Journal
BIOLOGICAL PSYCHIATRY-COGNITIVE NEUROSCIENCE AND NEUROIMAGING
Volume 3, Issue 5, Pages 463-472Publisher
ELSEVIER
DOI: 10.1016/j.bpsc.2017.11.012
Keywords
Alzheimer's disease; Cognition; Default mode network connectivity; Family history of dementia; Resting-state functional MRI; Subjective cognitive decline
Categories
Funding
- Alzheimer Nederland Fellowship [WE.15-2016-03]
- Gieske-Strijbis Fonds
- Canada Research Chair
- Canadian Institutes of Health Research Foundation Grant
- Canada Fund for Innovation Grant
- Alzheimer Society of Canada
- Brain Canada Research Grant
- Fonds de recherche Sante Quebec
- McGill University
- Fonds de Recherche du Quebec-Sante
- Pfizer Canada
- Levesque Foundation
- Douglas Hospital Research Centre and Foundation
- Government of Canada
- Canada Fund for Innovation
- Boehringer Ingelheim
- GE Healthcare
- Danone Research
- Merck
- Natural Sciences and Engineering Research Council of Canada
- Fonds de recherche du Quebec Nature et technologies
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BACKGROUND: Both subjective cognitive decline (SCD) and a family history of Alzheimer's disease (AD) portend risk of brain abnormalities and progression to dementia. Posterior default mode network (pDMN) connectivity is altered early in the course of AD. It is unclear whether SCD predicts similar outcomes in cognitively normal individuals with a family history of AD. METHODS: We studied 124 asymptomatic individuals with a family history of AD (age 64 +/- 5 years). Participants were categorized as having SCD if they reported that their memory was becoming worse (SCD+). We used extensive neuropsychological assessment to investigate five different cognitive domain performances at baseline (n = 124) and 1 year later (n = 59). We assessed interconnectivity among three a priori defined ROIs: pDMN, anterior ventral DMN, medial temporal memory system (MTMS), and the connectivity of each with the rest of brain. RESULTS: Sixty-eight (55%) participants reported SCD. Baseline cognitive performance was comparable between groups (all false discovery rate-adjusted p values > .05). At follow-up, immediate and delayed memory improved across groups, but the improvement in immediate memory was reduced in SCD+ compared with SCD- (all false discovery rate-adjusted p values < .05). When compared with SCD-, SOD+ subjects showed increased pDMN-MTMS connectivity (false discovery rate-adjusted p < .05). Higher connectivity between the MTMS and the rest of the brain was associated with better baseline immediate memory, attention, and global cognition, whereas higher MTMS and pDMN-MTMS connectivity were associated with lower immediate memory over time (all false discovery rate-adjusted p values < .05). CONCLUSIONS: SCD in cognitively normal individuals is associated with diminished immediate memory practice effects and a brain connectivity pattern that mirrors early AD-related connectivity failure.
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