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Sex and Cerebral Small Vessel Disease-specific Longitudinal Trajectories of Amyloid, Tau, and Neurodegeneration

Shaaban, C. Elizabeth (2022) Sex and Cerebral Small Vessel Disease-specific Longitudinal Trajectories of Amyloid, Tau, and Neurodegeneration. Master's Thesis, University of Pittsburgh. (Unpublished)

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The AT(N) model of Alzheimer’s disease (AD) posits a temporal evolution of β-amyloid (Aβ) accumulation followed by tau then neurodegeneration. We investigated whether longitudinal relationships of these pathologies varied by sex and cerebral small vessel disease burden (cSVD), hypothesizing stronger associations in women and those with high baseline cSVD. Participants included 37 non-demented older adults (mean 74 y/o at inclusion; 59% female; 89% white; 29% APOE4+). Tau was measured once at time 0 using 18F-AV-1451 in an AD composite region of interest. Global amyloid and cerebral metabolism in lateral temporal lobe (neurodegeneration) were measured at repeated annual visits (8 years before tau-PET to 2 years after), using 11C-PiB and 18F-fluorodeoxyglucose (FDG)-PET. cSVD at study inclusion was characterized by high or low white matter hyperintensity (WMH) volume on MRI. We calculated individual slopes of Aβ and cerebral metabolism up to the tau-PET visit (time -8 to 0) using linear mixed effects models. Using age-adjusted linear regression models, we examined associations of Aβ slope, tau, and cerebral metabolism slope or metabolism at the final visit (time>0). We tested effect modification by sex and WMH using interaction terms and stratified analyses when interaction p<0.10. Associations of Aβ slope with tau varied by sex (p-interaction=0.007) but not WMH. Greater increase in Aβ slope was associated with greater tau in women (β=3.5, p=0.004), but not men (β= -1.2, p=0.34). Tau did not predict cerebral metabolism at the final FDG visit (β=0.10, p=0.67), but increasing Aβ slope predicted hypometabolism at the final FDG visit (β= -2.1, p=0.01). Neither of these relationships varied by sex or WMH. Associations of cerebral metabolism slope with tau varied by sex (p-interaction=0.08), but not WMH. Decreasing cerebral metabolism slope was associated with greater tau in women (β= -16.3, p=0.05), but not men (β=4.7, p=0.59). Further adjustment for APOE4 (N=31) did not appreciably alter results. In non-demented older adults, we found that associations of Aβ and cerebral hypometabolism with later increased tau were stronger in women than men; cSVD did not modify these associations. Tau did not predict later cerebral metabolism, while Aβ did.


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Item Type: University of Pittsburgh ETD
Status: Unpublished
CreatorsEmailPitt UsernameORCID
Shaaban, C. ElizabethBeth.Shaaban@pitt.educesst520000-0002-3016-1951
ETD Committee:
TitleMemberEmail AddressPitt UsernameORCID
Committee CoChairSved,
Committee CoChairSesack,
Committee MemberCohen,
Committee MemberSnitz,
Date: 21 March 2022
Date Type: Publication
Defense Date: 30 November 2021
Approval Date: 21 March 2022
Submission Date: 3 December 2021
Access Restriction: 2 year -- Restrict access to University of Pittsburgh for a period of 2 years.
Number of Pages: 41
Institution: University of Pittsburgh
Schools and Programs: Dietrich School of Arts and Sciences > Neuroscience
Degree: MS - Master of Science
Thesis Type: Master's Thesis
Refereed: Yes
Uncontrolled Keywords: Alzheimer's disease, amyloid, tau, neurodegeneration, sex
Date Deposited: 21 Mar 2022 17:18
Last Modified: 21 Mar 2022 17:18


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