While schizophrenia is characterized by generalized cognitive deficits across the course of illness (1-3), emerging evidence suggests many medications can also negatively impact cognitive performance (4). We recently reported that anticholinergic medication burden (ACMB) accumulated from multiple medication classes—antipsychotics, antidepres-sants, and traditional anticholinergics (e.g., diphenhydra-mine, benztropine, trihexyphenidyl)—is associated with deficits across nearly all cognitive measures in individuals with schizophrenia in the cross-sectional, multi-site Consortium on the Genetics of Schizophrenia study (COGS-2) (5). These data align with other studies describing the impact of ACMB on outcomes in schizophrenia (6). While these findings are also consistent with results from studies of healthy older adults reporting increased cognitive impairment and elevated dementia risk with greater ACMB exposure, it is difficult to disambiguate the degree to which cognitive impairment results from residual symptoms or is driven by factors like cumulative ACMB in cross-sectional studies of medicated schizophrenia patients (7-10). Indeed, pharmacotherapy in addition to psychotherapy and psy-chosocial rehabilitation, is an essential component of comprehensive schizophrenia treatment and can help enhance cognitive health through symptom reduction. However, identifying objective measures of ACMB-associated cognitive impairment would significantly enhance treatment selection in routine clinical care, and ultimately improve outcomes for those living with schizophrenia.
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