Regional abdominal adiposity and related factors are associated with brain volumes and cognitive functioning in middle‐aged adults at high AD‐risk

Abstract

AbstractBackgroundAlzheimer’s dementia (AD) is one of the most challenging diseases, affecting individuals, their families, and society. There is evidence for the involvement of midlife obesity (measured by BMI) in mild cognitive impairment (MCI), dementia, and AD risk in late life. Regional abdominal adiposity has been related to metabolic syndrome and inflammation, both consistently linked to cognitive impairment and neuropathology of AD. The accelerating prevalence of obesity and dementia in our aging population further amplifies the potential public health impact of the proposed investigation.MethodThe Israel Registry for Alzheimer’s Prevention (IRAP) (N=500), which aims to examine the connection between longevity and dementia, was capitalized. Newly collected data ‐ regional abdominal adiposity (abdominal (AAT) visceral (VAT), subcutaneous (SAT), pancreatic, and hepatic adipose tissue) by MRI (N=92), and adiposity‐related factors of visceral fat (TNF‐α, Leptin), pancreases (PP, PYY), and liver (PAI‐1, Fetuin) via serum (N=26).ResultHigh pancreatic fat percentage was associated with lower hippocampal and IFG volumes, and lower executive memory function. High hepatic fat percentage was associated with lower hippocampal volume and lower executive memory function. High VAT percentage was associated with lower amygdalar and hippocampal volumes, while high VAT volume was associated with lower cognitive functioning (executive and working memory, language, and global cognition). Serum levels of PP, PAI‐1, and Fetuin were negatively associated with para‐hippocampal and IFG volumes. Serum levels of Leptin were associated with amygdala and hippocampal volumes. High levels of PYY, PAI‐1, and TNF‐α were associated with lower executive memory function.ConclusionGreater regional abdominal adiposity and related secreted factors are associated with poorer cognitive functions and lower volumes of cognition and BMI‐related brain regions, already in midlife in asymptomatic individuals enriched for AD risk, regardless of global body adiposity measured by BMI. These results strongly support our overall hypothesis that specific fat deposits in specific tissues and organs are differentially associated with cerebrovascular and AD‐related neuropathology and cognition, advancing the field to new potential mechanistic pathways underlying the adipose tissue‐brain link.