Alessandro Orlando1, A Richey Sharrett1, Andrea L C Schneider2, Rebecca F Gottesman3, David S Knopman4, Andreea Rawlings1, Thomas H Mosley5, Clifford R Jack6, Dean Wong7, James R Pike8, Josef Coresh1. 1. Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, USA. 2. Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. 3. National Institute of Neurological Disorders and Stroke Intramural Research Program, NIH, Bethesda, Maryland, USA. 4. Department of Neurology, Mayo Clinic Alix School of Medicine, Rochester, Minnesota, USA. 5. Department of Neurology, University of Mississippi Medical Center, Jackson, Mississippi, USA. 6. Department of Radiology, Mayo Clinic Alix School of Medicine, Rochester, Minnesota, USA. 7. Department of Radiology, Washington University School of Medicine in St. Louis, St. Louis, Missouri, USA. 8. Collaborative Studies Coordinating Center, University of North Carolina Gillings School of Public Health, Chapel Hill, North Carolina, USA.
Abstract
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.
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.
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