Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease

Sander Verfaillie, Alexa Pichet Binette, Etienne Vachon-Presseau, Shirin Tabrizi, Mélissa Savard, Pierre Bellec, Rik Ossenkoppele, Philip Scheltens, Wiesje M. van der Flier, John C.S. Breitner, Sylvia Villeneuve, Paul Aisen, Elena Anthal, Melissa Appleby, Gülebru Ayranci, Alan Barkun, Thomas Beaudry, Pierre Bellec, Fatiha Benbouhoud, Veronique BohbotJason Brandt, John Breitner, Leopoldina Carmo, Edouard Carrier Charles, Mallar Chakravarty, Laksanun Cheewakriengkrai, Louis Collins, Blandine Courcot, Doris Couture, Suzanne Craft, Claudio Cuello, Mahsa Dadar, Christian Dansereau, DasSamir, Dauar Tedeschi Marina, Doris Dea, Clement Debacker, Rene Desautels, Sylvie Dubuc, Guerda Duclair, Marianne Dufour, Mark Eisenberg, Rana El-Khoury, Pierre Etienne, Alan Evans, Anne Marie Faubert, Fabiola Ferdinand, Vladimir Fonov, Jacob Vogel, PREVENT-AD Research Group

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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, SCD+ 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.

Original languageEnglish
Pages (from-to)463-472
Number of pages10
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Issue number5
Publication statusPublished - 1 May 2018

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