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.

Amyloid deposition and small vessel disease are associated with cognitive function in older adults with type 2 diabetes.

Diabetes is associated with cognitive decline, but the underlying mechanisms are complex and their relationship with Alzheimer's Disease biomarkers is not fully understood. We assessed the association of small vessel disease (SVD) and amyloid burden with cognitive functioning in 47 non-demented older adults with type-2 diabetes from the Israel Diabetes and Cognitive Decline Study (mean age 78Y, 64% females). FLAIR-MRI, Vizamyl amyloid-PET, and T1W-MRI quantified white matter hyperintensities as a measure of SVD, amyloid burden, and gray matter (GM) volume, respectively. Mean hemoglobin A1c levels and duration of type-2 diabetes were used as measures of diabetic control. Cholesterol level and blood pressure were used as measures of cardiovascular risk. A broad neuropsychological battery assessed cognition. Linear regression models revealed that both higher SVD and amyloid burden were associated with lower cognitive functioning. Additional adjustments for type-2 diabetes-related characteristics, GM volume, and cardiovascular risk did not alter the results. The association of amyloid with cognition remained unchanged after further adjustment for SVD, and the association of SVD with cognition remained unchanged after further adjustment for amyloid burden. Our findings suggest that SVD and amyloid pathology may independently contribute to lower cognitive functioning in non-demented older adults with type-2 diabetes, supporting a multimodal approach for diagnosing, preventing, and treating cognitive decline in this population.