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1.
Neurobiol Aging ; 92: 135-140, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32417749

RESUMO

To assess volume loss and flortaucipir uptake in patients with semantic dementia (SD) over time. Eight SD patients (3 female) underwent clinical evaluations, flortaucipir positron emission tomography, and brain magnetic resonance imaging at 2 visits. Voxel-level comparisons of magnetic resonance imaging gray and white matter volume loss and flortaucipir positron emission tomography uptake were performed in SPM12, comparing SD patients to controls at each visit. T-tests on difference images and paired t-tests of flortaucipir uptake were also performed. At the voxel level, SD patients showed asymmetric, bilateral gray volume loss in the temporal lobes, which, via visual inspection, extended posteriorly at follow-up. White matter loss and flortaucipir uptake were noted in SD patients in the left temporal lobe only, which appeared to extend posteriorly, without involvement of the right hemisphere at follow-up. Longitudinal analyses did not support significant changes in flortaucipir uptake between visits. The biological mechanisms of flortaucipir signal in suspected underlying TAR-DNA binding protein 43 pathology are unknown. A 1-year interval is not sufficient time to demonstrate significant longitudinal flortaucipir uptake changes in SD.

2.
J Neurol ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388831

RESUMO

OBJECTIVE: To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive apraxia of speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). BACKGROUND: PAOS is a neurodegenerative syndrome in which patients present with apraxia of speech, a motor speech disorder affecting programming and planning of speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. METHODS: As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. RESULTS: Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). CONCLUSIONS: Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.

5.
ACS Sens ; 5(2): 292-293, 2020 02 28.
Artigo em Inglês | MEDLINE | ID: mdl-32106681
6.
J Alzheimers Dis ; 74(1): 377-389, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32039841

RESUMO

BACKGROUND: Rates of amyloid-ß (Aß) accumulation have been characterized across the cognitively normal to typical Alzheimer's dementia spectrum, but little is known about Aß accumulation in atypical Alzheimer's disease (AD) and other neurodegenerative diseases, such as frontotemporal lobar degeneration (FTLD). OBJECTIVE: We aimed tocharacterize longitudinal Aß accumulation anddetermine the influence of age, apolipoprotein E (APOE) genotype, disease duration, and sexin atypical AD and FTLD. METHODS: 322 patients (138 atypical AD, 184 FTLD) underwent Pittsburgh compound B PET scanning, with 73 having serialPiB-PET scans (42 atypical AD, 31 FTLD). Global Aß standard uptake value ratios were calculated for every scan. Mixed effects models were used to assess the effect of age, APOE genotype, disease duration, and sex on baseline and change measures of Aß. RESULTS: Atypical AD showed higher baseline Aß than FTLD. Rate of Aß accumulation was not associated with baseline Aß in either group. Older age was associated with greater baseline Aß and faster rates of accumulation in FTLD. In patients under age 70, atypical AD showed faster rates of accumulation than FTLD. APOEɛ4 genotype was associated with greater baseline Aß in FTLD but did not influence rates of accumulation. Rates of Aß accumulation were faster in FTLD patents with time from onset-to-PET≤4 years. Female sex was associated with faster rates of accumulation in atypical AD. CONCLUSION: Accumulation of Aß is observed in atypical AD and FTLD, although different demographic factors influence accumulation in these diseases providing insight into potentially different biological mechanisms of Aß deposition.

7.
Proc Natl Acad Sci U S A ; 117(7): 3509-3517, 2020 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-32019879

RESUMO

Personalized medicine offers great potential benefits for disease management but requires continuous monitoring of drugs and drug targets. For instance, the therapeutic window for lithium therapy of bipolar disorder is very narrow, and more frequent monitoring of sodium levels could avoid toxicity. In this work, we developed and validated a platform for long-term, continuous monitoring of systemic analyte concentrations in vivo. First, we developed sodium microsensors that circulate directly in the bloodstream. We used "red blood cell mimicry" to achieve long sensor circulation times of up to 2 wk, while being stable, reversible, and sensitive to sodium over physiologically relevant concentration ranges. Second, we developed an external optical reader to detect and quantify the fluorescence activity of the sensors directly in circulation without having to draw blood samples and correlate the measurement with a phantom calibration curve to measure in vivo sodium. The reader design is inherently scalable to larger limbs, species, and potentially even humans. In combination, this platform represents a paradigm for in vivo drug monitoring that we anticipate will have many applications in the future.


