Longitudinal Brain Atrophy Rates in Presymptomatic Carriers of Genetic Frontotemporal Dementia

Autor: Jackie M. Poos, Leonie D. M. Grandpierre, Emma L. van der Ende, Jessica L. Panman, Janne M. Papma, Harro Seelaar, Esther van den Berg, Ronald van 't Klooster, Esther Bron, Rebecca Steketee, Meike W. Vernooij, Yolande A. L. Pijnenburg, Serge A. R. B. Rombouts, John van Swieten, Lize C. Jiskoot
Přispěvatelé: Neurology, Radiology & Nuclear Medicine, Clinical Psychology, Amsterdam Neuroscience - Neurodegeneration
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Neurology, 99(24), E2661-E2671. Lippincott Williams & Wilkins
Neurology, 99(24), E2661-E2671. Lippincott Williams and Wilkins
Poos, J M, Grandpierre, L D M, van der Ende, E L, Panman, J L, Papma, J M, Seelaar, H, van den Berg, E, van't Klooster, R, Bron, E, Steketee, R, Vernooij, M W, Pijnenburg, Y A L, Rombouts, S A R B, van Swieten, J & Jiskoot, L C 2022, ' Longitudinal Brain Atrophy Rates in Presymptomatic Carriers of Genetic Frontotemporal Dementia ', Neurology, vol. 99, no. 24, pp. E2661-E2671 . https://doi.org/10.1212/WNL.0000000000201292
ISSN: 0028-3878
DOI: 10.1212/wnl.0000000000201292
Popis: Background and ObjectivesIt is important to identify at what age brain atrophy rates in genetic frontotemporal dementia (FTD) start to accelerate and deviate from normal aging effects to find the optimal starting point for treatment. We investigated longitudinal brain atrophy rates in the presymptomatic stage of genetic FTD using normative brain volumetry software.MethodsPresymptomaticGRN,MAPT, andC9orf72pathogenic variant carriers underwent longitudinal volumetric T1-weighted magnetic resonance imaging of the brain as part of a prospective cohort study. Images were automatically analyzed with Quantib® ND, which consisted of volume measurements (CSF and sum of gray and white matter) of lobes, cerebellum, and hippocampus. All volumes were compared with reference centile curves based on a large population-derived sample of nondemented individuals (n = 4,951). Mixed-effects models were fitted to analyze atrophy rates of the different gene groups as a function of age.ResultsThirty-fourGRN, 8MAPT, and 14C9orf72pathogenic variant carriers were included (mean age = 52.1, standard deviation = 7.2; 66% female). The mean follow-up duration of the study was 64 ± 33 months (median = 52; range 13–108).GRNpathogenic variant carriers showed a faster decline than the reference centile curves for all brain areas, though relative volumes remained between the 5th and 75th percentiles between the ages of 45 and 70 years. InMAPTpathogenic variant carriers, frontal lobe volume was already at the 5th percentile at age 45 years and showed a further decline between the ages 50 and 60 years. Temporal lobe volume started in the 50th percentile at age 45 years but showed fastest decline over time compared with other brain structures. Frontal, temporal, parietal, and cerebellar volume already started below the 5th percentile compared with the reference centile curves at age 45 years forC9orf72pathogenic variant carriers, but there was minimal decline over time until the age of 60 years.DiscussionWe provide evidence for longitudinal brain atrophy in the presymptomatic stage of genetic FTD. The affected brain areas and the age after which atrophy rates start to accelerate and diverge from normal aging slopes differed between gene groups. These results highlight the value of normative volumetry software for disease tracking and staging biomarkers in genetic FTD. These techniques could help in identifying the optimal time window for starting treatment and monitoring treatment response.
Databáze: OpenAIRE
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