DT‐01–03: Midlife adiposity and FTO genotype: State and trait predictors of brain function during aging
Year: 2013
Type: article
Abstract: Midlife adiposity and obesity are risk factors for Alzheimer's disease and vascular dementia. The fat-mass and obesity-related gene, FTO, is also associated with impaired memory performance over time even in middle-aged risk allele carriers. Moreover, both midlife adiposity and FTO are associated with greater regional brain atrophy in older adults. Despite evidence implicating both state (eg: body mass index; BMI) and trait (eg: FTO)-markers of adiposity with subsequent changes in brain structure and cognition, their specific influences on brain function during aging remain unknown. We examined whether midlife BMI and FTO genotype were associated with regionally specific patterns of longitudinal changes in brain function during aging. Sixty-nine cognitively normal participants (age at first scan, 69 ± 7.3 years) in the neuroimaging substudy of the Baltimore Longitudinal Study of Aging underwent 15 O-water positron emission tomography. Using voxel-based analysis, we compared longitudinal changes in regional resting-state cerebral blood flow (rCBF) over an 8-year period between 1) 41 obesity-associated risk allele carriers of FTO (FTO+) and 28 non-carriers (FTO-), and 2) 33 participants who were overweight in midlife (BMI ≥ 25 kg/m 2) and 36 with normal weight (BMI < 25 kg/m 2) All participants remained cognitively normal during the study. For FTO group comparisons, the predominant pattern was greater rCBF decline in the FTO+ group relative to FTO- in bilateral medial frontal and temporal regions, including the parahippocampal gyrus. Some brain regions including the cuneus, middle frontal and middle temporal gyri, showed greater increases in rCBF in the FTO+ group. Individuals overweight in midlife showed a bilateral, symmetrical pattern of greater rCBF decline relative to those with normal weight in the superior and inferior frontal, post-central and inferior temporal gyri. Some brain regions including the posterior cingulate and precuneus showed greater increments in rCBF in the overweight group. FTO genotype and midlife adiposity are associated with distinct patterns of longitudinal rCBF changes in older adults. The brain regions involved include those vulnerable to Alzheimer's pathology. These findings may represent early neural signatures of increased risk for AD and age-related memory impairment associated with midlife adiposity and FTO genotype. differences in longitudinal changes in regional cerebral blood flow (rCBF) between FTO+ and FTO- groups. Blue areas indicate significantly greater longitudinal decreases in rCBF in the FTO+ group; red areas, greater longitudinal increases in rCBF in the FTO- group Differences longitudinal changes in regional cerebral blood flow (rCBF) between midlife overweight and normal weight groups. Blue areas indicate significantly greater longitudinal deacreases in rCBF in the midlife overweight group; red areas, greater longitudinal increases in rCBF in the midlife overweight group.
Source: Alzheimer s & Dementia
Institutions: Johns Hopkins University, National Institute on Aging
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W1994313306