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Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials
Atri A, O'Brien JL, Sreenivasan A, Rastegar S, Salisbury S, DeLuca AN, O'Keefe KM, LaViolette PS et al.. Archives of neurology, 2011-05-01
Topic: Amyloid, tau and blood-test diagnosis
Objective To examine the feasibility and test-retest reliability of encoding-task functional magnetic resonance imaging (fMRI) in mild Alzheimer disease (AD). Design Randomized, double-blind, placebo-controlled study. Setting Memory clinical trials unit. Participants We studied 12 patients with mild AD (mean [SEM] Mini-Mental State Examination score, 24.0 [0.7]; mean Clinical Dementia Rating score, 1.0) who had been taking donepezil hydrochloride for more than 6 months from the placebo arm of a larger 24-week study (n = 24, 4 scans on weeks 0, 6, 12, and 24, respectively). Interventions Placebo and 3 face-name, paired-associate encoding, block-design blood oxygenation level-dependent fMRI scans in 12 weeks. Main outcome measures We performed whole-brain t maps (P Results Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data). Whole-brain maps were stable. Right and left hippocampal regions-of-interest intraclass correlation coefficients were 0.59 to 0.87 and 0.67 to 0.74, respectively. To detect 25.0% to 50.0% changes in week-0 to week-12 hippocampal activity using left-right extent or right magnitude with 80.0% power (2-sided α = .05) requires 14 to 51 patients. Using left magnitude requires 125 patients because of relatively small signal to variance ratios. Conclusions Encoding-task fMRI was successfully implemented in a single-site, 24-week, AD randomized controlled trial. Week 0 to 12 whole-brain t maps were stable, and test-retest reliability of hippocampal fMRI measures ranged from moderate to substantial. Right hippocampal magnitude may be the most promising of these candidate measures in a leveraged context. These initial estimates of test-retest reliability and power justify evaluation of encoding-task fMRI as a potential biomarker for signal of effect in exploratory and proof-of-concept trials in mild AD. Validation of these results with larger sample sizes and assessment in multisite studies is warranted.
Key findings
- Main outcome measures We performed whole-brain t maps (P Results Task tolerability and data yield were high (95 of 96 scans yielded favorable-quality data).
- Validation of these results with larger sample sizes and assessment in multisite studies is warranted.
Why it matters
This study found that memory task functional MRI was feasible and had good test-retest reliability in people with mild Alzheimer disease, though larger and multisite studies are needed. It is about a brain imaging method for use in trials, not about treating, curing or preventing the disease.
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Study details
- Study designrandomized controlled trial
- Participants24
- Effect size25.0% to 50.0%; 80.0%
- Evidence strengthHigh
How this study scored 64/100
Published in a peer-reviewed journal, and it is a randomised controlled trial.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Archives of neurology) |
| Journal's citation record | 3 / 4 | Archives of Neurology: journal h-index 353 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised 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 | 1 / 5 | 2011 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 24 participants |
| Effect reported | 2 / 3 | Effect reported as a number, without an interval or test |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 4 / 7 | Cited 40 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 2.4 citations a year over 17 year(s) since 2011 |
| Impact for its field and year | 2 / 6 | Cited 3.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 1 / 4 | Cited 5 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Reisa Anne Sperling: h-index 157 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | Harvard University: institution h-index 3,235 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 5 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 21555634) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 64 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Atri, A., O'Brien, J. L., Sreenivasan, A., Rastegar, S., Salisbury, S., DeLuca, A. N., et al. (2011). Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials. Archives of neurology. https://doi.org/10.1001/archneurol.2011.94
Vancouver
Atri A, O'Brien JL, Sreenivasan A, Rastegar S, Salisbury S, DeLuca AN, et al. Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials. Archives of neurology. 2011. doi:10.1001/archneurol.2011.94. PMID: 21555634.
BibTeX
@article{atri2011-21555634,
author = {Atri, A. and O'Brien, J. L. and Sreenivasan, A. and Rastegar, S. and Salisbury, S. and DeLuca, A. N. and O'Keefe, K. M. and LaViolette, P. S. and others},
title = {{Test-retest reliability of memory task functional magnetic resonance imaging in Alzheimer disease clinical trials}},
journal = {Archives of neurology},
year = {2011},
doi = {10.1001/archneurol.2011.94},
pmid = {21555634},
url = {https://doi.org/10.1001/archneurol.2011.94}
}
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