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Mapping the progression of progranulin-associated frontotemporal lobar degeneration

Abstract

Background A 55-year-old woman was followed over a 13-year period as part of a longitudinal study of people at risk for familial dementia. She was a member of a family with an autosomal dominant familial dementia that fulfilled consensus criteria for frontotemporal lobar degeneration. The patient was initially asymptomatic but developed progressive behavioral and cognitive decline characterized by apathy, impaired emotion recognition, mixed aphasia and parietal lobe dysfunction.

Investigations Clinical assessments, neuropsychometry, volumetric brain MRI, and genetic mutation screening.

Diagnosis Progranulin-associated frontotemporal lobar degeneration.

Management Explanation of the patient's condition and genetic counseling for her family.

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Figure 1: Timeline showing clinical assessments and progression of neuropsychological and neuroimaging deficits in a person at risk for frontotemporal lobar degeneration.
Figure 2: Series of five registered T1-weighted MRI scans of a patient with progranulin-associated frontotemporal lobar degeneration.
Figure 3: Coronal and sagittal MRI scans of a patient with progranulin-associated frontotemporal lobar degeneration, with voxel-compression-mapping overlay.

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Acknowledgements

This work was supported by the Alzheimer Research Trust and the Medical Research Council UK. The University College London Hospital/University College London, where the authors are based, received a proportion of funding from the UK Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. JD Rohrer is supported by a Wellcome Trust Research Training Fellowship. JD Warren is supported by a Wellcome Trust Intermediate Clinical Fellowship. J Barnes is supported by the Alzheimer Research Trust. NC Fox holds a Medical Research Council UK Senior Clinical Fellowship.

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Correspondence to Nick C Fox.

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The authors declare no competing financial interests.

Supplementary information

Supplementary Figure 1

Pedigree of a family (DRC255) with an autosomal dominant history of a dementia that met consensus criteria for frontotemporal lobar degeneration. Notable features of the familial phenotype were behavioral change and language output impairment. In this figure, circles represent females and squares males, and diamonds are anonymized individuals. Filled symbols represent affected family members. Deceased family members are marked with a diagonal line. The patient described in this paper is III.11. (DOC 115 kb)

Supplementary Table 1

Brain volumetric analysis of a patient with progranulin-associated frontotemporal lobar degeneration from baseline to 13 years after baseline. (A) Whole brain volume. (B) Hemisphere volume. (C) Ventricular volume. (D) Hemiventricular volume. (DOC 56 kb)

Supplementary Table 2

Neuropsychological assessments in a person at risk of frontotemporal lobar degeneration. (DOC 32 kb)

Supplementary Video 1

Detailed neurolinguistic analysis 2 years after symptom onset in a person at risk of frontotemporal lobar degeneration. (AVI 277 kb)

Supplementary Figure 2

Nonlinear, fluid registration of serial brain MRI scans of a patient with progranulin-associated frontotemporal lobar degeneration. The video illustrates progressive asymmetrical brain atrophy over a 2-year period between the scan at visit 6 (6 months before symptom onset) and the scan at visit 8 (18 months after symptom onset). (DOC 229 kb)

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Rohrer, J., Warren, J., Barnes, J. et al. Mapping the progression of progranulin-associated frontotemporal lobar degeneration. Nat Rev Neurol 4, 455–460 (2008). https://doi.org/10.1038/ncpneuro0869

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