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Article: Using Generative Artificial Intelligence to Classify Primary Progressive Aphasia from Connected Speech.

Rezaii, Neguine / Quimby, Megan / Wong, Bonnie / Hochberg, Daisy / Brickhouse, Michael / Touroutoglou, Alexandra / Dickerson, Bradford C / Wolff, Phillip

medRxiv : the preprint server for health sciences

2023

Abstract: Neurodegenerative dementia syndromes, such as Primary Progressive Aphasias (PPA), have traditionally been diagnosed based in part on verbal and nonverbal cognitive profiles. Debate continues about whether PPA is best subdivided into three variants and ... ...

Abstract	Neurodegenerative dementia syndromes, such as Primary Progressive Aphasias (PPA), have traditionally been diagnosed based in part on verbal and nonverbal cognitive profiles. Debate continues about whether PPA is best subdivided into three variants and also regarding the most distinctive linguistic features for classifying PPA variants. In this study, we harnessed the capabilities of artificial intelligence (AI) and natural language processing (NLP) to first perform unsupervised classification of concise, connected speech samples from 78 PPA patients. Large Language Models discerned three distinct PPA clusters, with 88.5% agreement with independent clinical diagnoses. Patterns of cortical atrophy of three data-driven clusters corresponded to the localization in the clinical diagnostic criteria. We then used NLP to identify linguistic features that best dissociate the three PPA variants. Seventeen features emerged as most valuable for this purpose, including the observation that separating verbs into high and low-frequency types significantly improves classification accuracy. Using these linguistic features derived from the analysis of brief connected speech samples, we developed a classifier that achieved 97.9% accuracy in predicting PPA subtypes and healthy controls. Our findings provide pivotal insights for refining early-stage dementia diagnosis, deepening our understanding of the characteristics of these neurodegenerative phenotypes and the neurobiology of language processing, and enhancing diagnostic evaluation accuracy.
Language	English
Publishing date	2023-12-26
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.12.22.23300470
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Article ; Online: Atrophy in behavioural variant frontotemporal dementia spans multiple large-scale prefrontal and temporal networks.

Eldaief, Mark C / Brickhouse, Michael / Katsumi, Yuta / Rosen, Howard / Carvalho, Nicole / Touroutoglou, Alexandra / Dickerson, Bradford C

Brain : a journal of neurology

2023 Volume 146, Issue 11, Page(s) 4476–4485

Abstract: The identification of a neurodegenerative disorder's distributed pattern of atrophy-or atrophy 'signature'-can lend insights into the cortical networks that degenerate in individuals with specific constellations of symptoms. In addition, this signature ... ...

Abstract	The identification of a neurodegenerative disorder's distributed pattern of atrophy-or atrophy 'signature'-can lend insights into the cortical networks that degenerate in individuals with specific constellations of symptoms. In addition, this signature can be used as a biomarker to support early diagnoses and to potentially reveal pathological changes associated with said disorder. Here, we characterized the cortical atrophy signature of behavioural variant frontotemporal dementia (bvFTD). We used a data-driven approach to estimate cortical thickness using surface-based analyses in two independent, sporadic bvFTD samples (n = 30 and n = 71, total n = 101), using age- and gender-matched cognitively and behaviourally normal individuals. We found highly similar patterns of cortical atrophy across the two independent samples, supporting the reliability of our bvFTD signature. Next, we investigated whether our bvFTD signature targets specific large-scale cortical networks, as is the case for other neurodegenerative disorders. We specifically asked whether the bvFTD signature topographically overlaps with the salience network, as previous reports have suggested. We hypothesized that because phenotypic presentations of bvFTD are diverse, this would not be the case, and that the signature would cross canonical network boundaries. Consistent with our hypothesis, the bvFTD signature spanned rostral portions of multiple networks, including the default mode, limbic, frontoparietal control and salience networks. We then tested whether the signature comprised multiple anatomical subtypes, which themselves overlapped with specific networks. To explore this, we performed a hierarchical clustering analysis. This yielded three clusters, only one of which extensively overlapped with a canonical network (the limbic network). Taken together, these findings argue against the hypothesis that the salience network is preferentially affected in bvFTD, but rather suggest that-at least in patients who meet diagnostic criteria for the full-blown syndrome-neurodegeneration in bvFTD encompasses a distributed set of prefrontal, insular and anterior temporal nodes of multiple large-scale brain networks, in keeping with the phenotypic diversity of this disorder.
MeSH term(s)	Humans ; Frontotemporal Dementia/pathology ; Reproducibility of Results ; Magnetic Resonance Imaging ; Brain/pathology ; Atrophy/pathology
Language	English
Publishing date	2023-05-19
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80072-7
ISSN	1460-2156 ; 0006-8950
ISSN (online)	1460-2156
ISSN	0006-8950
DOI	10.1093/brain/awad167
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Article ; Online: Gray to white matter signal ratio as a novel biomarker of neurodegeneration in Alzheimer's disease.

