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. 2025 Jan 14;17(1):e70052.
doi: 10.1002/dad2.70052. eCollection 2025 Jan-Mar.

Identifying cognitive test scores associated with early tau burden in Alzheimer's disease

Caitlin M Terao  1   2 , Madeline Wood Alexander  1   3 , R Philip Chalmers  2 , Silina Z Boshmaf  1 , Jane Paterson  1 , Sandra E Black  1   3   4 , Kathryn V Papp  5   6 , Reisa A Sperling  5   6 , Jennifer S Rabin  1   3   4   7
Affiliations

Identifying cognitive test scores associated with early tau burden in Alzheimer's disease

Caitlin M Terao et al. Alzheimers Dement (Amst). .

Abstract

Introduction: This study aimed to identify cognitive tests that optimally relate to tau positron emission tomography (PET) signal in the inferior temporal cortex (ITC), a neocortical region associated with early tau accumulation in Alzheimer's disease (AD).

Methods: We analyzed cross-sectional data from the harvard aging brain study (HABS) (n = 128) and the Anti-Amyloid Treatment in Asymptomatic Alzheimer's (A4) study (n = 393). We used elastic net regression to identify the most robust cognitive correlates of tau PET signal in the ITC. Secondary analyses examined whether the cognitive correlates remained significantly associated with tau after adjusting for structural brain measures.

Results: Episodic memory measures, including both total and "process" scores, were the most robust correlates of ITC tau across both cohorts. These cognitive test scores remained significant after accounting for structural brain measures.

Discussion: These findings highlight the potential of specific episodic memory test scores to detect and monitor neuropathological changes associated with early AD.

Highlights: Machine learning identified cognitive correlates of early Alzheimer's disease tau burden.Both traditional and process scores predicted early tau burden.Episodic memory scores were among the strongest correlates.Cognitive scores remained significant after accounting for structural brain measures.

Keywords: Alzheimer's pathology; elastic net regression; machine learning; neuropsychology; tau PET.

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Conflict of interest statement

S.E.B. has served as a paid consultant for Roche, Biogen, and NovoNordisk. S.E.B. serves on the advisory board for the Conference Board of Canada, World Dementia Council, National Institute of Neurological Disorders and Stroke, and the University of Rochester Contribution to the Mission and Scientific Leadership of the Small Vessel VCID Biomarker Validation Consortium. R.A.S. has received grants or contracts from the National Institute on Aging, Eli Lilly (public–private partnership trial funding), Eisai (public–private partnership trial funding), Alzheimer's Association, and GHR Foundation. R.A.S. has received consulting fees from Abbvie, AC Immune, Acumen, Alector, Biohaven, Bristol‐Myers Squibb, Ionis, Janssen, Oligomerix, Prothena, Roche, Shionogi, and Vaxxinity. J.S.R. was supported by the Temerty‐Tanz‐TDRA Seed Fund. K.V.P. was supported by a grant from the National Institutes of Health (R01AG084017‐01A1). C.M.T., M.W.A., R.P.C., S.Z.B., and J.P. have no conflicts of interest or funding sources to declare. Author disclosures are available in the Supporting Information.

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