A large-scale neuroimaging study revealed that both diabetes and prediabetes may be associated with accelerated brain aging, with these effects being more pronounced in men and individuals with poor cardiometabolic health. Researchers also found that a healthy lifestyle might mitigate these effects.
Researchers analyzed brain magnetic resonance imaging (MRI) data from 31,229 participants in the UK Biobank, aged 40 to 70 years. They used machine-learning techniques to estimate brain age based on 1,079 imaging-derived phenotypes across six MRI modalities. Brain age gap (BAG), defined as the difference between estimated brain age and chronological age, was used as the primary outcome measure.
Key Findings
Key findings from the study, published in Diabetes Care, included:
- Diabetes was associated with a BAG of 2.29 years (β = 2.01; 95% confidence interval [CI] = 1.70-2.32; P < .001).
- Prediabetes was linked to a BAG of 0.50 years (β = 0.22; 95% CI = 0.10-0.34; P < .001).
- In a longitudinal analysis of 2,414 participants with follow-up scans, diabetes was associated with a 0.27-year annual increase in BAG (95% CI = 0.01-0.53; P = .045).
- The association between diabetes and BAG was stronger in men (2.63 years) compared with women (1.76 years).
- Individuals with two or more cardiometabolic risk factors showed a stronger association between diabetes and BAG (3.08 years) compared with those with no risk factors or only one risk factor (1.96 years).
- A healthy lifestyle attenuated the diabetes-BAG association by 1.68 years.
Study Details
The study included 16,562 participants with normoglycemia, 13,518 with prediabetes, and 1,149 with diabetes at baseline. The mean age of participants was 54.8 ± 7.5 years, and 53.0% were female. Glycemic status was determined using medical history, medication use, and HbA1c levels. Prediabetes was defined as an HbA1c level of 5.7% to 6.4%, and diabetes was defined as an HbA1c level of ≥6.5% or previously diagnosed diabetes.
Additional baseline characteristics of the study population included:
- Mean BMI: 26.5 ± 4.2 kg/m²
- Hypertension prevalence: 21.1%
- Mean high-density lipoprotein (HDL) cholesterol: 57.2 ± 14.6 mg/dL
- Mean triglycerides: 144.5 ± 84.0 mg/dL
- Current smokers: 6.0%
- Heavy drinkers: 49.9%
- Physically active individuals: 40.0%.
Brain MRI scans were conducted using a Siemens Skyra 3T scanner. The researchers employed multiple machine-learning models to estimate brain age, with the least absolute shrinkage and selection operator regression model without feature selection ultimately chosen for its superior performance.
The study explored the role of cardiometabolic risk factors, including obesity, hypertension, low HDL cholesterol, and high triglycerides. A healthy lifestyle was defined as no smoking, no or light-to-moderate alcohol consumption, and high physical activity (≥3,000 MET-min/week).
A dose-response relationship between HbA1c levels and BAG was observed. Poorly controlled diabetes (HbA1c ≥8.0%) was associated with a BAG as high as 4.18 years (β = 3.90; 95% CI = 3.15-4.66; P < .001).
In sensitivity analyses, the researchers found that results remained consistent when using nonimputed data; findings were similar after adjusting for brain MRI assessment center; excluding participants with possible cognitive impairment or prodromal dementia did not significantly alter the results; and using diabetes status defined at the time of MRI scan yielded consistent results.
The authors noted several limitations of the study, including potential selection bias in the UK Biobank cohort and the use of HbA1c alone to classify glycemic status. They also acknowledged that the longitudinal analysis was limited by the small number of participants with follow-up scans.
The researchers concluded, "Diabetes and even prediabetes are associated with accelerated brain aging, especially among men and people with poor cardiometabolic health. However, a healthy lifestyle may counteract this."
No potential conflicts of interest relevant to this article were reported.