Assuntos
Monitoramento de Medicamentos/métodos , Eritrócitos/química , Sódio/sangue , Animais , Circulação Sanguínea , Monitoramento de Medicamentos/instrumentação , Fluorescência , Camundongos , Camundongos Nus , Mimetismo Molecular , Ratos
9.
Neuroimage Clin ; 25: 102152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935638

RESUMO

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. MATERIALS AND METHODS: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. RESULTS: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. CONCLUSION: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of disease spread through the brain. These findings will be important in the development of appropriate neuroimaging biomarkers for the different PSP variants.

10.
Am J Speech Lang Pathol ; 29(1S): 498-510, 2020 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-31639312

RESUMO

Purpose The primary aim was to examine the utility of the Western Aphasia Battery-Revised (WAB-R; Kertesz, 2007) for classifying variants of primary progressive aphasia (PPA). Traditional WAB-R metrics of Aphasia Quotient (AQ), subtest scores, WAB-R classification, and several novel metrics were examined. A secondary aim was to examine these same WAB-R metrics in individuals with primary progressive apraxia of speech (PPAOS). Method A retrospective analysis of WAB-R records from 169 participants enrolled in a study of neurodegenerative speech and language disorders was conducted. PPA/PPAOS classification was determined by consensus review of speech, language, and cognitive profiles. Scores on each of the WAB-R subtests were obtained to derive AQ, WAB-R aphasia profile, and 3 ratios reflecting relative performance on subtests. Results Mean AQ was significantly higher in the PPAOS group compared to all PPA variants except primary fluent aphasia. AQ above the normal cutoff was observed for 20% of participants with PPA. Significant main effects of group were noted for each of the subtests. Follow-up comparisons most frequently discriminated PPAOS, primary agrammatic aphasia (PAA), and logopenic progressive aphasia. Primary fluent aphasia and semantic dementia (SD) subtest scores were less distinctive, with the exception of Naming for SD, which was significantly lower than for PAA and PPAOS. When the WAB-R AQ detected aphasia, a classification of anomic aphasia was most frequently observed; this pattern held true for each of the PPA variants. The mean Information Content:Naming ratio was highest for SD, and the mean Comprehension:Fluency ratio was highest for PAA. Conclusions In the current study, AQ underestimated the presence of PPA and WAB-R classification did not distinguish among PPA classification determined by consensus. Performance on individual subtests and relative performance across subtests demonstrated inconsistent alignment with PPA classification. We conclude the WAB-R in isolation is inadequate to detect or characterize PPA. We instead suggest utilizing the WAB-R as 1 component of a comprehensive language and motor speech assessment when PPA is suspected.

