Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers
| Autor: | Pheth Sengdy, Ging-Yuek Robin Hsiung, Katie Dinelle, Phoenix Bouchard-Kerr, Claudia Jacova, Howard Feldman, Marjorie Gonzalez, Siobhan McCormick, Ian R. A. Mackenzie, A. Jon Stoessl, Matt Baker, Vesna Sossi, Itthipol Tawankanjanachot, Hyunsoo Steve Lee, Rosa Rademakers |
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| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
Adult
Male Pathology medicine.medical_specialty Clinical Sciences Statistical parametric mapping Brain mapping Asymptomatic Progranulins Fluorodeoxyglucose F18 mental disorders medicine Dementia Humans Prospective cohort study Aged Retrospective Studies Brain Mapping Neurology & Neurosurgery Neurosciences Middle Aged medicine.disease Magnetic Resonance Imaging Frontal Lobe Glucose Frontal lobe Positron-Emission Tomography Mutation Disease Progression Intercellular Signaling Peptides and Proteins Cognitive Sciences Female Neurology (clinical) Human medicine medicine.symptom Psychology Insula Frontotemporal dementia |
| Zdroj: | Neurology Neurology, vol 81, iss 15 |
| ISSN: | 0028-3878 |
| Popis: | Objective: In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [ 18 F]-fluorodeoxyglucose (FDG)-PET in progranulin ( GRN ) mutation carriers prior to frontotemporal dementia (FTD) onset. Methods: Nine mutation carriers (age 51.5 ± 13.5 years) and 11 noncarriers (age 52.7 ± 9.5 years) from 5 families with FTD due to GRN mutations underwent brain scanning with FDG-PET and MRI and clinical evaluation. Normalized FDG uptake values were calculated with reference to the pons. PET images were analyzed with regions of interest (ROI) and statistical parametric mapping (SPM) approaches. Results: Compared with noncarriers, GRN mutation carriers had a lowered anterior-to-posterior (AP) ratio of FDG uptake (0.86 ± 0.09 vs 0.92 ± 0.05) and less left-right asymmetry, consistent with an overall pattern of right anterior cerebral hypometabolism. This pattern was observed regardless of whether they were deemed clinically symptomatic no dementia or asymptomatic. Individual ROIs with lowered FDG uptake included right anterior cingulate, insula, and gyrus rectus. SPM analysis supported and extended these findings, demonstrating abnormalities in the right and left medial frontal regions, right insular cortex, right precentral and middle frontal gyri, and right cerebellum. Right AP ratio was correlated with cognitive and clinical scores (modified Mini-Mental State Examination r = 0.74; Functional Rating Scale r = −0.73) but not age and years to estimated onset in mutation carriers. Conclusion: The frontotemporal lobar degenerative process associated with GRN mutations appears to begin many years prior to the average age at FTD onset (late 50s–early 60s). Right medial and ventral frontal cortex and insula may be affected in this process but the specific regional patterns associated with specific clinical variants remain to be elucidated. |
| Databáze: | OpenAIRE |
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