PT  - JOURNAL ARTICLE
AU  - Neitzel, Julia
AU  - Franzmeier, Nicolai
AU  - Rubinski, Anna
AU  - Ewers, Michael
AU  - , 
TI  - Left frontal connectivity attenuates the adverse effect of entorhinal tau pathology on memory
AID  - 10.1212/WNL.0000000000007822
DP  - 2019 Jul 23
TA  - Neurology
PG  - e347--e357
VI  - 93
IP  - 4
4099  - http://n.neurology.org/content/93/4/e347.short
4100  - http://n.neurology.org/content/93/4/e347.full
SO  - Neurology2019 Jul 23; 93
AB  - 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.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