Associations between the use of histamine‐2 receptor antagonists vs. proton pump inhibitors and cognitive decline: A stratified longitudinal study in people with and without cognitive impairment
Bibliographic record
Abstract
Abstract Background Studies suggest associations between proton pump inhibitors (PPI) and higher dementia risk compared with no use; however, several studies did not consider histamine‐2 receptor antagonists (H2RAs), the other common acid suppressant for similar indications. Comparisons between them are clinically relevant, both in older people with and without cognitive impairment due to Alzheimer’s disease (AD). Method Participants using a PPI or H2RA were selected from the National Alzheimer's Coordinating Center database from September 2005 to February 2021. Cox regressions were used to compare 5‐year conversion from normal cognition to mild cognitive impairment (MCI) or dementia, and 5‐year conversion from MCI to dementia, between PPI and H2RA users. In a propensity score matched sample of clinically diagnosed mild‐moderate AD, a linear mixed‐effects regression was used to assess PPI vs. H2RA use in rates of decline in global cognition (Clinical Dementia Rating [CDR®] Sum of Boxes; CDR‐SOB) up to 5 years. Delayed memory recall (Wechsler Memory Scale–Logical Memory test) was explored using a mixed‐effects negative binomial regression. Demographics, smoking, alcohol abuse, baseline CDR‐SOB, comorbidities, concurrent medications used, and apolipoprotein E genotype were included as covariates in Cox regressions or in propensity score. Result Cognitively normal H2RA (n=547, events=62) vs. PPI users (n=2237, events=312) did not differ in their risk for MCI or AD (Hazard Ratio; HR [95% Confidence Interval; CI] = 1.067 [0.807‐1.410]). In MCI, H2RA use (n=288, events=75) was associated with faster 5‐year dementia conversion (HR [95% CI] = 1.402 [1.085‐1.811]), compared with PPI use (n=1413, events=355). In AD, H2RA (n=212) vs. PPI (n=636) use was not associated with differential rates of decline in global cognition (B [95% CI] = ‐0.023 [‐0.324, 0.277] CDR‐SOB per year). However, H2RA use was associated with faster memory decline (Rate Ratio [95% CI] = 0.783 [0.671‐0.915]) in AD, but no associations with memory decline were found in MCI or normal cognition. Conclusion Differential associations with cognitive decline were not observed in cognitively normal older people. Among people with MCI or AD, H2RA use was associated with faster rates of conversion to dementia, or memory decline, respectively. Anti‐cholinergic burden might explain the associations.
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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 | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.002 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".