The Role of Anticholinergic and Sedative Burden in Frailty and Cognitive Outcomes in Middle-aged and Older Adults with HIV
Bibliographic record
Abstract
Antiretroviral therapy has significantly increased the life expectancy of individuals living with HIV. However, aging with HIV presents unique challenges, including managing comorbidities. Anticholinergic and sedative medications, commonly used to manage these comorbidities, have been implicated in cognitive impairment and physical frailty. This thesis aims to estimate the extent to which anticholinergic and sedative burden is associated with physical frailty and cognitive outcomes in middle-aged and older adults living with HIV in Canada.The first manuscript aimed to estimate the extent to which anticholinergic and sedative burden is associated with physical frailty in middle-aged and older adults with HIV. This cross-sectional analysis examined data from the inaugural visit of 824 adults enrolled in the Positive Brain Health Now (BHN) study. Anticholinergic medications were identified using the Anticholinergic Cognitive Burden (ACB) Scale, Anticholinergic Risk Scale (ARS), Anticholinergic Drug Scale (ADS), and the Anticholinergic and Sedative Burden Catalog (ACSBC). Sedatives were identified using the Sedative Load Model (SLM) and the ACSBC. Physical frailty was assessed using a modified Fried Frailty Phenotype based on self-report items. Multivariable logistic regression models estimated odds ratios (ORs) with 95% Confidence Intervals (CI). The findings revealed that a high anticholinergic burden was associated with physical frailty using various anticholinergic burden scoring methods (OR range: 2.12-2.74; 95% CI range: 1.03-6.19). Similarly, a high sedative burden was also associated with increased odds of frailty (OR: 1.94 to 2.18; 95% CI range: 1.01-4.34).The second manuscript estimated the extent to which anticholinergic and sedative burden is associated with cognitive ability and perceived cognitive deficits in the same cohort. Cognitive ability was measured using the Brief Cognitive Ability Measure (B-CAM), and perceived cognitive deficits were measured using the Perceived Deficits Questionnaire. Multivariable Ordinary Least Squares and quantile regression were utilized to estimate average and distribution-specific effects, respectively. A high anticholinergic burden identified using the ACSBC-Ach was linked to worse cognitive ability (β = -3.81; 95% CI: -7.16, -0.46) and increased perceived cognitive deficits (β = 3.89; 95% CI: 1.08, 6.71). Using three or more sedatives identified using the SLM was associated with increased perceived cognitive deficits (β = 4.35; 95% CI: 0.92-7.78). More pronounced negative associations were observed among participants with lower cognitive ability and greater cognitive difficulties.The third manuscript employs Structural Equation Modeling (SEM) to disentangle the complex interactions between comorbidities, polypharmacy, and medication burdens on cognitive ability, perceived cognitive deficits, and physical frailty. The SEM approach revealed that anticholinergic and sedative burdens mediate the effects of comorbidities and polypharmacy on cognitive and frailty outcomes. Anticholinergic burden had a direct negative relationship with cognitive ability (βstd = -0.21, p<0.05) and an indirect effect on perceived cognitive deficits (βstd = 0.16, p<0.01) and frailty (βstd = 0.06, p<0.01) through sedative burden. Sedative burden was directly associated with perceived cognitive deficits (βstd = 0.18, p<0.01) and indirectly with frailty through perceived cognitive deficits (βstd = 0.07, p<0.01). In conclusion, this thesis highlights the significant impact of anticholinergic and sedative burden on physical frailty and cognitive outcomes in people aging with HIV. These findings contribute valuable evidence towards developing medication management and deprescribing strategies to reduce frailty and cognitive risks. Future research should focus on longitudinal studies and interventions to confirm these findings and explore the underlying mechanisms driving these 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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 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".