Prediabetes and the incidence of dementia in general population: a systematic review and meta‐analysis of prospective studies

Abstract

Background Continuous hyperglycaemia has been related with dementia. However, it remains unclear whether prediabetes poses a higher risk of dementia. A meta‐analysis was therefore conducted to comprehensively investigate the possible role of prediabetes as a risk factor of dementia. Methods Prospective cohort studies reporting the association of prediabetes and dementia were identified from PubMed, Web of Science, and Embase databases. A random‐effects model was applied to combine the results by incorporating the influence of heterogeneity. Subgroup analyses were also conducted to explore the influences of study features on the relationship. Sensitivity analysis re‐estimated the combined effect size after excluding single studies separately to explore the robustness of the results. Results Nine studies involving 29 986 adults from the general population, 6265 (20.9%) of whom had prediabetes, were included. It was shown that prediabetes was not independently associated with a higher incidence of dementia compared with normoglycaemia (adjusted risk ratio (RR): 1.01, 95% confidence interval (CI): 0.85–1.21, P = 0.89, I2 = 39%). Subgroup analyses according to the definitions of prediabetes, follow‐up duration, method for diagnosis of dementia, and quality score produced similar findings (P for all subgroup differences >0.05). In addition, prediabetes was not independently associated with the incidence of Alzheimer's disease (RR: 1.24, 95% CI: 0.98–1.56, P = 0.07, I2 = 0%) or vascular dementia (RR: 1.16, 95% CI: 0.70–1.92, P = 0.56, I2 = 0%). Different definitions of prediabetes have the potential to influence the results, as reflected in the subgroup analysis for Alzheimer's disease (RR: 1.30, 95% CI: 1.06–1.60, P = 0.01, I2 = 0%). Conclusions Prediabetes may not be an independent risk factor of all‐cause dementia or vascular dementia in the general adult population. However, changing the definition of prediabetes may have an impact on the outcome for Alzheimer's disease.

Cumulative effect of impaired fasting glucose on the risk of dementia in middle-aged and elderly people: a nationwide cohort study

“…This study had the advantage of comparing various glucose statuses such as IGT and high postprandial glucose state based on oral glucose tolerance test data. A recent systemic review and meta-analysis involving 29,986 adults from the general population found that prediabetes was not an independent risk factor for all-cause dementia, Alzheimer's disease, or vascular dementia 22 .…”

Long‐term impact of type 2 diabetes onset on dementia incidence rate among New Zealanders with impaired glucose tolerance: A tapered‐matched landmark analysis over 25 years

“…Observational studies also suggest an association between prediabetes, an intermediate mild degree of hyperglycemia, and increased dementia risk 9,10 . However, a recent systematic review revealed conflicting results, suggesting that prediabetes may not independently elevate dementia risk compared to normoglycemia, with potential influences from different prediabetes definitions 11 …”

“…9,10 However, a recent systematic review revealed conflicting results, suggesting that prediabetes may not independently elevate dementia risk compared to normoglycemia, with potential influences from different prediabetes definitions. 11 A retrospective cohort study in the United States, incorporating 2330 individuals with prediabetes defined by hemoglobin A1C (HbA1c), of whom 1040 developed T2D during follow-up, found an association between T2D onset and increased dementia risk. 12 Prediabetes, a condition indicating a high risk of developing diabetes, includes subtypes such as impaired glucose tolerance (IGT)-a state where blood glucose levels are higher than normal but not high enough for a diabetes diagnosis, typically identified through an oral glucose tolerance test (OGTT).…”

“… 9 , 10 However, a recent systematic review revealed conflicting results, suggesting that prediabetes may not independently elevate dementia risk compared to normoglycemia, with potential influences from different prediabetes definitions. 11 …”