11.
Cortex ; 124: 33-43, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31830664

RESUMO

Primary progressive apraxia of speech (PPAOS) is a term used to describe a neurodegenerative condition in which apraxia of speech (AOS; a planning and/or programming deficit) occurs in the absence of aphasia (a language deficit). PPAOS is strongly associated with 4-repeat tau pathology. Elevated flortaucipir ([18F]AV-1451; FTP) uptake has been observed cross-sectionally in patients with PPAOS and those with aphasia. Here, we evaluated longitudinal changes in previously-identified regions of uptake and their relationship with clinical presentation. Thirteen patients who were diagnosed with PPAOS (5 female) at presentation underwent FTP PET imaging at two visits (mean 1 year interval). Median age was 72, with a median of 4 years disease duration at initial testing. Beta-amyloid status was assessed with Pittsburgh Compound B (PiB), where a global PiB ratio>1.48 was deemed amyloid positive (n = 4). FTP uptake was assessed as cortical to cerebellar crus ratios (SUVr) in cortical regions of interest. A single hierarchical linear model (HLM) compared PPAOS patients to 52 cognitively unimpaired controls of similar age and sex. Annualized SUVr change was the outcome, predicted by region, clinical status, and age. Person-specific effects accounted for intra-patient correlations and contralateral regions were included as repeated measures. Changes in clinical measures were assessed using Wilcoxon signed-rank tests; statistically significant changes in the Montreal Cognitive Assessment, MDS-UPDRS, motor section, and PSP Rating Scale were noted between visits. Changes in FTP SUVr were greater for patients than controls. The strongest changes in PPAOS patients were in the precentral gyrus, pallidum, and mid and superior frontal gyri, per the HLM. Qualitatively, larger changes were seen in patients who had developed aphasia by the time of their baseline scan (n = 5). While the biological mechanisms of FTP signal in non-AD tauopathies are unknown, this study demonstrates the utility of FTP in tracking disease progression in 4R tauopathies.

12.
J Control Release ; 318: 109-123, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31843642

RESUMO

Targeted drug delivery to joint tissues like cartilage remains a challenge that has prevented clinical translation of promising osteoarthritis (OA) drugs. Local intra-articular (IA) injections of drugs suffer from rapid clearance from the joint space and slow diffusive transport through the dense, avascular cartilage matrix comprised of negatively charged glycosaminoglycans (GAGs). Here we apply drug carriers that leverage electrostatic interactions with the tissue's high negative fixed charge density (FCD) for delivering small molecule drugs to cartilage cell and matrix sites. We demonstrate that a multi-arm cationic nano-construct of Avidin (mAv) with 28 sites for covalent drug conjugation can rapidly penetrate through the full thickness of cartilage in high concentration and have long intra-cartilage residence time in both healthy and arthritic cartilage via weak-reversible binding with negatively charged aggrecans. mAv's intra-cartilage mean uptake was found to be 112× and 33× the equilibration bath concentration in healthy and arthritic (50% GAG depleted) cartilage, respectively. mAv was conjugated with Dexamethasone (mAv-Dex), a broad-spectrum glucocorticoid, using a combination of hydrolysable ester linkers derived from succinic anhydride (SA), 3,3-dimethylglutaric anhydride (GA) and phthalic anhydride (PA) in 2:1:1 M ratio that enabled 50% drug release within 38.5 h followed by sustained release in therapeutic doses over 2 weeks. A single 10 µM low dose of controlled release mAv-Dex (2:1:1) effectively suppressed IL-1α-induced GAG loss, cell death and inflammatory response significantly better than unmodified Dex over 2 weeks in cartilage explant culture models of OA. With this multi-arm design, <1 µM Avidin was needed - a concentration which has been shown to be safe, preventing further GAG loss and cytotoxicity. A charge-based cartilage homing drug delivery platform like this can elicit disease modifying effects as well as facilitate long-term symptomatic pain and inflammation relief by enhancing tissue specificity and prolonging intra-cartilage residence time of OA drugs. This nano-construct thus has high translational potential for enabling intra-cartilage delivery of a broad array of small molecule OA drugs and their combinations to chondrocytes, enabling OA treatment with a single injection of low drug doses and eliminating toxicity issues associated with multiple high dose injections.

