory and visuospatial function fit behavioral-variant frontotemporal dementia (Rascovsky 2011: at least 3 of 6 behavioral features plus functional decline).
• The supportive imaging signature of FTD is selective, often asymmetric atrophy of the frontal and/or anterior temporal lobes, with matching frontotemporal hypometabolism on FDG-PET; this distinguishes it from the midlife mimics.

Why the others are wrong

• Symmetric hippocampal and medial temporal atrophy is the classic pattern of Alzheimer disease, which is memory-dominant and points away from this frontal-predominant, memory-sparing picture.
• Confluent periventricular white matter changes reflect small-vessel ischemic disease seen in vascular dementia, which causes stepwise decline and focal deficits rather than an insidious behavioral syndrome.
• Cortical ribboning on diffusion-weighted imaging is the hallmark of Creutzfeldt-Jakob disease, which progresses rapidly (under a year) with myoclonus, not a 14-month behavioral course.