Zhengshi Yang1, Filippo Cieri1, Jefferson W Kinney2, Jeffrey L Cummings2, Dietmar Cordes1, Jessica Z K Caldwell1. 1. Department of Neurology, Cleveland Clinic Lou Ruvo Center for Brain Health, 888 W Bonneville Ave, Las Vegas, NV 89106, United States. 2. Department of Brain Health, University of Nevada, Mail Stop: 4022; 4505 S. Maryland Pkwy. Room 1172, Las Vegas, NV 89154, United States.
Abstract
Introduction: Late onset Alzheimer's disease (AD) is the most common form of dementia, in which almost 70% of patients are women. Hypothesis: We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. Methods: We studied cognitively healthy individuals from the Alzheimer's Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed. Result: Women had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men. Conclusion: Women overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD. Significance statement: Two thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.
Introduction: Late onset Alzheimer's disease (AD) is the most common form of dementia, in which almost 70% of patients are women. Hypothesis: We hypothesized that women show worse global FC metrics compared to men, and further hypothesized a sex-specific positive correlation between FC metrics and cognitive scores in women. Methods: We studied cognitively healthy individuals from the Alzheimer's Disease Neuroimaging Initiative cohort, with resting-state functional Magnetic Resonance Imaging. Metrics derived from graph theoretical analysis and functional connectomics were used to assess the global/regional sex differences in terms of functional integration and segregation, considering the amyloid status and the contributions of APOE E4. Linear mixed effect models with covariates (education, handedness, presence of apolipoprotein [APOE] E4 and intra-subject effect) were utilized to evaluate sex differences. The associations of verbal learning and memory abilities with topological network properties were assessed. Result: Women had a significantly lower magnitude of the global and regional functional network metrics compared to men. Exploratory association analysis showed that higher global clustering coefficient was associated with lower percent forgetting in women and worse cognitive scores in men. Conclusion: Women overall show lower magnitude on measures of resting state functional network topology and connectivity. This factor can play a role in their different vulnerability to AD. Significance statement: Two thirds of AD patients are women but the reasons for these sex difference are not well understood. When this late onset form dementia arises is too late to understand the potential causes of this sex disparities. Studies on cognitively healthy elderly population are a fundamental approach to explore in depth this different vulnerability to the most common form of dementia, currently affecting 6.2 million Americans aged 65 and older are, which means that >1 in 9 people (11.3%) 65 and older are affected by AD. Approaches such as resting-state functional network topology and connectivity may play a key role in understanding and elucidate sex-dependent differences relevant to late-onset dementia syndromes.
Authors: Bharat B Biswal; Maarten Mennes; Xi-Nian Zuo; Suril Gohel; Clare Kelly; Steve M Smith; Christian F Beckmann; Jonathan S Adelstein; Randy L Buckner; Stan Colcombe; Anne-Marie Dogonowski; Monique Ernst; Damien Fair; Michelle Hampson; Matthew J Hoptman; James S Hyde; Vesa J Kiviniemi; Rolf Kötter; Shi-Jiang Li; Ching-Po Lin; Mark J Lowe; Clare Mackay; David J Madden; Kristoffer H Madsen; Daniel S Margulies; Helen S Mayberg; Katie McMahon; Christopher S Monk; Stewart H Mostofsky; Bonnie J Nagel; James J Pekar; Scott J Peltier; Steven E Petersen; Valentin Riedl; Serge A R B Rombouts; Bart Rypma; Bradley L Schlaggar; Sein Schmidt; Rachael D Seidler; Greg J Siegle; Christian Sorg; Gao-Jun Teng; Juha Veijola; Arno Villringer; Martin Walter; Lihong Wang; Xu-Chu Weng; Susan Whitfield-Gabrieli; Peter Williamson; Christian Windischberger; Yu-Feng Zang; Hong-Ying Zhang; F Xavier Castellanos; Michael P Milham Journal: Proc Natl Acad Sci U S A Date: 2010-02-22 Impact factor: 11.205
Authors: Susanne Weis; Kaustubh R Patil; Felix Hoffstaedter; Alessandra Nostro; B T Thomas Yeo; Simon B Eickhoff Journal: Cereb Cortex Date: 2020-03-21 Impact factor: 5.357