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

Sander C.J Verfaillie,Pierre Bellec,Eduard Teigner,John C.S Breitner,Renuka Giles,Justin Miron,Justin Kat,Fabiola Ferdinand,Alexa Pichet Binette,Penelope Kostopoulos,Edouard Carrier Charles,Fatiha Benbouhoud,Reisa Sperling,Marianne Dufour,Miranda Tuwaig,Doris Couture,Cynthia Picard,Ginette Mayrand,Sylvie Dubuc,Wiesje M Van Der Flier,Pierre Rioux,Frenette Joanne,Shirin Tabrizi,Thomas Beaudry,Lisa-Marie Münter,Paule-Joanne Toussaint,Philip Scheltens,Elena Anthal,Blandine Courcot,Vinod Venugopalan,Rana El-Khoury,Holly Newbold-Fox,Yasser Ituria-Medina,Jean-Robert Maltais,Christina Kazazian,Christian Dansereau,Christine Tardif,Sulantha Mathotaarachchi,Judes Poirier,Natasha Rajah,Gerhard Maultaup,Laksanun Cheewakriengkrai,Anne-Marie Faubert,Mirela Petkova,Karen Wan,David Fontaine,Julie Gonneaud,Rick Hoge,David Maillet,Axel Mathieu,Diane Michaud,Claude Lepage,Vladimir Fonov,Leopoldina Carmo,Rik Ossenkoppele,Eunice Farah Saint-Fort,Renee Gordon,Dauar-Tedeschi Marina,Dassamir Dassamir,Josée Frappier,Jamie Near,Doris Dea,Elsa Yu,Illana Leppert,Sylvia Villeneuve,Seqian Wang,Jason Brandt,Angela Tam,Mahsa Dadar,Cécile Madjar,Vasavan Nair,Galina Pogossova,Guerda Duclair,Serge Gauthier,Pierre Orban,Tanya Lee,Suzanne Craft,Claudio Cuello,Laura Mahar,Mélissa Savard,Valérie Gervais,Louis Collins,David S Knopman ,Mark A Sager ,Tharick A Pascoal ,Paul S Aisen ,Guylaine Gagné ,Pierre‐François Meyer ,Isabelle Vallée ,Jeannie‐Marie Leoutsakos ,Pedro Rosa‐Neto ,Jacob W Vogel ,John C Morris ,Pierre N Tariot ,Clément Debacker ,Thomas J Montine ,M Mallar Chakravarty ,Véronique D Bohbot ,Pierre Étienne ,Véronique Pagé ,Anne Labonté ,René Desautels ,Étienne Vachon-Presseau ,Marie‐Élyse Lafaille‐Magnan ,Clifford R Jack ,Gülebru Ayrancı ,Mark J Eisenberg ,Louise Théroux ,Alan C Evans ,Zaven S Khachaturian ,Bradley T Hyman ,Jennifer Tremblay‐Mercier ,Ronald G Thomas ,Jens C Pruessner ,Alan N Barkun ,Melissa Appleby

doi:10.1016/j.bpsc.2017.11.012

Abstract

BackgroundBoth 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. MethodsWe 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. ResultsSixty-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). ConclusionsSCD in cognitively normal individuals is associated with diminished immediate memory practice effects and a brain connectivity pattern that mirrors early AD-related connectivity failure.

Full Text