13.
Analyst ; 145(4): 1169-1173, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-31872821

RESUMO

Tyrosinase is a key enzyme that has long been considered as a biomarker for melanoma as it catalyzes the oxidation of tyrosine and l-DOPA in melanogenesis. Recent studies also suggest a link between tyrosinase activity and Parkinson's disease; however, the mechanism of tyrosinase-mediated melanin formation in the brain is poorly understood. To better understand this connection, more advanced tools for the detection of tyrosinase in the brain are required. Herein, we successfully designed and synthesized a tyrosinase-targeting Gd(iii)-based MR contrast agent Tyr-GBCA 1. Tyr-GBCA 1 was synthesized by linking m-hydroxyphenyl to Gd-DOTA via a self-immolative linker. Tyr-GBCA 1 shows a 21% increase in the T1 relaxation rate (R1) in the presence of tyrosinase in artificial cerebral spinal fluid. Furthermore, Tyr-GBCA 1 is unreactive to hydrogen peroxide, which is a potential interferent in oxidation-based tyrosinase sensing systems. The reaction mechanism of the probe was studied by electrospray ionization (ESI) mass spectrometry and supports the cleavage of a reaction site.

14.
Sci Rep ; 9(1): 19888, 2019 12 27.
Artigo em Inglês | MEDLINE | ID: mdl-31882792

RESUMO

Synchronous assessment of multiple MRI contrast agents in a single scanning session would provide a new "multi-color" imaging capability similar to fluorescence imaging but with high spatiotemporal resolution and unlimited imaging depth. This multi-agent MRI technology would enable a whole new class of basic science and clinical MRI experiments that simultaneously explore multiple physiologic/molecular events in vivo. Unfortunately, conventional MRI acquisition techniques are only capable of detecting and quantifying one paramagnetic MRI contrast agent at a time. Herein, the Dual Contrast - Magnetic Resonance Fingerprinting (DC-MRF) methodology was extended for in vivo application and evaluated by simultaneously and dynamically mapping the intra-tumoral concentration of two MRI contrast agents (Gd-BOPTA and Dy-DOTA-azide) in a mouse glioma model. Co-registered gadolinium and dysprosium concentration maps were generated with sub-millimeter spatial resolution and acquired dynamically with just over 2-minute temporal resolution. Mean tumor Gd and Dy concentration measurements from both single agent and dual agent DC-MRF studies demonstrated significant correlations with ex vivo mass spectrometry elemental analyses. This initial in vivo study demonstrates the potential for DC-MRF to provide a useful dual-agent MRI platform.

15.
Dysphagia ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676923

RESUMO

Progressive supranuclear palsy (PSP) is the most common Parkinson-Plus syndrome and is associated with early onset of dysphagia relative to Parkinson Disease. The current study contributes to the growing understanding of swallowing dysfunction in PSP by describing oropharyngeal swallowing characteristics in a large prospective cohort of participants with PSP employing a nationally standardized videofluoroscopy protocol and a disease severity scale developed expressly for PSP. Participants were 51 adults diagnosed with PSP. Each participant underwent a clinical interview and standardized videofluorographic assessment. Swallowing function was characterized with the Modified Barium Swallow Impairment Scale (MBSImP) and Penetration-Aspiration Scale (PAS). Variables of interest were participant-reported difficulties with liquids and/or solids; overall impression score for each of the 17 individual MBSImP components, as well as Oral Total Sum and Pharyngeal Total Sum; and PAS. Data were described with median interquartile range, counts, and proportions. Spearman's rank correlations were calculated between MBSImP scores and participant-reported indices, FOIS, and PSP Rating Scale. Approximately two-thirds of participants reported difficulties with liquids, solids, or both, although fewer than 15% reported modifying consistencies. Videofluorographic findings included predominant oral phase impairments, including back and forth rocking motion of the tongue, delayed initiation of the pharyngeal swallow, and oral residue. Pharyngeal phase impairments were relatively infrequent and comparatively mild, with the exception of reduced tongue base retraction contributing to pharyngeal residue, and mildly disrupted laryngeal vestibule closure. Disease severity correlated significantly with oral (r = .0.42, p = .0.002) and pharyngeal (r = 0.41, p = .0.003) total sum scores as well as with the oral phase components of oral transport (r = .0.33, p = .0.02) and initiation of the pharyngeal swallow (r = .0.38, p = .0.007), and PAS for thin liquids (r = .0.44, p = .0.001). The PSP Rating Scale was not more strongly correlated with swallowing impairment than has been reported for other disease severity rating scales. Dysphagia is a common complaint of patients with PSP. The current findings corroborate and expand upon those reported in the literature, detailing relatively more frequent and more severe oral phase impairments and relatively spared hyolaryngeal excursion. Further research is needed to characterize the progression of dysphagia in PSP and to determine whether dysphagia varies in character or in rate of progression across variants of PSP.

