Frontotemporal Dementia

Olney, Nicholas; Spina, Salvatore; Miller, Bruce L.

doi:10.1016/j.ncl.2017.01.008

Cited by 317 publications

(352 citation statements)

References 243 publications

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“…Frontotemporal dementia (FTD), the leading cause of dementia in middle age, comprises a heterogeneous group of neurodegenerative conditions characterized by diverse cognitive and behavioral manifestations (Olney et al, 2017). Familial forms of the disease are often caused by mutations of the progranulin, tau, or C9orf72 gene, but sporadic forms are more common (Olney et al, 2017).…”

Section: The Nvu In Neurodegenerative Diseasementioning

confidence: 99%

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The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

Iadecola

2017

Neuron

1,646

1,649

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The concept of neurovascular unit (NVU), formalized at the 2001 Stroke Progress Review Group meeting of the National Institute of Neurological Disorders and Stroke, emphasizes the intimate relationship between the brain and its vessels. Since then, the NVU has attracted the interest of the neuroscience community resulting in considerable advances in the field. Here the current state-of-knowledge of the NVU will be assessed, focusing on one of its most vital roles: the coupling between neural activity and blood flow. The evidence supports a conceptual shift in the mechanisms of neurovascular coupling, from a unidimensional process involving neuronal-astrocytic signaling to local blood vessels, to a multidimensional one in which mediators released from multiple cells engage distinct signaling pathways and effector systems across the entire cerebrovascular network in a highly orchestrated manner. The recently appreciated NVU dysfunction in neurodegenerative diseases, although still poorly understood, supports emerging concepts that maintaining neurovascular health promotes brain health.

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Section: The Nvu In Neurodegenerative Diseasementioning

confidence: 99%

“…Familial forms of the disease are often caused by mutations of the progranulin, tau, or C9orf72 gene, but sporadic forms are more common (Olney et al, 2017). Resting CBF is reduced in the frontal, parietal and temporal cortex of presymptomatic patients, an effect independent of atrophy (Dopper et al, 2016).…”

Section: The Nvu In Neurodegenerative Diseasementioning

confidence: 99%

The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

Iadecola

2017

Neuron

1,646

1,649

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“…Tauopathies are subclassified as either primary or secondary, depending on the degree to which tau pathology occurs independently of other proteopathies (e.g., Aβ, α-syn, TDP-43). FTLD is a collection of non-AD neurodegenerative disorders affecting primarily the frontal and temporal lobes (157). FTLD can be further divided into three histological subtypes based upon the predominant proteopathy: FTLD-tau, FTLD-TDP, and FTLD-FUS (158).…”

Section: Non-ad Tauopathiesmentioning

confidence: 99%

Small-molecule PET Tracers for Imaging Proteinopathies

Mathis

Lopresti

Ikonomović

et al. 2017

Seminars in Nuclear Medicine

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In this chapter, we provide a review of the challenges and advances in developing successful positron emission tomography (PET) imaging agents for three major types of aggregated amyloid proteins – amyloid-beta (Aβ), tau, and alpha-synuclein (α-syn). These three amyloids are involved in the pathogenesis of a variety of neurodegenerative diseases, referred to as proteinopathies or proteopathies, that include Alzheimer’s disease, Lewy body dementias, multiple system atrophy, and frontal temporal dementias among others. In the Introduction, we briefly discuss the history of amyloid in neurodegenerative diseases and describe why progress in developing effective imaging agents has been hampered by the failure of crystallography to provide definitive ligand-protein interactions for rational radioligand design efforts. Instead, the field has relied on largely serendipitous, trial and error methods to achieve useful and specific PET amyloid imaging tracers for Aβ, tau, and α-syn deposits. Because many of the proteopathies involve more than one amyloid protein, it is important to develop selective PET tracers for the different amyloids to help assess the relative contribution of each to total amyloid burden. We utilize Pittsburgh Compound B (PiB) to illustrate some of the critical steps in developing a potent and selective Aβ PET imaging agent. Other selective Aβ and tau PET imaging compounds have followed similar pathways in their developmental processes. Success for selective α-syn PET imaging agents has not been realized yet, but work is ongoing in multiple laboratories throughout the world. In the tau sections, we provide background regarding 3-repeat (3R) and 4-repeat (4R) tau proteins and how they can affect the binding of tau radioligands in different tauopathies. We review the ongoing efforts to assess the properties of tau ligands, which are useful in 3R, 4R or combined 3R/4R tauopathies. Finally, we describe in the α-syn sections recent attempts to develop selective tracers to image α-synucleinopathies.

