Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease

Franzmeier, Nicolai; Duering, Marco; Weiner, Michael; Dichgans, Martin; Ewers, Michael; Stern, Yaakov; Alzheimer's Disease Neuroimaging Initiative

Objective: To test whether higher global functional connectivity of the left frontal cortex (LFC) in Alzheimer disease (AD) is associated with more years of education (a proxy of cognitive reserve [CR]) and mitigates the association between AD-related fluorodeoxyglucose (FDG)-PET hypometabolism and episodic memory. Methods: Forty-four amyloid-PET–positive patients with amnestic mild cognitive impairment (MCI-Ab1) and 24 amyloid-PET–negative healthy controls (HC) were included. Voxel-based linear regression analyses were used to test the association between years of education and FDG-PET in MCI-Ab1, controlled for episodic memory performance. Global LFC (gLFC) connectivity was computed through seed-based resting-state fMRI correlations between the LFC (seed) and each voxel in the gray matter. In linear regression analyses, education as a predictor of gLFC connectivity and the interaction of gLFC connectivity 3 FDG-PET hypometabolism on episodic memory were tested. Results: FDG-PET metabolism in the precuneus was reduced in MCI-Ab1 compared to HC (p 5 0.028), with stronger reductions observed in MCI-Ab1 with more years of education (p 5 0.006). In MCI-Ab1, higher gLFC connectivity was associated with more years of education (p 5 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p 5 0.027). Conclusions: Higher gLFC connectivity is a functional substrate of CR that helps to maintain episodic memory relatively well in the face of emerging FDG-PET hypometabolism in earlystage AD. Neurology® 2017;88:1054–1061



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February 11, 2022