Therapy Insight: type 2 diabetes mellitus and the risk of late-onset Alzheimer's disease.

A number of well-designed epidemiological studies have linked type 2 diabetes mellitus (T2DM) with an increased risk of Alzheimer's disease (AD). Several mechanisms could help to explain this proposed link, including insulin and insulin resistance, inflammatory cytokines, and oxidative stress. Obesity or physical inactivity might also influence AD through effects on hypertension, insulin sensitivity or inflammation. Typical AD pathology, such as amyloid-beta deposits, might be exacerbated by insulin dysregulation, T2DM itself, or microvascular disease that is a consequence of T2DM. T2DM patients are not routinely evaluated for cognitive outcomes, and cognitive impairment in T2DM is rarely treated. Similarly, AD patients are not routinely evaluated for T2DM or hyperinsulinemia. Current treatments for AD have only modest benefits, and several drugs that target metabolic and inflammatory pathways are being evaluated, most notably the statins, which reduce LDL and inflammation but might not influence amyloid- deposition, an important precursor for AD. Although some evidence supports a potentially important role for peroxisome proliferative activated receptor agonists such as glitazones, at present there are no published randomized clinical trials in AD patients of any drugs that target insulin or insulin resistance. Clinical implications of the T2DM-AD link include cognitive evaluations of patients with T2DM, and potential benefits for such patients through treatment with statins or diabetes drugs that target insulin.