TY - JOUR
T1 - Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers
AU - Jacova, Claudia
AU - Hsiung, Ging Yuek R.
AU - Tawankanjanachot, Itthipol
AU - Dinelle, Katie
AU - McCormick, Siobhan
AU - Gonzalez, Marjorie
AU - Lee, Hyunsoo
AU - Sengdy, Pheth
AU - Bouchard-Kerr, Phoenix
AU - Baker, Matthew
AU - Rademakers, Rosa
AU - Sossi, Vesna
AU - Stoessl, A. Jon
AU - Feldman, Howard H.
AU - Mackenzie, Ian R.
PY - 2013/10/8
Y1 - 2013/10/8
N2 - Objective: In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [18F]-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 = 20.73) but not age and years to estimated onset in mutation carriers. Conclusion: The frontotemporal lobar degenerative process associatedwith GRNmutations 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.
AB - Objective: In this prospective cohort study, we investigated cerebral glucose metabolism reductions on [18F]-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 = 20.73) but not age and years to estimated onset in mutation carriers. Conclusion: The frontotemporal lobar degenerative process associatedwith GRNmutations 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.
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U2 - 10.1212/WNL.0b013e3182a8237e
DO - 10.1212/WNL.0b013e3182a8237e
M3 - Article
C2 - 24005336
AN - SCOPUS:84888222366
SN - 0028-3878
VL - 81
SP - 1322
EP - 1331
JO - Neurology
JF - Neurology
IS - 15
ER -