Anticholinergic Burden in Individuals with Down Syndrome: An Examination of Risk and Clinical Implications

Background/objective: Down syndrome (DS) is characterized by premature aging, with comorbidities observed in the older population without DS, a high prevalence of multimorbidity and cognitive decline. The use of multiple medications further increases clinical complexity. The objective of this paper is to evaluate anticholinergic use and the anticholinergic burden (ACB) in a sample of persons with DS. Methods: cross-sectional retrospective study involving community-dwelling persons with DS, afferent to the DS clinics of the Fondazione Policlinico Universitario "A. Gemelli" (Rome, Italy). Individuals were assessed through a standardized clinical protocol. ACB was evaluated according to the anticholinergic cognitive burden scale, with a score ≥ 3 indicating high risk of anticholinergic side effects. Results: 337 individuals were taking ≥ 1 chronic medication, mean age was 37.7 (±14.6), 158 (43.8%) were females. 143 (39.6%) individuals took ≥ 1 medication with known anticholinergic burden, 51 (14.1%) individuals showed high risk ACB score. High risk ACB score prevalence increased with age (<18 years n = 0, 0%; 18-39 years n = 14, 8.2%; 40+ years n = 37, 22.3% p < 0.001). Polypharmacy was more prevalent among individuals with high ACB score (n = 20, 39.2% vs. n = 23, 7.4%, p < 0.001). The most prevalent drugs in individuals with high risk ACB score were antipsychotics (n = 34, 66.6% vs. n = 17, 33.3%, p < 0.001). The most prevalent comorbid condition was psychosis (n = 34, 66.6% vs. n = 16, 33.3%, p < 0.001). Discussion: individuals with DS show a high prevalence of anticholinergic drug use, increasing with age and associated with polypharmacy and psychiatric conditions. These medications are directly addressing the underlying psychiatric or neurological conditions in DS, rather than causing them. Nevertheless, these medications are often essential for managing psychiatric disorders, simultaneously increasing ACB, posing a risk of exacerbating pre-existing vulnerabilities (e.g., cognitive decline), which warrants the need for a more personalized strategy. Conclusions: A thorough assessment of drug history is mandatory in the DS population, to apply deprescribing, pharmacological switches, non-pharmacological approaches, to lower or even prevent high ACB, promoting overall a personalized and tailored approach to this population.