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  • 1
    Online Resource
    Online Resource
    The organization and anatomy of narrative comprehension and expression in Lewy body spectrum disorders.
    American Psychological Association (APA) ; 2012
    In:  Neuropsychology Vol. 26, No. 3 ( 2012), p. 368-384
    Details
    In: Neuropsychology, American Psychological Association (APA), Vol. 26, No. 3 ( 2012), p. 368-384
    Type of Medium: Online Resource
    ISSN: 1931-1559 , 0894-4105
    URL: Article
    DOI: 10.1037/a0027115
    Language: English
    Publisher: American Psychological Association (APA)
    Publication Date: 2012
    detail.hit.zdb_id: 2102776-6
    SSG: 5,2
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  • 2
    Online Resource
    Online Resource
    Divergent patterns of TDP‐43 and tau pathologies in primary progressive aphasia
    Wiley ; 2019
    In:  Annals of Neurology Vol. 85, No. 5 ( 2019-05), p. 630-643
    Details
    In: Annals of Neurology, Wiley, Vol. 85, No. 5 ( 2019-05), p. 630-643
    Abstract: To measure postmortem burden of frontotemporal lobar degeneration (FTLD) with TDP‐43 (FTLD‐TDP) or tau (FTLD‐Tau) proteinopathy across hemispheres in primary progressive aphasia (PPA) using digital histopathology and to identify clinicopathological correlates of these distinct proteinopathies. Methods In an autopsy cohort of PPA (FTLD‐TDP = 13, FTLD‐Tau = 14), we analyzed laterality and regional distribution of postmortem pathology, quantified using a validated digital histopathological approach, in available brain tissue from up to 8 cortical regions bilaterally. We related digital pathology to antemortem structural neuroimaging and specific clinical language features. Results Postmortem cortical pathology was left‐lateralized in both FTLD‐TDP (beta = −0.15, standard error [SE] = 0.05, p = 0.007) and FTLD‐Tau (beta = −0.09, SE = 0.04, p = 0.015), but the degree of lateralization decreased with greater overall dementia severity before death (beta = −8.18, SE = 3.22, p = 0.015). Among 5 core pathology regions sampled, we found greatest pathology in left orbitofrontal cortex (OFC) in FTLD‐TDP, which was greater than in FTLD‐Tau ( F = 47.07, df = 1,17, p 〈  0.001), and in left midfrontal cortex (MFC) in FTLD‐Tau, which was greater than in FTLD‐TDP ( F = 19.34, df = 1,16, p 〈  0.001). Postmortem pathology was inversely associated with antemortem magnetic resonance imaging cortical thickness (beta = −0.04, SE = 0.01, p = 0.007) in regions matching autopsy sampling. Irrespective of PPA syndromic variant, single‐word comprehension impairment was associated with greater left OFC pathology ( t = −3.72, df = 10.72, p = 0.004) and nonfluent speech with greater left MFC pathology ( t = −3.62, df = 12.00, p = 0.004) among the 5 core pathology regions. Interpretation In PPA, FTLD‐TDP and FTLD‐Tau have divergent anatomic distributions of left‐lateralized postmortem pathology that relate to antemortem structural imaging and distinct language deficits. Although other brain regions may be implicated in neural networks supporting these complex language measures, our observations may eventually help to improve antemortem diagnosis of neuropathology in PPA. Ann Neurol 2019;85:630–643
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    URL: Article
    DOI: 10.1002/ana.v85.5
    DOI: 10.1002/ana.25465
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2037912-2
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  • 3
    Online Resource
    Online Resource
    Microtubule-binding drugs offset tau sequestration by stabilizing microtubules and reversing fast axonal transport deficits in a tauopathy model
    Proceedings of the National Academy of Sciences ; 2005
    In:  Proceedings of the National Academy of Sciences Vol. 102, No. 1 ( 2005-01-04), p. 227-231
    Details
    In: Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 102, No. 1 ( 2005-01-04), p. 227-231
    Abstract: We tested the hypothesis that microtubule (MT)-binding drugs could be therapeutically beneficial in tauopathies by functionally substituting for the MT-binding protein tau, which is sequestered into inclusions of human tauopathies and transgenic mouse models thereof. Transgenic mice were treated for 12 weeks with weekly i.p. injections of 10 or 25 mg/m 2 paclitaxel (Paxceed). Both doses restored fast axonal transport in spinal axons, wherein MT numbers and stable (detyrosinated) tubulins were increased, compared with sham treatment, and only Paxceed ameliorated motor impairments in tau transgenic mice. Thus, MT-stabilizing drugs could have therapeutic potential for treating neurodegenerative tauopathies by offsetting losses of tau function that result from the sequestration of this MT-stabilizing protein into filamentous inclusions.
