Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

Olivia Wagemann; Yan Li; Jason Hassenstab; Andrew J. Aschenbrenner; Nicole S. McKay; Brian A. Gordon; Tammie L.S. Benzinger; Chengjie Xiong; Carlos Cruchaga; Alan E. Renton; Richard J. Perrin; Sarah B. Berman; Jasmeer P. Chhatwal; Martin R. Farlow; Gregory S. Day; Takeshi Ikeuchi; Mathias Jucker; Francisco Lopera; Hiroshi Mori; James M. Noble; Raquel Sánchez-Valle; Peter R. Schofield; John C. Morris; Alisha Daniels; Johannes Levin; Randall J. Bateman; Eric McDade; Jorge J. Llibre-Guerra

doi:10.1002/alz.13460

Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

Olivia Wagemann, Yan Li, Jason Hassenstab, Andrew J. Aschenbrenner, Nicole S. McKay, Brian A. Gordon, Tammie L.S. Benzinger, Chengjie Xiong, Carlos Cruchaga, Alan E. Renton, Richard J. Perrin, Sarah B. Berman, Jasmeer P. Chhatwal, Martin R. Farlow, Gregory S. Day, Takeshi Ikeuchi, Mathias Jucker, Francisco Lopera, Hiroshi Mori, James M. NobleRaquel Sánchez-Valle, Peter R. Schofield, John C. Morris, Alisha Daniels, Johannes Levin, Randall J. Bateman, Eric McDade, Jorge J. Llibre-Guerra

Research output: Contribution to journal › Article › peer-review

2 Scopus citations

Abstract

INTRODUCTION: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD). METHODS: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (¹¹C-PiB PET) and structural magnetic resonance imaging (MRI). RESULTS: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences. DISCUSSION: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD.

Original language	English
Pages (from-to)	47-62
Number of pages	16
Journal	Alzheimer's and Dementia
Volume	20
Issue number	1
DOIs	https://doi.org/10.1002/alz.13460
State	Published - Jan 2024

Keywords

cognition
dominantly inherited Alzheimer's disease
gender
presymptomatic Alzheimer's disease
sex

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Wagemann, O., Li, Y., Hassenstab, J., Aschenbrenner, A. J., McKay, N. S., Gordon, B. A., Benzinger, T. L. S., Xiong, C., Cruchaga, C., Renton, A. E., Perrin, R. J., Berman, S. B., Chhatwal, J. P., Farlow, M. R., Day, G. S., Ikeuchi, T., Jucker, M., Lopera, F., Mori, H., ... Llibre-Guerra, J. J. (2024). Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network. Alzheimer's and Dementia, 20(1), 47-62. https://doi.org/10.1002/alz.13460

@article{1972c1edd3984308b423595eb3f01bda,

title = "Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network",

abstract = "INTRODUCTION: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD). METHODS: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (11C-PiB PET) and structural magnetic resonance imaging (MRI). RESULTS: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences. DISCUSSION: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD.",

keywords = "cognition, dominantly inherited Alzheimer's disease, gender, presymptomatic Alzheimer's disease, sex",

author = "Olivia Wagemann and Yan Li and Jason Hassenstab and Aschenbrenner, {Andrew J.} and McKay, {Nicole S.} and Gordon, {Brian A.} and Benzinger, {Tammie L.S.} and Chengjie Xiong and Carlos Cruchaga and Renton, {Alan E.} and Perrin, {Richard J.} and Berman, {Sarah B.} and Chhatwal, {Jasmeer P.} and Farlow, {Martin R.} and Day, {Gregory S.} and Takeshi Ikeuchi and Mathias Jucker and Francisco Lopera and Hiroshi Mori and Noble, {James M.} and Raquel S{\'a}nchez-Valle and Schofield, {Peter R.} and Morris, {John C.} and Alisha Daniels and Johannes Levin and Bateman, {Randall J.} and Eric McDade and Llibre-Guerra, {Jorge J.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.",

