DIABETES SLOWS ALZHEIMER PROGRESSION!

October 29, 2009 — Rather than accelerating cognitive decline, diabetes mellitus (DM) appears to slow this decline in patients with Alzheimer's disease (AD), according to results of a new study.

This finding was unexpected in light of previous research that documented faster cognitive decline in diabetic patients without dementia.

The results may have important clinical implications, said the study's lead author, Caroline Sanz, MD, from the Department of Diabetology, Metabolic Diseases and Nutrition at the Institut National de la Santé et de la Recherche Médicale, Toulouse, France.

"DM could be a relevant factor in predicting the rapidity of cognitive decline in AD patients," she said in an email interview. "As well, it is hoped that earlier and prompt treatment of DM before dementia is diagnosed may prevent the cerebrovascular lesions and may delay the onset of cognitive decline."

The study results were published in the October 27 issue of Neurology.

Similar Cognitive Function

This study was part of the Réseau sur la maladie d'Alzheimer Français (REAL FR) study, a 4-year prospective cohort study of patients with AD and their caregivers from 16 memory centers in France.

Included were 608 patients who were enrolled between April 2000 and October 2002 and followed-up for 11 to 47 months (median, 26 months). At baseline, the subjects had a Mini-Mental State Examination (MMSE) score of between 10 and 26.

At the start of the study, 63 patients (10.4%) had DM. Patients were considered to have diabetes if they were taking antidiabetic medications and/or reported a history of DM.

Cognitive function was similar between those with and without diabetes (MMSE, 20 vs 21; P = .79).

Compared with nondiabetic patients, those with the disorder were more likely to be men, be somewhat younger, have hypertension and cardiovascular disease, and have a higher body mass index. Diabetic patients also had more limitations in activities of daily living.

Those with diabetes were using more medications than nondiabetic patients (5 vs 3). Among the diabetic patients, 16 were using diet alone to control their DM, 31 took oral blood glucose-lowering drugs, and 16 used insulin.

During the course of the study, researchers used the MMSE twice a year to assess cognitive function. They defined mild dementia as a MMSE score between 26 and 20 and moderate dementia as a MMSE score between 19 and 10.

During the study, 94 patients died, 76 withdrew consent, 67 were institutionalized, 65 were lost to follow-up, 59 left the study because of their own or their caregiver's medical problems, and 49 dropped out for other reasons. This left 198 patients at the end of the study.

Adjusted Model

The study found that cognitive decline was slower in patients with DM compared with patients without DM. In a model that adjusted for sex, age, education, dementia severity, cholinesterase-inhibitor use, and vascular factors, the mean difference in the rate of half-yearly cognitive decline between patients with and without DM was 0.38 MMSE points (SE = 0.15; P = .01).

Within the diabetes group, the rate of cognitive decline was similar between those using and those not using insulin (0.11; P = .68 in adjusted model) and between patients with diet-controlled diabetes compared with those taking antidiabetic medications (0.12; P = .65 in adjusted model).

Neuropathologic Differences

Neuropathologic differences between patients with and without DM may explain the slower cognitive decline among subjects with AD, said Dr. Sanz. Patients with diabetes may be more likely to have a mixed brain pathology (AD with cerebrovascular disease), and such patients tend to have a slower cognitive decline than patients with AD, she noted.

Diabetic patients with AD may take more cardiovascular medications such as antihypertension drugs, low-dose aspirin, or statins, and this might also contribute to a slower progression of cognitive decline. As well, insulin-sensitizing drugs may have beneficial cognitive effects.

One limitation of the study was that it lacked information on diabetes severity. In addition, underreporting of DM may have led to an underestimation of the effect of DM on cognitive decline.

Dr. Sanz pointed out that both diabetes and AD are common conditions in older people and that few effective treatment options exist to slow the progression of AD. "Identifying modifiable risk factors for prevention of AD is therefore important," she noted.

Dr. Sanz has disclosed no relevant financial relationships. For disclosures on other authors, please see original article.

Neurology. 2009;73:1359–1366. Abstract