Blood-Brain Glucose Transfer in Alzheimer's disease: Effect of GLP-1 Analog Treatment.

There are fewer than normal glucose transporters at the blood-brain barrier (BBB) in Alzheimer's disease (AD). When reduced expression of transporters aggravates the symptoms of AD, the transporters become a potential target of therapy. The incretin hormone GLP-1 prevents the decline of cerebral metabolic rate for glucose (CMR) in AD, and GLP-1 may serve to raise transporter numbers. We hypothesized that the GLP-1 analog liraglutide would prevent the decline of CMR in AD by raising blood-brain glucose transfer, depending on the duration of disease. We randomized 38 patients with AD to treatment with liraglutide (n = 18) or placebo (n = 20) for 6 months, and determined the blood-brain glucose transfer capacity (T ) in the two groups and a healthy age matched control group (n = 6). In both AD groups at baseline, T estimates correlated inversely with the duration of AD, as did the estimates of CMR that in turn were positively correlated with cognition. The GLP-1 analog treatment, compared to placebo, highly significantly raised the T estimates of cerebral cortex from 0.72 to 1.1 umol/g/min, equal to T estimates in healthy volunteers. The result is consistent with the claim that GLP-1 analog treatment restores glucose transport at the BBB.