Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2)

Krushnaa Sankhe; Shankar Tumati; Jamie Perin; Luc Rivet; Danielle Vieira; Paul B Rosenberg; Nathan Herrmann; David Shade; Alan J Lerner; Prasad R Padala; Olga Brawman-Mintzer; Christopher H van Dyck; Anton P Porsteinsson; Suzanne Craft; Allan I Levey; Jacobo Mintzer; Krista L Lanctôt

doi:10.1016/j.inpsyc.2024.100012

Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2)

Int Psychogeriatr. 2025 Mar;37(2):100012. doi: 10.1016/j.inpsyc.2024.100012. Epub 2024 Dec 4.

Authors

Krushnaa Sankhe¹, Shankar Tumati¹, Jamie Perin², Luc Rivet¹, Danielle Vieira¹, Paul B Rosenberg³, Nathan Herrmann⁴, David Shade², Alan J Lerner⁵, Prasad R Padala⁶, Olga Brawman-Mintzer⁷, Christopher H van Dyck⁸, Anton P Porsteinsson⁹, Suzanne Craft¹⁰, Allan I Levey¹¹, Jacobo Mintzer⁷, Krista L Lanctôt¹²

Affiliations

¹ Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada.
² Johns Hopkins University, Bloomberg School of Public Health, Baltimore, MD, USA.
³ Johns Hopkins University, Department of Medicine, Baltimore, MD, USA.
⁴ Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada.
⁵ University Hospitals Cleveland Medical Center, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
⁶ Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, AR, USA.
⁷ Ralph H. Johnson VA Medical Center, Medical University of South Carolina, Charleston, SC, USA.
⁸ Yale School of Medicine, New Haven, CT, USA.
⁹ University of Rochester School of Medicine and Dentistry, Rochester, NY, USA.
¹⁰ Wake Forest University, Winston-Salem, NC, USA.
¹¹ Emory Goizueta Alzheimer's Disease Research Center, Atlanta, GA, USA.
¹² Sunnybrook Research Institute, University of Toronto, Toronto, ON, Canada; Department of Psychiatry, University of Toronto, Toronto, ON, Canada. Electronic address: krista.lanctot@sunnybrook.ca.

PMID: 40086910
DOI: 10.1016/j.inpsyc.2024.100012

Abstract

Background: Previous trials have shown improvements in both apathy and cognition with methylphenidate (MPH).

Objectives: To assess whether changes in apathy correlated with changes in cognition in the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2).

Participants: Mild to moderate AD patients with clinically significant apathy randomized to MPH (20 mg/day) or placebo for 6 months.

Measurements: Apathy was measured with the Neuropsychiatric Inventory-apathy (NPI-A) domain. Cognition was measured using the Mini-Mental State Exam (MMSE), Hopkins Verbal Learning (immediate [HVLT-I], delayed [HVLT-D] recall), Digit Span (Forward [DF], Backward [DB]), Trail Making (TMT-A, TMT-B), Action Verbal Fluency (AV), Category Fluency (CF), and the Short Boston Naming Test (BNT).

Design: Linear mixed models included cognitive change scores as dependent variables and time, treatment, change in NPI-A and the interaction between treatment and change in NPI-A as independent variables, which were additionally adjusted for baseline NPI-A and cognitive scores, age, sex, level of education and presence of diabetes.

Results: 199 participants (66 % male) were included (98-MPH, 101-placebo). Among all participants, worsening CF was associated with worsening apathy (-0.15 (0.05), p = .003). In addition, change in HVLT-I was associated with the interaction between changes in apathy and treatment (-0.31 (0.07), p = 0.0000158).

Conclusion: Changes in apathy are mostly independent of cognitive changes and apathy response to MPH may be independent from cognition. These results are consistent with the view that apathy as a syndrome is related to but distinct from cognition.

Keywords: Alzheimer’s disease; Apathy; Cognition; Methylphenidate.

Publication types

Randomized Controlled Trial

MeSH terms

Aged
Aged, 80 and over
Alzheimer Disease* / drug therapy
Alzheimer Disease* / psychology
Apathy* / drug effects
Central Nervous System Stimulants* / therapeutic use
Cognition* / drug effects
Double-Blind Method
Female
Humans
Male
Mental Status and Dementia Tests
Methylphenidate* / therapeutic use
Neuropsychological Tests
Treatment Outcome

Substances

Methylphenidate
Central Nervous System Stimulants