DOI: 10.1002/alz.083167 ISSN: 1552-5260

Blood‐based biomarker profiles of community cohort of rural‐dwelling older adults

Justin B Miller, Christina G. Wong, Jefferson W Kinney, Samantha E John, Jeffrey L. Cummings, Jessica ZK Caldwell, Kirsten Calvin, Lorenzo G Pasia, Aaron Ritter
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



Geography may influence Alzheimer’s disease risk, but there have been few prospective studies with biomarker characterization among rural‐dwelling individuals. We present preliminary biomarker data from the rural cohort followed by the Nevada Exploratory Alzheimer’s Disease Research Center, with comparisons to a harmonized urban cohort.


Community‐dwelling adults over age 50 are enrolled and followed annually. Core assessments include medical exam, cognitive assessment, and blood‐based biomarkers of neurofilament light (NFL), phosphorylated tau (pTau181), and glial fibrillary acidic protein (GFAP) measured from plasma samples via the Quanterix Single Molecular Array (Simoa) HD‐X platform. Biomarker values exceeding 3 standard deviations from the combined sample mean were removed from analyses. Primary comparisons included ANCOVAs with main between‐group effects of cohort and cognitive status, accounting for both age and sex; interactions between cohort and impairment status were also explored. Correlations between biomarkers and cognitive screening (MoCA) were also assessed. Raw biomarker data were log transformed prior to analysis.


NFL was associated with age (F(1,143) = 53.26, p<.001) main effects of impairment status were found (F(1,143) = 9.81, p<.001) but there was no association with sex or differences between urban and rural cohorts. The interaction between impairment status and cohort was significant, such that NFL concentrations were lower for cognitively normal rural‐dwellers, but higher among those with impairment (F(1,143) = 9.95, p<.01). GFAP was associated with age (F(1,136) = 31.05), p<.001) and sex (F(1,136) = 12.46), p<.001), but there were no main effects of cohort or impairment status, and there was no interaction. Tau was associated with age (F(1,153) = 11.08, p<.01) but not sex, and there were no main effects of cohort or impairment status, and no interaction was found. NFL was not correlated with cognition in the urban cohort (r = ‐.11), but was inversely correlated in the rural cohort (r = ‐.34). All other correlations were significant.


Rural‐dwelling older adults with cognitive impairment had higher concentrations of NFL compared to an urban cohort from the same region, though among cognitively unimpaired individuals, rural‐dwellers had lower concentrations of NFL. There were no rural‐urban differences in pTau or GFAP. Neurodegeneration may be a more sensitive indicator of cognitive impairment relative to other biomarkers, which may facilitate detection of geographic health disparities.

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