Variability of clinical syndromes and cerebral glucose metabolism in symptomatic frontotemporal lobar degeneration associated with progranulin mutations

Licata, Abigail; Grimmer, Timo; Winkelmann, Juliane; Wagner, Matias; Goldhardt, Oliver; Riedl, Lina; Roßmeier, Carola; Yakushev, Igor; Diehl‐Schmid, Janine

doi:10.1080/21678421.2020.1779302

Cited by 2 publications

(4 citation statements)

References 27 publications

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“…PGRN mutation carriers, displayed large heterogeneity in their glucose hypometabolism patterns in studies with 9-10 patients, aligning with the fact that PGRN mutations cause FTD across the clinical spectrum (Jacova et al, 2013;Licata et al, 2020). Nevertheless, one study found that ∼80% of PGRN mutation carrying patients had glucose hypometabolism in the temporal regions of the brain, which extended beyond the boundaries of the frontotemporal region (Licata et al, 2020). C9 carriers were found to have glucose hypometabolism extending into the cerebellar cortex, occipital cortex, cingulate cortex, rolandic operculum, and caudate nuclei (Castelnovo et al, 2019;Diehl-Schmid et al, 2019).…”

Section: Impaired Glucose Metabolism In Frontotemporal Dementia Patientsmentioning

confidence: 65%

“…Familial FTD FDG-PET studies similarly identified glucose hypometabolism across subtypes with patterns mainly aligning to the clinical subtype of individual patients (Castelnovo et al, 2019;Clarke et al, 2021). PGRN mutation carriers, displayed large heterogeneity in their glucose hypometabolism patterns in studies with 9-10 patients, aligning with the fact that PGRN mutations cause FTD across the clinical spectrum (Jacova et al, 2013;Licata et al, 2020). Nevertheless, one study found that ∼80% of PGRN mutation carrying patients had glucose hypometabolism in the temporal regions of the brain, which extended beyond the boundaries of the frontotemporal region (Licata et al, 2020).…”

Section: Impaired Glucose Metabolism In Frontotemporal Dementia Patientsmentioning

confidence: 83%

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Frontotemporal Dementia and Glucose Metabolism

Garrett

Niccoli

2022

Front. Neurosci.

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Frontotemporal dementia (FTD), hallmarked by antero-temporal degeneration in the human brain, is the second most common early onset dementia. FTD is a diverse disease with three main clinical presentations, four different identified proteinopathies and many disease-associated genes. The exact pathophysiology of FTD remains to be elucidated. One common characteristic all forms of FTD share is the dysregulation of glucose metabolism in patients’ brains. The brain consumes around 20% of the body’s energy supply and predominantly utilizes glucose as a fuel. Glucose metabolism dysregulation could therefore be extremely detrimental for neuronal health. Research into the association between glucose metabolism and dementias has recently gained interest in Alzheimer’s disease. FTD also presents with glucose metabolism dysregulation, however, this remains largely an unexplored area. A better understanding of the link between FTD and glucose metabolism may yield further insight into FTD pathophysiology and aid the development of novel therapeutics. Here we review our current understanding of FTD and glucose metabolism in the brain and discuss the evidence of impaired glucose metabolism in FTD. Lastly, we review research potentially suggesting a causal relationship between FTD proteinopathies and impaired glucose metabolism in FTD.

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Section: Impaired Glucose Metabolism In Frontotemporal Dementia Patientsmentioning

confidence: 65%

Section: Impaired Glucose Metabolism In Frontotemporal Dementia Patientsmentioning

confidence: 83%

Frontotemporal Dementia and Glucose Metabolism

Garrett

Niccoli

2022

Front. Neurosci.

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“…The metabolic changes appeared before brain atrophy on MRI and approximately more than 10 years before clinical onset ( 57 ), suggesting that FDG-PET changes can be detected as early biomarkers in GRN mutation carriers. In symptomatic GRN mutation carriers, the asymmetrical hypometabolism of temporoparietal ( 56 ) and frontal ( 58 ) lobes was reported primarily based on a small number of cross-sectional studies or case reports. Hypometabolism patterns were observed to correlate with clinical manifestations ( 56 ), but another study failed to find clear metabolic change pattern in each clinical subtype ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

“…In symptomatic GRN mutation carriers, the asymmetrical hypometabolism of temporoparietal ( 56 ) and frontal ( 58 ) lobes was reported primarily based on a small number of cross-sectional studies or case reports. Hypometabolism patterns were observed to correlate with clinical manifestations ( 56 ), but another study failed to find clear metabolic change pattern in each clinical subtype ( 58 ).…”

Section: Discussionmentioning

confidence: 99%

Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects

et al. 2022

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Familial frontotemporal lobar degeneration (FTLD) is a pathologically heterogeneous group of neurodegenerative diseases with diverse genotypes and clinical phenotypes. Three major mutations were reported in patients with familial FTLD, namely, progranulin (GRN), microtubule-associated protein tau (MAPT), and the chromosome 9 open reading frame 72 (C9orf72) repeat expansion, which could cause neurodegenerative pathological changes years before symptom onset. Noninvasive quantitative molecular imaging with PET or single-photon emission CT (SPECT) allows for selective visualization of the molecular targets in vivo to investigate brain metabolism, perfusion, neuroinflammation, and pathophysiological changes. There was increasing evidence that several molecular imaging biomarkers tend to serve as biomarkers to reveal the early brain abnormalities in familial FTLD. Tau-PET with 18F-flortaucipir and 11C-PBB3 demonstrated the elevated tau position in patients with FTLD and also showed the ability to differentiate patterns among the different subtypes of the mutations in familial FTLD. Furthermore, dopamine transporter imaging with the 11C-DOPA and 11C-CFT in PET and the 123I-FP-CIT in SPECT revealed the loss of dopaminergic neurons in the asymptomatic and symptomatic patients of familial FTLD. In addition, PET imaging with the 11C-MP4A has demonstrated reduced acetylcholinesterase (AChE) activity in patients with FTLD, while PET with the 11C-DAA1106 and 11C-PK11195 revealed an increased level of microglial activation associated with neuroinflammation even before the onset of symptoms in familial FTLD. 18F-fluorodeoxyglucose (FDG)-PET indicated hypometabolism in FTLD with different mutations preceded the atrophy on MRI. Identifying molecular imaging biomarkers for familial FTLD is important for the in-vivo assessment of underlying pathophysiological changes with disease progression and future disease-modifying therapy. We review the recent progress of molecular imaging in familial FTLD with focused on the possible implication of these techniques and their prospects in specific mutation types.

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Variability of clinical syndromes and cerebral glucose metabolism in symptomatic frontotemporal lobar degeneration associated with progranulin mutations

Cited by 2 publications

References 27 publications

Frontotemporal Dementia and Glucose Metabolism

Frontotemporal Dementia and Glucose Metabolism

Molecular imaging biomarkers in familial frontotemporal lobar degeneration: Progress and prospects

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