Relationship between cognition and tau protein deposition measured by PET in subjects with normal cognition and within the Alzheimer’s disease spectrum: A meta‐analysis and systematic review

Abstract

AbstractBackgroundThere is no validated biomarker that has been shown to be useful in the diagnosis and monitoring of AD. Studies using PET have suggested a spatiotemporal relationship between disease progression and higher deposits of beta amyloid and tau‐protein.MethodStudies investigating cognition and tau protein deposition were searched in databases (PubMed, Cochrane) published in English as of July 2020. Twenty‐five studies of 340 sampled abstracts met inclusion criteria: participants had normal cognition and/or AD/MCI, memory or global composite and tau deposition measured by PET were examined. A meta‐analysis was performed of the correlation coefficients between memory performance and MMSE with tau protein deposition in the temporal lobe and entire cortex. Results of studies examining the relationship using a multivariable statistical approach were extracted for analysis.ResultStudies were grouped by statistical methodology used. Bivariate correlation analysis and multivariable statistical models were employed to examine the relationship. A meta‐analysis of the correlation coefficient estimating memory performance and tau‐protein deposition in the temporal lobe showed a moderate correlation between higher tau deposition and lower performance on memory tests (r = ‐0.45 (CI ‐0.51; ‐0.39), p = 0.02) across moderately heterogeneous studies (I2= 55%). MMSE and tau deposition in the entire cortex did not consistently correlate across studies with the association reported among a wide range of correlation coefficients (r = ‐0.49 (‐0.65; ‐0.29), I2= 84%). Multivariable models predicting memory performance by tau‐protein deposition in temporal lobe found higher coefficient estimates when the sample was either stratified by beta amyloid load deposition or beta amyloid was included as an interaction. Furthermore, global cognitive composites from retrospective longitudinal cognitive data showed steeper cognitive decline when beta amyloid and tau protein were present.ConclusionThere is growing evidence supporting the role of tau‐protein as a biomarker that correlates with cognitive and memory decline in AD. There is a spatiotemporal relationship between beta amyloid and tau protein that leads to the development of dementia, which has to be further elucidated. Longitudinal studies will provide a better understanding of tau‐protein aggregation in the brain and its biological interaction with beta amyloid to explain disease progression in AD.