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Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease

BACKGROUND: An aging society has increased rates of late onset Alzheimer disease dementia (ADD), the most common form of age-related dementia. This neurodegenerative disease disproportionately affects women. METHODS: We use data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to examine...

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Autores principales: Cieri, Filippo, Zhuang, Xiaowei, Cordes, Dietmar, Kaplan, Nikki, Cummings, Jeffery, Caldwell, Jessica
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864917/
https://www.ncbi.nlm.nih.gov/pubmed/35193682
http://dx.doi.org/10.1186/s13195-022-00973-1
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author Cieri, Filippo
Zhuang, Xiaowei
Cordes, Dietmar
Kaplan, Nikki
Cummings, Jeffery
Caldwell, Jessica
author_facet Cieri, Filippo
Zhuang, Xiaowei
Cordes, Dietmar
Kaplan, Nikki
Cummings, Jeffery
Caldwell, Jessica
author_sort Cieri, Filippo
collection PubMed
description BACKGROUND: An aging society has increased rates of late onset Alzheimer disease dementia (ADD), the most common form of age-related dementia. This neurodegenerative disease disproportionately affects women. METHODS: We use data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to examine sex differences in cortical thickness (CT) and memory performance. Analyses of covariance (ANCOVA) models were used to examine effects of sex and diagnosis (DX) on CT and verbal memory. For regions demonstrating significant interaction effects of sex and DX, we tested whether sex moderated cognition-thickness relationships. We used machine learning as a complementary method to explore multivariate CT differences between women and men. RESULTS: Women demonstrated greater CT in many brain regions. More specifically, men showed relatively consistent CT declines in all stages, from normal control (NC) to ADD in the bilateral cingulate cortex, bilateral temporal regions, and left precuneus; women had more stable CT in these regions between NC and mild cognitive impairment (MCI) stages, but sharper declines from MCI to ADD. Similarly, for the Rey Auditory Verbal Learning Test (RAVLT), ANCOVA analyses showed that women had significantly better immediate and delayed recall scores than men, at NC and MCI stages, but greater differences, cross-sectionally, from MCI to ADD than men. We found significant sex moderation effects between RAVLT-immediate scores and CT of right isthmus-cingulate for all subjects across DX. Partial correlation analyses revealed that increased CT of right isthmus-cingulate was associated with better verbal learning in women, driven by positron emission tomography defined amyloid positive (Aβ+) subjects. Significant sex-moderation effects in cognition-thickness relationships were further found in the right middle-temporal, left precuneus, and left superior temporal regions in Aβ+ subjects. Using a machine learning approach, we investigated multivariate CT differences between women and men, showing an accuracy in classification of 75% for Aβ+ cognitively NC participants. CONCLUSIONS: Sex differences in memory and CT can play a key role in the different vulnerability and progression of ADD in women compared to men. Machine learning indicates sex differences in CT are most relevant early in the ADD neurodegeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-022-00973-1.
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spelling pubmed-88649172022-02-28 Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease Cieri, Filippo Zhuang, Xiaowei Cordes, Dietmar Kaplan, Nikki Cummings, Jeffery Caldwell, Jessica Alzheimers Res Ther Research BACKGROUND: An aging society has increased rates of late onset Alzheimer disease dementia (ADD), the most common form of age-related dementia. This neurodegenerative disease disproportionately affects women. METHODS: We use data from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) to examine sex differences in cortical thickness (CT) and memory performance. Analyses of covariance (ANCOVA) models were used to examine effects of sex and diagnosis (DX) on CT and verbal memory. For regions demonstrating significant interaction effects of sex and DX, we tested whether sex moderated cognition-thickness relationships. We used machine learning as a complementary method to explore multivariate CT differences between women and men. RESULTS: Women demonstrated greater CT in many brain regions. More specifically, men showed relatively consistent CT declines in all stages, from normal control (NC) to ADD in the bilateral cingulate cortex, bilateral temporal regions, and left precuneus; women had more stable CT in these regions between NC and mild cognitive impairment (MCI) stages, but sharper declines from MCI to ADD. Similarly, for the Rey Auditory Verbal Learning Test (RAVLT), ANCOVA analyses showed that women had significantly better immediate and delayed recall scores than men, at NC and MCI stages, but greater differences, cross-sectionally, from MCI to ADD than men. We found significant sex moderation effects between RAVLT-immediate scores and CT of right isthmus-cingulate for all subjects across DX. Partial correlation analyses revealed that increased CT of right isthmus-cingulate was associated with better verbal learning in women, driven by positron emission tomography defined amyloid positive (Aβ+) subjects. Significant sex-moderation effects in cognition-thickness relationships were further found in the right middle-temporal, left precuneus, and left superior temporal regions in Aβ+ subjects. Using a machine learning approach, we investigated multivariate CT differences between women and men, showing an accuracy in classification of 75% for Aβ+ cognitively NC participants. CONCLUSIONS: Sex differences in memory and CT can play a key role in the different vulnerability and progression of ADD in women compared to men. Machine learning indicates sex differences in CT are most relevant early in the ADD neurodegeneration. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13195-022-00973-1. BioMed Central 2022-02-22 /pmc/articles/PMC8864917/ /pubmed/35193682 http://dx.doi.org/10.1186/s13195-022-00973-1 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Cieri, Filippo
Zhuang, Xiaowei
Cordes, Dietmar
Kaplan, Nikki
Cummings, Jeffery
Caldwell, Jessica
Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease
title Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease
title_full Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease
title_fullStr Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease
title_full_unstemmed Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease
title_short Relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and Alzheimer disease
title_sort relationship of sex differences in cortical thickness and memory among cognitively healthy subjects and individuals with mild cognitive impairment and alzheimer disease
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8864917/
https://www.ncbi.nlm.nih.gov/pubmed/35193682
http://dx.doi.org/10.1186/s13195-022-00973-1
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