Longitudinal diffusion tensor imaging in frontotemporal dementia
Open accessAbstract
Objective: Novel biomarkers for monitoring progression in neurodegenerative conditions are needed. Measurement of microstructural changes in white matter (WM) using diffusion tensor imaging (DTI) may be a useful outcome measure. Here we report trajectories of WM change using serial DTI in a cohort with behavioral variant frontotemporal dementia (bvFTD). Methods: Twenty‐three patients with bvFTD (12 having genetic mutations), and 18 age‐matched control participants were assessed using DTI and neuropsychological batteries at baseline and ∼1.3 years later. Baseline and follow‐up DTI scans were registered using a groupwise approach. Annualized rates of change for DTI metrics, neuropsychological measures, and whole brain volume were calculated. DTI metric performances were compared, and sample sizes for potential clinical trials were calculated. Results: In the bvFTD group as a whole, rates of change in fractional anisotropy (FA) and mean diffusivity (MD) within the right paracallosal cingulum were greatest (FA: −6.8%/yr, p < 0.001; MD: 2.9%/yr, p = 0.01). MAPT carriers had the greatest change within left uncinate fasciculus (FA: −7.9%/yr, p < 0.001; MD: 10.9%/yr, p < 0.001); sporadic bvFTD and C9ORF72 carriers had the greatest change within right paracallosal cingulum (sporadic bvFTD, FA: −6.7%/yr, p < 0.001; MD: 3.8%/yr, p = 0.001; C9ORF72 , FA: −6.8%/yr, p = 0.004). Sample size estimates using FA change were substantially lower than neuropsychological or whole brain measures of change. Interpretation: Serial DTI scans may be useful for measuring disease progression in bvFTD, with particular trajectories of WM damage emerging. Sample size calculations suggest that longitudinal DTI may be a useful biomarker in future clinical trials. ANN NEUROL 2015;77:33–46
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DTI studies concluded sensitive detection of white matter changes in an early phase of bvFTD over varying follow-up time (0.5 to 2.5 years).
“A relatively large amount of studies on diffusion tensor imaging (DTI), visualizing the microstructure of white matter (WM) tracts, concluded sensitive detection of WM changes in an early phase of the disease, over varying follow-up time (0.5 to 2.5 years)”
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 Mahoney et al., 2015
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- Authors
- Mahoney, C. J., Simpson, I. J. A., Nicholas, J. M., Fletcher, P. D., Downey, L. E., Golden, H. L., Clark, C. N., Schmitz, N., Rohrer, J. D., Schott, J. M., Zhang, H., Ourselin, S., Warren, J. D., & Fox, N. C.
- Affiliations
- UCL Queen Square Institute of Neurology (GB)
- London School of Hygiene & Tropical Medicine (GB)
- University College London (GB)
- Dementia Research Centre UCL Institute of Neurology, University College London London United Kingdom
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2014-11-17
- Volume
- 77
- Issue
- 1
- Pages
- 33-46
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC4305215
- OpenAlex
- W1556842271
- Cited by
- 101
- References
- 42
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 2 · 2023: 8 · 2022: 3 · 2021: 13 · 2020: 11 · 2019: 15 · 2018: 10 · 2017: 9 · 2016: 9 · 2015: 5 · 2014: 1
- FWCI
- 6.10
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- St George's Online Research Archive (St George's University of London) (acceptedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Sussex Research Online (University of Sussex) (submittedVersion, cc-by)
- UCL Discovery (University College London) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- Medical Research Council (G0801306)
- Wellcome Trust (091673/Z/10/Z)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Neurology › Amyotrophic Lateral Sclerosis Research
- Keywords
- behavioral variant frontotemporal dementia, white matter microstructure, fractional anisotropy, mean diffusivity, disease progression biomarkers, uncinate fasciculus, genetic frontotemporal dementia, sample size determination, clinical trial outcome measures
- MeSH terms
- Aged, Brain, Cognition Disorders, Female, Humans, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Sensitivity and Specificity, Case-Control Studies, Anisotropy, Disease Progression, Diffusion Tensor Imaging, Frontotemporal Dementia, White Matter
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