Brain and ventricular volumetric changes in frontotemporal lobar degeneration over 1 year
Open accessAbstract
BACKGROUND: Measurement of volumetric changes with MR might be a useful surrogate endpoint for clinical trials in frontotemporal lobar degeneration (FTLD). Because there is only limited longitudinal imaging data currently available, we measured the rate of change over 1 year of whole brain volume (WBV) and ventricular volume (VV) in patients with FTLD. METHODS: Subjects with an FTLD cognitive syndrome were recruited from five centers using standard clinical diagnostic criteria for behavioral variant frontotemporal dementia (bvFTD), progressive nonfluent aphasia (PNFA), semantic dementia (SMD), and progressive logopenic aphasia. Structural brain imaging, using three-dimensional T1-weighted sequences at 1.5 teslas, and cognitive, behavioral, and functional assessments were performed at baseline and approximately 1 year later. The boundary shift integral algorithm was used to determine change in WBV and VV. RESULTS: There were 76 patients (mean age 64 years; 41 men and 35 women) who had usable baseline and annual scans. The group-wise annualized change was -1.62% (SD 1.03, range +0.69 to -3.6) for WBV and 11.6% (SD 5.9, range -1.3 to 23.9) for VV. Rates of change were similar among bvFTD, PNFA, and SMD groups. Longitudinal changes in WBV and VV were correlated with decline on clinical global and cognitive measures. CONCLUSIONS: Multicenter, serial measurements of whole brain volume (WBV) and ventricular volume (VV) from magnetic resonance scans were feasible in patients with frontotemporal lobar degeneration (FTLD). Using WBV or VV as outcome measures would require recruiting (at 80% power) 139 or 55 subjects per group to detect a small (25%) or medium-sized (40%) effect in a randomized, placebo-controlled trial of a putative agent for FTLD.
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Whole brain atrophy and ventricular volume increased in both genetic and sporadic bvFTD, in several one-year follow-up studies and one six-month follow-up.
“Whole brain atrophy and ventricular volume increased in both genetic and sporadic bvFTD, in several one-year follow-up studies and one six-month follow-up (Knopman et al., 2009; Gordon et al., 2010; Lam et al., 2014; Floeter et al., 2016; Sheelakumari et al., 2018; Manera et al., 2019; Gordon et al., 2021).”
From The pursuit for markers of disease progression in behavioral variant frontotemporal dementia: a scoping review to optimize outcome measures for clinical trials (2024) · cites this paper as Knopman et al., 2009
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- Authors
- Knopman, D. S., Jack, C. R., Kramer, J. H., Boeve, B. F., Caselli, R. J., Graff-Radford, N. R., Mendez, M. F., Miller, B. L., & Mercaldo, N. D.
- Affiliations
- Mayo Clinic (US)
- From the Mayo Clinic (D.S.K., C.R.J., B.F.B.), Rochester, MN; University of California (J.H.K.), San Francisco, CA; Mayo Clinic (R.J.C.), Scottsdale, AZ; Mayo Clinic (N.R.G.-R.), Jacksonville, FL; University of California (M.F.M.), Los Angeles, CA; University of California (B.L.M.), San Francisco, CA; and National Alzheimer's Coordinating Center (N.D.M.), Seattle, WA.
- ORCID
- Venue
- Neurology
- Published
- 2009-05-26
- Volume
- 72
- Issue
- 21
- Pages
- 1843-1849
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC2690986
- OpenAlex
- W2061821269
- Cited by
- 85
- References
- 27
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 5 · 2020: 4 · 2019: 7 · 2018: 7 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 7 · 2012: 9
- FWCI
- 5.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Pfizer
- National Institutes of Health (AG016976, AG023501, AG11378, U01 AG24904, AG19610, R01 AG11378, AG19724)
- University of California, San Francisco
- Pfizer Pharmaceuticals
- National Institute on Aging (R01AG11378, AG 016976, AG-016570, P30-AG-19610, P50‐AG16574, U01AG06786, AG 16574, U01AG016976, AG-19610, P50AG016570, U01AG006786, U01AG24904, AG-19724, R01AG011378, AG-11378, AG023501, P30AG019610, R01AG023195, P01-AG19724, P01AG019724, P50AG023501, P50AG016574)
- National Institute of Neurological Disorders and Stroke
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- frontotemporal lobar degeneration, total brain volume, ventricular volume, volume change, surrogate endpoints, behavioral variant frontotemporal dementia, progressive nonfluent aphasia, semantic dementia, longitudinal MRI, clinical trial design, cognitive decline
- MeSH terms
- Aged, Algorithms, Aphasia, Brain, Cerebral Ventricles, Clinical Trials as Topic, Dementia, Female, Follow-Up Studies, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Severity of Illness Index, Linear Models, Aphasia, Primary Progressive
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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