Alzheimer’s & Dementia: Translational Research & Clinical Interventions (Jul 2023)

Effects of methylphenidate on neuropsychiatric symptoms in Alzheimer's disease: Evidence from the ADMET 2 study

  • Emily D. Clark,
  • Jamie Perin,
  • Nathan Herrmann,
  • Olga Brawman‐Mintzer,
  • Krista L. Lanctôt,
  • Alan J. Lerner,
  • Jacobo Mintzer,
  • Prasad R. Padala,
  • Paul B. Rosenberg,
  • Susie Sami,
  • David M. Shade,
  • Christopher H. vanDyck,
  • Anton P. Porsteinsson,
  • for the ADMET‐2 Study Group

DOI
https://doi.org/10.1002/trc2.12403
Journal volume & issue
Vol. 9, no. 3
pp. n/a – n/a

Abstract

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Abstract INTRODUCTION Methylphenidate has been shown to improve apathy in patients with Alzheimer's disease (AD). The authors evaluated the impact of methylphenidate on neuropsychiatric symptoms (NPS) of AD, excluding apathy, using data from the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) study. METHODS A secondary analysis was conducted on data from the ADMET 2 study to determine the effect of methylphenidate on Neuropsychiatric Inventory (NPI) scores outside of apathy. Caregiver scores were compared from baseline to month 6 in 199 participants receiving methylphenidate (20 mg/day) or placebo regarding the presence or absence of individual neuropsychiatric symptoms, emergence of new symptoms, and individual domain scores. RESULTS No clinically meaningful improvement was observed in any NPI domain, excluding apathy, in participants treated with methylphenidate compared to placebo after 6 months. A statistical difference between groups was appreciated in the domains of elation/euphoria (P = 0.044) and appetite/eating disorders (P = 0.014); however, these findings were not considered significant. DISCUSSION Methylphenidate is a selective agent for symptoms of apathy in patients with AD with no meaningful impact on other NPS. Findings from this secondary analysis are considered exploratory and multiple limitations should be considered when interpreting these results, including small sample size and use of a single questionnaire. HIGHLIGHTS Methylphenidate was not associated with significant improvement on the Neuropsychiatric Inventory in domains outside of apathy. Methylphenidate did not show a statistically significant emergence of new neuropsychiatric symptoms (NPS) throughout the 6‐month treatment period compared to placebo. Methylphenidate appears to be a highly selective agent for apathy in Alzheimer's disease, potentially supporting catecholaminergic dysfunction as the driving force behind this presentation of symptoms.

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