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

Sankhe K, Tumati S, Perin J, Rivet L, Vieira D, Rosenberg PB, Herrmann N, Shade D, Lerner AJ, Padala PR, Brawman-Mintzer O, van Dyck CH, Porsteinsson AP, Craft S, Levey AI, Mintzer J, Lanctôt KL. Correlation between changes in apathy and cognition in Alzheimer's disease associated apathy: Analysis of the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2). International psychogeriatrics. 2025 Mar 1; 37(2):100012.

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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.