Objective: Cholinesterase inhibitors (CEI) are prescribed for dementia to maintain or improve memory. Selective serotonin reuptake inhibitors (SSRI) are also recognized as first-line agents for psychiatric symptoms seen in dementia. What proportion of outpatients actually respond to these drugs is still unclear. Our objective was to investigate the proportion of responders to these medications in a clinical outpatient setting. Methods: We used the Johns Hopkins Electronic Medical Record System to identify patients with dementia who were prescribed a CEI or SSRI for the first time between 2010 and 2021. Treatment effects were assessed through free-text entries in clinical notes documented by clinicians. Responses were scored using a simple three-point Likert scale named the NOte-based evaluation method for Treatment Efficacy (NOTE) in addition to the CIBIC-plus, a seven-point Likert scale that has been proven in clinical trials. To validate NOTE, the relationship between NOTE and CIBIC-plus, and between NOTE and change in MMSE (Mini-Mental State examination) before and after medication were examined. Inter-rater reliability was evaluated by Krippendorff's alpha. The proportion of responders were calculated. Results: The NOTE showed excellent inter-rater reliability and correlated well with CIBIC-plus and change in MMSE scores. Out of 115 CEI cases, 27.0% reported improvement and 34.8% reported stable symptoms in cognition; out of 225 SSRI cases, 69.3% reported improvement in neuropsychiatric symptoms. Adverse events were reported in 43.5% of CEI and 23.6% of SSRI cases. Conclusion: NOTE showed high validity in measuring the pharmacotherapy effects based on unstructured clinical entries. Among outpatients, more than a quarter reported improvement and more than a third reported stable symptoms with CEI, which are consistent with what was reported in clinical trials for Alzheimer's disease. Similarly, two-thirds responded to SSRI, which is also consistent with results reported in clinical trials of agitation or depression associated with Alzheimer's disease.

KOi is a consultant for "AnatomyWorks" and "Corporate-M." This arrangement is being managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.

This study is supported by grants from the National Institutes of Health [R21AG070404]; and the Richman Family Precision Medicine Center of Excellence, Baltimore, MD [Venture Discovery Fund].

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The study was conducted under the oversight of a Johns Hopkins institutional review board (IRB00228485 and IRB00268645). This board follows the principles of the Declaration of Helsinki. Informed consent was waived because the source of the data was the Johns Hopkins Electronic Medical Record, which contains patient information collected as part of routine medical care. It would have been impossible to collect this information on such a large number of patients without unduly interrupting the clinical workflow of data capture without a waiver. All downstream analyses using this resource were done using Health Insurance Portability and Accountability Act (HIPAA) defined limited datasets.

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