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Polypharmacy in patients with HIV influences perceived cognitive deficits and physical frailty through an anticholinergic and sedative burden.
“In older adults with HIV, having multiple health conditions often leads to taking more medications, which can increase the burden of drugs with anticholinergic or sedative effects,” Henry Ukachukwu Michael, BPharm, MSc, notes. “This combination can impair cognitive abilities, leading to concerns about attention, memory, and planning day-to-day activities while contributing to physical frailty. To improve cognitive function and physical function in this population, it may be essential to reduce the use of these medications.”
Michael and colleagues cross-sectionally analyzed data from the inaugural visits of 824 older people living with HIV in Canada taking part in the Positive Brain Health Now study. Eligible participants recruited from five HIV outpatient sites between 2014 and 2016 were 35 years of age or older, diagnosed with HIV for at least one year, and capable of providing informed consent in English or French. Patients with evident dementia, active CNS infections, psychotic disorders, or substance use disorders within the previous year were excluded.
The findings were published in JAIDS.
Study Parameters
The analysis included 824 patients (mean age, 53.0 years; 84.7% men). Participants had been living with HIV for a mean of 16.9 years. The median nadir CD4 T cell count was 215 cells/μL; all patients were on ART. The median number of comorbidities was one, and the mean Charlson Comorbidity Index was 5.22.
The mean cognitive ability measured by the Brief Cognitive Ability Measure (BCAM) was 56.4 out of 100, with higher scores being better. The mean perceived cognitive deficit score, assessed using the Perceived Deficits Questionnaire (PDQ), was 47.3 out of 80, with a higher score indicating more concerns. Frailty was found in 15.5% of the study population.
Overall, polypharmacy affected 19.8% of participants, with 41.4% reporting anticholinergic use with 12.9% reporting high anticholinergic burden, and 38% reporting sedative use with 11.5% high sedative burden.
Using the Wilson-Cleary (W-C) framework as the model for the study, the researchers performed cross-sectional structural equation modeling (SEM) to link comorbidity, polypharmacy, and anticholinergic and sedative burden to cognitive ability, physical frailty, and perceived cognitive deficits.
Polypharmacy’s Effects on Cognition and Frailty
After adjusting the model for age, sex, education, nadir CD4 T-cell count, HIV duration, and anxiety and depression symptoms, they found that:
- Anticholinergic burden had a direct significant negative relationship with cognitive ability (βstd=-0.21; P<0.05) and had indirect effects on perceived cognitive deficits (standardized regression estimates [βstd]=0.16, P<0.01) and frailty (βstd=0.06; P<0.05) through sedative burden.
- Sedative burden was directly associated with perceived cognitive deficits (βstd=0.18; P<0.01) and was indirectly linked with frailty through perceived cognitive deficits (βstd=0.07; P<0.05).
- Comorbidity exerted indirect effects on perceived cognitive deficits (βstd=0.02; P<0.05) and physical frailty (βstd=0.01; P<0.05) through anticholinergic and sedative burden.
- Polypharmacy exerted indirect effects on perceived cognitive deficits (βstd= 0.08, P<0.01) and physical frailty (βstd= 0.03, P<0.05) through anticholinergic and sedative burden.
Michael talked with Physician’s Weekly (PW) about this research and its potential impact on patients who live with HIV along with other medical conditions.
PW: Why was this study important to conduct?
Michael: Older adults with HIV often face complex health challenges, including multiple conditions that require numerous medications, which can have serious side effects. Understanding how these medications, especially those with anticholinergic and sedative effects, impact cognitive and physical health helps design better, safer care. By identifying how medication burden contributes to memory concerns and frailty, this study offers insight into targeted strategies, like careful medication management, to improve the quality of life of this population with unique health needs.
Did the results surprise you?
The results mostly aligned with our expectations. Previous research has shown that polypharmacy, particularly involving anticholinergic and sedative medications, can negatively impact cognitive and physical health in older adults.
However, some findings were surprising. For instance, the slight positive effect of polypharmacy suggests that, when managed well, multiple medications might support cognitive health by addressing underlying health issues. Another unexpected result was the stronger link between self-reported cognitive concerns and frailty, whereas these concerns didn’t align with cognitive test scores. This suggests that self-reported cognitive issues may better reflect difficulties in real-life activities than formal cognitive tests, underscoring the value of considering patients’ perceptions in managing frailty.
How could the results impact patients with HIV and comorbidities?
The findings may encourage routine self-reported cognitive and mental health screenings, which can capture patients’ everyday challenges and identify risks linked to frailty.
One of the study’s key insights was that anxiety and depression strongly drive adverse health outcomes, highlighting the importance of mental health monitoring. Also, the results suggest that deprescribing—careful reduction or discontinuation of unnecessary or harmful medications—may benefit older adults with HIV, particularly for anticholinergic and sedative drugs that impair cognitive and physical health. By combining these approaches, clinicians could create more personalized, safer care plans that support patients’ cognitive health, physical resilience, and overall QOL.
What questions remain unanswered?
Several questions remain. This study was cross-sectional, and future research will involve longitudinal analysis to track changes over time, refining tools to measure anticholinergic and sedative burden, and deprescribing trials to see if reducing these burdens improves outcomes. Developing integrated care models will also be essential for providing comprehensive support to people with HIV.
Is there anything else you would like to mention?
Clinicians should be aware of the cumulative impact of medications beyond just primary anticholinergics and sedatives, as some drugs indirectly affect these receptors and add to the overall burden. Managing this through deprescribing and incorporating non-pharmacological strategies, such as cognitive and physical therapies, requires a multidisciplinary approach. Collaboration among clinicians, pharmacists, nurses, physiotherapists, and psychologists can help optimize care, reduce risks, and improve patients’ QOL.