Putcha, Deepti / Katsumi, Yuta / Brickhouse, Michael / Flaherty, Ryn / Salat, David H / Touroutoglou, Alexandra / Dickerson, Bradford C

NeuroImage. Clinical

2022 Volume 37, Page(s) 103303

Abstract: Alzheimer's disease (AD) is characterized neuropathologically by β-amyloid (Aβ) plaques, hyperphosphorylated tau neurofibrillary tangles, and neurodegeneration, which lead to a phenotypically heterogeneous cognitive-behavioral dementia syndrome. Our ... ...

Abstract	Alzheimer's disease (AD) is characterized neuropathologically by β-amyloid (Aβ) plaques, hyperphosphorylated tau neurofibrillary tangles, and neurodegeneration, which lead to a phenotypically heterogeneous cognitive-behavioral dementia syndrome. Our understanding of how these neuropathological and neurodegeneration biomarkers relate to each other is still evolving. A relatively new approach to measuring structural brain change, gray matter to white matter signal intensity ratio (GWR), quantifies the signal contrast between these tissue compartments, and has emerged as a promising marker of AD-related neurodegeneration. We sought to validate GWR as a novel MRI biomarker of neurodegeneration in 29 biomarker positive individuals across the atypical syndromic spectrum of AD. Bivariate correlation analyses revealed that GWR was associated with cortical thickness, tau PET, and amyloid PET, with GWR showing a larger magnitude of abnormality than cortical thickness. We also found that combining GWR, cortical thickness, and amyloid PET better explained observed tau PET signal than using these modalities alone, suggesting that the three imaging biomarkers contribute independently and synergistically to explaining the variance in the distribution of tau pathology. We conclude that GWR is a uniquely sensitive in vivo marker of neurodegenerative change that reflects pathological mechanisms which may occur prior to cortical atrophy. By using all of these imaging biomarkers of AD together, we may be better able to capture, and possibly predict, AD neuropathologic changes in vivo. We hope that such an approach will ultimately contribute to better endpoints to evaluate the efficacy of therapeutic interventions as we move toward an era of disease-modifying treatments for this devastating disease.
MeSH term(s)	Humans ; Alzheimer Disease/pathology ; White Matter/pathology ; Positron-Emission Tomography ; Amyloid beta-Peptides/metabolism ; Magnetic Resonance Imaging ; Amyloid/metabolism ; Biomarkers ; tau Proteins/metabolism ; Gray Matter/pathology ; Cognitive Dysfunction/pathology
Chemical Substances	Amyloid beta-Peptides ; Amyloid ; Biomarkers ; tau Proteins
Language	English
Publishing date	2022-12-24
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2701571-3
ISSN	2213-1582 ; 2213-1582
ISSN (online)	2213-1582
ISSN	2213-1582
DOI	10.1016/j.nicl.2022.103303
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Article ; Online: Clinical, radiologic, and pathologic features of the globular glial tauopathy subtype of frontotemporal lobar degeneration in right temporal variant frontotemporal dementia with salient features of Geschwind syndrome.

