Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA

Mandelli, Maria Luisa; Vitali, Paolo; Santos, Miguel; Henry, Maya L.; Gola, Kelly A.; Rosenberg, Lynne; Dronkers, Nina F.; Miller, Bruce L.; Seeley, William W.

doi:10.1016/j.cortex.2015.10.012

Cited by 58 publications

(50 citation statements)

References 61 publications

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“…3D T1-weighted images with a magnetization-prepared rapid gradient echo sequence (MPRAGE) were obtained from patients and controls using either a 1.5 31 , 3 31 , or 4 Tesla 32 scanner.…”

Section: Methodsmentioning

confidence: 99%

Typical and atypical pathology in primary progressive aphasia variants

Spinelli

Mandelli

Miller

et al. 2017

Annals of Neurology

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Objective To characterize in vivo signatures of pathological diagnosis in a large cohort of patients with primary progressive aphasia (PPA) variants defined by current diagnostic classification. Methods Extensive clinical, cognitive, neuroimaging, and neuropathological data were collected from 69 patients with sporadic PPA, divided into 29 semantic (svPPA), 25 non-fluent (nfvPPA), 11 logopenic (lvPPA), and 4 mixed PPA. Patterns of grey matter (GM) and white matter (WM) atrophy at presentation were assessed and tested as predictors of pathological diagnosis using support vector machine (SVM) algorithms. Results A clinical diagnosis of PPA was associated with frontotemporal lobar degeneration (FTLD) with TDP inclusions in 40.5%, FTLD-tau in 40.5%, and Alzheimer’s disease (AD) pathology in 19% of cases. Each variant was associated with one typical pathology: 24/29 (83%) svPPA showed FTLD-TDP type C, 22/25 (88%) nfvPPA showed FTLD-tau, and all 11 lvPPA had AD. Within FTLD-tau, 4R-tau pathology was commonly associated with nfvPPA, whereas Pick’s disease was observed in a minority of subjects across all variants except for lvPPA. Compared with pathologically typical cases, svPPA-tau showed significant extrapyramidal signs, greater executive impairment, and severe striatal and frontal GM and WM atrophy. nfvPPA-TDP patients lacked general motor symptoms or significant WM atrophy. Combining GM and WM volumes, SVM analysis showed 92.7% accuracy to distinguish FTLD-tau and FTLD-TDP pathologies across variants. Interpretation Each PPA clinical variant is associated with a typical and most frequent cognitive, neuroimaging, and neuropathological profile. Specific clinical and early anatomical features may suggest rare and atypical pathological diagnosis in vivo.

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“…3D T1-weighted images with a magnetization-prepared rapid gradient echo sequence (MPRAGE) were obtained from patients and controls using either a 1.5 31 , 3 31 , or 4 Tesla 32 scanner.…”

Section: Methodsmentioning

confidence: 99%

Typical and atypical pathology in primary progressive aphasia variants

Spinelli

Mandelli

Miller

et al. 2017

Annals of Neurology

Self Cite

325

340

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“…A flow diagram showing the identification and exclusion of studies is provided in Figure 1. Ultimately, a total of 37 studies were included in the meta-analysis, including 19 on bvFTD (one study included three bvFTD groups) (Rosen et al, 2002;Grossman et al, 2004;Boccardi et al, 2005;Kanda et al, 2008;Seeley et al, 2008;Ash et al, 2009;Kipps et al, 2009;Libon et al, 2009;Pardini et al, 2009;Hornberger et al, 2011;Farb et al, 2013;Massimo et al, 2013;Lagarde et al, 2015;Yokoyama et al, 2015;Dermody et al, 2016;Mandelli et al, 2016;Melloni et al, 2016;Buhour et al, 2017a;Bertoux et al, 2018) and 18 on ALS (Chang et al, 2005;Grosskreutz et al, 2006;Agosta et al, 2007;Mezzapesa et al, 2007;Thivard et al, 2007;Grossman et al, 2008;Cosottini et al, 2012;Tedeschi et al, 2012;Meoded et al, 2013;Cerami et al, 2014;Zhang et al, 2014;Devine et al, 2015;Raaphorst et al, 2015;Tavazzi et al, 2015;Zhu et al, 2015;Buhour et al, 2017b;Kim et al, 2017;Christidi et al, 2018…”

Section: Study Selection and Characteristicsmentioning

confidence: 99%

Comparison of Gray Matter Atrophy in Behavioral Variant Frontal Temporal Dementia and Amyotrophic Lateral Sclerosis: A Coordinate-Based Meta-Analysis

Chen

Xiao

et al. 2020

Front. Aging Neurosci.

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Background: There is growing evidence supporting behavioral variant frontotemporal dementia (bvFTD) and amyotrophic lateral sclerosis (ALS) as extreme points of a disease spectrum. The aim of this study was to delineate the common and different patterns of gray matter atrophy associated with bvFTD and with ALS by pooling together the results of previous voxel-based morphometry (VBM) studies. Methods:We retrieved VBM studies that investigated gray matter atrophy in bvFTD patients vs. controls and in ALS patients vs. controls. Stereotactic data were extracted from those studies and subsequently tested for convergence and differences using activation likelihood estimation (ALE). A behavioral analysis using the BrainMap database was performed to assess the functional roles of the regions affected by bvFTD and/or ALS.Results: Our study demonstrated a convergence of gray matter atrophy in the frontolimbic structures that involve the bilateral anterior insula and anterior cingulate cortex. Comparing the pattern of GM atrophy in bvFTD and ALS patients revealed greater atrophy in the frontomedial cortex, bilateral caudate, left anterior insula, and right thalamus in those with bvFTD and a higher degree of atrophy in the right motor cortex of those with ALS. Behavioral analysis revealed that the pattern of the affected regions contributed to the dysfunction of emotional and cognitive processing in bvFTD patients and the dysfunction of motor execution in ALS patients. Conclusion:Our results revealed a shared neural basis between bvFTD and ALS subjects, as well as a specific and distinct neural signature that underpinned the clinical manifestations of those two diseases. Those findings outlined the role of the frontomedial-caudate circuit in the development of bvFTD-like deficits in ALS patients.

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“…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. [8][9][10][11] Changes in neuronal connectivity observed by DTI stresses the involvement of white matter structures. Mendes et al identified focal microhemorrhages in their cohort of FTD patients with unique focal prevalence for each sub-diagnosis.…”

Section: Introductionmentioning

confidence: 98%

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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Two insular regions are differentially involved in behavioral variant FTD and nonfluent/agrammatic variant PPA

Cited by 58 publications

References 61 publications

Typical and atypical pathology in primary progressive aphasia variants

Typical and atypical pathology in primary progressive aphasia variants

Comparison of Gray Matter Atrophy in Behavioral Variant Frontal Temporal Dementia and Amyotrophic Lateral Sclerosis: A Coordinate-Based Meta-Analysis

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

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