Diabetes Accelerates Conversion of Mild Cognitive Impairment to Dementia

Susan Jeffrey

January 13, 2010

January 11, 2010 — Results of a new study confirm that the presence of diabetes mellitus in people with mild cognitive impairment (MCI) is associated with an increased risk for progression to dementia.

Although previous studies have shown a link between diabetes and both MCI and dementia, it has not been clear whether diabetes increases the risk for conversion from one to the other, the researchers write.

"Our study demonstrates that individuals with mild cognitive impairment and diabetes are at increased risk of developing dementia," the researchers, with lead author Latha Velayudhan, DNB (Psychiatry), from the Institute of Psychiatry, King's College London, United Kingdom, conclude. "This suggests the need for studies of improved diabetes control and related approaches as possible strategies for early intervention."

Their findings are published in the January issue of the British Journal of Psychiatry.

Early Identification

People with MCI are at increased risk of developing dementia, although conversion rates range from 1% to more than 25% per year, depending on the study, the investigators write. "Prediction of progression to dementia — conversion — is of considerable clinical importance," they note. "To date, there is no variable other than cognitive impairment itself that unequivocally increases the risk of conversion."

Type 2 diabetes mellitus has been linked to accelerated cognitive decline in elderly people, development of MCI, and increased risk for dementia, including Alzheimer's disease and vascular dementia. However, although the association between diabetes and dementia risk is "robust," they note, it is not yet clear whether diabetes increases the risk for conversion from MCI to dementia.

In this article, Dr. Velayudhan and colleagues looked at the association between diabetes and dementia conversion in a population of 103 people with MCI by Peterson's criteria.

During 4 years of follow-up, 19 progressed to dementia, mostly probable or possible Alzheimer's disease, the diagnosis in 84%. After adjustment for sociodemographic factors, presence of the apolipoprotein E4 risk allele, premorbid IQ, and other health conditions, only diabetes mellitus was significantly associated with progression to dementia .

Table. Risk of Conversion to Dementia Associated With Diabetes Mellitus

Factor Hazard Ratio 95% CI
Diabetes mellitus 2.9 1.1 – 1.73

CI = confidence interval

This cohort was mostly white European participants, they note. Repeating this investigation in different populations where diabetes prevalence is higher, such as some ethnic groups, would be of interest.

Possible mechanisms by which diabetes might increase dementia risk include insulin resistance syndrome, disturbances in insulin homeostasis in the brain, and/or hyperinsulinemia, among others, the study authors write.

"Whatever the mechanism, with an expected increase in prevalence of diabetes in people of all ages, including older adults, the risk of developing dementia may increase," they conclude. "Identification of those at particular risk of progression might help to target early treatment — both pharmacological and social."

Findings Not Surprising

Asked for comment on these new findings, Bill Thies, PhD, chief medical and science officer for the Alzheimer's Association, pointed out that there is now a "pretty solid body of evidence" linking diabetes and Alzheimer's disease, at least at the epidemiologic level.

However, "exactly what the mechanism might be is not entirely clear," Dr. Thies added. Type 2 diabetes increases vascular risk, for example, which in turn has been linked to Alzheimer's disease, or the link may have something more directly to do with glucose metabolism or some other effect of insulin in the brain. Although trials of rosiglitazone, used to treat type 2 diabetes, had no effect in patients with Alzheimer's disease, some small studies have suggested that inhaled insulin may improve performance on some measures in Alzheimer's disease, he added.

In that context, then, the findings of the current study are not surprising, Dr. Thies concluded, but "it's always a good thing to document that the things you think are true really are."

The study was funded by the Alzheimer's Research Trust and the UK Medical Research Council and through the National Institute for Health Research, Specialist Biomedical Research Center for Mental Health at the South London & Maudsley National Health Service Foundation Trust, and King's College London. The authors have disclosed no relevant financial relationships.

Br J Psychiatry. 2010;196:36-40.