Josephy-Hernandez, Sylvia / Brickhouse, Michael / Champion, Samantha / Kim, David Dongkyung / Touroutoglou, Alexandra / Frosch, Matthew / Dickerson, Bradford C

Neurocase

2022 Volume 28, Issue 4, Page(s) 375–381

Abstract: Globular Glial Tauopathy (GGT) is a rare form of Frontotemporal Lobar Degeneration (FTLD) consisting of 4-repeat tau globular inclusions in astrocytes and oligodendrocytes. We present the pathological findings of GGT in a previously published case of a ... ...

Abstract	Globular Glial Tauopathy (GGT) is a rare form of Frontotemporal Lobar Degeneration (FTLD) consisting of 4-repeat tau globular inclusions in astrocytes and oligodendrocytes. We present the pathological findings of GGT in a previously published case of a 73-year-old woman with behavioral symptoms concerning for right temporal variant frontotemporal dementia with initial and salient features of Geschwind syndrome. Clinically, she lacked motor abnormalities otherwise common in previously published GGT cases. Brain MRI showed focal right anterior temporal atrophy (indistinguishable from five FTLD-TDP cases) and subtle ipsilateral white matter signal abnormalities. Brain autopsy showed GGT type III and Alzheimer's neuropathologic changes. .
MeSH term(s)	Female ; Humans ; Frontotemporal Dementia/diagnostic imaging ; Frontotemporal Dementia/pathology ; tau Proteins/metabolism ; Tauopathies/diagnostic imaging ; Tauopathies/pathology ; Pick Disease of the Brain/pathology ; Frontotemporal Lobar Degeneration/diagnostic imaging ; Frontotemporal Lobar Degeneration/pathology ; Brain/pathology ; Atrophy/pathology
Chemical Substances	tau Proteins
Language	English
Publishing date	2022-10-17
Publishing country	England
Document type	Case Reports ; Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1302651-3
ISSN	1465-3656 ; 1355-4794
ISSN (online)	1465-3656
ISSN	1355-4794
DOI	10.1080/13554794.2022.2130805
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Article ; Online: Association of Regional Cortical Network Atrophy With Progression to Dementia in Patients With Primary Progressive Aphasia.

Katsumi, Yuta / Quimby, Megan / Hochberg, Daisy / Jones, Amelia / Brickhouse, Michael / Eldaief, Mark C / Dickerson, Bradford C / Touroutoglou, Alexandra

Neurology

2022 Volume 100, Issue 3, Page(s) e286–e296

Abstract: Background and objectives: Patients with primary progressive aphasia (PPA) have gradually progressive language deficits during the initial phase of the illness. As the underlying neurodegenerative disease progresses, patients with PPA start losing ... ...

