Given the extreme increase in (pre)diabetes and dementia with age, understanding the relation between glucose metabolism and brain integrity is critical. We investigated 1) the effects of chronological and biological age on associations between parameters of glucose metabolism and brain integrity in elderly 2) whether any relation found are generalized or specific for areas enriched for insulin receptors expression.

From the Leiden Longevity Study, 132 non-diabetic subjects were included. For chronological age, subjects were categorized in three tertiles (49-62.9 (mean 59.1)yrs, 63.2-68.9 (mean 65.9)yrs, 69.3-84.3 (mean 75.9)yrs respectively). For biological age, subjects were categorized as offspring from long lived siblings (mean age: 66.6yrs) and partners thereof (mean age: 65.8yrs). Oral glucose tolerance test derived parameters comprised fasted levels and areas under the curve (AUC) for glucose and insulin, insulinogenic index and homeostatic model assessment of insulin resistance (HOMA-IR). Integrity of grey matter (GM), white matter (WM), subcortical structures enriched for insulin receptor expression (amygdala, hippocampus, striatum) and control structures (thalamus, pallidum) were assessed using (3Tesla) MRI magnetization transfer imaging (MTI) peak height measurements.

In the youngest age tertile only, fasted insulin, AUC insulin, insulinogenic index and HOMA-IR  were negatively associated with reduced MTI peak height in the amygdala, hippocampus, striatum, pallidum, WM (p=0.010, p=0.010, p=0.075 and p=0.012 respectively) and GM (p=0.025, p=0.010, p=0.012 and p=0.019 respectively). In the offspring, fasted insulin, AUC insulin, insulinogenic index and HOMA-IR were negatively associated with decreased MTI peak height in hippocampus, striatum, pallidum, WM (p=0.005, p=0.001, p=0.005 and p=0.006 respectively) and GM (p=0.007, p<0.001, p<0.001 and p=0.007 respectively). In partners, peripheral insulin action was not associated with brain integrity, except in the thalamus.

Parameters of reduced peripheral insulin action (but not glucose) were associated with generalized, reduced brain integrity in chronologically and biologically younger subjects only. Our future research will focus on disentangling whether reduced peripheral insulin action is a cause or consequence of reduced brain integrity.