From a recent study published in Diabetes careresearchers examined the link between prediabetes and brain aging. They also examined whether modifiable lifestyle factors could weaken the association.
Study: Diabetes, prediabetes and brain aging: the role of a healthy lifestyle. Image credits: Josh Namdar/Shutterstock.com
Background
Diabetes is a major risk factor for dementia, although its impact on premature brain aging is unknown. According to magnetic resonance imaging (MRI), diabetes has been associated with global brain shrinkage, an increased burden of small vessel disease, and microstructural lesions before cognitive symptoms.
Prediabetes has been associated with mild cerebrovascular and neurodegenerative abnormalities, although its relationship with cognitive decline and dementia is debatable.
The brain age gap (BAG) indicates a deviation from normal aging, which increases the risk of cognitive decline and dementia.
Early diagnosis of accelerated brain aging could aid in the rapid identification and treatment of individuals at risk for dementia. However, longitudinal evidence on the link between prediabetes and brain age is limited, and lifestyle choices may influence the relationship.
About the study
In the current study, researchers examined the impact of a healthy lifestyle on the risk of dementia in individuals with prediabetes or diabetes.
The study included 31,229 dementia-free adult participants from the United Kingdom Biobank, aged 40 to 70 years. Exclusion criteria included chronic neurological disorders, insulin-dependent diabetes and subjects with missing glycated hemoglobin (HbA1c).
Researchers diagnosed prediabetes and diabetes using American Diabetes Association criteria, medical history, medications and baseline HbA1c levels. HbA1c ≥6.5% indicates diabetes, 5.7% to 6.4% indicates prediabetes, and <5.7% indicates normoglycemia. Diabetes was well controlled (HbA1c <7%), moderately controlled (≥7.0 to <8%), or poorly controlled (≥8.0%).
Participants’ follow-ups for 11 years included one or two brain MRI scans. Brain age was estimated from 1,079 MRI image-derived phenotypes (IDPs) using least absolute shrinkage and selection operator regression model (LASSO) with Bayesian optimization and without feature selection.
The researchers obtained the IDPs using T1-weighted MRI, T2-weighted MRI, T2-weighted fluid-attenuated inversion recovery (FLAIR), diffusion MRI, and functional MRI (fMRI) in rest and task phases. The team derived BAC by subtracting chronological age from brain age.
Linear regressions estimated beta coefficients for the association between glycemic status and BAC, and restricted cubic splines modeled nonlinear associations between HbA1c and BAC. Researchers also conducted a joint exposure analysis by including a variable that combined glycemic status and lifestyle in linear regressions.
Study covariates included sociodemographic factors, cardiometabolic risk factors, and lifestyle behaviors (physical activity, smoking, and alcohol consumption). Socio-demographic factors included education and socio-economic status. Cardiometabolic risk factors included body mass index (BMI), blood pressure, antihypertensive medications, high-density lipoprotein (HDL) cholesterol, and triglycerides.
In the sensitivity analysis, researchers used BAC estimates from other machine learning models and unimputed data, considering MRI assessment center as a covariate and excluding individuals with prodromal or undiagnosed dementia.
Results
Among the study participants, the average age was 55 years; 53% were female, 13,518 (43%) had prediabetes and 1,149 (3.7%) had diabetes. Compared with normoglycemic individuals, those with prediabetes tended to be older, male, less educated, physically inactive, with cardiometabolic risk factors, and of lower socioeconomic status.
Prediabetes (β=0.2) and diabetes (β=2.0) were related to significantly high BAC levels. The team found that brain age exceeds chronological age by 0.5 years in prediabetes patients and by 2.3 years in people with diabetes. Diabetes significantly increased BAC over time, an annual increase of 0.3 years, and BAC increased to 4.2 years in individuals with poor glycemic control.
The association between prediabetes and high BAC was especially robust in men with at least two risk factors for cardiometabolic disease. Specifically, brain age in men with prediabetes exceeded their chronological age by 0.8 years, compared to 0.3 years in women.
In addition, BAC increased to 2.6 years for men with diabetes, compared to 1.8 years for women. Similarly, among those with at least two factors that increase cardiometabolic risk, prediabetes and diabetes were associated with BAC values of 1.3 and 3.1 years, respectively, compared with 0.2 and 2.0 years among those with fewer cardiometabolic risk factors.
However, healthy lifestyle habits (high physical activity, not drinking excessively and not smoking) weakened the relationship between diabetes and BAC.
The brain age of diabetic patients with a healthy lifestyle exceeded their chronological age by 0.8 years, and that of individuals with a non-optimal lifestyle exceeded their chronological age by 2.5 years. Practicing healthy lifestyle habits was associated with a decrease in BAC over 1.7 years. Sensitivity analyzes yielded similar findings.
Conclusion
The study found that diabetes and prediabetes are linked to accelerated brain aging, making these diseases suitable targets for lifestyle interventions to maintain brain health.
Men with poor cardiometabolic health showed the most robust associations, suggesting that preventive measures may benefit them most. Adopting a healthy lifestyle, including physical activity, not smoking, and avoiding heavy drinking, can help alleviate these effects.