The Role of Anticholinergic and Sedative Burden in Frailty and Cognitive Outcomes in Middle-aged and Older Adults with HIV
Notice bibliographique
Résumé
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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Comment cette classification a été obtenuedéplier
Prédiction machine sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Le volet Gemma est une étiquette directe du modèle pour chaque travail de la base, lue sur la notice réduite au titre. Le volet Codex est un classifieur appris des 10 348 étiquettes directes de Codex et calibré sur les taux pondérés de l'échantillon; les champs sans appui suffisant ne portent aucun appel Codex. Le mode candidate est l'union des deux volets; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont pas des étiquettes humaines.
Scores du classifieur distillé par catégorie (deux têtes)
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,001 | 0,004 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,001 |
| Bibliométrie | 0,001 | 0,001 |
| Études des sciences et des technologies | 0,001 | 0,000 |
| Communication savante | 0,001 | 0,000 |
| Science ouverte | 0,000 | 0,001 |
| Intégrité de la recherche | 0,000 | 0,001 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,001 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule source (Gemma direct ou Codex distillé), pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».