DOI: 10.1002/alz.080299 ISSN: 1552-5260

Association of MRI markers of vascular injury and neurodegeneration and cognitive decline in diverse cohorts: Findings from KHANDLE and STAR

Yi Lor, Charles Decarli, Rachel Peterson, Kristen M George, Paola Gilsanz, Dan M. Mungas, Elizabeth Rose Mayeda, Lisa L. Barnes, Rachel A. Whitmer
  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Geriatrics and Gerontology
  • Neurology (clinical)
  • Developmental Neuroscience
  • Health Policy
  • Epidemiology



MRI biomarkers of vascular injury and neurodegeneration are associated with cognitive decline, but relatively little is known about cognitive change in diverse populations. Our objective is to examine associations of hippocampal volume and white matter integrity on cognitive change over 3 years.


KHANDLE (age 65+) and STAR (age 50+) are harmonized cohorts of racially/ethnically diverse long‐term members of Kaiser Permanente Northern California. A random sub‐sample of participants received neuroimaging with 3T MRI to measure regional brain volumes and white matter integrity. Hippocampal volume (cm3), log white matter hyperintensities (log‐WMH) (cm3), free water (FW) (cm3), and fractional anisotropy (FA) MRI measures were normalized on intracranial volume and age at scan. Cognitive decline was assessed across three waves using the Spanish English Neuropsychological Assessment Scale measuring executive function (EF) and verbal episodic memory (VEM). Linear mixed models allowing for random intercept and slope estimated the associations of MRI metrics and cognition adjusting for baseline age, education, gender/sex, interview mode (in‐person vs phone), and interactions of these covariates with time from baseline, to adjust for effects of covariates on both baseline cognition and cognitive change.


Among 592 participants with neuroimaging, 59% were women, 47% were college educated, and 52% were Black adults (Table 1). Hippocampal volume was positively associated with baseline VEM (β = 0.268; CI = 0.153, 0.383) and EF change (β = 0.051; CI = 0.009, 0.094) (Table 2, Plot 1). FW was negatively associated with baseline EF (β = ‐6.561; CI = ‐10.758, ‐2.364), baseline VEM (β = ‐5.557; CI = ‐10.03, ‐1.084) and EF decline (β = ‐1.667; CI = ‐3.268, ‐0.066). FA was positively associated with baseline EF (β = 6.222; CI = 3.217, 9.228) and baseline VEM (β = 6.944; CI = 3.768, 10.119). Log‐WMH was negatively associated with baseline EF (β = ‐0.068; CI = ‐0.116, ‐0.020) and VEM (β = ‐0.082; CI = ‐0.132, ‐0.032).


All MRI markers were associated with baseline cognition, but only hippocampal volume and FW were associated with cognitive change. MRI measures of neurodegeneration and white matter integrity may be predictive of cognition and short‐term decline in diverse groups of older adults. Future analyses will examine associations with cognitive impairment.

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