Left frontal cortex connectivity underlies cognitive reserve in prodromal Alzheimer disease
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
... 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 GLOSSARY Ab 5 b-amyloid; AD 5 Alzheimer disease; ADNI 5 Alzheimer's Disease Neuroimaging Initiative; BNT 5 Boston Naming Test; CR 5 cognitive reserve; EPI 5 echo-planar imaging; FDG 5 fluorodeoxyglucose; gLFC 5 global left frontal cortex; GM 5 gray matter; HC 5 healthy controls; LFC 5 left frontal cortex; MCI 5 mild cognitive impairment; MEM 5 episodic memory composite score; OP 5 occipital pole; ROI 5 region of interest; SUVR 5 standardized uptake value ratio; TMT-B 5 Trail-Making Test B.