Longitudinal structural and metabolic changes in frontotemporal dementia
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Abstract
Objective To compare the sensitivity of structural MRI and 18F-fludeoxyglucose PET (18FDG-PET) to detect longitudinal changes in frontotemporal dementia (FTD).
Methods Thirty patients with behavioral variant FTD (bvFTD), 7 with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA), 16 with semantic variant primary progressive aphasia (svPPA), and 43 cognitively normal controls underwent 2–4 MRI and 18FDG-PET scans (total scans/visit = 270) as part of the Frontotemporal Lobar Degeneration Neuroimaging Initiative study. Linear mixed-effects models were carried out voxel-wise and in regions of interest to identify areas showing decreased volume or metabolism over time in patients as compared to controls.
Results At baseline, patients with bvFTD showed bilateral temporal, dorsolateral, and medial prefrontal atrophy/hypometabolism that extended with time into adjacent structures and parietal lobe. In nfvPPA, baseline atrophy/hypometabolism in supplementary motor cortex extended with time into left greater than right precentral, dorsolateral, and dorsomedial prefrontal cortex. In svPPA, baseline atrophy/hypometabolism encompassed the anterior temporal and medial prefrontal cortex and longitudinal changes were found in temporal, orbitofrontal, and lateral parietal cortex. Across syndromes, there was substantial overlap in the brain regions showing volume and metabolism loss. Even though the pattern of metabolic decline was more extensive, metabolic changes were also more variable and sample size estimates were similar or higher for 18FDG-PET compared to MRI.
Conclusion Our findings demonstrated the sensitivity of 18FDG-PET and structural MRI for tracking disease progression in FTD. Both modalities showed highly overlapping patterns of longitudinal change and comparable sample size estimates to detect longitudinal changes in future clinical trials.
Glossary
- Aβ=
- β-amyloid;
- bvFTD=
- behavioral variant frontotemporal dementia;
- CDR=
- Clinical Dementia Rating;
- CI=
- confidence interval;
- CN=
- cognitively normal;
- DARTEL=
- diffeomorphic anatomical registration through exponentiated lie algebra;
- 18FDGPET=
- 18F-fludeoxyglucose PET;
- FDR=
- false discovery rate;
- FTD=
- frontotemporal dementia;
- FTLD=
- frontotemporal lobar degeneration;
- LBNL=
- Lawrence Berkeley National Laboratory;
- MNI=
- Montreal Neurologic Institute;
- nfvPPA=
- nonfluent variant primary progressive aphasia;
- ROI=
- region of interest;
- SMA=
- supplementary motor area;
- SPM12=
- Statistical Parametric Mapping version 12;
- svPPA=
- semantic variant primary progressive aphasia;
- TDP=
- TAR DNA-binding protein;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- UCSF=
- University of California San Francisco
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
- Received April 2, 2019.
- Accepted in final form December 13, 2019.
- © 2020 American Academy of Neurology
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