Spotlight on glycemia and dementia

Several recent studies looked at the connection between dementia and diabetes or prediabetes.

The first study, published by Alzheimer's & Dementia on Oct. 13, looked at the effect of metformin on risk of dementia. It included 1,393 type 2 diabetes patients who were at least 50 years old and had normal cognition at baseline, gathered from the National Alzheimer's Coordinating Center database in 2005 to 2021. A total of 104 developed dementia over a four-year median follow-up. The 754 patients who reported taking metformin had significantly lower risk of developing dementia (risk difference [RD], −3.2%; 95% CI, −6.2% to −0.2%). The association varied when patients were divided into subgroups by potential dementia risk factors; the effect was only significant among those with no neuropsychiatric disorders and no use of NSAIDs (RD, −8.7%; 95% CI, −13.4% to −4.1%). Patients with neuropsychiatric disorders not taking antidepressants had an increased risk of dementia on metformin (RD, 8.6%; 95% CI, 1.8% to 15.5%), while those with no neuropsychiatric disorders taking NSAIDs and those with neuropsychiatric disorders taking antidepressants had neutral results. “Our findings showed that neuropsychiatric disorders and antidepressant use were the important factors that would influence the association between metformin and the onset of dementia,” said the authors, who called for the findings to be validated in a more extensive and diverse population.

The second study, published by Scientific Reports on Nov. 23, examined the relationship between impaired fasting glucose (IFG) and dementia. It included 1,463,066 middle-aged and elderly Korean patients from a population-based database, among whom 7,614 cases of dementia (5,603 of them Alzheimer disease) occurred during a median of 6.4 years of follow-up. IFG was defined as a fasting blood glucose level of 100 to 125 mg/dL (5.6 to 6.9 mmol/L). The study found a significant trend towards a higher risk of all-cause dementia (P=0.014 for trend) and Alzheimer disease (P=0.005 for trend) with IFG, but the effect was modest and only significant in those without obesity. The study authors concluded that the results support the association between prediabetes and incident dementia and indicate that hyperglycemia might make a relatively greater contribution to the development of dementia in patients who are not obese. Limitations include lack of detailed information on risk factors, postprandial glucose level, HbA1c level, or glucose variability. However, it is the first study to examine repeated exposure to IFG using consecutive health data in almost 1.5 million people and “suggests that even mild hyperglycemia in people regarded as being at low risk should not be overlooked,” the study authors wrote.

Finally, a review published by Cureus on Nov. 27 assessed the effect of oral antidiabetic agents and insulin on risk of dementia. It included 52 studies and found that in most, oral medications significantly reduced the risk and incidence of dementia in patients with type 2 diabetes. Sulfonylureas, however, were shown to increase the risk of dementia in most studies. Pioglitazone seemed to be the most successful at reducing risk, especially when used with metformin. “Metformin appeared to be particularly effective in maintaining a positive effect on immediate and delayed recall, which could contribute to preserving cognitive function,” observed the study authors, although they noted that overall, among the oral drugs, “thiazolidinediones may be the most beneficial drug class for reducing the risk of dementia.” They called for additional research to determine whether early intervention with specific classes of antidiabetic drugs could help prevent development of dementia.