Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies

Kanda, Tomonori; Ishii, Kazunari; Uemura, Takafumi; Miyamoto, Naokazu; Yoshikawa, Toshiki; Kono, Atsushi K.; Mori, Etsuro

doi:10.1007/s00259-008-0871-5

Cited by 96 publications

(57 citation statements)

References 28 publications

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“…Neuroimaging findings in early bvFTD have been equivocal, with some studies reporting no medial temporal lobe atrophy 29 or hypometabolism in bvFTD, 30 whereas others have found clear changes. 31 Also, atrophy does not equate with underfunctioning and further studies should explore structure and function of key memory-related structures in FTD.…”

Section: Discussionmentioning

confidence: 99%

How preserved is episodic memory in behavioral variant frontotemporal dementia?

Hornberger¹,

Piguet²,

Graham³

et al. 2010

Neurology

189

120

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Objective: Studies have shown variable memory performance in patients with behavioral variant frontotemporal dementia (bvFTD). Our study investigated whether this variability is due to the admixture of patients with true bvFTD and phenocopy patients. We also sought to compare performance of patients with bvFTD and patients with Alzheimer disease (AD). Methods:We analyzed neuropsychological memory performance in patients with a clinical diagnosis of bvFTD divided into those who progressed (n ϭ 50) and those who remained stable (n ϭ 39), patients with AD (n ϭ 64), and healthy controls (n ϭ 64). Results:Patients with progressive bvFTD were impaired on most memory tests to a similar level to that of patients with early AD. Findings from a subset of patients with progressive bvFTD with confirmed FTLD pathology (n ϭ 10) corroborated these findings. By contrast, patients with phenocopy bvFTD performed significantly better than progressors and patients with AD. Logistic regression revealed that patients with bvFTD can be distinguished to a high degree (85%) on the immediate recall score of a word list learning test (Rey Auditory Verbal Learning Test). Conclusions:Our results provide evidence for an underlying memory deficit in "real" or progressive behavioral variant frontotemporal dementia (bvFTD) similar to Alzheimer disease, though the groups differ in orientation scores, with patients with bvFTD being intact. Exclusion solely based on impaired neuropsychological memory performance can potentially lead to an underdiagnosis of FTD. Neurology Our study focuses on episodic memory in frontotemporal dementia (FTD). "Severe amnesia" is currently an exclusion criterion for the behavioral subtype of FTD (bvFTD), 1 yet 10% of pathologically confirmed cases have reported memory symptoms in the initial stages of disease, 2 and occasional cases have severe amnesia, 3 as emphasized in early descriptions of Pick's. 4 Recently this and other findings have put into question the reliability of current diagnostic criteria for bvFTD. [5][6][7] To date, surprisingly few studies have investigated episodic memory in bvFTD, with inconsistent results. Such inconsistency could, at least in part, be explained by recent studies which have shown that clinically diagnosed patients with bvFTD vary in their prognosis [8][9][10] ; some show rapid progression while others show little or no progression over a decade. The 2 patient groups can be discriminated on MRI and PET findings despite exhibiting equivalent degrees of behavioral disturbance. [8][9][10] This heterogeneity of bvFTD might explain previous findings: if only the progressive group shows brain atrophy, then this group is more likely to exhibit From the Prince

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Section: Discussionmentioning

confidence: 99%

How preserved is episodic memory in behavioral variant frontotemporal dementia?

Hornberger¹,

Piguet²,

Graham³

et al. 2010

Neurology

189

120

View full text Add to dashboard Cite

show abstract

“…Reflecting astrocytic metabolism, the percentage enrichment of [4,[5][6][7][8][9][10][11][12][13] C]glutamate, [4,[5][6][7][8][9][10][11][12][13] C]glutamine and [1,2-13 C]GABA were significantly increased in the cerebral cortex of pR5 mice compared with controls ( Figure 2B). Calculation of M þ 2 isotopomers from NMRS results demonstrated that the percentage enrichment of M þ 2 glutamate and glutamine were increased, whereas that of M þ 2 GABA remained unaltered (Table 3).…”

