A 72-year-old retired schoolteacher presents with 2 years of progressive short-term memory loss, misplacing items, and word-finding difficulty. She became lost in a familiar neighborhood last month. MMSE is 18/30. Gait is preserved, and there are no visual hallucinations or behavioral changes. T1-weighted coronal MRI through the temporal lobes shows the pattern marked **A** in the diagram — bilateral hippocampal and medial temporal atrophy with widening of the choroidal fissure and enlargement of the temporal horns. Parietal and posterior cingulate cortices show mild atrophy; frontal and occipital lobes are preserved. Which of the following pathological hallmarks is most directly responsible for the neuronal loss and atrophy pattern seen at **A**?
A. Multifocal lacunar infarcts and confluent white-matter hyperintensities in the subcortical regions
B. Intracytoplasmic inclusions of alpha-synuclein with relative preservation of hippocampal volume
C. Extracellular amyloid-β plaques and intraneuronal hyperphosphorylated tau tangles, beginning in the entorhinal cortex and hippocampus
D. Frontotemporal 'knife-blade' atrophy with early behavioral disinhibition and language decline
Explanation
Why option 1 is right
The structure marked A — bilateral hippocampal and medial temporal atrophy — is the hallmark imaging finding of Alzheimer disease (AD). According to the NIA-AA 2024 framework and Braak staging, AD pathology begins with extracellular amyloid-β plaques (cleaved from APP by β- and γ-secretase, accumulating as Aβ42) and intraneuronal neurofibrillary tangles of hyperphosphorylated tau. These lesions initiate in the entorhinal cortex and hippocampus (Braak stages I–II), causing neuronal loss and the characteristic medial temporal atrophy seen on MRI. The pattern of atrophy spreading from hippocampus to limbic and neocortical association areas correlates with the progressive amnestic decline observed in this patient. This is the only option that directly explains the pathophysiology of the atrophy pattern at A.
Why each distractor is wrong
Option 2: Alpha-synuclein inclusions are the pathological hallmark of dementia with Lewy bodies (DLB), which characteristically shows relative preservation of hippocampal volume and occipital hypometabolism — the opposite of the pattern at A. The clinical presentation (no visual hallucinations, no parkinsonism) also excludes DLB.
Option 3: Frontotemporal 'knife-blade' atrophy with early behavioral disinhibition is the signature of frontotemporal dementia (FTD/Pick disease, marked B). This patient has preserved frontal lobes and no behavioral changes — she has memory loss and disorientation, not disinhibition or language primacy.
Option 4: Multifocal lacunar infarcts and confluent white-matter hyperintensities are the pathological basis of vascular dementia (marked D). This patient has no history of stroke, preserved gait, and a pattern of selective medial temporal atrophy — not the diffuse subcortical white-matter disease of vascular dementia.
High-YieldNEET PG
Bilateral hippocampal and medial temporal atrophy on coronal MRI is pathognomonic for Alzheimer disease; it reflects Braak stage I–II amyloid-β and tau pathology beginning in the entorhinal cortex and hippocampus.
