This $775,706 R01 grant awarded by the National Institute of Mental Health (NIMH) under the Mental Health Research Grants (CFDA 93.242) program will support a prospective study on the neural mechanisms and impacts of anticholinergic burden reduction in mid- to late-life patients with schizophrenia spectrum disorders (SSD). The University of Pittsburgh, the prime recipient, will conduct a randomized controlled trial over 6 months involving 80 SSD patients aged 40-70 to evaluate the effects of anticholinergic medication deprescription on cognition, neural function, and quality of life. Additionally, the study will include a sample of 25 healthy volunteers to establish normative baselines. The research aims to yield new insights into the neurobiological underpinnings of cognitive impairment in mid- to late-life SSD and identify potential treatment targets to improve functional outcomes in this patient population.