Counterfactual analysis of differential comorbidity risk factors in Alzheimer’s disease and related dementias
Bibliographic record
Abstract
Alzheimer's disease and related dementias (ADRD) is a multifactorial disease that involves several different etiologic mechanisms with various comorbidities. There is also significant heterogeneity in the prevalence of ADRD across diverse demographics groups. Association studies on such heterogeneous comorbidity risk factors are limited in their ability to determine causation. We aim to compare counterfactual treatment effects of various comorbidity in ADRD in different racial groups (African Americans and Caucasians). We used 138,026 ADRD and 1:1 matched older adults without ADRD from nationwide electronic health records, which extensively cover a large population's long medical history in breadth. We matched African Americans and Caucasians based on age, sex, and high-risk comorbidities (hypertension, diabetes, obesity, vascular disease, heart disease, and head injury) to build two comparable cohorts. We derived a Bayesian network of 100 comorbidities and selected comorbidities with potential causal effect to ADRD. We estimated the average treatment effect (ATE) of the selected comorbidities on ADRD using inverse probability of treatment weighting. Late effects of cerebrovascular disease significantly predisposed older African Americans (ATE = 0.2715) to ADRD, but not in the Caucasian counterparts; depression significantly predisposed older Caucasian counterparts (ATE = 0.1560) to ADRD, but not in the African Americans. Our extensive counterfactual analysis using a nationwide EHR discovered different comorbidities that predispose older African Americans to ADRD compared to Caucasian counterparts. Despite the noisy and incomplete nature of the real-world data, the counterfactual analysis on the comorbidity risk factors can be a valuable tool to support the risk factor exposure studies.
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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 | 0.107 | 0.179 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.007 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.002 | 0.003 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.003 | 0.003 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.004 | 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".