MRS in presymptomatic
            <i>MAPT</i>
            mutation carriers

Kantarci, Kejal; Boeve, Bradley F.; Wszołek, Zbigniew K.; Rademakers, Rosa; Whitwell, Jennifer L.; Baker, Mary V.; Senjem, Matthew L.; Samikoglu, Ali R.; Knopman, David S.; Petersen, Ron; Jack, Clifford R.

doi:10.1212/wnl.0b013e3181f073c7

Cited by 49 publications

(64 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The elevation in mIns may be associated with glial or microglial activation, a characteristic feature of these diseases (134). An elevated mIns level appears early in dementia, preceding the decrease in tNAA concentration (Fig 8), atrophy, and associated neuronal loss and cognitive impairment, as demonstrated in presymptomatic carriers for familial Alzheimer disease (135) and in patients with frontotemporal lobar degeneration mutations (136). 1 H MR spectroscopy may also be used to monitor treatment response in neurodegenerative diseases.…”

Section: Special Review: Clinical Proton Mr Spectroscopy In Central Nmentioning

confidence: 99%

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Öz¹,

Alger²,

Barker³

et al. 2014

Radiology

556

356

View full text Add to dashboard Cite

A large body of published work shows that proton (hydrogen 1 [ 1 H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1 H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1 H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1 H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.q RSNA, 2014 Online supplemental material is available for this article. G.O. (e-mail: gulin@cmrr.umn.edu). 2 The complete list of authors and affiliations is at the end of this article.q RSNA, 2014 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. Radiology H MR Spectrum of the Brain: Metabolites and Their Biomarker PotentialMR spectroscopy provides a very different basic "readout" than MR imaging, namely a spectrum rather than an techniques were developed. These early localization techniques included pointresolved spectroscopy (PRESS) (1,2) and stimulated echo acquisition mode (STEAM) (3), methods that are now widely used in clinical MR spectroscopy applications.Preliminary studies revealed large differences in metabolite levels in acute stroke (4), chronic multiple sclerosis (5), and brain tumors compared with healthy brain (6). Although this work stimulated a surge of interest in 1 H MR spectroscopy for diagnosing and assessing CNS disorders during the early days of the "Decade of the Brain" (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999), many suboptimal patient studies (7) and the lack of consistent guidelines have led to a situation where, 20 years later, MR spectroscopy is still considered an "investigational technique" by some medical professionals and health care organizations. However, the ability to make an early, noninvasive diagnosis or to increase confidence in a suspected diagnosis is highly valued by patients and clinicians alike. As a result, an increasing number of imaging centers are incorporating MR spectroscopy into their clinical protocols for brain...

show abstract

Section: Special Review: Clinical Proton Mr Spectroscopy In Central Nmentioning

confidence: 99%

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Öz¹,

Alger²,

Barker³

et al. 2014

Radiology

556

356

View full text Add to dashboard Cite

show abstract

“…A study assessing asymptomatic PGRN mutation carriers failed to find any evidence of grey matter atrophy, but did find DTI abnormalities in the left uncinate fasciculus and fronto-occipital fasciculus[83]. Studies in asymptomatic MAPT mutation carriers have also failed to identify grey matter atrophy, but have demonstrated functional connectivity abnormalities in the salience and default-mode network on resting state fMRI[9], and abnormalities in metabolite levels using magnetic resonance spectroscopy[84], that match the findings observed in bvFTD. There is also a suggestion that abnormalities on PET using microglial activation and striatal dopaminergic ligands could be identified in asymptomatic MAPT carriers[85].…”

Section: Neuroimaging Associations With Genetic Abnormalitiesmentioning

confidence: 99%

Recent Advances in the Imaging of Frontotemporal Dementia

Whitwell

Josephs

2012

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

Neuroimaging has played an important role in the characterization of the frontotemporal dementia (FTD) syndromes, demonstrating neurodegenerative signatures that can aid in the differentiation of FTD from other neurodegenerative disorders. Recent advances have been driven largely by the refinement of the clinical syndromes that underlie FTD, and by the discovery of new genetic and pathological features associated with FTD. Many new imaging techniques and modalities are also now available that allow the assessment of other aspects of brain structure and function, such as diffusion tensor imaging and resting state functional MRI. Studies have utilized these recent techniques, as well as traditional volumetric MRI, to provide further insight into disease progression across the many clinical, genetic and pathological variants of FTD. Importantly, neuroimaging signatures have been identified that will improve the clinician’s ability to predict underlying genetic and pathological features, and hence ultimately improve patient diagnosis.

