The aging US population and the recent rise in the prevalence of obesity are two phenomena of great importance to public health. In addition, research suggests that midlife body mass index (BMI) is a risk factor for dementia, a particularly costly disease, in later life. BMI could influence brain health by adversely impacting cerebral white matter. Recently, greater BMI has been associated with lower white matter fractional anisotropy (FA), an index of tissue microstructure, as measured by diffusion-tensor imaging (DTI) in midlife. The aim of this study was to investigate the role of abdominal obesity, the most metabolically active adipose tissue compartment, and white matter microstructure in midlife. Community dwelling participants (N=168) between the ages of 40 – 62 underwent MRI scanning at 3T and a general health assessment. Inferences were made on whole brain white matter tracts using full-tensor, high-dimension normalization and tract based spatial statistics. Higher waist circumference was associated with higher FA, indicating more directional diffusion in several white matter tracts controlling for age, sex, triglycerides, systolic blood pressure, fasting glucose, and HDL-cholesterol. Post-hoc analysis reveled that greater waist circumference was associated with lower axial diffusivity (AD), indicating lower parallel diffusion; lower radial diffusivity (RD), indicating lower perpendicular diffusion; and lower mean diffusivity (MD), indicating restricted diffusion. This is the first study to report a positive relationship between obesity and FA, indicating a more complicated view of this relationship in the aging brain.

Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive memory impairment and the presence of amyloid plaques and neurofibrillary tangles. The associated neuropathology originates in brain areas responsible for olfaction, which makes olfactory tasks potentially useful for assessing AD. The strongest genetic risk factor for AD is the apolipoprotein E (ApoE) ɛ4 allele that has been associated with increased cognitive and olfactory deficits. While individuals carrying one ɛ4 allele of the ApoE gene are at increased risk for AD relative to non-carriers, those with two copies of the ɛ4 allele demonstrate an even higher risk for developing AD. Furthermore, homozygous ApoE ɛ4/4 individuals diagnosed with AD are known to have heightened amyloid burden and a more rapid rate of cognitive decline relative to heterozygous ɛ3/4 ApoE carriers. All of these factors suggest there are differences in severity and progression of AD as a function of possessing one versus two ɛ4 alleles. The current study investigated olfactory functioning in homozygous ɛ4/4 older adults diagnosed with probable AD. Compared to demographically matched ɛ3/3 and ɛ3/4 individuals, ɛ4/4 individuals showed deficits in odor identification and remote odor memory as measured by odor familiarity ratings. The current findings suggest that these particular domains of olfactory functioning may be more impaired in AD ɛ4/4 homozygotes compared to ɛ3/4 heterozygotes and ɛ3/3 homozygotes. These deficits give insight into how the presence of two ɛ4 alleles may differentially affect the progression of AD and suggest the usefulness of odor tasks in detecting those at risk for AD.

Arterial stiffness, particularly the stiffness of the carotid artery, mediated reductions in CVC related to MetS.

In midlife, greater PUFA intake (ω-3 and ω-6) may be associated with lower cerebral glutamate, potentially indicating more efficient cellular reuptake of glutamate. SFA intake, on the other hand, was linked with poorer memory performance. These results suggest that dietary fat intake modification may be an important intervention target for the prevention of cognitive decline.

Intact memory and problem solving are key to functional independence and quality of life in older age. Considering the unprecedented demographic shift toward a greater number of older adults than children in the United States in the next few decades, it is critically important for older adults to maintain work productivity and functional independence for as long as possible. Implementing early interventions focused on modifiable risk factors for cognitive decline at midlife is a strategy with the highest chance of success at present, bearing in mind the current lack of dementia cures. We present a selective, narrative review of evidence linking nutrition, body composition, vascular health, and brain function in midlife to highlight the phenotypic heterogeneity of obesity-related brain vulnerability and to endorse the development of individually tailored lifestyle modification plans for primary prevention of cognitive decline.