16.
Aphasiology ; 33(11): 1410-1417, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31741547

RESUMO

Background: Past research has demonstrated that electroencephalography (EEG) is sensitive to what we now know as Primary Progressive Aphasia (PPA); however, the EEG profiles of patients with Primary Progressive Apraxia of Speech (PPAOS) and PPA, in the context of current consensus criteria, have not been studied. Aims: The primary goal of this study was to explore the EEG profiles of patients of the nonfluent/ agrammatic variant of PPA (agPPA) and PPAOS. Methods and Procedures: Three patients with agPPA and five patients with PPAOS (two with aphasia) completed a head MRI scan and clinical EEG recording. Clinical radiologists and electrophysiologists reviewed respective imaging, blinded to clinical diagnosis. Outcomes and Results: Patients with PPAOS who did not have aphasia had normal EEGs, while those with aphasia demonstrated theta slowing. Patients with agPPA also showed theta slowing, with one exception. MRI scans showed non-specific, age-related changes across clinical presentations. Conclusions: This preliminary study suggests theta slowing is consistent with neurodegenerative aphasia, but not isolated apraxia of speech. EEG is a low-cost mechanism to identify possible biomarkers for use when clinical severity limits behavioral examinations or expert examiners are unavailable.

17.
Can J Diabetes ; 43(8): 647-654, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31564623

RESUMO

Maturity-onset diabetes of the young (MODY) is a group of monogenic disorders that accounts for 1% to 5% of diabetes. The most common mutations are those in the hepatocyte nuclear factor-1-alpha (HNF-1-alpha) and in the glucokinase (GCK) genes. Although management of MODY is well established, no guidelines currently exist for management during pregnancy. Both maternal glycemic control and fetal mutation status are factors that may influence outcomes during pregnancy. The primary aim of this project was to describe cases of MODY during pregnancy to highlight the clinical implications of management of this disorder during pregnancy. The Ottawa Hospital is the primary referral centre for high-risk obstetrical patients, including those with diabetes in pregnancy, in Ottawa, Canada. Referrals between 2008 and 2018 were reviewed and a case series of three women and five pregnancies is described. Together with the illustrative cases, a literature review of MODY in pregnancy is used to highlight clinical considerations unique to MODY in pregnancy. We describe 5 pregnancies with MODY-2 (GCK mutation) and MODY 3 (HNF-1-alpha mutation). Important issues identified included monitoring of fetal growth and individualization of maternal glycemic control, particularly in cases where fetal mutation status is unknown. Management of MODY in pregnancy is challenging and there is little evidence to guide recommendations. Fetal growth can be used to guide management of maternal glycemic targets when fetal mutation status is unknown.


Assuntos
Diabetes Mellitus Tipo 2 , Gravidez em Diabéticas/etiologia , Adulto , Gerenciamento Clínico , Feminino , Humanos , Gravidez
18.
Brain Lang ; 197: 104676, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31419589

RESUMO

Many patients who meet core/root criteria for Primary Progressive Aphasia (PPA) are not classifiable as a recognized variant and are often excluded from neuroimaging studies. Here, we detail neurological, neuropsychological, speech and language assessments, and anatomic and molecular neuroimaging (MRI, PiB-PET, and FDG-PET) for fifteen (8 female) clinically unclassifiable PPA patients. Median age of onset was 64 years old with median 3 years disease duration at exam. Three patients were amyloid positive on PiB-PET. 14/15 patients had abnormal FDG-PETs with left predominant hypometabolism, affecting frontal, temporal, parietal, and even occipital lobes. Patients had mild to severe clinical presentations. Visualization of the FDG-PETs principal component analysis revealed patterns of hypometabolism similar to those seen in the PPA variants and suggests the brain regions affected in unclassifiable PPA patients are no different from those who are more easily classifiable. These findings may inform future modifications to the diagnostic criteria to improve diagnostic classification.


