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. 2021 Sep:105:86-98.
doi: 10.1016/j.neurobiolaging.2021.04.003. Epub 2021 Apr 22.

Multimodal neuroimaging of sex differences in cognitively impaired patients on the Alzheimer's continuum: greater tau-PET retention in females

Lauren Edwards  1 , Renaud La Joie  2 , Leonardo Iaccarino  1 , Amelia Strom  1 , Suzanne L Baker  3 , Kaitlin B Casaletto  1 , Yann Cobigo  1 , Harli Grant  1 , Minseon Kim  1 , Joel H Kramer  1 , Taylor J Mellinger  1 , Julie Pham  1 , Katherine L Possin  1 , Howard J Rosen  1 , David N Soleimani-Meigooni  1 , Amy Wolf  1 , Bruce L Miller  1 , Gil D Rabinovici  4
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Free PMC article

Multimodal neuroimaging of sex differences in cognitively impaired patients on the Alzheimer's continuum: greater tau-PET retention in females

Lauren Edwards et al. Neurobiol Aging. 2021 Sep.
Free PMC article

Abstract

We assessed sex differences in amyloid- and tau-PET retention in 119 amyloid positive patients with mild cognitive impairment or Alzheimer's disease (AD) dementia. Patients underwent 3T-MRI, 11C-PIB amyloid-PET and 18F-Flortaucipir tau-PET. Linear ordinary least squares regression models tested sex differences in Flortaucipir-PET SUVR in a summary temporal region of interest as well as global PIB-PET. No sex differences were observed in demographics, Clinical Dementia Rating Sum of Boxes (CDR-SoB), Mini-Mental State Exam (MMSE), raw episodic memory scores, or cortical thickness. Females had higher global PIB SUVR (ηp²=.043, p=.025) and temporal Flortaucipir SUVR (ηp²=.070, p=.004), adjusting for age and CDR-SoB. Sex differences in temporal Flortaucipir-PET remained significant when controlling additionally for PIB SUVR and APOE4 status (ηp²=.055, p=.013), or when using partial volume-corrected data. No sex differences were present in areas of known Flortaucipir off-target binding. Overall, females demonstrated greater AD regional tau-PET burden than males despite clinical comparability. Further characterization of sex differences will provide insight into AD pathogenesis and support development of personalized therapeutic strategies.

Keywords: Alzheimer's disease; Amyloid; Apolipoprotein E; Positron emission tomography; Sex differences; Tau.

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Figures

Figure 1.
Figure 1.
Sex-stratified box plots of (A) global PIB PET, (B) temporal meta-ROI FTP PET, (C) individual AD ROI FTP PET, and (D) regions off-target FTP binding. Partial η2 and p-values of Model 1 group sex differences are reported.
Figure 2.
Figure 2.
Sex difference in temporal meta-ROI tau PET signal as a function of global amyloid PET signal. All global PIB SUVRs exceeded a value of 1.21 and are therefore in the amyloid-positive range, per study design (Villeneuve et al., 2015). For a given level of amyloid, female AD patients demonstrated greater temporal FTP SUVR than males per Model 2 analysis (ηp2 = .058, p = .009) as described in Table 3. The effect of amyloid on temporal meta-ROI tau PET was not significant (ηp2 = .012, p = .24), and when added to the model, no interaction between sex and global amyloid PET was observed (ηp2 =.004, p =.52).
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