@article{3f7f0c6d7e0543c6b4d5b75b66a83f54,
title = "Impact of sex and APOE ε4 on the association of cognition and hippocampal volume in clinically normal, amyloid positive adults",
abstract = "Introduction: Cognitive decline follows pathological changes including neurodegeneration on the Alzheimer's disease continuum. However, it is unclear which cognitive domains first become affected by neurodegeneration in amyloid-positive individuals and if sex or apolipoprotein (APOE) ε4 status differences affect this relationship. Methods: Data from 1233 cognitively unimpaired, amyloid-positive individuals 65 to 85 years of age were studied to assess the effect of hippocampal volume (HV) on cognition and to evaluate differences due to sex and APOE ε4 status. Results: Lower HV was linked with worse performance on measures of memory (free recall, total recall, logical memory delayed recall, Mini-Mental State Examination [MMSE]), executive functioning (digit symbol substitution, DSS), and the Preclinical Alzheimer's Cognitive Composite (PACC). Among both women and APOE ε4+ individuals, all cognitive measures, except MMSE, were associated with HV. DSS and PACC had the largest effect sizes in differentiating early and intermediate stage neurodegeneration. Discussion: Despite all cognitive measures being associated with HV, cognitive tests show differences in detecting early or late signs of neurodegeneration. Differences exist in association between cognition and neurodegeneration based on sex and APOE ε4 status.",
keywords = "APOE ε4, cognition, FCSRT96, hippocampal volume, logical memory, MMSE, PACC, Sex",
author = "Petersen, {Kellen K.} and Ellen Grober and Lipton, {Richard B.} and Sperling, {Reisa A.} and Buckley, {Rachel F.} and Aisen, {Paul S.} and Ali Ezzati",
note = "Funding Information: The A4 Study is a secondary prevention trial in preclinical Alzheimer's disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public‐private‐philanthropic partnership, including funding from the National Institutes of Health‐National Institute on Aging, Eli Lilly and Company, Alzheimer's Association, Accelerating Medicines Partnership, GHR Foundation, and an anonymous foundation and additional private donors, with in‐kind support from Avid and Cogstate. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer's Association and GHR Foundation. The A4 and LEARN Studies are led by Reisa Sperling at Brigham and Women's Hospital, Harvard Medical School and by Paul Aisen at the Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de‐identified data in order to advance the quest to find a successful treatment for Alzheimer's disease. The authors would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available on: a4study.org/a4‐study‐team. This work was financially supported by grants from the National Institutes of Health (NIA K23 AG063993, Ezzati; NIA P01 AG03949, Lipton), the Alzheimer's Association (Ezzati, 2019‐AACSF‐641329), the Cure Alzheimer's Fund (Ezzati, Lipton), and the Leonard and Sylvia Marx Foundation (Lipton). Funding Information: The A4 Study is a secondary prevention trial in preclinical Alzheimer's disease, aiming to slow cognitive decline associated with brain amyloid accumulation in clinically normal older individuals. The A4 Study is funded by a public-private-philanthropic partnership, including funding from the National Institutes of Health-National Institute on Aging, Eli Lilly and Company, Alzheimer's Association, Accelerating Medicines Partnership, GHR Foundation, and an anonymous foundation and additional private donors, with in-kind support from Avid and Cogstate. The companion observational Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) Study is funded by the Alzheimer's Association and GHR Foundation. The A4 and LEARN Studies are led by Reisa Sperling at Brigham and Women's Hospital, Harvard Medical School and by Paul Aisen at the Alzheimer's Therapeutic Research Institute (ATRI), University of Southern California. The A4 and LEARN Studies are coordinated by ATRI at the University of Southern California, and the data are made available through the Laboratory for Neuro Imaging at the University of Southern California. The participants screening for the A4 Study provided permission to share their de-identified data in order to advance the quest to find a successful treatment for Alzheimer's disease. The authors would like to acknowledge the dedication of all the participants, the site personnel, and all of the partnership team members who continue to make the A4 and LEARN Studies possible. The complete A4 Study Team list is available on: a4study.org/a4-study-team. This work was financially supported by grants from the National Institutes of Health (NIA K23 AG063993, Ezzati; NIA P01 AG03949, Lipton), the Alzheimer's Association (Ezzati, 2019-AACSF-641329), the Cure Alzheimer's Fund (Ezzati, Lipton), and the Leonard and Sylvia Marx Foundation (Lipton). Publisher Copyright: {\textcopyright} 2022 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals, LLC on behalf of Alzheimer's Association.",
year = "2022",
doi = "10.1002/dad2.12271",
language = "English (US)",
volume = "14",
journal = "Alzheimer's and Dementia: Diagnosis, Assessment and Disease Monitoring",
issn = "2352-8729",
publisher = "Elsevier BV",
number = "1",
}
