Affiliation:
1. Department of Epidemiology & Biostatistics University of California San Francisco California USA
2. Department of Epidemiology Boston University School of Public Health Boston Massachusetts USA
3. Memory and Aging Center University of California San Francisco California USA
4. Departments of Psychiatry and Behavioral Sciences University of California San Francisco California USA
5. Departments of Neurology University of California San Francisco USA
6. Department of Epidemiology Mailman School of Public Health Columbia University New York New York USA
7. Kaiser Permanente Center for Health Research Portland Oregon USA
Abstract
AbstractINTRODUCTIONWe estimated the ages when associations between Alzheimer's disease (AD) genes and brain volumes begin among middle‐aged and older adults.METHODSAmong 45,616 dementia‐free participants aged 45–80, linear regressions tested whether genetic risk score for AD (AD‐GRS) had age‐dependent associations with 38 regional brain magnetic resonance imaging volumes. Models were adjusted for sex, assessment center, genetic ancestry, and intracranial volume.RESULTSAD‐GRS modified the estimated effect of age (per decade) on the amygdala (−0.41 mm3 [−0.42, −0.40]); hippocampus (−0.45 mm3 [−0.45, −0.44]), nucleus accumbens (−0.55 mm3 [−0.56, −0.54]), thalamus (−0.38 mm3 [−0.39, −0.37]), and medial orbitofrontal cortex (−0.23 mm3 [−0.24, −0.22]). Trends began by age 45 for the nucleus accumbens and thalamus, 48 for the hippocampus, 51 for the amygdala, and 53 for the medial orbitofrontal cortex. An AD‐GRS excluding apolipoprotein E (APOE) was additionally associated with entorhinal and middle temporal cortices.DISCUSSIONAPOE and other genes that increase AD risk predict lower hippocampal and other brain volumes by middle age.
Subject
Psychiatry and Mental health,Cellular and Molecular Neuroscience,Geriatrics and Gerontology,Neurology (clinical),Developmental Neuroscience,Health Policy,Epidemiology