Younger Age at Diabetes Onset Associated with Higher Risk of Dementia, According to New Study

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Findings from a community-based study showed that prediabetes in midlife was “modestly” associated with dementia risk, but researchers noted that this risk was explained by the subsequent development of diabetes.

Investigators also found that earlier age at diabetes onset was associated with a significantly greater risk of dementia.

“Taken together, our findings suggest that preventing prediabetes progression, especially in younger individuals, may be an important way to reduce the dementia burden,” wrote first author Jiaqi Hu, PhD student, Johns Hopkins Bloomberg School of Public Health, and colleagues in Diabetologia.

Hu and colleagues conducted the study to evaluate whether the association of prediabetes with dementia can be explained by the intervening onset of diabetes. They analyzed data from the Atherosclerosis Risk in Communities (ARIC) study, which originally enrolled nearly 16 000 adults aged 45-64 years between 1987 and 1989 from 4 US counties.

For the current study, data were collected from 11 656 adults (mean age 56.8 years; 55.3% women) without diabetes at baseline and who completed visit 2 of the ARIC study (1990-1992), which was the first visit where HbA_1c and cognitive function were measured.

Prediabetes was defined as HbA_1c 5.7%–6.4%. Participants without prediabetes (HbA_1c <5.7%) served as the study reference group. Incident diabetes was defined either as self-reported physician diagnosis or diabetes medication use reported by participants during in person visits or annual telephone calls, according to the study. Investigators categorized age at diabetes diagnosis as <60, 60–69, 70–79, or 80–93 years.

Dementia was determined through an expert committee review of cognitive function assessments, informant reports, and hospitalization codes. Demographics, lifestyle factors, and clinical factors were collected at baseline. Follow-up was measured from visit 2 to the first diagnosis of dementia or censoring due to death, loss to follow-up, or administrative censoring on December 31, 2019.

FINDINGS

Of the full cohort, 20% (n=2330) had prediabetes at baseline. Overall, there were 3143 participants who developed diabetes during a median 15.9 years of follow-up. Participants with prediabetes were more likely to develop diabetes compared with those without prediabetes (44.6% vs 22.5%).

A total of 2247 participants developed dementia during a median 24.7 years of follow-up, according to researchers. The development of dementia varied by prediabetes and incident diabetes status. For example, among participants with prediabetes, the cumulative incidence of dementia was 16.6% higher in those who developed diabetes compared to those who did not (23.9% vs 20.5%).

Before accounting for incident diabetes, researchers observed that prediabetes was significantly associated with the risk of dementia (hazard ratio [HR] 1.12, 95% CI 1.01-1.24). However, after they adjusted for incident diabetes, the associated was attenuated and nonsignificant (HR 1.05, 95% CI 0.94-1.16).

In multivariable adjusted models, adults who were diagnosed with diabetes at younger than 60 years of age had the highest risk of dementia (HR 2.92, 95% CI 2.06-4.14). Participants diagnosed with diabetes between 80-93 years of age did not have a statistically significantly elevated risk of dementia (HR 1.13, 95% CI 0.94-1.35).

“Improving early detection and engagement in people with prediabetes to prevent or delay the progression to diabetes may have long-term population benefits for dementia prevention,” wrote Hu and coauthors.

Reference: Hu J, Fang M, Pike JR, et al. Prediabetes, intervening diabetes and subsequent risk of dementia: the Atherosclerosis Risk in Communities (ARIC) study. Diabetologia. Published online May 24, 2023. doi:10.1007/s00125-023-05930-7.