TY - JOUR
T1 - APOE4 Status is Related to Differences in Memory-Related Brain Function in Asymptomatic Older Adults with Family History of Alzheimer's Disease
T2 - Baseline Analysis of the PREVENT-AD Task Functional MRI Dataset
AU - Rabipour, Sheida
AU - Rajagopal, Sricharana
AU - Yu, Elsa
AU - Pasvanis, Stamatoula
AU - Lafaille-Magnan, Marie Elyse
AU - Breitner, John
AU - Rajah, M. Natasha
N1 - Funding Information:
We thank members of the Rajah lab, the Cerebral Imaging Centre, and the Stop-AD Centre at the Douglas Hospital Research Centre for their helpful contributions to this work; especially Dr. R. Gordon for her help with E-Prime and Ms. C. Madjar for her help with data collection and quality control. We also acknowledge the Fonds de Recherche Québec – Santé, Natural Sciences and Engineering Research Council, and Canadian Institutes of Health Research for their support of our work.
Funding Information:
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/).
Publisher Copyright:
© 2020 - IOS Press and the authors. All rights reserved.
PY - 2020
Y1 - 2020
N2 - Background: Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's disease (AD). Older adults with the apolipoprotein E ϵ4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. Objective: Here we report the baseline episodic memory task functional MRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease cohort in Montreal, Canada, in which 327 healthy older adults were scanned within 15 years of their parent's conversion to AD. Methods: Volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to spatial source recollection and object-only (recognition) memory. We used multivariate partial least squares (PLS) to test the hypothesis that +APOE4 adults with family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal, and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also examined group differences in the correlation between event-related brain activity and memory performance. Results: We found group similarities in memory performance and in task-related brain activity in the recollection network, but differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. Conclusion: These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with first-degree family history of AD.
AB - Background: Episodic memory decline is one of the earliest symptoms of late-onset Alzheimer's disease (AD). Older adults with the apolipoprotein E ϵ4 (+APOE4) genetic risk factor for AD may exhibit altered patterns of memory-related brain activity years prior to initial symptom onset. Objective: Here we report the baseline episodic memory task functional MRI results from the PRe-symptomatic EValuation of Experimental or Novel Treatments for Alzheimer's Disease cohort in Montreal, Canada, in which 327 healthy older adults were scanned within 15 years of their parent's conversion to AD. Methods: Volunteers were scanned as they encoded and retrieved object-location spatial source associations. The task was designed to discriminate between brain activity related to spatial source recollection and object-only (recognition) memory. We used multivariate partial least squares (PLS) to test the hypothesis that +APOE4 adults with family history of AD would exhibit altered patterns of brain activity in the recollection-related memory network, comprised of medial frontal, parietal, and medial temporal cortices, compared to APOE4 non-carriers (-APOE4). We also examined group differences in the correlation between event-related brain activity and memory performance. Results: We found group similarities in memory performance and in task-related brain activity in the recollection network, but differences in brain activity-behavior correlations in ventral occipito-temporal, medial temporal, and medial prefrontal cortices during episodic encoding. Conclusion: These findings are consistent with previous literature on the influence of APOE4 on brain activity and provide new perspective on potential gene-based differences in brain-behavior relationships in people with first-degree family history of AD.
KW - Alzheimer's disease
KW - Apolipoprotein E polymorphism
KW - associative learning
KW - brain-behavior relationships
KW - episodic memory
KW - familial history
KW - task-related functional MRI
UR - http://www.scopus.com/inward/record.url?scp=85087530098&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85087530098&partnerID=8YFLogxK
U2 - 10.3233/JAD-191292
DO - 10.3233/JAD-191292
M3 - Article
C2 - 32474466
AN - SCOPUS:85087530098
SN - 1387-2877
VL - 76
SP - 97
EP - 119
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - 1
ER -