Chronic High Glucose Levels Increase Risk for Cognitive Impairment

How to Get Your Older Patients to Monitor Blood Sugar

Chronically elevated glycosylated hemoglobin (Hb) A1c levels in older women may increase their risk of developing mild cognitive impairment or dementia, according to a study published in the Journal of Nutrition, Health and Aging (2006; 10:287-291). This is the first study to prospectively investigate the association between HbA_1c levels and cognitive difficulties.

A total of 1983 postmenopausal women (mean age, 67 years) were assessed for dementia every year for 4 years. At baseline, 53 (2.7%) women had a diagnosis of diabetes, 41 (2.1%) had a history of myocardial infarction, 7 (0.4%) had a history of stroke, and 115 (5.8%) had elevated depression scores. Mean baseline HbA_1c was 5.8% (range, 3.0%-12.1%).

At the end of the 4 years, 69 women were diagnosed with mild cognitive impairment, 17 were diagnosed with dementia of any etiology, and 15 were diagnosed with Alzheimer&#8217;s disease. For each 1% increase in HbA_1c, the risk of cognitive impairment or dementia within 4 years increased by 40%. Women whose HbA_1c was ≥7% at baseline were 4 times more likely to have cognitive decline or dementia than women whose HbA_1c was <7%.

Even when the 53 women who had diabetes at baseline were excluded and other confounders were accounted for (ie, age, race, education, and depression), there was still a significant association between elevated HbA_1c levels and risk for cognitive impairment or dementia.

&#8220;Now you can identify people who are at risk for mild cognitive impairment or dementia and monitor them closely with glycosylated hemoglobin. We need to take people who are at risk and see whether we can target them for trials or interventions for better blood glucose control,&#8221; said lead investigator Kristine Yaffe, MD, of the University of California, San Francisco.

The authors listed a number of possible reasons why chronically high blood sugar may cause cognitive impairment, ranging from the overall effects of diabetic complications to direct and indirect brain damage to a possible association between the enzymes that help degrade insulin and the potential of Alzhei-mer&#8217;s disease.

&#8220;There are a lot of clinical implications. This is further confirmation of metabolic deregulation in terms of glucose, and this may be associated with cognitive impairment. If you know someone who has diabetes, this is another reason you want to have tight control,&#8221; Dr Yaffe told IMWR.

The study group was comprised mainly of white, older women with osteoporosis, so whether these findings apply to men or to other groups of women is not known.

David Parks, MD, of Washington University School of Medicine in St. Louis, said that while this study did have some limitations, it was sufficiently powered to serve as a wake-up call to physicians about another possible adverse outcome of elevated blood glucose.

He called the study an important first step that he hopes will lead to more research in this area.

&#8220;I am not surprised by these findings,&#8221; Dr Parks told IMWR. &#8220;One of the most pervasive causes of dementia is microvascular. Diabetes is a killer that is known to cause microvascular disease from the retina to the kidney. I have suspected this kind of disease complication over the years, and this study does an excellent job of demonstrating the association in an objective, scientific way.&#8221;