Interactive effects of blood–brain barrier breakdown and Alzheimer's disease biomarker status on cognitive decline in older adults without dementia

INTRODUCTION Some research suggests that blood–brain barrier (BBB) integrity is altered in Alzheimer's disease (AD). Few studies have examined markers of BBB integrity and their interactions with AD risk factors on multi‐domain cognition. METHODS 83 older adults without dementia underwent lumbar puncture, apolipoprotein E (APOE) genotyping, and neuropsychological testing with up to 5 years of follow‐up. Soluble platelet‐derived growth factor receptor beta (sPDGFRβ) was measured in cerebrospinal fluid. RESULTS Higher baseline sPDGFRβ was associated with better cross‐sectional attention, visuospatial, and executive functioning, but with steeper longitudinal decline in executive function. When considering AD risk status, higher sPDGFRβ was associated with faster longitudinal decline in all cognitive domains in biomarker‐positive relative to biomarker‐negative individuals and in language in APOE ɛ4‐positive relative to ɛ4‐negative individuals. DISCUSSION Elevated sPDGFRβ may increase risk of cognitive decline, particularly in individuals with a higher risk for AD. Future studies should explore mechanisms that contribute to these relationships. Highlights Cerebrospinal fluid (CSF) soluble platelet‐derived growth factor receptor beta (sPDGFRβ) is a promising marker of blood–brain barrier (BBB) integrity. Higher sPDGFRβ was cross‐sectionally associated with better cognition at baseline. Higher sPDGFRβ was longitudinally associated with steeper decline in cognition, particularly among amyloid beta (Aβ) 42/Aβ40+ individuals. CSF concentration of sPDGFRβ may predict cognitive decline in those with increased dementia risk.