Abstract	Background and objectives: Patients with primary progressive aphasia (PPA) have gradually progressive language deficits during the initial phase of the illness. As the underlying neurodegenerative disease progresses, patients with PPA start losing independent functioning due to the development of nonlanguage cognitive or behavioral symptoms. The timeline of this progression from the mild cognitive impairment stage to the dementia stage of PPA is variable across patients. In this study, in a sample of patients with PPA, we measured the magnitude of cortical atrophy within functional networks believed to subserve diverse cognitive and affective functions. The objective of the study was to evaluate the utility of this measure as a predictor of time to subsequent progression to dementia in PPA. Methods: Patients with PPA with largely independent daily function were recruited through the Massachusetts General Hospital Frontotemporal Disorders Unit. All patients underwent an MRI scan at baseline. Cortical atrophy was then estimated relative to a group of amyloid-negative cognitively normal control participants. For each patient, we measured the time between the baseline visit and the subsequent visit at which dementia progression was documented or last observation. Simple and multivariable Cox regression models were used to examine the relationship between cortical atrophy and the likelihood of progression to dementia. Results: Forty-nine patients with PPA (mean age = 66.39 ± 8.36 years, 59.2% females) and 25 controls (mean age = 67.43 ± 4.84 years, 48% females) were included in the data analysis. Greater baseline atrophy in not only the left language network (hazard ratio = 1.47, 95% CI = 1.17-1.84) but also in the frontoparietal control (1.75, 1.25-2.44), salience (1.63, 1.25-2.13), default mode (1.55, 1.19-2.01), and ventral frontotemporal (1.41, 1.16-1.71) networks was associated with a higher risk of progression to dementia. A multivariable model identified contributions of the left frontoparietal control (1.94, 1.09-3.48) and ventral frontotemporal (1.61, 1.09-2.39) networks in predicting dementia progression, with no additional variance explained by the language network (0.75, 0.43-1.31). Discussion: These results suggest that baseline atrophy in cortical networks subserving nonlanguage cognitive and affective functions is an important predictor of progression to dementia in PPA. This measure should be included in precision medicine models of prognosis in PPA.
MeSH term(s)	Female ; Humans ; Middle Aged ; Aged ; Male ; Aphasia, Primary Progressive ; Brain/pathology ; Neurodegenerative Diseases/pathology ; Neuropsychological Tests ; Magnetic Resonance Imaging ; Atrophy/pathology
Language	English
Publishing date	2022-10-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000201403
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Article ; Online: Fractionating the Rey Auditory Verbal Learning Test: Distinct roles of large-scale cortical networks in prodromal Alzheimer's disease.

Putcha, Deepti / Brickhouse, Michael / Wolk, David A / Dickerson, Bradford C

Neuropsychologia

2019 Volume 129, Page(s) 83–92

Abstract: Successful episodic memory calls upon a number of different cognitive processes that are supported by the coordination of several large-scale cortical networks. Previous work from our group has demonstrated dissociable anatomic substrates at different ... ...

Abstract	Successful episodic memory calls upon a number of different cognitive processes that are supported by the coordination of several large-scale cortical networks. Previous work from our group has demonstrated dissociable anatomic substrates at different stages of memory in patients with dementia due to Alzheimer's disease (AD). The aim of the current study was to extend the understanding of brain-behavior associations underlying a commonly administered neuropsychological assessment of verbal episodic memory (Rey Auditory Verbal Learning Test; RAVLT) by determining the cortical network contributions to the performance at early vs. late stages of list learning, delayed recall, and retention, in 235 very mild biomarker positive (A+/T+/N+) individuals diagnosed with amnestic mild cognitive impairment (aMCI; MMSE = 27.7). We measured cortical atrophy in four large-scale cortical networks impacted by AD: default mode (DMN), dorsal attention (DAN), frontoparietal (FPN), and language (LN) networks. We also evaluated the role of hippocampal atrophy at each stage of memory performance. Partial correlation analyses controlling for age, sex, and education and corrected for multiple comparisons revealed that early learning was most strongly associated with cortical thickness in the DAN, while late learning was most strongly associated with hippocampal volume, but also related to cortical thickness in the DAN, FPN, DMN, and LN. Delayed recall was associated most strongly with hippocampal volume, but was also related to cortical thickness in the FPN and DMN, while retention was associated only with hippocampal volume. These findings are consistent with prior models of the neural substrates of different stages of verbal list learning and retrieval, provide new insights into the cortical networks undergoing neurodegeneration even at very mild stages of prodromal AD, and inform our thinking about the networks and regions being interrogated by this kind of neuropsychological assessment of episodic memory.
MeSH term(s)	Aged ; Aged, 80 and over ; Alzheimer Disease/diagnostic imaging ; Alzheimer Disease/pathology ; Alzheimer Disease/physiopathology ; Amnesia/diagnostic imaging ; Amnesia/pathology ; Amnesia/physiopathology ; Cerebral Cortex/diagnostic imaging ; Cerebral Cortex/pathology ; Cerebral Cortex/physiopathology ; Cognitive Dysfunction/diagnostic imaging ; Cognitive Dysfunction/pathology ; Cognitive Dysfunction/physiopathology ; Female ; Hippocampus/diagnostic imaging ; Hippocampus/pathology ; Hippocampus/physiopathology ; Humans ; Magnetic Resonance Imaging ; Male ; Memory, Episodic ; Mental Recall/physiology ; Nerve Net/diagnostic imaging ; Nerve Net/pathology ; Nerve Net/physiopathology ; Neuropsychological Tests ; Prodromal Symptoms ; Retention, Psychology/physiology ; Verbal Learning/physiology
Language	English
Publishing date	2019-03-28
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	207151-4
ISSN	1873-3514 ; 0028-3932
ISSN (online)	1873-3514
ISSN	0028-3932
DOI	10.1016/j.neuropsychologia.2019.03.015
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Article ; Online: Word retrieval across the biomarker-confirmed Alzheimer's disease syndromic spectrum.

