TY - JOUR
T1 - Subjective Cognitive Decline Is Associated With Altered Default Mode Network Connectivity in Individuals With a Family History of Alzheimer's Disease
AU - PREVENT-AD Research Group
AU - Verfaillie, Sander C.J.
AU - Pichet Binette, Alexa
AU - Vachon-Presseau, Etienne
AU - Tabrizi, Shirin
AU - Savard, Mélissa
AU - Bellec, Pierre
AU - Ossenkoppele, Rik
AU - Scheltens, Philip
AU - van der Flier, Wiesje M.
AU - Breitner, John C.S.
AU - Villeneuve, Sylvia
AU - Aisen, Paul
AU - Anthal, Elena
AU - Appleby, Melissa
AU - Ayranci, Gülebru
AU - Barkun, Alan
AU - Beaudry, Thomas
AU - Benbouhoud, Fatiha
AU - Bohbot, Veronique
AU - Brandt, Jason
AU - Carmo, Leopoldina
AU - Carrier Charles, Edouard
AU - Chakravarty, Mallar
AU - Cheewakriengkrai, Laksanun
AU - Collins, Louis
AU - Courcot, Blandine
AU - Couture, Doris
AU - Craft, Suzanne
AU - Cuello, Claudio
AU - Dadar, Mahsa
AU - Dansereau, Christian
AU - DasSamir,
AU - Marina, Dauar Tedeschi
AU - Dea, Doris
AU - Debacker, Clement
AU - Desautels, Rene
AU - Dubuc, Sylvie
AU - Duclair, Guerda
AU - Dufour, Marianne
AU - Eisenberg, Mark
AU - El-Khoury, Rana
AU - Etienne, Pierre
AU - Evans, Alan
AU - Faubert, Anne Marie
AU - Ferdinand, Fabiola
AU - Fonov, Vladimir
AU - Fontaine, David
AU - Frappier, Josée
AU - Joanne, Frenette
AU - Morris, John
N1 - Funding Information:
This work was supported by Alzheimer Nederland Fellowship Grant No. WE.15-2016-03 (to SCJV), Gieske-Strijbis Fonds, a Canada Research Chair, a Canadian Institutes of Health Research Foundation Grant, a Canada Fund for Innovation Grant, and a joint Alzheimer Society of Canada and Brain Canada Research Grant (to SV), a Gieske-Strijbis Fonds Research Grant (to WvdF and SCJV), a fellowship from the Alzheimer Society of Canada and Fonds de recherche Santé Québec (to APB), and a Canada Research Chair Grant (to JB). PREVENT-AD was launched in 2011 as a $13.5 million, 7-year public–private partnership using funds provided by McGill University, the Fonds de Recherche du Québec–Santé, an unrestricted research grant from Pfizer Canada, the Levesque Foundation, the Douglas Hospital Research Centre and Foundation, the Government of Canada, and the Canada Fund for Innovation. Private sector contributions are facilitated by the Development Office of the McGill University Faculty of Medicine and by the Douglas Hospital Research Centre Foundation ( http://www.douglas.qc.ca/ ).
Funding Information:
The computational resources used to perform the data analysis were provided by Compute Canada ( https://computecanada.ca ) and McGill’s Centre for High-Performance Computing ( http://www.hpc.mcgill.ca ), which is funded in part by the Natural Sciences and Engineering Research Council of Canada (Major Resources Support), Fonds de recherche du Québec – Nature et technologies, and McGill University. The funding sources had no role in the design and conduct of the study, in the collection, analysis, interpretation of the data or in the preparation, review or approval of the manuscript. Finally, we would like to acknowledge the participants of the PREVENT-AD cohort for dedicating their time and energy to help us collect these data.
Publisher Copyright:
© 2017 Society of Biological Psychiatry
PY - 2018/5/1
Y1 - 2018/5/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Cognition
KW - Default mode network connectivity
KW - Family history of dementia
KW - Resting-state functional MRI
KW - Subjective cognitive decline
UR - http://www.scopus.com/inward/record.url?scp=85041617475&partnerID=8YFLogxK
U2 - 10.1016/j.bpsc.2017.11.012
DO - 10.1016/j.bpsc.2017.11.012
M3 - Article
C2 - 29735156
AN - SCOPUS:85041617475
SN - 2451-9022
VL - 3
SP - 463
EP - 472
JO - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
JF - Biological Psychiatry: Cognitive Neuroscience and Neuroimaging
IS - 5
ER -