    Type of Medium: Online Resource
    ISSN: 0027-8424 , 1091-6490
    URL: Article
    DOI: 10.1073/pnas.0406361102
    RVK:
    TA 1000
    RVK:
    WA 15000
    Language: English
    Publisher: Proceedings of the National Academy of Sciences
    Publication Date: 2005
    detail.hit.zdb_id: 209104-5
    detail.hit.zdb_id: 1461794-8
    SSG: 11
    SSG: 12
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  • 4
    Online Resource
    Online Resource
    Remote neuropsychological assessment using the UDS v3.0 T‐Cog: Preliminary data among participants at the Penn ADRC
    Wiley ; 2021
    In:  Alzheimer's & Dementia Vol. 17, No. S6 ( 2021-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S6 ( 2021-12)
    Abstract: Due to the COVID‐19 pandemic, collection of the Uniform Data Set (UDS) at Alzheimer’s Disease Research Centers (ADRCs) transitioned to remote administration via the T‐Cog. Feasibility of data collection and dissemination of normative data in individuals across the cognitive spectrum will be necessary for accurate utilization of remotely‐captured neurocognitive performance and classification of cognitive function. Method Data was included from individuals who completed a remote T‐Cog protocol during their annual NACC evaluation. Additional data included demographics, informant‐reported functioning, self‐reported depression and consensus diagnosis. Descriptive and general linear model (GLM) statistics were used to characterize the overall sample and test for differences in performance across diagnostic groups. Result A total of 151 participants with normal cognition (NC; N=103), mild cognitive impairment (MCI; N=32) and Alzheimer’s disease (AD; N=16) were administered the T‐Cog (Age = 75.2 + 7.2, Education=16.3 + 3.1; 62% Female; 75% White). Data were collected via telephone (68%), video‐conference (29%), or a combination (3%). Time to completion ranged from 38‐120 minutes (M=58 + 14 minutes), with NCs showing a significantly lower ( p 〈 0.05) mean completion time (54 minutes) than those with MCI (65 minutes) and AD (69 minutes). Across the battery, 80% of responses were deemed “extremely valid”, 19% were “questionably valid” and 〈 1% were “invalid”. Contributors to poor validity included hearing impairment (34%), distractions (16%), interruptions (6%), lack of effort/disinterest (9%), fatigue (3%), emotional issues (6%), or other reasons (25%). Diagnostic groups varied on tests of global cognition and functioning, as measured by the MoCA‐Blind and Global CDR, with the highest performance among NC, followed by MCI, and AD ( p‐values 〈 0.01). Nearly all T‐Cog measures of language, memory, and executive functioning abilities showed expected differences across diagnostic categories (covarying for age, sex and education; p 〈 0.05). Comparisons to prior in‐person UDS neurocognitive testing across all diagnostic groups will also be presented. Conclusion Preliminary feasibility and performance data on the T‐Cog reveals expected differences in T‐Cog performance. Comparisons to within‐subject in‐person testing and deviations from in‐person norms will be presented to further explore the validity of remote cognitive testing and identify tests that show particular promise in discriminating between diagnostic groups.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v17.S6
    DOI: 10.1002/alz.056540
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 5
    Online Resource
    Online Resource
    Evaluation of Linguistic Markers of Word-Finding Difficulty and Cognition in Parkinson's Disease
    American Speech Language Hearing Association ; 2018
    In:  Journal of Speech, Language, and Hearing Research Vol. 61, No. 7 ( 2018-07-13), p. 1691-1699
    Details
    In: Journal of Speech, Language, and Hearing Research, American Speech Language Hearing Association, Vol. 61, No. 7 ( 2018-07-13), p. 1691-1699
