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Clinicopathological correlation — MRCPsych Paper A MCQ

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HardNeuropathologyClinicopathological correlationMRCPsych Paper A

An 88-year-old man enrolled in a longitudinal ageing study remained independent in all activities of daily living. Serial neuropsychological assessments, including one performed 3 months before his death, showed no objective cognitive impairment. At autopsy, there is moderate neocortical amyloid-beta plaque deposition and sparse entorhinal neurofibrillary degeneration corresponding to Braak stage II, without significant cerebrovascular, Lewy body or TDP-43 pathology. Which interpretation best accounts for the clinicopathological findings?

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Correct answer: D — Clinicopathological resilience to Alzheimer-type neuropathological change

Explanation lettering: C = shown as A · E = shown as B · B = shown as C · A = shown as E

The best answer is D. Alzheimer-type neuropathological change can be present without a clinical dementia syndrome. Preserved serial cognition and daily functioning exclude Alzheimer dementia, while amyloid deposition with limited tau pathology illustrates clinicopathological resilience, potentially reflecting cognitive reserve and insufficient total pathological burden. A conflates biological or pathological change with dementia, which requires clinically significant cognitive and functional impairment. B is incorrect because primary age-related tauopathy is characterised by tau pathology with absent or minimal amyloid-beta deposition, rather than being driven by amyloid. C would require amyloid deposition within cerebral vessel walls, which is not described. E is false because amyloid plaque burden does not invariably produce cognitive impairment and correlates less closely with clinical severity than advanced tau, neuronal and synaptic pathology.

Reference: Cholerton B et al. Association of Cognition and Dementia With Neuropathologic Changes of Alzheimer Disease and Other Conditions in the Oldest Old. Neurology. 2022;99:e1489-e1502. https://pubmed.ncbi.nlm.nih.gov/35705500/