TY - JOUR
T1 - Amyloid and Tau Pathology Associations With Personality Traits, Neuropsychiatric Symptoms, and Cognitive Lifestyle in the Preclinical Phases of Sporadic and Autosomal Dominant Alzheimer's Disease
AU - Dominantly Inherited Alzheimer Network (DIAN)
AU - PREVENT-AD Research Group
AU - Pichet Binette, Alexa
AU - Vachon-Presseau, Étienne
AU - Morris, John C.
AU - Bateman, Randall J.
AU - Benzinger, Tammie
AU - Collins, D. Louis
AU - Poirier, Judes
AU - Breitner, John C.S.
AU - Villeneuve, Sylvia
AU - Allegri, Ricardo
AU - Amtashar, Fatima
AU - Bateman, Randy
AU - Berman, Sarah
AU - Bodge, Courtney
AU - Brandon, Susan
AU - Brooks, William (Bill)
AU - Buck, Jill
AU - Buckles, Virginia
AU - Chea, Sochenda
AU - Chhatwal, Jasmeer
AU - Chrem, Patricio
AU - Chui, Helena
AU - Cinco, Jake
AU - Clifford, Jack
AU - Cruchaga, Carlos
AU - D‘Mello, Mirelle
AU - Donahue, Tamara
AU - Douglas, Jane
AU - Edigo, Noelia
AU - Erekin-Taner, Nilufer
AU - Fagan, Anne
AU - Farlow, Marty
AU - Farrar, Angela
AU - Feldman, Howard
AU - Flynn, Gigi
AU - Fox, Nick
AU - Franklin, Erin
AU - Fujii, Hisako
AU - Gant, Cortaiga
AU - Gardener, Samantha
AU - Ghetti, Bernardino
AU - Gordon, Brian
AU - Hassenstab, Jason
AU - Holtzman, David
AU - Karch, Celeste
AU - Marcus, Daniel
AU - McDade, Eric
AU - Perrin, Richard
AU - Raichle, Marc
AU - Xiong, Chengjie
N1 - Funding Information:
This work was supported by a Canada Research Chair, a Canadian Institutes of Health Research Foundation Grant, a Canada Fund for Innovation Grant, and an Alzheimer’s Association Grant (to SV ) and a joint Alzheimer Society of Canada and Fonds de recherche Santé Québec fellowship (to APB). 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/ ). Data collection and sharing for this project was supported by DIAN (UF1AG032438) funded by the National Institute on Aging , the German Center for Neurodegenerative Diseases , Raul Carrea Institute for Neurological Research, partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development , and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute .
Funding Information:
This work was supported by a Canada Research Chair, a Canadian Institutes of Health Research Foundation Grant, a Canada Fund for Innovation Grant, and an Alzheimer's Association Grant (to SV) and a joint Alzheimer Society of Canada and Fonds de recherche Santé Québec fellowship (to APB). 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/). Data collection and sharing for this project was supported by DIAN (UF1AG032438) funded by the National Institute on Aging, the German Center for Neurodegenerative Diseases, Raul Carrea Institute for Neurological Research, partial support by the Research and Development Grants for Dementia from Japan Agency for Medical Research and Development, and the Korea Health Technology R&D Project through the Korea Health Industry Development Institute. This manuscript has been reviewed by DIAN Study investigators for scientific content and consistency of data interpretation with previous DIAN Study publications. We acknowledge the altruism of the participants and their families and contributions of the DIAN research and support staff at each of the participating sites for their contributions to this study. We acknowledge the staff of the PREVENT-AD as well as the Brain Imaging Centre of the Douglas Mental Health University Institute and the PET and cyclotron units of the Montreal Neurological Institute. We also acknowledge the participants of the PREVENT-AD cohort for dedicating their time and energy to helping us collect these data. The authors report no biomedical financial interests or potential conflicts of interest.
Publisher Copyright:
© 2020 Society of Biological Psychiatry
PY - 2021/4/15
Y1 - 2021/4/15
N2 - Background: Major prevention trials for Alzheimer's disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods: A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results: In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p =.014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p =.006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p =.005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions: In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.
AB - Background: Major prevention trials for Alzheimer's disease (AD) are now focusing on multidomain lifestyle interventions. However, the exact combination of behavioral factors related to AD pathology remains unclear. In 2 cohorts of cognitively unimpaired individuals at risk of AD, we examined which combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle (years of education or lifetime cognitive activity) related to the pathological hallmarks of AD, amyloid-β, and tau deposits. Methods: A total of 115 older adults with a parental or multiple-sibling family history of sporadic AD (PREVENT-AD [PRe-symptomatic EValuation of Experimental or Novel Treatments for AD] cohort) underwent amyloid and tau positron emission tomography and answered several questionnaires related to behavioral attributes. Separately, we studied 117 mutation carriers from the DIAN (Dominant Inherited Alzheimer Network) study group cohort with amyloid positron emission tomography and behavioral data. Using partial least squares analysis, we identified latent variables relating amyloid or tau pathology with combinations of personality traits, neuropsychiatric symptoms, and cognitive lifestyle. Results: In PREVENT-AD, lower neuroticism, neuropsychiatric burden, and higher education were associated with less amyloid deposition (p =.014). Lower neuroticism and neuropsychiatric features, along with higher measures of openness and extraversion, were related to less tau deposition (p =.006). In DIAN, lower neuropsychiatric burden and higher education were also associated with less amyloid (p =.005). The combination of these factors accounted for up to 14% of AD pathology. Conclusions: In the preclinical phase of both sporadic and autosomal dominant AD, multiple behavioral features were associated with AD pathology. These results may suggest potential pathways by which multidomain interventions might help delay AD onset or progression.
KW - Alzheimer's
KW - PET
KW - Prevention
KW - Reserve
KW - Resistance
KW - Risk factors
UR - http://www.scopus.com/inward/record.url?scp=85082547156&partnerID=8YFLogxK
U2 - 10.1016/j.biopsych.2020.01.023
DO - 10.1016/j.biopsych.2020.01.023
M3 - Article
C2 - 32228870
AN - SCOPUS:85082547156
SN - 0006-3223
VL - 89
SP - 776
EP - 785
JO - Biological Psychiatry
JF - Biological Psychiatry
IS - 8
ER -