Apoptosis protein markers in comorbid type 2 diabetes mellitus and depression; mediators of vascular contributions to cognitive impairment
Bibliographic record
Abstract
Abstract Background Cerebrovascular disease and apoptosis are independently associated with an increased risk of dementia, for which depression and type 2 diabetes mellitus (T2DM) are risk factors. This study investigated whether the association between concentrations of apoptosis‐related proteins and cerebrovascular MRI markers differ by T2DM and depression status. Method We used a cross‐sectional cohort from the UK Biobank participants and stratified by: neither T2DM nor depression; depression only; T2DM only; T2DM with depression. Depression was accessed from ICD‐10 records or a physician diagnosis of major depression. T2DM was ascertained as ICD‐10 status, physician diagnosis of T2DM, glycated hemoglobin>=48mmol/mol, or based on use of an antidiabetic medication. Concentrations of apoptosis‐related proteins (B‐cell lymphoma‐2 [BCL‐2]; BCL‐2‐associated X protein [BAX]; caspase‐3) were quantified from peripheral blood plasma by antibody‐based Olink Explore 3072 Proximity Extension Assay. White matter fractional anisotropy (FA) and mean diffusivity (MD) were quantified from diffusion tensor images. White matter hyperintensity (WMH) volumes were quantified from T2‐weighted fluid‐attenuated inversion recovery images at 3T. Linear regression models were used to evaluate associations between apoptosis protein concentrations and vascular imaging outcomes across the strata and controlling for age, sex, ethnicity, body mass index, total cholesterol, hypertension, and total intracranial volume. Result 1309 were included in the study ( N = 1018 with neither T2DM nor depression (52% female, age=53.5±7.6 years), N = 102 with depression only (68% female, age=54.1±7.8 years), N = 161 with T2DM only (36% female, age=55.5±6.8 years), N = 28 with both T2DM and depression (50% female, age=53.4±8.2 years). In T2DM and depression, higher concentrations of BAX were correlated with lower FA (β=‐0.086, 95% CI=[‐0.045,‐0.011]), higher MD (β=0.066, 95% CI=[3.29×10 −6 , 3.41×10 −5 ]) and greater WMH volumes (β=0.082, 95% CI=[0.002, 0.009); higher BAX‐to‐BCL2 ratio was correlated with lower FA (β=‐0.067, 95% CI=[‐0.041,‐0.004]) and higher WMH volumes (β=0.064, 95% CI=[0.082,0.009]); and higher caspase‐3 concentrations were correlated with lower FA (β=‐0.072, 95% CI=[‐0.039,‐0.006]), higher MD (β=0.057, 95% CI=[1.11×10 −6 , 3.04×10 −5 ]) and greater WMH volumes (β=0.077, 95% CI=[0.002,0.009]) (all, p <.05). Conclusion These findings suggest that among individuals with T2DM and depression, elevated peripheral blood apoptosis markers are associated with cerebral microvascular complications, pointing to unique pathophysiological elements underlying mood and metabolic comorbidity.
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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 | 0.000 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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".