Functional neuroanatomical associations of working memory in early‐onset Alzheimer's disease

Objective To characterize metabolic correlates of working memory impairment in clinically defined subtypes of early‐onset Alzheimer's disease. Background Established models of working memory suggest a key role for frontal lobe function, yet the association in Alzheimer's disease between working memory impairment and visuospatial and language symptoms suggests that temporoparietal neocortical dysfunction may be responsible. Methods Twenty‐four patients with predominantly early‐onset Alzheimer's disease were clinically classified into groups with predominantly amnestic, multidomain or visual deficits. Patients underwent neuropsychological evaluation focused on the domains of episodic and working memory, T1‐weighted magnetic resonance imaging and brain fluorodeoxyglucose positron emission tomography. Fluorodeoxyglucose positron emission tomography data were analysed by using a region‐of‐interest approach. Results Patients with multidomain and visual presentations performed more poorly on tests of working memory compared with amnestic Alzheimer's disease. Working memory performance correlated with glucose metabolism in left‐sided temporoparietal, but not frontal neocortex. Carriers of the apolipoprotein E4 gene showed poorer episodic memory and better working memory performance compared with noncarriers. Conclusions Our findings support the hypothesis that working memory changes in early‐onset Alzheimer's disease are related to temporoparietal rather than frontal hypometabolism and show dissociation from episodic memory performance. They further support the concept of subtypes of Alzheimer's disease with distinct cognitive profiles due to prominent neocortical dysfunction early in the disease course. Copyright © 2017 John Wiley & Sons, Ltd.