Higher proportion of visceral adipose tissue is associated with smaller regional brain volumes in older adults with type 2 diabetes: Triglycerides may be in the pathway

Background Numerous studies have identified an increased risk for Alzheimer’s dementia (AD) in Type II Diabetes (T2D). However, the T2D biological characteristics contributing to this risk are still unknown. Adiposity assessed by body mass index (BMI) is one of the main causes of T2D and has been consistently linked to higher dementia risk, faster cognitive decline, and related neural injury. However, the contribution of fat specifically cannot be derived from BMI, which encompasses different adipose tissues, bone, and muscle mass. In this study we examined whether regional abdominal adiposity contributes to AD‐related regional brain volume and mechanism underlying it, in older adults with T2D participating in the Israel Diabetes and Cognitive Decline (IDCD) study. Method Regional abdominal adiposity was measured so far in 60 participants, including hepatic and pancreatic adiposity and abdominal adipose tissue (AAT), composed of subcutaneous and visceral adipose tissues (SAT and VAT). Brain volumes were assessed for regions associated with cognitive decline (hippocampus, cingulate gyrus, amygdala, and ventromedial prefrontal cortex (vmPFC)). Linear regressions examined associations of regional abdominal adiposity with regional brain volumes adjusting for sociodemographics, BMI and intracranial volume. We also tested if triglycerides, the main components of fat and associated with dementia risk, mediated these associations. Result Greater VAT:AAT ratio was associated with smaller volumes of the vmPFC (r = ‐0.38; p = 0.026) and hippocampal (r = ‐0.44; p = 0.005) volumes but not with amygdala and cingulate gyrus volumes. The SAT:AAT ratio was associated with greater volumes of the vmPFC (r = 0.40; p = 0.026) and hippocampus (r = 0.48; p = 0.004) but not with amygdala and cingulate. No associations were found between hepatic and pancreatic adiposity with brain volumes. Higher VAT:AAT ratio was associated with higher triglyceride levels (r = 0.38; p = 0.036) which in turn were associated with lower hippocampal volume (r = ‐0.45, p = 0.05). Triglycerides partially mediated the association between VAT:AAT ratio and hippocampal volume (r = ‐0.36; p = 0.03). Triglycerides did not mediate any other associations. Conclusion In older adults with T2D, a higher proportion of visceral fat may have a detrimental impact on brain regions relevant to cognitive functioning. Higher proportions of subcutaneous fat may have a protective role. Triglycerides, implicated in insulin resistance and chronic systemic inflammation may mediate the VAT‐hippocampus link.