Abdominal fat depots are related to lower cognitive functioning and brain volumes in middle-aged males at high Alzheimer's risk.

OBJECTIVE: High BMI, which poorly represents specific fat depots, is linked to poorer cognition and higher dementia risk, with different associations between sexes. This study examined associations of abdominal fat depots with cognition and brain volumes and whether sex modifies this association. METHODS: A total of 204 healthy middle-aged offspring of Alzheimer's dementia patients (mean age = 59.44, 60% females) underwent abdominal magnetic resonance imaging to quantify hepatic, pancreatic, visceral, and subcutaneous adipose tissue and to assess cognition and brain volumes. RESULTS: In the whole sample, higher hepatic fat percentage was associated with lower total gray matter volume (ß = -0.17, p < 0.01). Primarily in males, higher pancreatic fat percentage was associated with lower global cognition (males: ß = -0.27, p = 0.03; females: ß = 0.01, p = 0.93) executive function (males: ß = -0.27, p = 0.03; females: ß = 0.02, p = 0.87), episodic memory (males: ß = -0.28, p = 0.03; females: ß = 0.07, p = 0.48), and inferior frontal gyrus volume (males: ß = -0.28, p = 0.02; females: ß = 0.10, p = 0.33). Visceral and subcutaneous adipose tissue was inversely associated with middle frontal and superior frontal gyrus volumes in males and females. CONCLUSIONS: In middle-aged males at high Alzheimer's dementia risk, but not in females, higher pancreatic fat was associated with lower cognition and brain volumes. These findings suggest a potential sex-specific link between distinct abdominal fat with brain health.

The association between regional adiposity, cognitive function, and dementia-related brain changes: a systematic review.

Background: Adiposity has been previously associated with cognitive impairment and Alzheimer's disease and related disorders (ADRD). Body mass index (BMI) is the most common measure of global adiposity, but inconsistent results were found since it is a global measurement. BMI does not represent regional fat distribution which differs between sexes, race, and age. Regional fat distribution may contribute differently to cognitive decline and Alzheimer's disease (AD)-related brain changes. Fat-specific targeted therapies could lead to personalized improvement of cognition. The goal of this systematic review is to explore whether regional fat depots, rather than central obesity, should be used to understand the mechanism underlying the association between adiposity and brain. Methods: This systematic review included 33 studies in the English language, conducted in humans aged 18 years and over with assessment of regional adiposity, cognitive function, dementia, and brain measures. We included only studies that have assessed regional adiposity using imaging technics and excluded studies that were review articles, abstract only or letters to editor. Studies on children and adolescents, animal studies, and studies of patients with gastrointestinal diseases were excluded. PubMed, PsychInfo and web of science were used as electronic databases for literature search until November 2022. Results: Based on the currently available literature, the findings suggest that different regional fat depots are likely associated with increased risk of cognitive impairment, brain changes and dementia, especially AD. However, different regional fat depots can have different cognitive outcomes and affect the brain differently. Visceral adipose tissue (VAT) was the most studied regional fat, along with liver fat through non-alcoholic fatty liver disease (NAFLD). Pancreatic fat was the least studied regional fat. Conclusion: Regional adiposity, which is modifiable, may explain discrepancies in associations of global adiposity, brain, and cognition. Specific regional fat depots lead to abnormal secretion of adipose factors which in turn may penetrate the blood brain barrier leading to brain damage and to cognitive decline.

Stability in BMI over time is associated with a better cognitive trajectory in older adults.

OBJECTIVE: Evidence on simultaneous changes in body mass index (BMI) and cognitive decline, which better reflect the natural course of both health phenomena, is limited. METHODS: We capitalized on longitudinal data from 15,977 initially non-demented elderly from the Alzheimer's Disease Centers followed for 5 years on average. Changes in BMI were defined as (1) last minus first BMI, (2) mean of all follow-up BMIs minus first BMI, and (3) standard deviation of BMI change from baseline and all follow-up visits (representing variability). RESULTS: Participants with significant changes in BMI (increase or decrease of ≥5%), or who had greater variability in BMI, had faster cognitive decline. This pattern was consistent irrespective of normal (BMI < 25; N = 5747), overweight (25 ≤ BMI < 30; N = 6302), or obese (BMI ≥ 30; N = 3928) BMI at baseline. CONCLUSIONS: Stability in BMI predicts better cognitive trajectories suggesting clinical value in tracking BMI change, which is simple to measure, and may point to individuals whose cognition is declining.

Long-term trajectories and current BMI are associated with poorer cognitive functioning in middle-aged adults at high Alzheimer's disease risk.

INTRODUCTION: We examined relationships of body mass index (BMI) with cognition in middle-aged adults at Alzheimer's disease (AD) risk due to parental family history. METHODS: Participants are offspring of AD patients from the Israel Registry of Alzheimer's Prevention (N = 271). Linear regressions assessed associations of BMI and cognition, and whether associations differed by maternal/paternal history. Analyses of covariance examined associations of long-term trajectories of BMI with cognition. RESULTS: Higher BMI was associated with worse language (P = .045). Interactions of BMI with parental history were significant for episodic memory (P = .023), language (p = .027), working memory (P = .006), global cognition (P = .008); associations were stronger among participants with maternal history. Interactions of BMI trajectories with parental history were significant for episodic memory (P = .017), language (P = .013), working memory (P = .001), global cognition (P = .005), with stronger associations for maternal history. DISCUSSION: Higher BMI and overweight/obese trajectories were associated with poorer cognition in adults with maternal history of AD, but not those with paternal history.