year = "2024",

month = jan,

doi = "10.1002/alz.13460",

language = "English",

volume = "20",

pages = "47--62",

journal = "Alzheimer's and Dementia",

issn = "1552-5260",

number = "1",

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Wagemann, O, Li, Y , Hassenstab, J , Aschenbrenner, AJ , McKay, NS , Gordon, BA , Benzinger, TLS , Xiong, C , Cruchaga, C, Renton, AE, Perrin, RJ, Berman, SB, Chhatwal, JP, Farlow, MR, Day, GS, Ikeuchi, T, Jucker, M, Lopera, F, Mori, H, Noble, JM, Sánchez-Valle, R, Schofield, PR, Morris, JC , Daniels, A, Levin, J, Bateman, RJ , McDade, E & Llibre-Guerra, JJ 2024, 'Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network', Alzheimer's and Dementia, vol. 20, no. 1, pp. 47-62. https://doi.org/10.1002/alz.13460

TY - JOUR

T1 - Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

AU - Wagemann, Olivia

AU - Li, Yan

AU - Hassenstab, Jason

AU - Aschenbrenner, Andrew J.

AU - McKay, Nicole S.

AU - Gordon, Brian A.

AU - Benzinger, Tammie L.S.

AU - Xiong, Chengjie

AU - Cruchaga, Carlos

AU - Renton, Alan E.

AU - Perrin, Richard J.

AU - Berman, Sarah B.

AU - Chhatwal, Jasmeer P.

AU - Farlow, Martin R.

AU - Day, Gregory S.

AU - Ikeuchi, Takeshi

AU - Jucker, Mathias

AU - Lopera, Francisco

AU - Mori, Hiroshi

AU - Noble, James M.

AU - Sánchez-Valle, Raquel

AU - Schofield, Peter R.

AU - Morris, John C.

AU - Daniels, Alisha

AU - Levin, Johannes

AU - Bateman, Randall J.

AU - McDade, Eric

AU - Llibre-Guerra, Jorge J.

PY - 2024/1

Y1 - 2024/1

N2 - INTRODUCTION: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD). METHODS: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (11C-PiB PET) and structural magnetic resonance imaging (MRI). RESULTS: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences. DISCUSSION: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD.

AB - INTRODUCTION: Studies suggest distinct differences in the development, presentation, progression, and response to treatment of Alzheimer's disease (AD) between females and males. We investigated sex differences in cognition, neuroimaging, and fluid biomarkers in dominantly inherited AD (DIAD). METHODS: Three hundred twenty-five mutation carriers (55% female) and one hundred eighty-six non-carriers (58% female) of the Dominantly Inherited Alzheimer Network Observational Study were analyzed. Linear mixed models and Spearman's correlation explored cross-sectional sex differences in cognition, cerebrospinal fluid (CSF) biomarkers, Pittsburgh compound B positron emission tomography (11C-PiB PET) and structural magnetic resonance imaging (MRI). RESULTS: Female carriers performed better than males on delayed recall and processing speed despite similar hippocampal volumes. As the disease progressed, symptomatic females revealed higher increases in MRI markers of neurodegeneration and memory impairment. PiB PET and established CSF AD markers revealed no sex differences. DISCUSSION: Our findings suggest an initial cognitive reserve in female carriers followed by a pronounced increase in neurodegeneration coupled with worse performance on delayed recall at later stages of DIAD.

KW - cognition

KW - dominantly inherited Alzheimer's disease

KW - gender

KW - presymptomatic Alzheimer's disease

KW - sex

UR - http://www.scopus.com/inward/record.url?scp=85171778468&partnerID=8YFLogxK

U2 - 10.1002/alz.13460

DO - 10.1002/alz.13460

M3 - Article

C2 - 37740921

AN - SCOPUS:85171778468

SN - 1552-5260

VL - 20

SP - 47

EP - 62

JO - Alzheimer's and Dementia

JF - Alzheimer's and Dementia

IS - 1

ER -

Investigation of sex differences in mutation carriers of the Dominantly Inherited Alzheimer Network

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