Effects of anticholinergic medication use on brain integrity in persons living with HIV and persons without HIV

Abstract

Objective: This study examined relationships between anticholinergic medication burden and brain integrity in people living with HIV (PLWH) and people without HIV (HIV−). Methods: Neuropsychological performance z-scores (learning, retention, executive function, motor/psychomotor speed, language domains, and global cognition), and neuroimaging measures (brain volumetrics and white matter fractional anisotropy) were analyzed in PLWH (n = 209) and HIV− (n = 95) grouped according to the Anticholinergic Cognitive Burden (ACB) scale (0 = no burden, 1–3 = low burden, >3 = high burden). Neuropsychological performance and neuroimaging outcomes were compared between HIV− and PLWH with high anticholinergic burden. Within a cohort of PLWH (n = 90), longitudinal change in ACB score over ∼2 years was correlated to the rate of change per month of study interval in neuropsychological performance and neuroimaging measures. Results: A higher number of anticholinergic medications and ACB was observed in PLWH compared with HIV− (P < 0.05). A higher ACB was associated with worse motor/psychomotor performance, smaller occipital lobe, putamen, subcortical gray matter and total gray matter volumes in HIV−; and poorer executive function, retention and global cognition, smaller brain volumes (frontal, parietal and temporal lobes, hippocampus, amygdala, cortex, subcortical gray matter and total gray matter), and reduced fractional anisotropy (posterior corpus callosum, perforant pathway) in PLWH. PLWH with high anticholinergic burden performed worse on tests of learning and executive function compared with HIV− with high anticholinergic burden. Longitudinally, PLWH who reduced their ACB over time had better neuropsychological performance and neuroimaging measures. Conclusion: Anticholinergic medications were associated with worse neuropsychological performance and reduced structural brain integrity, and these effects were more widespread in PLWH. Use of anticholinergic medications should be carefully monitored in older adults with deprescription considered whenever possible.

Medication burden and clustering in people living with HIV undergoing therapeutic drug monitoring

“…19 In this setting anticholinergic burden is an emerging issue in ageing HIV-positive participants and may be studied in detail in the setting of clustered PP. 20,21 Although exploratory, the analysis of clusters including ARVs classes showed different patterns for INSTI/NNRTIs (co-administered with the major group of concomitant medications observed in the general analysis) and PIs: the latter seemed to group with drugs used to treat hypertension and cardiovascular disorders. This is an unexpected finding due to the adverse metabolic effect and the potential for cardiovascular toxicity that have been described with certain PIs.…”

“…Clustering of this drug class with CNS‐active molecules may also prioritize this group of patients for medication review 19 . In this setting anticholinergic burden is an emerging issue in ageing HIV‐positive participants and may be studied in detail in the setting of clustered PP 20,21 …”

Polypharmacy Is Associated With Falls in Women With and Without HIV

“…37 Indeed, we have previously shown that some specific medications are associated with increased falls among middle-aged and older PWH. 22 Many NCAE medications are frequently prescribed to PWH, 29,38 who are more also likely to have NCI than their seronegative counterparts. 39,40 NCAE medications may therefore have an even greater effect on falls risk among older PWH who are already at high risk for falls.…”

Anticholinergic and Sedative Medications Are Associated With Neurocognitive Performance of Well Treated People With Human Immunodeficiency Virus

“…Medications with anticholinergic (ACH) activity have been associated with dementia in the elderly general population [ 20 ]. Furthermore, a high ACH burden has been associated with smaller brain volumes and poorer whiter matter structural integrity, and these effects were shown to be more widespread in PWH compared to the general population suggesting that PWH may be more susceptible to ACH medications neurocognitive effects [ 21 ]. Many commonly used medications by PWH have ACH activity (eg, antidepressants, antipsychotics, antihistamines).…”

“…Many commonly used medications by PWH have ACH activity (eg, antidepressants, antipsychotics, antihistamines). It was recently reported that use of ACH medication is higher in PWH compared to the general population [ 21 ] and that polypharmacy is associated with an increased risk of ACH medication use [ 22 ]. Anticholinergic medication use is a potentially modifiable risk factor that should be evaluated in this high-risk population.…”