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  1. Article ; Online: Tractography of supplementary motor area projections in progressive speech apraxia and aphasia

    Adrian Valls Carbo / Robert I. Reid / Nirubol Tosakulwong / Stephen D. Weigand / Joseph R. Duffy / Heather M. Clark / Rene L. Utianski / Hugo Botha / Mary M. Machulda / Edythe A. Strand / Christopher G. Schwarz / Clifford R. Jack / Keith A. Josephs / Jennifer L. Whitwell

    NeuroImage: Clinical, Vol 34, Iss , Pp 102999- (2022)

    2022  

    Abstract: Progressive apraxia of speech (AOS) is a motor speech disorder affecting the ability to produce phonetically or prosodically normal speech. Progressive AOS can present in isolation or co-occur with agrammatic aphasia and is associated with degeneration ... ...

    Abstract Progressive apraxia of speech (AOS) is a motor speech disorder affecting the ability to produce phonetically or prosodically normal speech. Progressive AOS can present in isolation or co-occur with agrammatic aphasia and is associated with degeneration of the supplementary motor area. We aimed to assess breakdowns in structural connectivity from the supplementary motor area in patients with any combination of progressive AOS and/or agrammatic aphasia to determine which supplementary motor area tracts are specifically related to these clinical symptoms. Eighty-four patients with progressive AOS or progressive agrammatic aphasia were recruited by the Neurodegenerative Research Group and underwent neurological, speech/language, and neuropsychological testing, as well as 3 T diffusion magnetic resonance imaging. Of the 84 patients, 36 had apraxia of speech in isolation (primary progressive apraxia of speech, PPAOS), 40 had apraxia of speech and agrammatic aphasia (AOS-PAA), and eight had agrammatic aphasia in isolation (progressive agrammatic aphasia, PAA). Tractography was performed to identify 5 distinct tracts connecting to the supplementary motor area. Fractional anisotropy and mean diffusivity were assessed at 10 positions along the length of the tracts to construct tract profiles, and median profiles were calculated for each tract. In a case-control comparison, decreased fractional anisotropy and increased mean diffusivity were observed along the supplementary motor area commissural fibers in all three groups compared to controls. PPAOS also had abnormal diffusion in tracts from the supplementary motor area to the putamen, prefrontal cortex, Broca’s area (frontal aslant tract) and motor cortex, with greatest abnormalities observed closest to the supplementary motor area. The AOS-PAA group showed abnormalities in the same set of tracts, but with greater involvement of the supplementary motor area to prefrontal tract compared to PPAOS. PAA showed abnormalities in the left prefrontal and frontal aslant tracts ...
    Keywords DTI ; Tractography ; Apraxia of speech ; Agrammatism ; Primary progressive aphasia ; Frontal aslant tract ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 796
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Causal structure discovery identifies risk factors and early brain markers related to evolution of white matter hyperintensities

    Xinpeng Shen / Sheelakumari Raghavan / Scott A. Przybelski / Timothy G. Lesnick / Sisi Ma / Robert I. Reid / Jonathan Graff-Radford / Michelle M. Mielke / David S. Knopman / Ronald C. Petersen / Clifford R. Jack Jr. / György J. Simon / Prashanthi Vemuri

    NeuroImage: Clinical, Vol 35, Iss , Pp 103077- (2022)

    2022  

    Abstract: Our goal was to understand the complex relationship between age, sex, midlife risk factors, and early white matter changes measured by diffusion tensor imaging (DTI) and their role in the evolution of longitudinal white matter hyperintensities (WMH). We ... ...

    Abstract Our goal was to understand the complex relationship between age, sex, midlife risk factors, and early white matter changes measured by diffusion tensor imaging (DTI) and their role in the evolution of longitudinal white matter hyperintensities (WMH). We identified 1564 participants (1396 cognitively unimpaired, 151 mild cognitive impairment and 17 dementia participants) with age ranges of 30–90 years from the population-based sample of Mayo Clinic Study of Aging. We used computational causal structure discovery and regression analyses to evaluate the predictors of WMH and DTI, and to ascertain the mediating effect of DTI on WMH. We further derived causal graphs to understand the complex interrelationships between midlife protective factors, vascular risk factors, diffusion changes, and WMH. Older age, female sex, and hypertension were associated with higher baseline and progression of WMH as well as DTI measures (P ≤ 0.003). The effects of hypertension and sex on WMH were partially mediated by microstructural changes measured on DTI. Higher midlife physical activity was predictive of lower WMH through a direct impact on better white matter tract integrity as well as an indirect effect through reducing the risk of hypertension by lowering BMI. This study identified key risks factors, early brain changes, and pathways that may lead to the evolution of WMH.
    Keywords Diffusion MRI ; White matter health ; FLAIR ; White matter hyperintensities ; Causal discovery ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 610
    Language English
    Publishing date 2022-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Evidence against a temporal association between cerebrovascular disease and Alzheimer’s disease imaging biomarkers

    Petrice M. Cogswell / Emily S. Lundt / Terry M. Therneau / Carly T. Mester / Heather J. Wiste / Jonathan Graff-Radford / Christopher G. Schwarz / Matthew L. Senjem / Jeffrey L. Gunter / Robert I. Reid / Scott A. Przybelski / David S. Knopman / Prashanthi Vemuri / Ronald C. Petersen / Clifford R. Jack

    Nature Communications, Vol 14, Iss 1, Pp 1-

    2023  Volume 12

    Abstract: Abstract Whether a relationship exists between cerebrovascular disease and Alzheimer’s disease has been a source of controversy. Evaluation of the temporal progression of imaging biomarkers of these disease processes may inform mechanistic associations. ... ...