    Abstract: Early cognitive symptoms such as word-finding difficulty (WFD) in daily conversation are common in Parkinson's disease (PD), but studies have been limited by a lack of feasible, quantitative measures. Linguistic analysis, focused on pauses in speech, may yield markers of impairment of cognition and communication in PD. The objective of this study was to evaluate the relationship of linguistic markers in semistructured speech to WFD symptoms and cognitive function in PD. Method Speech recordings of description of the Cookie Theft picture in 53 patients with PD without dementia and 23 elderly controls were analyzed with Praat software. Montreal Cognitive Assessment (MoCA; Nasreddine et al., 2005), category naming fluency, and confrontation naming tests were administered. Questionnaires rating WFD symptoms and cognitive instrumental activities of daily living were completed. We determined the relationships between (a) pause length and location, (b) MoCA score, and (c) WFD symptoms, using Pearson's correlations and multivariate regression models. Results Compared with controls, patients with PD had more pauses within utterances as well as fewer words per minute and a lower percentage of well-formed sentences. Pauses within utterances differed significantly between PD–mild cognitive impairment and normal cognition ( p 〈 .001). Words per minute and percentage of well-formed sentences were predictive of MoCA in multivariate regression models. Pauses before verbs were associated with patient-reported severity of WFD symptoms ( p = .006). Conclusions Linguistic markers including pauses within utterances distinguish patients with PD with mild cognitive symptoms from elderly controls. These markers are associated with global cognitive function before the onset of dementia. Pauses before verbs and grammatical markers may index early cognitive symptoms such as WFD that may interfere with functional communication. Supplemental Material https://doi.org/10.23641/asha.6615401
    Type of Medium: Online Resource
    ISSN: 1092-4388 , 1558-9102
    URL: Article
    DOI: 10.1044/2018_JSLHR-L-17-0304
    Language: English
    Publisher: American Speech Language Hearing Association
    Publication Date: 2018
    detail.hit.zdb_id: 2070420-3
    SSG: 5,2
    SSG: 7,11
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  • 6
    Online Resource
    Online Resource
    Cognitive and neurodegenerative profile differences between “mismatch MCI” (A+T‐N+ MCI) And “prodromal AD” (A+T+N+ MCI) increase with time : Biomarkers (non‐neuroimaging): Longitudinal and prognostic biomarker studies
    Wiley ; 2020
    In:  Alzheimer's & Dementia Vol. 16, No. S5 ( 2020-12)
    Details
    In: Alzheimer's & Dementia, Wiley, Vol. 16, No. S5 ( 2020-12)
    Abstract: Per the Amyloid/Tau/Neurodegeneration (A/T/N) framework, beta‐amyloid accumulates during preclinical Alzheimer’s Disease (AD), followed by tau, then neurodegeneration. As AD symptoms are most linked to tau and neurodegeneration, both are expected by the MCI stage of disease. Thus, A+T‐N+ MCI (“mismatch MCI”) is thought to have both AD pathophysiology and non‐AD pathology, with the latter (given absence of tau) driving neurodegeneration and symptoms. We investigate the cognitive and neurodegenerative profile of mismatch MCI compared to “standard” A+T+N+ MCI (“prodromal AD”). Method A+ (by CSF) and N+ (by hippocampal volume 〈 90 th ‐percentile for A+ dementia) MCI patients from ADNI2/GO were grouped by tau status (based on CSF p‐tau): mismatch MCI (T‐; n=44; 34 followed longitudinally) and prodromal AD (T+; n=84; 61 followed longitudinally) (Table 1). Baseline AVLT immediate‐memory first trial, AVLT delayed recall, animal naming (category fluency), and Trails‐B‐minus‐Trails‐A (executive function; log‐transformed) z‐scores were compared. Longitudinal cognition was analyzed using mixed‐effects models. A Kaplan‐Meier analysis compared dementia‐free survival. Whole‐brain voxel‐wise analyses compared cortical thicknesses of each MCI group to A‐ controls. Medial temporal lobe (MTL) subregion volumes, determined using ASHS‐T1 (Xie, 2019) on T1‐weighted MRI, were compared at baseline and longitudinally. Result Mismatch MCI had less baseline delayed‐recall impairment (Figure 1), but was similar on other domains. Time*group interaction terms for longitudinal cognition were all significant (p 〈 0.05), indicating slower decline in mismatch MCI (Figure 2). Mismatch MCI had longer dementia‐free survival (Figure 3, p 〈 0.001).Whole‐brain voxel‐wise analyses revealed differential cortical thinning in MCI groups VS controls, with prodromal AD having more extensive atrophy, especially in the MTL (Figure 4). Mismatch MCI had lower mean anterior‐to‐posterior hippocampal volume ratio (p=0.016). While baseline entorhinal cortex, BA35, BA36, and parahippocampal cortex volumes were comparable (both groups had significant atrophy compared to controls), mismatch MCI had slower atrophy in these regions and the hippocampus (Table 2). Conclusion Mismatch MCI’s lower anterior‐to‐posterior hippocampal volume suggests possible enrichment in individuals with TDP‐43, a common non‐AD pathology, given previous work suggesting TDP‐43 preferentially affects the anterior hippocampus. Overall, these results support the concept that mismatch MCI and prodromal AD have different underlying pathologic profiles in light of their divergent cognition and neurodegenerative topography.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    URL: Article
    DOI: 10.1002/alz.v16.S5
    DOI: 10.1002/alz.046030
    Language: English
    Publisher: Wiley
    Publication Date: 2020
    detail.hit.zdb_id: 2201940-6
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  • 7
    Online Resource
    Online Resource
    Effects of the Insulin Sensitizer Metformin in Alzheimer Disease : Pilot Data From a Randomized Placebo-controlled Crossover Study
    Ovid Technologies (Wolters Kluwer Health) ; 2017
    In:  Alzheimer Disease & Associated Disorders Vol. 31, No. 2 ( 2017-04), p. 107-113
    Details
    In: Alzheimer Disease & Associated Disorders, Ovid Technologies (Wolters Kluwer Health), Vol. 31, No. 2 ( 2017-04), p. 107-113
    Abstract: Epidemiological studies have identified a robust association between type II diabetes mellitus and Alzheimer disease (AD), and neurobiological studies have suggested the presence of central nervous system insulin resistance in individuals with AD. Given this association, we hypothesized that the central nervous system–penetrant insulin-sensitizing medication metformin would be beneficial as a disease-modifying and/or symptomatic therapy for AD, and conducted a placebo-controlled crossover study of its effects on cerebrospinal fluid (CSF), neuroimaging, and cognitive biomarkers. Twenty nondiabetic subjects with mild cognitive impairment or mild dementia due to AD were randomized to receive metformin then placebo for 8 weeks each or vice versa. CSF and neuroimaging (Arterial Spin Label MRI) data were collected for biomarker analyses, and cognitive testing was performed. Metformin was found to be safe, well-tolerated, and measureable in CSF at an average steady-state concentration of 95.6 ng/mL. Metformin was associated with improved executive functioning, and trends suggested improvement in learning/memory and attention. No significant changes in cerebral blood flow were observed, though post hoc completer analyses suggested an increase in orbitofrontal cerebral blood flow with metformin exposure. Further study of these findings is warranted.
