Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers

Claudia Jacova, Ging Yuek R Hsiung, Itthipol Tawankanjanachot, Katie Dinelle, Siobhan McCormick, Marjorie Gonzalez, Hyunsoo Lee, Pheth Sengdy, Phoenix Bouchard-Kerr, Matthew Baker, Rosa V Rademakers, Vesna Sossi, A. Jon Stoessl, Howard H. Feldman, Ian R. Mackenzie

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1322-1331
Number of pages10
JournalNeurology
Volume81
Issue number15
DOIs
StatePublished - Oct 8 2013

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Prednisolone
Dementia
Frontotemporal Dementia
Glucose
Mutation
Brain
Pons
Gyrus Cinguli
Fluorodeoxyglucose F18
Frontal Lobe
Prefrontal Cortex
Cerebral Cortex
Cerebellum
Cohort Studies
Carrier
Prospective Studies
Onset
Insula
Cortex

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Jacova, C., Hsiung, G. Y. R., Tawankanjanachot, I., Dinelle, K., McCormick, S., Gonzalez, M., ... Mackenzie, I. R. (2013). Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology, 81(15), 1322-1331. https://doi.org/10.1212/WNL.0b013e3182a8237e

Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. / Jacova, Claudia; Hsiung, Ging Yuek R; Tawankanjanachot, Itthipol; Dinelle, Katie; McCormick, Siobhan; Gonzalez, Marjorie; Lee, Hyunsoo; Sengdy, Pheth; Bouchard-Kerr, Phoenix; Baker, Matthew; Rademakers, Rosa V; Sossi, Vesna; Stoessl, A. Jon; Feldman, Howard H.; Mackenzie, Ian R.

In: Neurology, Vol. 81, No. 15, 08.10.2013, p. 1322-1331.

Research output: Contribution to journalArticle

Jacova, C, Hsiung, GYR, Tawankanjanachot, I, Dinelle, K, McCormick, S, Gonzalez, M, Lee, H, Sengdy, P, Bouchard-Kerr, P, Baker, M, Rademakers, RV, Sossi, V, Stoessl, AJ, Feldman, HH & Mackenzie, IR 2013, 'Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers', Neurology, vol. 81, no. 15, pp. 1322-1331. https://doi.org/10.1212/WNL.0b013e3182a8237e
Jacova C, Hsiung GYR, Tawankanjanachot I, Dinelle K, McCormick S, Gonzalez M et al. Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. Neurology. 2013 Oct 8;81(15):1322-1331. https://doi.org/10.1212/WNL.0b013e3182a8237e
Jacova, Claudia ; Hsiung, Ging Yuek R ; Tawankanjanachot, Itthipol ; Dinelle, Katie ; McCormick, Siobhan ; Gonzalez, Marjorie ; Lee, Hyunsoo ; Sengdy, Pheth ; Bouchard-Kerr, Phoenix ; Baker, Matthew ; Rademakers, Rosa V ; Sossi, Vesna ; Stoessl, A. Jon ; Feldman, Howard H. ; Mackenzie, Ian R. / Anterior brain glucose hypometabolism predates dementia in progranulin mutation carriers. In: Neurology. 2013 ; Vol. 81, No. 15. pp. 1322-1331.
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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 V

AU - Sossi, Vesna

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