2 results
P104: Heterogeneity of Response to methylphenidate in apathetic patients in the ADMET 2 Trial
- KL Lanctôt, L Rivet, S Tumati, J Perin, D Vieira, PB Rosenberg, N Herrmann, AJ Lerner, PR Padala, O Brawman-Mintzer, CH van Dyck, A Porsteinsson, S Craft, A Levey, JE Mintzer
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 02 February 2024, pp. 125-126
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- Article
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Background:
Apathy is the most common neuropsychiatric symptom in Alzheimer’s disease (AD), however there are no approved treatments. In the recent Apathy in Dementia Methylphenidate Trial 2 (ADMET 2), methylphenidate treatment resulted in a significant reduction in apathy with a small to medium effect size. We assessed response in ADMET 2 to identify individuals likely to benefit from methylphenidate.
Methods:In ADMET 2, AD patients with clinically significant apathy were randomized to methylphenidate or placebo. Twenty-three potential predictors of treatment outcome chosen a priori for evaluation were divided into levels (e.g. anxiety present/absent). For each predictor, change in Neuropsychiatric Inventory apathy (NPI-A) due to methylphenidate for each level was estimated. Predictors with larger differences in effect (>= 2pt NPI-A) between levels were selected. Participants were then grouped into 10 subgroups by their index scores, constructed based on model-based prediction of response (NPI-A >=4).
Results:In total 177 participants (66% male, mean (SD) age 75.7 (8.0), Mini-Mental State Examination 18.9 (4.8)) had 3 month follow-up data. Six potential predictors met criteria for multivariate modelling. The median Index score was -1.33 (range: -8.35 to 6.83). Methylphenidate was more efficacious in participants with no NPI anxiety (change in NPI-A - 2.21, Standard Error (SE):0.60, p=0.0004) or agitation (-2.63, SE: 0.68, p=0.0002), and who were on cholinesterase inhibitors (ChEI) (-2.44, SE:0.62, p=0.0001), between 52-72 years of age (- 2.93, SE:1.05, p=0.007), had normal diastolic blood pressure (-2.43, SE: 1.03, p=0.02), and more functional impairment (-2.56, SE: 1.16, p=0.03) as measured by the Alzheimer’s Disease Cooperative Study Activities of Daily Living scale. After 3 months of methylphenidate, 79% of participants with a higher index score (>median) responded (>= 4pt NPI-A) and 49% of those with a lower index score responded.
Conclusions:Individuals who were less anxious or agitated, younger, on a ChEI, had normal diastolic blood pressure, and with more impaired function were more likely to benefit from methylphenidate when compared to placebo. Consistent with its potential activating effects, methylphenidate may be particularly beneficial for apathetic AD participants with lower baseline anxiety and agitation.
P105: Measuring clinically relevant change in apathy symptoms in ADMET 2
- S Tuma, N Herrmann, J Perin, PB Rosenberg, AJ Lerner, PR Padala, O Brawman-Mintzer, CH van Dyck, A Porsteinsson, S CraG, A Levey, D Shade, JE Mintzer, KL Lanctôt
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- Journal:
- International Psychogeriatrics / Volume 35 / Issue S1 / December 2023
- Published online by Cambridge University Press:
- 02 February 2024, pp. 126-127
-
- Article
-
- You have access Access
- Export citation
-
Objective:
Treatments trials for apathy in Alzheimer’s disease assess change scores on widely used assessment scales. Here, we aimed to determine whether such change scores on the Neuropsychiatric Inventory - Apathy (NPI-A) scale indicate clinically meaningful change.
Methods:Participants completing the Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) were included. Participants in this randomized trial received methylphenidate or placebo for 6- months along with a psychosocial intervention. Assessments included Clinical Global Impression of Change in apathy (CGIC-A) and the NPI-A. Participants in both groups with complete data at the six-month visit were included. CGIC-A was assessed as improved (minimal, moderate or marked), no change, or worsened (minimal, moderate or marked). For CGIC-A levels, mean and standard deviation (SD) of the change in NPI-A from baseline was calculated. Spearman correlation determined the association between change in NPI-A and CGIC-A, and Mann-Whitney U tests determined differences between the ‘no change’ group and the ‘improved’ and ‘worsened’ groups. Effect size (mean NPI-A difference between either ‘improved’ and ‘no change’/ SD of overall change) were calculated. Differences were also assessed at 3 months as a sensitivity analysis.
Results:Overall, 177 participants were included (median age: 77years, Mini Mental State Examination score: 19.3 (4.8), baseline NPI-A [mean, SD]: 7.9, 2.3), change in NPI-A: -3.7 (3.9). On the CGIC-A, 69 were improved, 82 showed no change, and 26 worsened. The Spearman correlation between NPI-A change and CGIC-A was 0.41 (p= 1x 10-8). The change in NPI-A among participants who improved was -5.3 (4.1) [W=1873, p= 3x10-4], among those who worsened was -1.2 (3.1) (W= 1426.5, p= 0.009) compared to those with no change (-3.2 [3.4]),. The NPI-A score for minimal clinical improvement was -4.5 (4.6) with a small effect size of -0.32, which was consistent at 3-months (-0.31).
Conclusion:A minimal clinically significant improvement over 3 and 6-months corresponded to a mean decline of 4.5 points on the NPI-A; however, there is considerable overlap in the NPI-A between levels of clinical impression of change.