Assessing Cognitive Decline and Dementia Risk in Black and White Older Adults with Blood Biomarkers pTau217, GFAP, NfL, and Aβ ratio

Alzheimer’s disease blood-based biomarkers are a cost-effective early-detection method that, for precision medicine reasons, needs to be studied in both Blackand White. Few studies have a long follow-up of cognition. We studied a blood-biomarkers panel, cognitive decline, and dementia risk in a large number of Black and White participants.

Methods

Participants without dementia were followed annually up to 15 years, after plasma biomarker measurement (NfL, GFAP, amyloid-beta 42/40 ratio, pTau217). Data included demographics, medical history, blood tests (e.g., kidney function), MMSE, APOEε4, annual evaluations of cognition, and clinician-based dementia evaluation. The biomarkers’ association with comorbidities, cognitive decline, and risk of dementia was examined within race. To examine racial differences, we repeated analyses using a subset Mahalanobis-balanced 1:1 on sex, age, education, Latino/Non-Latino, and clinical status (hypertension, diabetes, GFR, BMI, and heart disease).

Results

Biomarkers were measured in 431 Black and 583 White (respectively mean age of 77 and 80, 17% and 21% men), generating a balanced sample of 366:366. Biomarker’s levels were similar between races. Within races, the associations of blood biomarkers with multiple comorbidities (especially kidney dysfunction and BMI) remained after controlling for demographics, APOE ε4, and dementia or death within 5 years. Men had lower GFAP levels than women (all p=<0.001). pTau217 was associated with decline in global cognition and all domains within races, and when comparing races, it was associated with a faster decline in global cognition and semantic memory in Black. The discrimination of dementia of pTau217 (AUC _{3year, Black} 0.81, CI=0.74, 0.89; AUC _{3year, White} 0.77, CI=0.71, 0.83) was good relative to age alone (AUC _{3 year, Black} 0.69, CI=0.58, 0.79; AUC _{3 year, White} 0.68, CI=0.62, 0.75), and MMSE (AUC _{3 year, Black} 0.81, CI=0.74, AUC _{3 year, White} 0.89; AUC _{3 year, White} 0.72, CI=0.65, 0.80). The discrimination of pTau217 did not improve by adding race or other biomarker information.

Discussion

pTau217 was highly associated with dementia risk and cognitive decline. The association of blood biomarkers with cognitive decline in Black and White participants was similar. Higher levels of pTau217 were, however, associated with semantic memory decline in Black adults. The combination of pTau217 with other biomarkers or MMSE did not improve dementia discrimination.