Identifying the optimal combinations of modifiable dementia risk factors to target in multidomain intervention – Three-year longitudinal findings from the Canadian longitudinal study on aging
Bibliographic record
Abstract
BACKGROUND: Recent multidomain prevention trials for dementia have shifted toward more targeted approaches, focusing on specific combinations of risk factors and interventions at certain times. However, the optimal combinations of modifiable risk factors that can be targeted to maximize intervention effect remain unclear. Identifying risk factor combinations with the highest prevalence and largest effect sizes can enhance efficiency of trial design. OBJECTIVES: To identify risk factor combinations that are both highly prevalent and have the most detrimental effect on cognition, and to assess their interaction effect and synergism. DESIGN: Longitudinal analysis of Canadian Longitudinal Study on Aging (CLSA). SETTING: Community. PARTICIPANTS: 30,097 adults aged 45 to 85 at baseline MEASUREMENTS: The five most prevalent dyad, triad, and tetrad combinations of 12 modifiable risk factors were identified. Cognition was assessed with a composite Z-score from a neuropsychological test battery. Linear mixed effect models were used to examine the association between the identified combinations and 3-year cognitive changes. Interaction was assessed on additive scale, and synergism was explored. RESULTS: The combinations that were both highly prevalent and had the most detrimental effect on global cognition were: hearing loss and physical inactivity for the dyad (mean difference in change score = -0.07 SD; 95 % CI: -0.09 to -0.06; p < 0.001; effect size = -0.28), hearing loss, physical inactivity, and hypertension for the triad (mean difference in change score = -0.07; 95 % CI: -0.09 to -0.06; p < 0.001; effect size = -0.28), and hearing loss, physical inactivity, hypertension, and sleep disturbance for the tetrad (mean difference in change score = -0.05; 95 % CI: -0.07 to -0.03; p < 0.001; effect size = -0.20). Similar patterns were observed for memory and executive function. A significant synergistic interaction was observed between hearing loss and physical inactivity for global cognition (p = 0.005). CONCLUSIONS: The combined effect of multiple risk factors varied by its combinations. The combination of hearing loss and physical inactivity offers a greater potential benefit than other dyad combinations. Hypertension and sleep disturbance can be further included for triad and tetrad combinations. Auditory health and exercise should be prioritized for multidomain interventions.
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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 | 0.019 | 0.020 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.004 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.002 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| 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".