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Abstract
Objective To investigate whether higher global left frontal cortex (gLFC) connectivity, a putative neural substrate of cognitive reserve, attenuates the effect of entorhinal tau PET levels on episodic memory in older adults.
Methods Cross-sectional 18F-AV-1451 PET (to assess tau pathology), 18F-AV-45 or 18F-BAY94-9172 PET (to assess β-amyloid [Aβ]), and resting-state fMRI were obtained in 125 elderly participants from the Alzheimer's Neuroimaging Initiative, including 82 cognitively normal participants (amyloid PET-positive [Aβ+], n = 27) and 43 patients with amnestic mild cognitive impairment (Aβ+ = 15). Resting-state fMRI gLFC connectivity was computed for each participant as the average functional connectivity between the left frontal cortex (LFC) (seed) and each remaining voxel in the gray matter. As a measure of tau pathology, we assessed the mean tau PET uptake in the entorhinal cortex. In linear mixed-effects regression analysis, we tested the interaction term gLFC connectivity × entorhinal tau PET on delayed free recall performance. In addition, we assessed whether higher connectivity of the whole frontoparietal control network (FPCN), of which the LFC is a major hub, is associated with reserve.
Results Higher entorhinal tau PET was strongly associated with poorer delayed free recall performance (β/SE = −0.49/0.07, p < 0.001). A significant gLFC connectivity × entorhinal tau PET interaction was found (β/SE = 0.19/0.06, p = 0.003), such that at higher levels of gLFC connectivity, the decrease in memory score per unit of entorhinal tau PET was attenuated. The FPCN connectivity × tau interaction was also significant (β/SE = 0.10/0.04, p = 0.012).
Conclusion Both gLFC and FPCN connectivity are associated with higher resilience against the adverse effect of early-stage entorhinal tau pathology on memory performance.
Glossary
- AD=
- Alzheimer disease;
- ADNI=
- Alzheimer's Disease Neuroimaging Initiative;
- BOLD=
- blood oxygenation level–dependent;
- CDR=
- Clinical Dementia Rating;
- CI=
- confidence interval;
- CN=
- cognitively normal;
- EPI=
- echoplanar imaging;
- FPCN=
- frontoparietal control network;
- gLFC=
- global left frontal cortex;
- GM=
- gray matter;
- LFC=
- left frontal cortex;
- M1=
- primary motor cortex;
- MCI=
- mild cognitive impairment;
- MMSE=
- Mini-Mental State Examination;
- MNI=
- Montreal Neurologic Institute;
- PVC=
- partial volume corrected;
- RAVLT=
- Rey Auditory Verbal Learning Task;
- ROI=
- region of interest;
- SUVR=
- standardized uptake value ratio;
- TR=
- repetition time;
- WM=
- white matter
Footnotes
Go to Neurology.org/N 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 (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found in the coinvestigators list at links.lww.com/WNL/A927.
- Received October 23, 2018.
- Accepted in final form March 8, 2019.
- © 2019 American Academy of Neurology
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