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Development of methodology for conducting clinical trials in frontotemporal lobar degeneration
Knopman DS, Kramer JH, Boeve BF, Caselli RJ, Graff-Radford NR, Mendez MF, Miller BL, Mercaldo N.. Brain : a journal of neurology, 2008-10-01
Topic: Brain proteins, microglia and lab models
To design clinical trials for the frontotemporal lobar degenerations (FTLD), knowledge about measurement of disease progression is needed to estimate power and enable the choice of optimal outcome measures. The aim here was to conduct a multicentre, 1 year replica of a clinical trial in patients with one of four FTLD syndromes, behavioural variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), progressive logopenic aphasia (PLA) and semantic dementia (SMD). Patients with one of the four FTLD syndromes were recruited from five academic medical centres over a 2 year period. Standard operationalized diagnostic criteria were used. In addition to clinical inclusion and exclusion criteria, patients were required to exhibit focal frontal, temporal or insular brain atrophy or dysfunction by neuroimaging. Patients underwent neuropsychological, functional, behavioural, neurological and MR imaging assessment at baseline and approximately 12 months later. Potential outcome measures were examined for their rates of floor and ceiling values at baseline and end of study, their mean changes and variances. The neuropsychological tests were combined into two cognitive composites -- one for language functions and the other for executive functions. There were 107 patients who underwent baseline assessment and 78 who completed a follow-up assessment within 10-16 months. Two global measures, the FTLD-modified Clinical Dementia Rating (FTLD-modified CDR) and the Clinical Global Impression of Change (CGIC) demonstrated decline in the majority of patients. Several cognitive measures showed negligible floor or ceiling scores either at baseline or follow-up. Scores declined at follow-up in the majority of patients. The cognitive, executive and combined composites were shown to be sensitive to change across all FTLD syndromes. Patients improved at follow-up on the behavioural scales -- the Frontal Behavioural Inventory (22%) and the Neuropsychiatric Inventory (28%) -- suggesting that these instruments may not be ideal for clinical trial use. It was feasible to recruit FTLD patients in a simulated multi-centre trial. There are several candidate outcome measures -- including the FTLD-CDR and the cognitive composites -- that could be used in clinical trials across the spectrum of FTLD.
Key findings
- Two global measures, the FTLD-modified Clinical Dementia Rating (FTLD-modified CDR) and the Clinical Global Impression of Change (CGIC) demonstrated decline in the majority of patients.
- Patients improved at follow-up on the behavioural scales -- the Frontal Behavioural Inventory (22%) and the Neuropsychiatric Inventory (28%) -- suggesting that these instruments may not be ideal for clinical trial use.
Why it matters
This study tested how to run a one-year trial in people with frontotemporal lobar degeneration and found that two global measures showed decline in most patients, while two behavioural scales did not work well for trials. It is about designing future trials, not about treating, curing or preventing Alzheimer's disease.
Study details
- Participants107
- Evidence strengthLow
How this study scored 58/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Brain : a journal of neurology) |
| Journal's citation record | 4 / 4 | Brain: journal h-index 503 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2008 — within 20 year(s) of the newest study here |
| Sample size | 2 / 4 | 107 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) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 6 / 7 | Cited 445 times (OpenAlex, 2026-10-10) |
| Citations per year | 4 / 5 | 22.2 citations a year over 20 year(s) since 2008 |
| Impact for its field and year | 3 / 6 | Cited 7.1× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 3 / 6 | Cited by 26 other studies in this library |
| Still being cited | 3 / 4 | Cited 93 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Nathaniel David Mercaldo: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 3 / 3 | University of Washington: institution h-index 3,540 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 4 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 18829698) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 58 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
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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 names 8 authors; APA and Vancouver show the first six, BibTeX and the downloads carry all of them. Check the citation against the original before you use it.
APA 7th
Knopman, D. S., Kramer, J. H., Boeve, B. F., Caselli, R. J., Graff-Radford, N. R., Mendez, M. F., et al. (2008). Development of methodology for conducting clinical trials in frontotemporal lobar degeneration. Brain : a journal of neurology. https://doi.org/10.1093/brain/awn234
Vancouver
Knopman DS, Kramer JH, Boeve BF, Caselli RJ, Graff-Radford NR, Mendez MF, et al. Development of methodology for conducting clinical trials in frontotemporal lobar degeneration. Brain : a journal of neurology. 2008. doi:10.1093/brain/awn234. PMID: 18829698.
BibTeX
@article{knopman2008-18829698,
author = {Knopman, D. S. and Kramer, J. H. and Boeve, B. F. and Caselli, R. J. and Graff-Radford, N. R. and Mendez, M. F. and Miller, B. L. and Mercaldo, N.},
title = {{Development of methodology for conducting clinical trials in frontotemporal lobar degeneration}},
journal = {Brain : a journal of neurology},
year = {2008},
doi = {10.1093/brain/awn234},
pmid = {18829698},
url = {https://doi.org/10.1093/brain/awn234}
}
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