Insulin resistance and body mass index are associated with TSPO PET in cognitively unimpaired elderly

Abstract

<p>Metabolic risk factors are associated with peripheral low-grade inflammation and an increased risk for dementia. We evaluated if metabolic risk factors i.e. insulin resistance, body mass index (BMI), serum cholesterol values, or high sensitivity C-reactive protein associate with central inflammation or beta-amyloid (Aβ) accumulation in the brain, and if these associations are modulated by <em>APOE4</em> gene dose. Altogether 60 cognitively unimpaired individuals (mean age 67.7 years (SD 4.7); 63% women; 21 <em>APOE3/3</em>, 20 <em>APOE3/4</em> and 19 <em>APOE4</em>/<em>4</em>) underwent positron emission tomography with [¹¹C]PK11195 targeting TSPO (18 kDa translocator protein) and [¹¹C]PIB targeting fibrillar Aβ. [¹¹C]PK11195 distribution value ratios and [¹¹C]PIB standardized uptake values were calculated in a cortical composite region of interest typical for Aβ accumulation in Alzheimer’s disease. Associations between metabolic risk factors, [¹¹C]PK11195, and [¹¹C]PIB uptake were evaluated with linear models adjusted for age and sex. Higher logarithmic HOMA-IR (standardized beta 0.40, p = 0.002) and BMI (standardized beta 0.27, p = 0.048) were associated with higher TSPO availability. Voxel-wise analyses indicated that this association was mainly seen in the parietal cortex. Higher logarithmic HOMA-IR was associated with higher [¹¹C]PIB (standardized beta 0.44, p = 0.02), but only in <em>APOE4/4</em> homozygotes. BMI and HOMA-IR seem to influence TSPO availability in the brain.</p>