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Abstract
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-Aβ+) 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-Aβ+, 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 × FDG-PET hypometabolism on episodic memory were tested.
Results: FDG-PET metabolism in the precuneus was reduced in MCI-Aβ+ compared to HC (p = 0.028), with stronger reductions observed in MCI-Aβ+ with more years of education (p = 0.006). In MCI-Aβ+, higher gLFC connectivity was associated with more years of education (p = 0.021). At higher levels of gLFC connectivity, the association between precuneus FDG-PET hypometabolism and lower memory performance was attenuated (p = 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 early-stage AD.
GLOSSARY
- Aβ=
- β-amyloid;
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- BNT=
- Boston Naming Test;
- CR=
- cognitive reserve;
- EPI=
- echo-planar imaging;
- FDG=
- fluorodeoxyglucose;
- gLFC=
- global left frontal cortex;
- GM=
- gray matter;
- HC=
- healthy controls;
- LFC=
- left frontal cortex;
- MCI=
- mild cognitive impairment;
- MEM=
- episodic memory composite score;
- OP=
- occipital pole;
- ROI=
- region of interest;
- SUVR=
- standardized uptake value ratio;
- TMT-B=
- Trail-Making Test B
Footnotes
Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
Data used in preparation of this article were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. The ADNI investigators contributed to the design and implementation of ADNI and/or provided data. The ADNI list is available at Neurology.org.
Supplemental data at Neurology.org
- Received May 19, 2016.
- Accepted in final form December 20, 2016.
- © 2017 American Academy of Neurology
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