Assessing Cognitive Decline and Dementia Risk in Black and White Older Adults With Blood Biomarkers pTau217, GFAP,...

Alzheimer disease blood-based biomarkers are a cost-effective method for early detection. Few studies provide long-term follow-up of cognition in Black participants. We assessed biomarker association with cognitive decline and dementia risk in Black and White participants.

Plasma biomarkers (neurofilament light chain, glial fibrillary acidic protein [GFAP], amyloid-β 42/40 ratio, phosphorylated tau at threonine 217 [pTau217]) were measured in participants from a community-based Chicago cohort without dementia at the time of blood draw. They were evaluated annually for up to 15 years for cognition and dementia. Data included medical history, blood tests (e.g., kidney function), Mini-Mental State Examination (MMSE) score, and APOEε4. Associations of biomarkers with comorbidities, cognitive decline, and risk of dementia were examined within racial groups. To examine racial differences, we repeated the analysis using a Mahalanobis-balanced 1:1 match on biological sex, age, education, Latino/non-Latino status, longitudinal data availability, and clinical status (hypertension, diabetes, glomerular filtration rate, body mass index [BMI], and heart disease).

Biomarkers were measured in 431 Black and 583 White participants (mean age of 77 and 80 years and 17% and 21% of men, respectively), generating a balanced sample of 366:366. Biomarker levels were similar across races. Within racial groups, the associations of biomarkers with multiple comorbidities (especially kidney dysfunction and BMI) remained after controlling for demographics, APOEε4 status, and dementia or death within 5 years. Men had lower GFAP than women (all p < 0.001). Within racial groups, pTau217 was associated with a decline in global cognition and domains (all p < 0.001), and between races, pTau217 was associated with a faster decline in global cognition (β = -0.03, SE = 0.012, p = 0.018) and semantic memory (β = -0.068, SE = 0.016, p < 0.001) in Black individuals. The discrimination of dementia by pTau217 (area under the curve [AUC]_{3-year, Black} 0.81, 95% CI 0.74-0.89; AUC_{3-year, White} 0.77, 95% CI 0.71-0.83) was good relative to age (AUC_{3-year, Black} 0.69, 95% CI 0.58-0.79; AUC_{3-year, White} 0.68, 95% CI 0.62-0.75) and MMSE score (AUC_{3-year, Black} 0.81, 95% CI 0.74-0.89; AUC_{3-year, White} 0.72, 95% CI 0.65-0.80). The discrimination by pTau217 did not improve when adding other biomarkers or MMSE score.

pTau217 was highly associated with dementia risk and cognitive decline. The association of biomarkers with cognitive decline in Black and White participants was similar. Higher pTau217 was, however, associated with global and semantic memory decline in Black adults. Generalizability is a limitation.