Impact of Insulin Sensitizers on the Incidence of Dementia: A Meta-Analysis

Abstract

Background: Abundant evidence from epidemiological and clinical studies has proven that diabetes mellitus (DM) is correlated with an increased incidence of dementia and Alzheimer's disease (AD). Insulin resistance is considered to play an important role in the associations between DM and dementia. However, whether insulin sensitizer drugs are effective in preventing dementia still remains unclear. Methods: Electronic searches of PubMed, EMBASE, Google Scholar, and the ISI Web of Science were conducted to identify studies that reported about the associations between insulin sensitizers and the incidence of dementia. The included studies were reviewed, and a meta-analysis was performed using STATA to determine the combined relative risk (RR) for the incidence of dementia when using insulin sensitizers. Subgroup analysis and meta regression were also conducted. Results: In total, nine comparisons out of six studies were qualified for inclusion, and data from 544,093 participants were evaluated. The results of the meta-analysis revealed a combined RR of 0.78 (95% CI 0.64-0.95, p = 0.015) for the incidence of dementia when using insulin sensitizers. The incidence rate of dementia was reduced with either metformin (RR 0.79, 95% CI 0.62-1.01, p = 0.064) or thiazolidinediones (RR 0.75, 95% CI 0.56-1.00, p = 0.050), both with a marginal trend toward significance. Conclusions: The results indicate that insulin sensitizer drugs might provide protection against incident dementia. Controlled studies with large samples should be conducted to further confirm these conclusions and provide information for clinical strategies.

Metabolic Syndrome, Insulin Resistance, and Cognitive Dysfunction: Does Your Metabolic Profile Affect Your Brain?

“…The concept of precision medicine is emerging in relation to the prevention and treatment of AD (33), and the abundant evidence of various AD phenotypes, of which the metabolic phenotype is one, suggests that it is extremely relevant in this field. A recent meta-analysis (34) indicated that insulin-sensitizer drugs, like metformin and thiazolidinediones, might be useful in the prevention of dementia in patients with diabetes. Whether there is a direct mechanistic link is still controversial, but evidence from rat studies has shown that the glucagon-like peptide 1 analog liraglutide, another insulin sensitizer, interacts directly with processes leading to amyloid plaques and neurofibrillary tangles, which are the two pathological hallmarks of AD (35,36).…”

Astrocytic transporters in Alzheimer's disease

“…Therapeutic interventions seeking to enhance astrocytic lactate transport may provide a more fruitful endeavour. MCT1 knockout mice show deficits in long term memory (109) Metformin, the antidiabetic drug, has received a lot of attention with regards to its potential act as a novel therapeutic strategy in managing AD (112)(113)(114). This links into the emerging hypothesis that AD should be classed as a third type of diabetes (115,116).…”

Association of Serum Manganese Levels with Alzheimer’s Disease and Mild Cognitive Impairment: A Systematic Review and Meta‐Analysis

“…Current treatments only offer symptomatic improvement without stopping disease progression [8]. Therefore, identifying the risk factors for dementia is important for effectively preventing or postponing the onset of AD [9,10]. …”