TY - JOUR
T1 - Sex differences in functional and molecular neuroimaging biomarkers of Alzheimer's disease in cognitively normal older adults with subjective memory complaints
AU - INSIGHT-preAD Study Group
AU - the Alzheimer Precision Medicine Initiative (APMI)
AU - Cavedo, Enrica
AU - Chiesa, Patrizia A.
AU - Houot, Marion
AU - Ferretti, Maria Teresa
AU - Grothe, Michel J.
AU - Teipel, Stefan J.
AU - Lista, Simone
AU - Habert, Marie Odile
AU - Potier, Marie Claude
AU - Dubois, Bruno
AU - Hampel, Harald
AU - Bakardjian, Hovagim
AU - Benali, Habib
AU - Bertin, Hugo
AU - Bonheur, Joel
AU - Boukadida, Laurie
AU - Boukerrou, Nadia
AU - Cavedo, Enrica
AU - Chiesa, Patrizia
AU - Colliot, Olivier
AU - Dubois, Bruno
AU - Dubois, Marion
AU - Epelbaum, Stéphane
AU - Gagliardi, Geoffroy
AU - Genthon, Remy
AU - Habert, Marie Odile
AU - Hampel, Harald
AU - Houot, Marion
AU - Kas, Aurélie
AU - Lamari, Foudil
AU - Levy, Marcel
AU - Metzinger, Christiane
AU - Mochel, Fanny
AU - Nyasse, Francis
AU - Poisson, Catherine
AU - Potier, Marie Claude
AU - Revillon, Marie
AU - Santos, Antonio
AU - Andrade, Katia Santos
AU - Sole, Marine
AU - Surtee, Mohmed
AU - de Schotten, Michel Thiebaud
AU - Vergallo, Andrea
AU - Younsi, Nadjia
AU - Aguilar, Lisi Flores
AU - Babiloni, Claudio
AU - Baldacci, Filippo
AU - Benda, Norbert
AU - Black, Keith L.
AU - Ritchie, Craig
N1 - Funding Information:
M.T.F. is supported by a research grant from the Synapsis Foundation (Alzheimer's research Switzerland); she is the co-founder and President of the Women's Brain Project. E.C., P.A.C., M.H., M.J.G., S.J.T., S.L., M.-C.P., and B.D. have nothing to declare. H.H. serves as Senior Associate Editor for the Journal Alzheimer's & Dementia ; he received lecture fees from Biogen and Roche, research grants from Pfizer, Avid, and MSD Avenir (paid to the institution), travel funding from Functional Neuromodulation, Axovant, Eli Lilly and company, Takeda and Zinfandel, GE-Healthcare and Oryzon Genomics, consultancy fees from Jung Diagnostics, Cytox Ltd., Axovant, Anavex, Takeda and Zinfandel, GE Healthcare, Oryzon Genomics, and Functional Neuromodulation, and participated in scientific advisory boards of Functional Neuromodulation, Axovant, Eli Lilly and company, Cytox Ltd., GE Healthcare, Takeda and Zinfandel, Oryzon Genomics and Roche Diagnostics. H.H. is co-inventor in the following patents as a scientific expert and has received no royalties:
Funding Information:
The study was promoted by INSERM in collaboration with ICM, IHU-A-ICM, and Pfizer and has received a support within the “ Investissement d'Avenir ” (ANR-10-AIHU-06) program. The study was promoted in collaboration with the “ CHU de Bordeaux ” (coordination CIC EC7), the promoter of Memento cohort, funded by the Foundation Plan Alzheimer. The study was further supported by AVID/Lilly.
Funding Information:
The research leading to these results was supported by the Colam Initiatives and the 'Fondation pour la Recherche sur Alzheimer ', Paris, France. This publication benefited from the support of the Program “PHOENIX” led by the Sorbonne University Foundation and sponsored by la Fondation pour la Recherche sur Alzheimer.
Publisher Copyright:
© 2018 the Alzheimer's Association
PY - 2018/9
Y1 - 2018/9
N2 - Introduction: Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers. Methods: Positron emission tomography brain amyloid load, neurodegeneration (hippocampus and basal forebrain volumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose–positron emission tomography metabolism), and brain resting-state functional connectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117). A linear mixed-effects model was performed to investigate sex effects and sex∗apolipoprotein E genotype interaction on each marker as well as sex∗amyloid group interaction for non-amyloid markers. Results: Men compared with women showed higher anterior cingulate cortex amyloid load (P =.009), glucose hypometabolism in the precuneus (P =.027), posterior cingulate (P <.001) and inferior parietal (P =.043) cortices, and lower resting-state functional connectivity in the default mode network (P =.024). No brain volumetric markers showed differences between men and women. Sex∗apolipoprotein E genotype and sex∗amyloid status interactions were not significant. Discussion: Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.
AB - Introduction: Observational multimodal neuroimaging studies indicate sex differences in Alzheimer's disease pathophysiological markers. Methods: Positron emission tomography brain amyloid load, neurodegeneration (hippocampus and basal forebrain volumes adjusted to total intracranial volume, cortical thickness, and 2-deoxy-2-[fluorine-18]fluoro-D-glucose–positron emission tomography metabolism), and brain resting-state functional connectivity were analyzed in 318 cognitively intact older adults from the INSIGHT-preAD cohort (female n = 201, male n = 117). A linear mixed-effects model was performed to investigate sex effects and sex∗apolipoprotein E genotype interaction on each marker as well as sex∗amyloid group interaction for non-amyloid markers. Results: Men compared with women showed higher anterior cingulate cortex amyloid load (P =.009), glucose hypometabolism in the precuneus (P =.027), posterior cingulate (P <.001) and inferior parietal (P =.043) cortices, and lower resting-state functional connectivity in the default mode network (P =.024). No brain volumetric markers showed differences between men and women. Sex∗apolipoprotein E genotype and sex∗amyloid status interactions were not significant. Discussion: Our findings suggest that cognitively intact older men compared with women have higher resilience to pathophysiological processes of Alzheimer's disease.
KW - APOE
KW - Aging
KW - Alzheimer's disease
KW - Amyloid
KW - Basal forebrain
KW - Cognitively intact older individuals
KW - Cortical thickness
KW - FDG-PET
KW - Hippocampus
KW - Metabolism
KW - Sex
UR - http://www.scopus.com/inward/record.url?scp=85052864283&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2018.05.014
DO - 10.1016/j.jalz.2018.05.014
M3 - Review article
C2 - 30201102
AN - SCOPUS:85052864283
VL - 14
SP - 1204
EP - 1215
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 9
ER -