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

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

doi:10.1016/j.neurobiolaging.2021.04.003

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

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

Authors

Lauren Edwards¹, Renaud La Joie², Leonardo Iaccarino¹, Amelia Strom¹, Suzanne L Baker³, Kaitlin B Casaletto¹, Yann Cobigo¹, Harli Grant¹, Minseon Kim¹, Joel H Kramer¹, Taylor J Mellinger¹, Julie Pham¹, Katherine L Possin¹, Howard J Rosen¹, David N Soleimani-Meigooni¹, Amy Wolf¹, Bruce L Miller¹, Gil D Rabinovici⁴

Affiliations

¹ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA.
² Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA. Electronic address: [email protected].
³ Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA.
⁴ Memory and Aging Center, Department of Neurology, Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA; Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, CA, USA; Helen Wills Neuroscience Institute, University of California Berkeley, Berkeley, CA, USA; Department of Radiology and Biomedical Imaging, University of California San Francisco, San Francisco, CA, USA.

PMID: 34049062
PMCID: PMC8820163
DOI: 10.1016/j.neurobiolaging.2021.04.003

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 (η_p²=.043, p=.025) and temporal Flortaucipir SUVR (η_p²=.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 (η_p²=.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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aged
Alzheimer Disease / diagnostic imaging*
Alzheimer Disease / metabolism*
Brain / diagnostic imaging*
Brain / metabolism*
Cognitive Dysfunction / diagnostic imaging*
Cognitive Dysfunction / metabolism*
Female
Humans
Magnetic Resonance Angiography / methods
Male
Middle Aged
Neuroimaging / methods*
Positron-Emission Tomography / methods*
Sex Characteristics*
tau Proteins / metabolism*

Substances

tau Proteins

Abstract

Publication types

MeSH terms

Substances

Grants and funding