p-Tau/Aβ42 ratio associates with cognitive decline in Alzheimer's disease, mild cognitive impairment, and cognitively unimpaired older adults.

Objective: Among the cerebrospinal fluid (CSF)-based measures of Alzheimer's disease (AD) pathology, the ratiometric measure of p-tau/Aβ42 shows the best diagnostic accuracy. However, few studies have linked the p-tau/Aβ42 ratio to cognition directly. The goal of this study was to examine whether a CSF-based p-tau/Aβ42 ratio predicts changes in global cognitive functioning, episodic memory, and executive functioning over a 2-year period in cognitively unimpaired (CU) older adults, in individuals with mild cognitive impairment (MCI), and in those with AD.

Method: This study involves secondary analysis of data from 1,215 older adults available in the Alzheimer's Disease Neuroimaging Initiative. Neuropsychological composite variables, collected at baseline, 6-month, 12-month, and 24-month follow-ups, of global cognition, episodic memory, and executive functioning, were included. Generalized least square linear models were constructed to examine the effect of CSF p-tau/Aβ42, diagnostic group, and change over time on cognitive scores.

Results: CSF p-tau/Aβ42 ratio predicted cognitive decline, both on global cognition and episodic memory, in individuals with MCI and AD, but not in CU older adults. The p-tau/Aβ42 ratio, in contrast, predicted decline in executive functioning for all three diagnostic groups.

Conclusions: Our study, which included individuals with CU, MCI, and AD, provides evidence of differential cognitive consequences of accumulated AD pathology across diagnostic groups, particularly in the domains of global cognition and episodic memory. Additionally, AD pathology was associated with worsening executive functioning across all three diagnostic groups, suggesting that declines in executive functioning may occur well before declines in other cognitive domains. (PsycInfo Database Record (c) 2025 APA, all rights reserved).