    Type of Medium: Online Resource
    ISSN: 0893-0341
    URL: Article
    DOI: 10.1097/WAD.0000000000000202
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2017
    detail.hit.zdb_id: 2048789-7
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  • 8
    Online Resource
    Online Resource
    Self- and Partner-Reported Subjective Memory Complaints: Association with Objective Cognitive Impairment and Risk of Decline
    IOS Press ; 2022
    In:  Journal of Alzheimer's Disease Reports Vol. 6, No. 1 ( 2022-07-22), p. 411-430
    Details
    In: Journal of Alzheimer's Disease Reports, IOS Press, Vol. 6, No. 1 ( 2022-07-22), p. 411-430
    Abstract: Background: Episodic memory decline is a hallmark of Alzheimer’s disease (AD). Subjective memory complaints (SMCs) may represent one of the earliest signs of impending cognitive decline. The degree to which self- or partner-reported SMCs predict cognitive change remains unclear. Objective: We aimed to evaluate the relationship between self- and partner-reported SMCs, objective cognitive performance, AD biomarkers, and risk of future decline in a well-characterized longitudinal memory center cohort. We also evaluated whether study partner characteristics influence reports of SMCs. Methods: 758 participants and 690 study partners were recruited from the Penn Alzheimer’s Disease Research Center Clinical Core. Participants included those with Normal Cognition, Mild Cognitive Impairment, and AD. SMCs were measured using the Prospective and Retrospective Memory Questionnaire (PRMQ), and were evaluated for their association with cognition, genetic, plasma, and neuroimaging biomarkers of AD, cognitive and functional decline, and diagnostic progression over an average of four years. Results: We found that partner-reported SMCs were more consistent with cognitive test performance and increasing symptom severity than self-reported SMCs. Partner-reported SMCs showed stronger correlations with AD-associated brain atrophy, plasma biomarkers of neurodegeneration, and longitudinal cognitive and functional decline. A 10-point increase on baseline PRMQ increased the annual risk of diagnostic progression by approximately 70%. Study partner demographics and relationship to participants influenced reports of SMCs in AD participants only. Conclusion: Partner-reported SMCs, using the PRMQ, have a stronger relationship with the neuroanatomic and cognitive changes associated with AD than patient-reported SMCs. Further work is needed to evaluate whether SMCs could be used to screen for future decline.
    Type of Medium: Online Resource
    ISSN: 2542-4823
    URL: Article
    DOI: 10.3233/ADR-220013
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2022
    detail.hit.zdb_id: 2955863-3
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  • 9
    Online Resource
    Online Resource
    Oh brother, where art tau? Amyloid, neurodegeneration, and cognitive decline without elevated tau
    Elsevier BV ; 2021
    In:  NeuroImage: Clinical Vol. 31 ( 2021), p. 102717-
    Details
    In: NeuroImage: Clinical, Elsevier BV, Vol. 31 ( 2021), p. 102717-
    Type of Medium: Online Resource
    ISSN: 2213-1582
    URL: Article
    DOI: 10.1016/j.nicl.2021.102717
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2701571-3
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  • 10
    Online Resource
    Online Resource
    Long‐term epilepsy outcome dynamics revealed by natural language processing of clinic notes
    Wiley ; 2023
    In:  Epilepsia Vol. 64, No. 7 ( 2023-07), p. 1900-1909
    Details
    In: Epilepsia, Wiley, Vol. 64, No. 7 ( 2023-07), p. 1900-1909
    Abstract: Electronic medical records allow for retrospective clinical research with large patient cohorts. However, epilepsy outcomes are often contained in free text notes that are difficult to mine. We recently developed and validated novel natural language processing (NLP) algorithms to automatically extract key epilepsy outcome measures from clinic notes. In this study, we assessed the feasibility of extracting these measures to study the natural history of epilepsy at our center. Methods We applied our previously validated NLP algorithms to extract seizure freedom, seizure frequency, and date of most recent seizure from outpatient visits at our epilepsy center from 2010 to 2022. We examined the dynamics of seizure outcomes over time using Markov model‐based probability and Kaplan–Meier analyses. Results Performance of our algorithms on classifying seizure freedom was comparable to that of human reviewers (algorithm F 1 = .88 vs. human annotator = .86). We extracted seizure outcome data from 55 630 clinic notes from 9510 unique patients written by 53 unique authors. Of these, 30% were classified as seizure‐free since the last visit, 48% of non‐seizure‐free visits contained a quantifiable seizure frequency, and 47% of all visits contained the date of most recent seizure occurrence. Among patients with at least five visits, the probabilities of seizure freedom at the next visit ranged from 12% to 80% in patients having seizures or seizure‐free at the prior three visits, respectively. Only 25% of patients who were seizure‐free for 6 months remained seizure‐free after 10 years. Significance Our findings demonstrate that epilepsy outcome measures can be extracted accurately from unstructured clinical note text using NLP. At our tertiary center, the disease course often followed a remitting and relapsing pattern. This method represents a powerful new tool for clinical research with many potential uses and extensions to other clinical questions.
    Type of Medium: Online Resource
    ISSN: 0013-9580 , 1528-1167
    URL: Article
    DOI: 10.1111/epi.17633
    RVK:
    XA 10000
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2002194-X
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