Section: Concentrations Of Metabolitesmentioning

confidence: 99%

“…The transfer of metabolites between neurons and astrocytes in cortex appeared to remain normal. This was indicated by the increase in percentage enrichment of both [4-13 C] glutamate and glutamine (which can suggest normal transfer of glutamate from neurons to astrocytes) and in that of [4,[5][6][7][8][9][10][11][12][13] …”

Section: Decreased Glutamate Level In Hippocampusmentioning

confidence: 99%

Glutamate Metabolism is Impaired in Transgenic Mice with Tau Hyperphosphorylation

Nilsen

Rae

Ittner

et al. 2013

J Cereb Blood Flow Metab

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In neurodegenerative diseases including Alzheimer's disease and frontotemporal dementia, the protein tau is hyperphosphorylated and eventually aggregates to develop neurofibrillary tangles. Here, the consequences of tau hyperphosphorylation on both neuronal and astrocytic metabolism and amino-acid neurotransmitter homeostasis were assessed in transgenic mice expressing the pathogenic mutation P301L in the human tau gene (pR5 mice) compared with nontransgenic littermate controls. Mice were injected with the neuronal and astrocytic substrate [1-13 C]glucose and the astrocytic substrate [1,2-13 C]acetate. Hippocampus and cerebral cortex extracts were analyzed using 1 H and 13 C nuclear magnetic resonance spectroscopy, gas chromatography-mass spectrometry and high-performance liquid chromatography. The glutamate level was reduced in the hippocampus of pR5 mice, accompanied by reduced incorporation of 13 C label derived from [1-13 C]glucose in glutamate. In the cerebral cortex, glucose utilization as well as turnover of glutamate, glutamine, and GABA, were increased. This was accompanied by a relative increase in production of glutamate via the pyruvate carboxylation pathway in cortex. Overall, we revealed that astrocytes as well as glutamatergic and GABAergic neurons in the cortex of pR5 mice were in a hypermetabolic state, whereas in the hippocampus, where expression levels of mutant human tau are the highest, glutamate homeostasis was impaired.

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“…48 According to a VBM study of FTD, 49 metabolic and atrophic changes occur in the bilateral frontal and temporal lobes, whereas the affected regions of metabolism are larger and more severe than those of atrophy in the frontal lobe. In patients with semantic dementia, asymmetrically severely decreased temporal metabolism can be demonstrated on FDG-PET images (Fig 8).…”

Section: Frontotemporal Lobe Degenerationmentioning

confidence: 99%

PET Approaches for Diagnosis of Dementia

Ishii

2013

AJNR Am J Neuroradiol

106

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SUMMARY:There is increasing use of neuroimaging modalities, including PET, for diagnosing dementia. For example, FDG-PET demonstrates hypometabolic regions in the posterior cingulate gyri, precuneus, and parietotemporal association cortices, while amyloid PET indicates amyloid deposition in Alzheimer disease and mild cognitive impairment due to Alzheimer disease. Furthermore, the use of combination PET with structural MR imaging can improve the diagnostic accuracy of dementia. In other neurodegenerative dementias, each disease exhibits a specific metabolic reduction pattern. In dementia with Lewy bodies, occipital glucose metabolism is decreased, while in frontotemporal dementia, frontal and anterior temporal metabolism is predominantly decreased. These FDG-PET findings and positive or negative amyloid deposits are important biomarkers for various neurodegenerative dementias. ABBREVIATIONS:A␤ ϭ amyloid ␤ peptide; AD ϭ Alzheimer disease; APOE ϭ apolipoprotein E; CBD ϭ corticobasal degeneration; DLB ϭ dementia with Lewy

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Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies

Abstract: In FTD, metabolic and morphologic changes occur in the bilateral frontal lobe and temporal lobe with a limited asymmetry whereas there was considerable discordance in the AD group.

Cited by 96 publications

References 28 publications

How preserved is episodic memory in behavioral variant frontotemporal dementia?

How preserved is episodic memory in behavioral variant frontotemporal dementia?

Glutamate Metabolism is Impaired in Transgenic Mice with Tau Hyperphosphorylation

PET Approaches for Diagnosis of Dementia

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