Baseline plasma total tau predicts longitudinal cognitive and functional decline in aging adults

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AbstractBackgroundPlasma total‐tau (t‐tau) is an emerging biomarker of neurodegeneration and cognitive decline; however, findings are mixed regarding what specific cognitive domains are affected and it is unknown whether plasma t‐tau predicts early functional changes in aging adults at risk for dementia. This study examined baseline plasma t‐tau in relation to longitudinal cognitive and functional trajectories among community‐dwelling older adults.MethodVanderbilt Memory and Aging Project participants free of clinical dementia or stroke (n=332, 73±8 years, 40% mild cognitive impairment (MCI)) underwent baseline fasting venous blood draw and serially completed a comprehensive neuropsychological protocol and a 50‐item informant functional abilities questionnaire at study entry, 18‐month, 3‐year, and 5‐year intervals (mean 4.5±1.2 year follow‐up). Plasma t‐tau concentration was measured using single molecule array technology. Linear mixed effects models related baseline t‐tau to cognitive and functional trajectories through interaction with follow‐up time adjusting for baseline age, sex, education, race/ethnicity, apolipoprotein E (APOE) ∑4 status, modified Framingham Stroke Risk Profile, and cognitive diagnosis. Subsequent models assessed t‐tau x cognitive diagnosis and t‐tau x APOE‐∑4 interactions on cognitive and functional trajectories.ResultA higher baseline concentration of t‐tau was associated with faster decline in processing speed (p<.05). Baseline t‐tau concentration interacted with diagnosis on longitudinal trajectories of processing speed (p‐values<.03). After excluding outliers, higher baseline t‐tau was associated with faster decline in language, processing speed, and functional abilities (p‐values<.05) with t‐tau interacting with diagnosis on each of these measures (p‐values<.05). Baseline t‐tau interacted with APOE‐∑4 status on longitudinal trajectories of language after outlier exclusion (p‐values<.04). Associations linking baseline t‐tau with faster decline were largely driven by participants with MCI (p‐values<.05) and APOE‐∑4 carriers (p‐values<.04).ConclusionAmong community‐dwelling aging adults free of clinical dementia, higher baseline plasma t‐tau concentration was associated with faster cognitive and functional decline over a mean 4.5‐year follow‐up. Processing speed was consistently implicated, especially in individuals with MCI. T‐tau may reflect non‐specific brain changes involving widely distributed neuronal networks, leading to slowed processing, a common complaint in aging adults. Taken together, results suggest that plasma t‐tau may be a useful biomarker for cognitive and functional decline in at‐risk individuals.