Assuntos
Afasia Primária Progressiva/patologia , Afasia Primária Progressiva/fisiopatologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Neuroimagem , Idoso , Feminino , Humanos , Testes de Linguagem , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Análise de Componente Principal , Fala/fisiologia
19.
Mov Disord Clin Pract ; 6(6): 452-461, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31392246

RESUMO

Background: The Movement Disorder Society clinical criteria for progressive supranuclear palsy (PSP) provide a framework for assessing the presence/severity of clinical symptoms and define a speech/language variant of PSP. Objectives: To evaluate the clinical criteria in a cohort of speech/language patients with longitudinal follow-up. Methods: A total of 52 patients presenting with progressive apraxia of speech and/or agrammatic aphasia were followed longitudinally for up to 6 visits with clinical assessments and magnetic resonance imaging. We assessed oculomotor, postural instability, and akinesia diagnostic levels and determined whether patients met criteria for possible PSP-speech/language or probable PSP at each visit. Kaplan-Meier curves assessed time-to-event probabilities according to age. Statistical parametric mapping and midbrain volume were assessed according to disease progression. Results: Few PSP symptoms were observed early in the disease, with oculomotor abnormalities and falls first observed 2 years after onset. Falls were more common than vertical supranuclear gaze palsy. Bradykinesia and rigidity commonly developed but axial was rarely greater than appendicular rigidity. During follow-up, 54% met criteria for possible PSP-speech/language, 38% for probable PSP-Richardson's syndrome, and 38% for probable PSP-parkinsonism, most commonly 6 to 6.9 years after onset. The probability of developing PSP was greater when onset was at an age older than 70 years. Patients who progressed to probable PSP had more parkinsonism and oculomotor impairment at baseline and greater midbrain atrophy when compared with those who did not develop probable PSP. Conclusions: Symptoms typical of PSP commonly develop in patients presenting with a progressive speech/language disorder. Older age appears to be an important prognostic factor in these patients.

20.
Transl Behav Med ; 9(6): 1034-1039, 2019 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-31314091

RESUMO

Sharing of physical activity spaces is supported by the American Heart Association and other leading public health authorities as one strategy to increase access to physical activity. The purpose of this study was to identify facilities within Pasadena, TX, that currently provide opportunities for active recreation, sport, and other forms of physical activity and analyze community access to these spaces from a geospatial perspective. Geospatial analysis was used to identify physical activity spaces and issues relevant to access. Using a community-based approach, the research team worked with partners to create a list of individuals responsible for each of the physical activity spaces. These "facility administrators" were contacted by email and then phone for a total of four attempts. Respondents were asked to complete an online shared use survey. An asset map was created from both local geospatial data (Pasadena, TX) and data from a facility access and shared use survey. Of the 39 facility administrators, 23 responded to the survey and consisted of the park director, school principals, lead pastors and clergy, and business owners. A total of 53 facilities were identified within the priority zip codes, including 30 parks, 25 schools, 9 faith-based organizations, and 4 others (a business, a nonprofit health care center, and two community-based organizations). Overall, there were 131 total amenities, and playgrounds, outdoor basketball courts, and ball fields were the most common types. Some facilities had multiple amenities at their location, including many of the parks and schools. Additionally, respondents noted other types of amenities where activity took place such as parking lots, grassy areas, classrooms, and other indoor areas. Many of the amenities, 102, were open to the general public and 28 were found to be in good condition. Findings suggest that there is inadequate access to physical activity spaces in this underserved community. There is a need for additional play spaces in Northern Pasadena and for future research bridging community health and geospatial mapping.

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