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Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial
Mintzer J, Lanctôt KL, Scherer RW, Rosenberg PB, Herrmann N, van Dyck CH, Padala PR, Brawman-Mintzer O et al.. JAMA neurology, 2021-11-01
Topic: Amyloid, tau and blood-test diagnosis
Importance Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality. Objective To measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease. Results Of 200 participants, 99 were assigned to methylphenidate and 101 to placebo. A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, -1.25; 95% CI, -2.03 to -0.47; P = .002). The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01). At 6 months, the odds ratio of having an improved rating on the Alzheimer's Disease Cooperative Study Clinical Global Impression of Change for methylphenidate compared with placebo was 1.90 (95% CI, 0.95-3.84; P = .07). Cognitive measures and quality of life were not significantly different between groups. No significant differences in the safety profile were noted between treatment groups.
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APA 7th
Mintzer, J., Lanctôt, K. L., Scherer, R. W., Rosenberg, P. B., Herrmann, N., van Dyck, C. H., et al. (2021). Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA neurology. https://doi.org/10.1001/jamaneurol.2021.3356
Vancouver
Mintzer J, Lanctôt KL, Scherer RW, Rosenberg PB, Herrmann N, van Dyck CH, et al. Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial. JAMA neurology. 2021. doi:10.1001/jamaneurol.2021.3356. PMID: 34570180.
BibTeX
@article{mintzer2021-34570180,
author = {Mintzer, J. and Lanctôt, K. L. and Scherer, R. W. and Rosenberg, P. B. and Herrmann, N. and van Dyck, C. H. and Padala, P. R. and Brawman-Mintzer, O. and others},
title = {{Effect of Methylphenidate on Apathy in Patients With Alzheimer Disease: The ADMET 2 Randomized Clinical Trial}},
journal = {JAMA neurology},
year = {2021},
doi = {10.1001/jamaneurol.2021.3356},
pmid = {34570180},
url = {https://doi.org/10.1001/jamaneurol.2021.3356}
}
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Key findings
- Importance Apathy, characterized by diminished will or initiative and one of the most prevalent neuropsychiatric symptoms in individuals with Alzheimer disease, is associated with significant caregiver burden, excess disability, increased medical costs, and mortality.
- Objective To measure whether methylphenidate compared with placebo decreases the severity of apathy in individuals with Alzheimer disease.
- Results Of 200 participants, 99 were assigned to methylphenidate and 101 to placebo.
- A larger decrease was found from baseline to 6 months in the NPI apathy score in those receiving methylphenidate compared with placebo (mean difference, -1.25; 95% CI, -2.03 to -0.47; P = .002).
- The largest decrease in the NPI apathy score was observed in the first 100 days, with a significant hazard ratio for the proportion of participants with no apathy symptoms receiving methylphenidate compared with placebo (hazard ratio, 2.16; 95% CI, 1.19-3.91; P = .01).
Why it matters
In this trial of 200 patients with Alzheimer disease, methylphenidate produced a larger decrease in apathy scores than placebo over 6 months, with no significant differences in cognitive measures, quality of life, or safety profile between groups. This supports methylphenidate for treating apathy as a symptom, not for curing or preventing Alzheimer's disease.
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Study details
- Study designlongitudinal study
- Participants200
- Evidence strengthHigh
How this study scored 73/100
Published in a leading specialty journal, and it is a randomized controlled trial. Scored zero for effect reported because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 70 of the 96 points we could judge it on, which is 73 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (JAMA neurology) |
| Journal's citation record | 2 / 4 | JAMA Neurology: journal h-index 235 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomized controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 3 / 5 | 2021 — within 6 year(s) of the newest study here |
| Sample size | 2 / 4 | 200 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 1 / 2 | Randomized (as stated in the record) |
| Times cited | 5 / 7 | Cited 117 times (OpenAlex, 2026-10-10) |
| Citations per year | 3 / 5 | 16.7 citations a year over 7 year(s) since 2021 |
| Impact for its field and year | 4 / 6 | Cited 12.5× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 6 other studies in this library |
| Still being cited | 3 / 4 | Cited 72 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | OpenAlex's profile for last-listed author Prakash Kishor Babani holds only 2 work(s), too few to judge a track record — left out of this score |
| Institution's track record | 2 / 3 | Johns Hopkins University: institution h-index 2,306 (OpenAlex) |
| Multicenter collaboration | 3 / 3 | OpenAlex lists 15 institution(s) in 2 countries |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 34570180) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 70 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 70 of the 96 points we could judge it on is 73 out of 100. |
| Total | 73 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1001/jamaneurol.2021.3356
- PubMed: 34570180
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
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