Investigating the Association of Frailty Score and Diabetes with Relative Brain Age : Insights from the UK Biobank
Bibliographic record
Abstract
BACKGROUND: Aging and type 2 diabetes (T2D) are both associated with brain cortical atrophy and structural brain changes. Frailty also appears linked to cortical atrophy and reduced brain volume. The joint impact of T2D and frailty on brain health is not known. This study investigates the association between frailty and T2D with relative brain age (RBA), a cortical thickness-based measure reflecting deviations from normative brain aging trajectories, in the UK Biobank. METHOD: We selected UK Biobank participants aged ≥55 years for whom an MRI was available. T2D status was classified as non-diabetic, controlled (HbA1c 6.5-7%), or uncontrolled (HbA1c >7%). Frailty was assessed using an adapted Cardiovascular Health Study phenotype, categorizing participants as non-frail, pre-frail, or frail. RBA was estimated from cortical thickness and regional brain volume data using the Brain AGE framework, which includes age-bias correction. Linear regression examined the relative contributions of age, sex, HbA1c, and frailty, and their interaction (HbA1c_Frailty_Interaction) to RBA. ANCOVA and post-hoc analyses assessed group differences, and box plots illustrated RBA by frailty (Figure 1a) and diabetes status (Figure 1b), while scatterplots visualized the interaction effects (Figure 2). RESULT: As expected, age showed no significant association (p = 0.29) with bias-corrected RBA. Being male was associated with higher RBA (β=1.023, p <0.001). Linear regression identified HbA1c and frailty as significant predictors of RBA. Higher HbA1c levels and frailty scores were associated with elevated RBA, explaining 28.1% and 5.2% of variance, respectively. ANCOVA revealed significant effects of HbA1c (F=57.79, p <0.001) and frailty (F=6.46, p = 0.0016) on RBA. Post-hoc analysis showed that frail participants had significantly higher RBA compared to non-frail and pre-frail groups (Figure 1a). Uncontrolled diabetes was associated with the highest RBA, exceeding both controlled diabetes and non-diabetic groups (Figure 1b). Furthermore, a significant interaction was observed between HbA1c and frailty (β=0.007, p <0.001), indicating that HbA1c had a deleterious effect on RBA, but not individuals with frailty (Figure 2). CONCLUSION: Frailty and poor glycemic control (HbA1c >7%) independently contribute to accelerated brain aging, as indicated by elevated RBA and their effects are modified according to one and other. Targeted strategies addressing these factors are crucial for reducing brain aging and dementia risk.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.016 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.005 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.001 | 0.000 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".