Putcha, Deepti / Dickerson, Bradford C / Brickhouse, Michael / Johnson, Keith A / Sperling, Reisa A / Papp, Kathryn V

Neuropsychologia

2020 Volume 140, Page(s) 107391

Abstract: Alzheimer's disease (AD) is now conceptualized as a biological entity defined by amyloid and tau deposition and neurodegeneration, with heterogeneous clinical presentations. With the aid of in vivo biomarkers, clinicians are better poised to examine ... ...

Abstract	Alzheimer's disease (AD) is now conceptualized as a biological entity defined by amyloid and tau deposition and neurodegeneration, with heterogeneous clinical presentations. With the aid of in vivo biomarkers, clinicians are better poised to examine clinical syndromic variability arising from a common pathology. Word retrieval deficits, measured using verbal fluency and confrontation naming tests, are hallmark features of the early clinical stages of the amnestic presentations of AD, specifically in category fluency and naming with relatively spared letter fluency. As yet, there is no consensus regarding performance on these tests in atypical clinical phenotypes of AD, including posterior cortical atrophy (PCA) and logopenic primary progressive aphasia (lvPPA), in individuals who are amyloid-positive (Aβ+) but present with different clinical profiles and patterns of neurodegeneration compared to amnestic AD. The goal of the current study is to determine how Aβ+ individuals across the syndromic spectrum of AD perform on three different word retrieval tasks. A secondary goal is to determine the neuroanatomical substrates underlying word retrieval performance in these Aβ+ individuals. Thirty-two Aβ+ participants with the amnestic presentation, 16 with Aβ+ PCA, 22 with Aβ+ lvPPA, and 99 amyloid-negative (Aβ-) control participants were evaluated with verbal fluency and visual confrontation naming tests as well as high-resolution MRI. The Aβ+ patient groups were rated at very mild or mild levels of severity (CDR 0.5 or 1) and had comparable levels of global cognitive impairment (average MMSE = 23.7 ± 3.9). Behaviorally, we found that the word retrieval profile of PCA patients is comparable to that of amnestic patients, characterized by intact letter fluency but impaired category fluency and visual confrontation naming, while lvPPA patients demonstrated impairment across all tests of word retrieval. Across all AD variants, we observed that letter fluency was associated with cortical thickness in prefrontal, central precuneus, lateral parietal and temporal cortex, while category fluency and naming were associated with cortical thickness in left middle frontal gyrus, posterior middle temporal gyrus, and lateral parietal cortex. Visual confrontation naming was uniquely associated with atrophy in inferior temporal and visual association cortex. We conclude that a better understanding of the word retrieval profiles and underlying neurodegeneration across the AD syndromic spectrum will help improve interpretation of neuropsychological profiles with regard to the localization of neurodegeneration, particularly in the atypical AD variants.
MeSH term(s)	Aged ; Alzheimer Disease/complications ; Alzheimer Disease/pathology ; Aphasia, Primary Progressive/diagnostic imaging ; Aphasia, Primary Progressive/pathology ; Atrophy/pathology ; Biomarkers ; Cerebral Cortex/pathology ; Female ; Humans ; Male ; Middle Aged ; Neuropsychological Tests
Chemical Substances	Biomarkers
Language	English
Publishing date	2020-02-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	207151-4
ISSN	1873-3514 ; 0028-3932
ISSN (online)	1873-3514
ISSN	0028-3932
DOI	10.1016/j.neuropsychologia.2020.107391
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Article: The personalized Alzheimer's disease cortical thickness index predicts likely pathology and clinical progression in mild cognitive impairment.

