Plasma-based brain age as a potential biomarker for cognitive health and risk of brain-related disorders

Understanding brain aging is essential for identifying early markers of cognitive decline. This study aimed to develop plasma-based biomarkers of brain aging and examine their associations with cognitive function. We used data from 53,005 UK Biobank participants (2006–2010) with available Olink proteomics data (mean age 57 ± 8 years, 54% women). Protein levels were used to estimate brain age, organismal age, and conventional proteomic age using Least Absolute Shrinkage and Selection Operator (LASSO) regression. We assessed the relationships between these biological ages and cognitive function using multivariable-adjusted linear regression models, and their association with incident Alzheimer’s disease (AD) and stroke using Cox proportional hazards models. Findings were validated in 2066 participants from the Framingham Heart Study (FHS) Offspring cohort (Exam 8, 2002–2005, mean age 67 ± 9 years, 55% women), also using the Olink platform. Accelerated brain aging is significantly associated with poorer cognitive performance, whereas organismal and conventional proteomic ages are not. All three biological age measures are linked to increased risk of AD and stroke, but brain aging shows the strongest association (hazard ratio (HR) for AD: 1.79 [95% confidence interval (CI): 1.66–1.93]; HR for stroke: 1.25 [95% CI: 1.17–1.33]). In the FHS validation, brain aging is associated with lower performance in cognitive domains such as attention and visual memory, and with increased risk of AD (HR: 1.64 [95% CI: 1.37–1.97]). Plasma-based biomarkers of brain aging may offer a promising tool for monitoring cognitive health and identifying individuals at risk for age-related diseases. This study looked at blood proteins to find signs of brain aging and their link to cognitive function. Researchers used protein data from over 53,000 people in the UK Biobank and a machine learning technique to create different “biological age” scores. The brain aging score was strongly tied to lower cognitive performance and a higher risk of Alzheimer’s disease and stroke. The findings were tested in the Framingham Heart Study and showed similar results—older brain age was linked to worse memory and a higher risk of Alzheimer’s disease. This suggests that blood tests focused on brain aging could help doctors spot early signs of cognitive decline and act sooner to prevent age-related diseases. Wang et al. develop plasma-based biomarkers of brain aging using proteomic data from the UK Biobank and validate their findings in the Framingham Heart Study. Acceleration in plasma-based brain aging is linked to poorer cognitive performance and shows a positive association with Alzheimer’s disease and all-cause mortality.