Evidence suggests that diabetes is a risk factor for Alzheimer disease. But how does it affect those who already have AD? The results of a large, prospective French study, released in today’s Neurology, may seem counterintuitive. Writing for the REAL.FR study group, Caroline Sanz, Inserm U558, Toulouse, France, and colleagues report slower cognitive decline over a four-year period in AD patients with diabetes mellitus (DM) compared to AD patients without diabetes. The difference was apparent even after adjusting for confounding variables, such as prescription diabetes medication, and the results confirm similar findings reported in smaller studies (see Mielke et al., 2007).

Before the study, the researchers hypothesized that diabetes would accelerate cognitive decline, and they suggest several plausible explanations for the unexpected results. DM patients receive more medications, such as anti-hypertension drugs, for example, that might protect against cardiovascular risks for cognitive decline. Sanz and colleagues also posit that the underlying pathology may be different between AD patients with and without diabetes. In fact, researchers led by Suzanne Craft, University of Washington, Seattle, have shown that people with dementia and DM have more microvascular lesions and greater cognitive decline at lower plaque burdens compared to dementia patients who are DM-free (see ARF related news story). Insulin sensitivity/resistance might also be a confounding issue for those with DM. The role of insulin resistance in brain aging and dementia is the topic of an Alzforum Webinar this Thursday led by Craft. For more information and to join the discussion, see the Webinar background page.—Tom Fagan.

Reference:
Sanz C, Andrieu S, Sinclair A, Hanaire H, Vellas B, for the REAL.FR Study Group. Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology 2008 October 27; 73:1359-1366. Abstract

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  1. This is indeed a confusing result, as previous large-scale studies have shown an increased risk of type 2 diabetes mellitus patients for developing AD, for example, the recent study by Xu et al., 2009.

    One important confounding variable is, Are the T2DM patients on drugs to treat diabetes? The study by Sanz et al. does not mention this at all. I can’t access the full paper, but the abstract states: "Sixty-three participants (10.4 percent) had DM at baseline. In a mixed model adjusted for sex, age, educational level, dementia severity, cholinesterase inhibitor use, and vascular factors (hypertension, atrial fibrillation, coronary heart disease, and hypercholesterolemia), there were no differences between the groups in MMSE baseline scores (–0.75, p = 0.20), but cognitive decline was slower in the group with DM (0.38, p = 0.01)."

    It does not appear that there was a control for diabetes treatments. If diabetes has been successfully treated in those patients, they should not have a higher risk of developing AD at all. Some people even find that some T2DM drugs protect people from developing AD; see, for example, Beeri et al., 2008.

    References:

    . Uncontrolled diabetes increases the risk of Alzheimer's disease: a population-based cohort study. Diabetologia. 2009 Jun;52(6):1031-9. PubMed.

    . Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology. 2008 Sep 2;71(10):750-7. PubMed.

References

News Citations

  1. Diabetes-Insulin Roundup: Dementia Connection Grows Stronger, Part 2

Webinar Citations

  1. The Role of Insulin Resistance in Brain Aging and Dementia

Paper Citations

  1. . Vascular factors predict rate of progression in Alzheimer disease. Neurology. 2007 Nov 6;69(19):1850-8. PubMed.
  2. . Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology. 2009 Oct 27;73(17):1359-66. PubMed.

Further Reading

Papers

  1. . Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology. 2009 Oct 27;73(17):1359-66. PubMed.

Primary Papers

  1. . Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology. 2009 Oct 27;73(17):1359-66. PubMed.