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“…Frontotemporal dementia (FTD) used to be an umbrella term for clinical syndromes comprising progressive behavioral disturbances and language deficits due to focal neurodegeneration in parts of the frontal and temporal lobes (FTLD). Current classifications differentiate the behavioral variant of frontotemporal dementia (bvFTD) and three subtypes of primary progressive aphasia (PPA) specified as agrammatic variant (avPPA), semantic variant (svPPA) and logopenic variant (lvPPA) (Figure ) . The underlying histopathology is variable and includes different forms of tauopathies, TDP43‐proteinopathies and atypical Alzheimer dementia (AD) pathology – the latter being associated with lvPPA (“atypical AD”).…”

Section: Introductionmentioning

confidence: 99%

“…Clinical neuropsychological testing is the diagnostic key for bvFTD and PPA types, whereas neuroimaging is mainly used to rule out differential diagnoses and comorbidities. [3][4][5] A majority of MRI studies dealing with differential diagnoses of these dementia forms focused on focal atrophy analyzing volumetric data or morphometric patterns. 6,7 More recent studies showed alterations in functional connectivity with diffusion tensor imaging (DTI) and in brain activity with arterial spin labeling (ASL) or with BOLD imaging.…”

Section: Introductionmentioning

confidence: 99%

MR fingerprinting as a diagnostic tool in patients with frontotemporal lobe degeneration: A pilot study

et al. 2019

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Several very rare forms of dementia are associated with characteristic focal atrophy predominantly of the frontal and/or temporal lobes and currently lack imaging solutions to monitor disease. Magnetic resonance fingerprinting (MRF) is a recently developed technique providing quantitative relaxivity maps and images with various tissue contrasts out of a single sequence acquisition. This pilot study explores the utility of MRF‐based T1 and T2 mapping to discover focal differences in relaxation times between patients with frontotemporal lobe degenerative dementia and healthy controls. 8 patients and 30 healthy controls underwent a 3 T MRI including an axial 2D spoiled gradient echo MRF sequence. T1 and T2 relaxation maps were generated based on an extended phase graphs algorithm‐founded dictionary involving inner product pattern matching. A region of interest (ROI)‐based analysis of T1 and T2 relaxation times was performed with FSL and ITK‐SNAP. Depending on the brain region analyzed, T1 relaxation times were up to 10.28% longer in patients than in controls reaching significant differences in cortical gray matter (P = .047) and global white matter (P = .023) as well as in both hippocampi (P = .001 left; P = .027 right). T2 relaxation times were similarly longer in the hippocampus by up to 19.18% in patients compared with controls. The clinically most affected patient had the most control‐deviant relaxation times. There was a strong correlation of T1 relaxation time in the amygdala with duration of the clinically manifest disease (Spearman Rho = .94; P = .001) and of T1 relaxation times in the left hippocampus with disease severity (Rho = .90, P = .002). In conclusion, MRF‐based relaxometry is a promising and time‐saving new MRI tool to study focal cerebral alterations and identify patients with frontotemporal lobe degeneration. To validate the results of this pilot study, MRF is worth further exploration as a diagnostic tool in neurodegenerative diseases.

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Frontotemporal Dementia

Cited by 317 publications

References 243 publications

The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

The Neurovascular Unit Coming of Age: A Journey through Neurovascular Coupling in Health and Disease

Small-molecule PET Tracers for Imaging Proteinopathies

MR fingerprinting as a diagnostic tool in patients with frontotemporal lobe degeneration: A pilot study

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