High Blood Glucose Linked to Dementia Even Without Diabetes

Megan Brooks

August 08, 2013

Higher blood glucose levels, shy of the diabetic range, increase the risk for dementia in adults, new data from the longitudinal Adult Changes in Thought (ACT) study suggest.

"We considered blood glucose levels far into the normal (nondiabetic) range, and even there found an association between higher glucose levels and dementia risk," Paul K. Crane, MD, associate professor of medicine at the University of Washington School of Medicine, Seattle, and affiliate investigator at the Group Health Research Institute in Seattle, told Medscape Medical News.

He said the results suggest that the "clinical determination of diabetes/not diabetes may miss important associations still there for people who are categorized as not having diabetes."

The study is published in the August 8 issue of the New England Journal of Medicine.

Diabetes Already a Risk Factor

Although diabetes is a risk factor for dementia, it's been unclear whether higher glucose levels, short of diabetes, also increase the risk for dementia. "Most studies that have investigated associations between glucose metabolism and the risk of dementia have focused on diabetes itself, and they have yielded inconsistent results," the authors note.

For their study, Dr. Crane and colleagues had access to 35,264 clinical measurements of glucose levels and 10,208 measurements of glycated hemoglobin from 839 men and 1228 women without dementia at baseline. Their mean age at baseline was 76 years.

During a median follow-up of 6.8 years, 524 participants developed dementia, including 74 with diabetes and 450 without.

Dr. Paul Crane

Among participants without diabetes, higher average glucose levels within the preceding 5 years were associated with increased risk for dementia (P = .01). At a glucose level of 115 mg/dL, as compared with 100 mg/dL, the adjusted hazard ratio for dementia was 1.18 (95% confidence interval [CI], 1.04 - 1.33).

Higher average glucose levels were also related to an increased risk for dementia in those with diabetes (P = .002). At a glucose level of 190 mg/dL, as compared with 160 mg/dL, the adjusted hazard ratio for dementia risk was 1.40 (95% CI, 1.12 - 1.76). The findings were consistent across of variety of sensitivity analyses, the authors say.

The data suggest that higher levels of glucose may have "deleterious effects on the aging brain," the authors say.

The ACT study is "unique in being linked to clinical data from a healthcare delivery system along with research-quality dementia diagnoses," Dr. Crane told Medscape Medical News.

The findings are based on an average of 17 blood glucose measurements per person, "very rich data," senior author Eric B. Larson, MD, from Group Health Research Institute and University of Washington, added in a statement.

"This work is increasingly relevant because of the worldwide epidemics of dementia, obesity and diabetes," Dr. Crane said.

Modest Effect

Last month in a publication in JAMA Neurology, reported by Medscape Medical News at that time, data from the Baltimore Longitudinal Study of Aging failed to show a link between glucose intolerance, diabetes or insulin resistance Alzheimer's disease or amyloid-β accumulation in the brain.

Richard J. O'Brien, MD, PhD, chair, Department of Neurology, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, was an author on that study. Asked for his thoughts on the ACT data, Dr. O'Brien said it should be noted that "the effect is modest but they have a much larger sample size and we could have missed a small effect like that."

He said it should also be noted that the outcomes of the 2 studies are different. "Their outcome is dementia — they have no way of knowing about the specific Alzheimer's component to that outcome. It is certainly possible that vascular disease related to diabetes is the important factor increasing the rate of dementia. Dementia is often multifactorial — with Alzheimer's and vascular disease being the two biggest contributors," he noted. "The vascular component is difficult to detect clinically because it is often asymptomatic — only pathology can detect it."

Dr. Crane and colleagues say the underlying mechanisms of the association between elevated glucose levels and dementia need to be clarified in future studies.

"This was an observational study, and clinical practice really should not change based on the results of this study," Dr. Crane cautioned. "We do not know whether interventions designed to lower blood glucose would also lower dementia risk. That important question requires a different study design.

"However, from other research, including research from the ACT study, we know that exercise is associated with reduced dementia risk," he added. "Exercises such as walking or aerobic exercises in swimming pools are well tolerated and fun."

The study was funded by the National Institutes of Health. Disclosures for authors are available at NEJM.org. Dr. O'Brien has disclosed no relevant financial relationships.

N Engl J Med. 2013;369:540-548. Abstract

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