Racine, Annie M / Brickhouse, Michael / Wolk, David A / Dickerson, Bradford C

Alzheimer's & dementia (Amsterdam, Netherlands)

2018 Volume 10, Page(s) 301–310

Abstract: Introduction: An Alzheimer's disease (AD) biomarker adjusted for age-related brain changes should improve specificity for AD-related pathological burden.: Methods: We calculated a brain-age-adjusted "personalized AD cortical thickness index" (pADi) ... ...

Abstract	Introduction: An Alzheimer's disease (AD) biomarker adjusted for age-related brain changes should improve specificity for AD-related pathological burden. Methods: We calculated a brain-age-adjusted "personalized AD cortical thickness index" (pADi) in mild cognitive impairment patients from the Alzheimer's Disease Neuroimaging Initiative. We performed receiver operating characteristic analysis for discrimination between patients with and without cerebrospinal fluid evidence of AD and logistic regression in an independent sample to determine if a dichotomized pADi predicted conversion to AD dementia. Results: Receiver operating characteristic area under the curve was 0.69 and 0.72 in the two samples. Three empirical methods identified the same cut-point for pADi in the discovery sample. In the validation sample, 83% of pADi+ mild cognitive impairment patients were cerebrospinal fluid AD biomarker positive. pADi+ mild cognitive impairment patients (n = 63, 38%) were more likely to progress to AD dementia after 1 (odds ratio = 2.9) and 3 (odds ratio = 2.6) years. Discussion: The pADi is a personalized, magnetic resonance imaging-derived AD biomarker that predicts progression to dementia.
Language	English
Publishing date	2018-03-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2832898-X
ISSN	2352-8729
ISSN	2352-8729
DOI	10.1016/j.dadm.2018.02.007
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Article ; Online: Regional prefrontal cortical atrophy predicts specific cognitive-behavioral symptoms in ALS-FTD.

Ratti, Elena / Domoto-Reilly, Kimiko / Caso, Christina / Murphy, Alyssa / Brickhouse, Michael / Hochberg, Daisy / Makris, Nikos / Cudkowicz, Merit E / Dickerson, Bradford C

Brain imaging and behavior

2021 Volume 15, Issue 5, Page(s) 2540–2551

Abstract: Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) may present typical behavioral variant FTD symptoms. This study aims to determine whether profile and severity of cognitive-behavioral symptoms in ALS/ALS-FTD are predicted by regional ... ...