    Abstract Abstract Whether a relationship exists between cerebrovascular disease and Alzheimer’s disease has been a source of controversy. Evaluation of the temporal progression of imaging biomarkers of these disease processes may inform mechanistic associations. We investigate the relationship of disease trajectories of cerebrovascular disease (white matter hyperintensity, WMH, and fractional anisotropy, FA) and Alzheimer’s disease (amyloid and tau PET) biomarkers in 2406 Mayo Clinic Study of Aging and Mayo Alzheimer’s Disease Research Center participants using accelerated failure time models. The model assumes a common pattern of progression for each biomarker that is shifted earlier or later in time for each individual and represented by a per participant age adjustment. An individual’s amyloid and tau PET adjustments show very weak temporal association with WMH and FA adjustments (R = −0.07 to 0.07); early/late amyloid or tau timing explains <1% of the variation in WMH and FA adjustment. Earlier onset of amyloid is associated with earlier onset of tau (R = 0.57, R2 = 32%). These findings support a strong mechanistic relationship between amyloid and tau aggregation, but not between WMH or FA and amyloid or tau PET.
    Keywords Science ; Q
    Subject code 610
    Language English
    Publishing date 2023-05-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Neuroimaging correlates of gait abnormalities in progressive supranuclear palsy

    Irene Sintini / Kenton Kaufman / Hugo Botha / Peter R. Martin / Stacy R. Loushin / Matthew L. Senjem / Robert I. Reid / Christopher G. Schwarz / Clifford R. Jack Jr / Val J. Lowe / Keith A. Josephs / Jennifer L. Whitwell / Farwa Ali

    NeuroImage: Clinical, Vol 32, Iss , Pp 102850- (2021)

    2021  

    Abstract: Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear ... ...

    Abstract Progressive supranuclear palsy is a neurodegenerative disorder characterized primarily by tau inclusions and neurodegeneration in the midbrain, basal ganglia, thalamus, premotor and frontal cortex. Neurodegenerative change in progressive supranuclear palsy has been assessed using MRI. Degeneration of white matter tracts is evident with diffusion tensor imaging and PET methods have been used to assess brain metabolism or presence of tau protein deposits. Patients with progressive supranuclear palsy present with a variety of clinical syndromes; however early onset of gait impairments and postural instability are common features. In this study we assessed the relationship between multimodal imaging biomarkers (i.e., MRI atrophy, white matter tracts degeneration, flortaucipir-PET uptake) and laboratory-based measures of gait and balance abnormalities in a cohort of nineteen patients with progressive supranuclear palsy, using univariate and multivariate statistical analyses. The PSP rating scale and its gait midline sub-score were strongly correlated to gait abnormalities but not to postural imbalance. Principal component analysis on gait variables identified velocity, stride length, gait stability ratio, length of gait phases and dynamic stability as the main contributors to the first component, which was associated with diffusion tensor imaging measures in the posterior thalamic radiation, external capsule, superior cerebellar peduncle, superior fronto-occipital fasciculus, body and splenium of the corpus callosum and sagittal stratum, with MRI volumes in frontal and precentral regions and with flortaucipir-PET uptake in the precentral gyrus. The main contributor to the second principal component was cadence, which was higher in patients presenting more abnormalities on mean diffusivity: this unexpected finding might be related to compensatory gait strategies adopted in progressive supranuclear palsy. Postural imbalance was the main contributor to the third principal component, which was related to flortaucipir-PET ...
    Keywords Progressive supranuclear palsy ; Diffusion tensor imaging ; Gait ; Balance ; MRI ; PET ; Computer applications to medicine. Medical informatics ; R858-859.7 ; Neurology. Diseases of the nervous system ; RC346-429
    Subject code 616
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Elsevier
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech

    Keith A. Josephs / Joseph R. Duffy / Heather M. Clark / Rene L. Utianski / Edythe A. Strand / Mary M. Machulda / Hugo Botha / Peter R. Martin / Nha Trang Thu Pham / Julie Stierwalt / Farwa Ali / Marina Buciuc / Matthew Baker / Cristhoper H. Fernandez De Castro / Anthony J. Spychalla / Christopher G. Schwarz / Robert I. Reid / Matthew L. Senjem / Clifford R. Jack /
    Val J. Lowe / Eileen H. Bigio / Ross R. Reichard / Eric. J. Polley / Nilufer Ertekin-Taner / Rosa Rademakers / Michael A. DeTure / Owen A. Ross / Dennis W. Dickson / Jennifer L. Whitwell

    Nature Communications, Vol 12, Iss 1, Pp 1-

    2021  Volume 17

    Abstract: Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy- ... ...

    Abstract Progressive apraxia of speech (PAOS) is a neurodegenerative syndrome of multiple etiologies which affects spoken communication. Here, the authors characterized the molecular pathology, biochemistry, genetics and longitudinal neuroimaging of 32 autopsy-confirmed patients with PAOS who were followed over 10 years.
    Keywords Science ; Q
    Language English
    Publishing date 2021-06-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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