Factors associated with age at tau pathology onset and time from tau onset to dementia

Margo B Heston; Jordan P Teague; Karly A Cody; Yuetiva Deming; Elena Ruiz de Chavez; Jacob Morse; Nathaniel A Chin; Corinne D Engelman; Richard J Chappell; Rebecca E Langhough; Carey E Gleason; Lindsay R Clark; Megan L Zuelsdorff; Tobey J Betthauser; Alzheimer’s Disease Neuroimaging Initiative

doi:10.1101/2025.03.11.25323773

Factors associated with age at tau pathology onset and time from tau onset to dementia

medRxiv [Preprint]. 2025 Mar 13:2025.03.11.25323773. doi: 10.1101/2025.03.11.25323773.

Authors

Margo B Heston^{1

2

3}, Jordan P Teague^{1

2

4}, Karly A Cody⁵, Yuetiva Deming^{1

2}, Elena Ruiz de Chavez^{1

2}, Jacob Morse^{1

2}, Nathaniel A Chin^{1

2}, Corinne D Engelman^{1

6}, Richard J Chappell^{1

7}, Rebecca E Langhough^{1

2

8}, Carey E Gleason^{1

2

9}, Lindsay R Clark^{1

2

9}, Megan L Zuelsdorff^{1

3

10}, Tobey J Betthauser^{1

2

3

4}; Alzheimer’s Disease Neuroimaging Initiative

Affiliations

¹ Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, MC 2420, Madison, WI 53792-2420.
² Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, 1685 Highland Avenue, 5158 Medical Foundation Centennial Building, Madison, WI 53705-2281.
³ Center for Health Disparities Research, University of Wisconsin School of Medicine and Public Health, 600 Highland Avenue, Madison, WI 53792-2420.
⁴ Department of Medical Physics, University of Wisconsin-Madison School of Medicine and Public Health, 1111 Highland Ave, Rm 1005 Madison, WI 53705-2275.
⁵ Department of Neurology and Neurological Sciences, Stanford University Center for Academic Medicine, 453 Quarry Road, Palo Alto, CA 94304.
⁶ Department of Population Health Sciences, University of Wisconsin-Madison School of Medicine and Public Health, 610 Walnut Street, Room 675, Madison, WI 53726.
⁷ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison School of Medicine and Public Health, 610 Walnut Street, WARF Room 201, Madison, WI 53726.
⁸ Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, 610 Walnut Street, 9th Floor, Madison, WI 53726.
⁹ Madison Geriatric Research Education and Clinical Center (GRECC), William S. Middleton Veterans Affairs Hospital, 2500 Overlook Terrace, Madison, WI 53705.
¹⁰ University of Wisconsin-Madison School of Nursing, Signe Skott Cooper Hall, 701 Highland Avenue, Madison, WI 53705.

Abstract

Introduction: Elevated tau is temporally proximal to dementia onset but less is known about factors influencing T+ onset age and time to dementia following T+ in Alzheimer's disease. We used sampled iterative localized approximation (SILA) estimated T+ onset age (ETOA) to investigate factors associated with T+ age and time from T+ to dementia onset in ADNI.

Methods: Using SILA-estimated A+ and T+ onset ages derived from ¹⁸F-Flortaucipir, ¹⁸F-Florbetapir, and ¹⁸F-Florbetaben PET and Cox proportional hazards and accelerated failure time models, we analyzed APOE, sex, amyloid burden, age, educational attainment, and literacy associations with ETOA and time from T+ to dementia.

Results: Higher amyloid, APOE-ε4, lower education, and lower literacy associated with younger ETOA. Older ETOA and higher amyloid associated with shorter time from T+ to dementia.

Discussion: This work highlights the prognostic value of ETOA and the need to better characterize factors contributing to ETOA and dementia onset in AD.

Keywords: APOE; Alzheimer’s disease; SILA; amyloid beta; dementia risk; estimated tau onset age; literacy exposure; social determinants of health; temporal modeling.

Publication types

Preprint

Abstract

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