show abstract

“…Case studies assessing imaging in asymptomatic MAPT carriers show mixed results, with atrophy and hypometabolism observed in some asymptomatic subjects, but not others. [11][12][13][14][15] Resting-state fMRI has recently emerged as a sensitive biomarker to detect changes in brain functional connectivity. 16 -18 Functional connectivity is altered in patients with bvFTD, 19 with reduced connectivity observed in the salience network that plays a role in processing social-emotional and homeostatically relevant stimuli, 20 and increased connectivity in the anti-correlated default mode network (DMN), involved in episodic memory function.…”

mentioning

confidence: 99%

Altered functional connectivity in asymptomatic MAPT subjects

Josephs²,

et al. 2011

Self Cite

View full text Add to dashboard Cite

Objective: To determine whether functional connectivity is altered in subjects with mutations in the microtubule associated protein tau (MAPT) gene who were asymptomatic but were destined to develop dementia, and to compare these findings to those in subjects with behavioral variant frontotemporal dementia (bvFTD). Methods:In this case-control study, we identified 8 asymptomatic subjects with mutations in MAPT and 8 controls who screened negative for mutations in MAPT. Twenty-one subjects with a clinical diagnosis of bvFTD were also identified and matched to 21 controls. All subjects had resting-state fMRI. In-phase functional connectivity was assessed between a precuneus seed in the default mode network (DMN) and a fronto-insular cortex seed in the salience network, and the rest of the brain. Atlas-based parcellation was used to assess functional connectivity and gray matter volume across specific regions of interest. Results:The asymptomatic MAPT subjects and subjects with bvFTD showed altered functional connectivity in the DMN, with reduced in-phase connectivity in lateral temporal lobes and medial prefrontal cortex, compared to controls. Increased in-phase connectivity was also observed in both groups in the medial parietal lobe. Only the bvFTD group showed altered functional connectivity in the salience network, with reduced connectivity in the fronto-insular cortex and anterior cingulate. Gray matter loss was observed across temporal, frontal, and parietal regions in bvFTD, but not in the asymptomatic MAPT subjects. Conclusions:Functional connectivity in the DMN is altered in MAPT subjects before the occurrence of both atrophy and clinical symptoms, suggesting that changes in functional connectivity are early features of the disease. Neurology ® 2011;77:866-874 GLOSSARY AD ϭ Alzheimer disease; BOLD ϭ blood oxygenation level-dependent; bvFTD ϭ behavioral variant frontotemporal dementia; DMN ϭ default mode network; FOV ϭ field of view; FTD ϭ frontotemporal dementia; FWE ϭ familywise error; ICA ϭ independent component analysis; MPRAGE ϭ magnetization-prepared rapid acquisition gradient echo; PPND ϭ pallido-ponto-nigral degeneration; ROI ϭ region of interest; TE ϭ echo time; TIV ϭ total intracranial volume; TR ϭ repetition time.Frontotemporal dementia (FTD) is a progressive neurodegenerative disorder characterized by behavioral and language deficits.1,2 A large proportion of subjects with FTD have an autosomal dominant pattern of inheritance, 3,4 with many showing mutations in the microtubule associated protein tau (MAPT) gene.5 Subjects with mutations in MAPT typically present with behavioral variant FTD (bvFTD), with poor semantic abilities, 6 -8 and show predominant temporal atrophy, with less severe involvement of frontal and parietal lobes.9,10 Families characterized by the presence of mutations in MAPT provide the ideal construct to identify preclinical disease changes. Case studies assessing imaging in asymptomatic MAPT carriers show

show abstract

MRS in presymptomatic MAPT mutation carriers

Cited by 49 publications

References 36 publications

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Recent Advances in the Imaging of Frontotemporal Dementia

Altered functional connectivity in asymptomatic MAPT subjects

Contact Info

Product

Resources

About