Abstract	Amyotrophic Lateral Sclerosis-Frontotemporal Dementia (ALS-FTD) may present typical behavioral variant FTD symptoms. This study aims to determine whether profile and severity of cognitive-behavioral symptoms in ALS/ALS-FTD are predicted by regional cortical atrophy. The hypothesis is that executive dysfunction can be predicted by dorsolateral prefrontal cortical (dlPFC) atrophy, apathy by dorsomedial PFC (dmPFC) and anterior cingulate cortical (ACC) atrophy, disinhibition by orbitofrontal cortical (OFC) atrophy. 3.0 Tesla MRI scans were acquired from 22 people with ALS or ALS-FTD. Quantitative cortical thickness analysis was performed with FreeSurfer. A priori-defined regions of interest (ROI) were used to measure cortical thickness in each participant and calculate magnitude of atrophy in comparison to 115 healthy controls. Spearman correlations were used to evaluate associations between frontal ROI cortical thickness and cognitive-behavioral symptoms, measured by Neuropsychiatric Inventory Questionnaire (NPI-Q) and Clinical Dementia Rating (CDR) scale. ALS-FTD participants exhibited variable degrees of apathy (NPI-Q/apathy: 1.6 ± 1.2), disinhibition (NPI-Q/disinhibition: 1.2 ± 1.2), executive dysfunction (CDR/judgment-problem solving: 1.7 ± 0.8). Within the ALS-FTD group, executive dysfunction correlated with dlPFC atrophy (ρ:-0.65;p < 0.05); similar trends were seen for apathy with ACC (ρ:-0.53;p < 0.10) and dmPFC (ρ:-0.47;p < 0.10) atrophy, for disinhibition with OFC atrophy (ρ:-0.51;p < 0.10). Compared to people with ALS, those with ALS-FTD showed more diffuse atrophy involving precentral gyrus, prefrontal, temporal regions. Profile and severity of cognitive-behavioral symptoms in ALS-FTD are predicted by regional prefrontal atrophy. These findings are consistent with established brain-behavior models and support the role of quantitative MRI in diagnosis, management, counseling, monitoring and prognostication for a neurodegenerative disorder with diverse phenotypes.
MeSH term(s)	Amyotrophic Lateral Sclerosis/diagnostic imaging ; Atrophy ; Behavioral Symptoms ; Cognition ; Frontotemporal Dementia/diagnostic imaging ; Humans ; Magnetic Resonance Imaging
Language	English
Publishing date	2021-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2377165-3
ISSN	1931-7565 ; 1931-7557
ISSN (online)	1931-7565
ISSN	1931-7557
DOI	10.1007/s11682-021-00456-1
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Article ; Online: Quantification of motor speech impairment and its anatomic basis in primary progressive aphasia.

Cordella, Claire / Quimby, Megan / Touroutoglou, Alexandra / Brickhouse, Michael / Dickerson, Bradford C / Green, Jordan R

Neurology

2019 Volume 92, Issue 17, Page(s) e1992–e2004

Abstract: Objective: To evaluate whether a quantitative speech measure is effective in identifying and monitoring motor speech impairment (MSI) in patients with primary progressive aphasia (PPA) and to investigate the neuroanatomical basis of MSI in PPA.: ... ...

Abstract	Objective: To evaluate whether a quantitative speech measure is effective in identifying and monitoring motor speech impairment (MSI) in patients with primary progressive aphasia (PPA) and to investigate the neuroanatomical basis of MSI in PPA. Methods: Sixty-four patients with PPA were evaluated at baseline, with a subset (n = 39) evaluated longitudinally. Articulation rate (AR), a quantitative measure derived from spontaneous speech, was measured at each time point. MRI was collected at baseline. Differences in baseline AR were assessed across PPA subtypes, separated by severity level. Linear mixed-effects models were conducted to assess groups differences across PPA subtypes in rate of decline in AR over a 1-year period. Cortical thickness measured from baseline MRIs was used to test hypotheses about the relationship between cortical atrophy and MSI. Results: Baseline AR was reduced for patients with nonfluent variant PPA (nfvPPA) compared to other PPA subtypes and controls, even in mild stages of disease. Longitudinal results showed a greater rate of decline in AR for the nfvPPA group over 1 year compared to the logopenic and semantic variant subgroups. Reduced baseline AR was associated with cortical atrophy in left-hemisphere premotor and supplementary motor cortices. Conclusions: The AR measure is an effective quantitative index of MSI that detects MSI in mild disease stages and tracks decline in MSI longitudinally. The AR measure also demonstrates anatomic localization to motor speech-specific cortical regions. Our findings suggest that this quantitative measure of MSI might have utility in diagnostic evaluation and monitoring of MSI in PPA.
MeSH term(s)	Aged ; Aphasia, Primary Progressive/diagnostic imaging ; Aphasia, Primary Progressive/pathology ; Aphasia, Primary Progressive/physiopathology ; Atrophy/diagnostic imaging ; Atrophy/pathology ; Comprehension/physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Motor Cortex/diagnostic imaging ; Motor Cortex/pathology ; Speech/physiology
Language	English
Publishing date	2019-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/WNL.0000000000007367
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In stock of ZB MED Cologne/Königswinter

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