Obesity, hypercholesterolemia, hypertension, and dysfunctional insulin signaling in diabetes are accompanied by increased intima-media thickness, progressive hardening of large arteries, and excess pulsatility, all of which can ultimately affect the brain’s blood supply.18,39,40,41,42,43,44 The prefrontal, posterior cingulate, and occipital cortices are particularly susceptible to vascular damage,45 and this is consistent with our observations of lower CBF in these areas. The gene discussed is INS; the disease is familial hypercholesterolemia.