Brain Imaging Features Associated with 20-Year Cognitive Decline in a Community-Based Multiethnic Cohort without Dementia

Alessandro Orlando, A. Richey Sharrett, Andrea L.C. Schneider, Rebecca F. Gottesman, David S. Knopman, Andreea Rawlings, Thomas H. Mosley, Clifford R. Jack, Dean Wong, James R. Pike, Josef Coresh

Research output: Contribution to journalArticlepeer-review


Introduction: This study aimed to characterize the association of cognitive decline starting in midlife with brain pathology in late life in the absence of dementia. Methods: Nondemented Atherosclerosis Risk in Communities participants with brain imaging, all cognitive factor scores (CFSs), and nonmissing covariates were included. CFSs were collected at three visits across 21 years (1990-2013) (short-term cognitive change [1990-1996], long-term cognitive change [1990-2013]), and brain magnetic resonance imaging and florbetapir positron emission tomography (PET) imaging were collected in 2011-13 (PET subset n = 327). Outcomes of interest were total and regional brain volumes (cm3), log2 (white matter hyperintensity volume), white matter integrity (fractional anisotropy, mean diffusivity), ≥1 lacunar infarct (3-20 mm), and elevated brain β-amyloid (SUVR >1.2). Multivariable linear/logistic regression related outcomes to CFS slopes after adjusting for demographics and total intracranial volume. Results: At baseline, the 1,734 participants had a mean (SD) age of 55 (5.2) years, and were 60% female and 26% Black. After adjustment, a 1-SD larger long-term decline in CFS was associated with a smaller relative total brain volume by 1.2% (95% CI: 1.0, 1.5), a smaller relative temporal lobe meta region volume by 1.9% (1.5, 2.3), a 13% (9, 17) larger volume of white matter hyperintensities, a 1.3-fold (1.2, 1.4) higher odds of having ≥1 lacune, and 1.7-fold (1.3, 2.2) higher odds of elevated brain β-amyloid deposition and worse white matter integrity. Some long-term associations were also found for midlife short-term declines in CFS. Conclusions: This study provides evidence that starting in midlife, short-term and long-term declines in cognition are associated with multiple deleterious late-life differences in nondemented brains.

Original languageEnglish
Pages (from-to)183-191
Number of pages9
Issue number3
StatePublished - Aug 1 2022


  • Brain
  • Cognitive decline
  • Cohort
  • Imaging
  • Longitudinal design


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