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Locascio, Joseph

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Locascio

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Joseph

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Locascio, Joseph
Author's Publications: search.filters.isAuthorOfPublication.24407305-ecb7-4b27-a474-7d77a74aa42a

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    Adolescents’ use of the built environment for physical activity
    (BioMed Central, 2015) Oreskovic, Nicolas; Perrin, James; Robinson, Alyssa I; Locascio, Joseph; Blossom, Jeff; Chen, Minghua L; Winickoff, Jonathan; Field, Alison E.; Green, Chloe; Goodman, Elizabeth
    Background: Physical activity is a health-enhancing behavior, but few adolescents achieve the recommended levels of moderate-to-vigorous physical activity. Understanding how adolescents use different built environment spaces for physical activity and activity varies by location could help in designing effective interventions to promote moderate-to-vigorous physical activity. The objective of this study was to describe the locations where adolescents engage in physical activity and compare traditional intensity-based measures with continuous activity when describing built environment use patterns among adolescents. Methods: Eighty adolescents aged 11–14 years recruited from community health and recreation centers. Adolescents wore accelerometers (Actigraph GT3X) and global positioning system receivers (QStarz BT-Q1000XT) for two separate weeks to record their physical activity levels and locations. Accelerometer data provided a continuous measure of physical activity and intensity-based measures (sedentary time, moderate-to-vigorous physical activity). Physical activity was mapped by land-use classification (home, school, park, playground, streets & sidewalks, other) using geographic information systems and this location-based activity was assessed for both continuous and intensity-based physical activity derived from mixed-effects models which accounted for repeated measures and clustering effects within person, date, school, and town. Results: Mean daily moderate-to-vigorous physical activity was 22 minutes, mean sedentary time was 134 minutes. Moderate-to-vigorous physical activity occurred in bouts lasting up to 15 minutes. Compared to being at home, being at school, on the streets and sidewalks, in parks, and playgrounds were all associated with greater odds of being in moderate-to-vigorous physical activity and achieving higher overall activity levels. Playground use was associated with the highest physical activity level (β = 172 activity counts per minute, SE = 4, p < 0.0001) and greatest odds of being in moderate-to-vigorous physical activity (odds ratio 8.3, 95% confidence interval 4.8-14.2). Conclusion: Adolescents were more likely to engage in physical activity, and achieved their highest physical activity levels, when using built environments located outdoors. Novel objective methods for determining physical activity can provide insight into adolescents’ spatial physical activity patterns, which could help guide physical activity interventions. Promoting zoning and health policies that encourage the design and regular use of outdoor spaces may offer another promising opportunity for increasing adolescent physical activity.
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    Specifically neuropathic Gaucher's mutations accelerate cognitive decline in Parkinson's
    (John Wiley and Sons Inc., 2016) Liu, Ganqiang; Boot, Brendon; Locascio, Joseph; Jansen, Iris E.; Winder‐Rhodes, Sophie; Eberly, Shirley; Elbaz, Alexis; Brice, Alexis; Ravina, Bernard; van Hilten, Jacobus J.; Cormier‐Dequaire, Florence; Corvol, Jean‐Christophe; Barker, Roger A.; Heutink, Peter; Marinus, Johan; Williams‐Gray, Caroline H.; Scherzer, Clemens; Scherzer, C.; Hyman, B.T.; Ivinson, A.J.; Trisini‐Lipsanopoulos, A.; Franco, D.; Burke, K.; Sudarsky, L.R.; Hayes, M.T.; Umeh, C.C.; Growdon, J.H.; Schwarzschild, M.A.; Hung, A.Y.; Flaherty, A.W.; Wills, A.‐M.; Mejia, N.I.; Gomperts, S.N.; Khurana, V.; Selkoe, D.J.; Yi, T.; Page, K.; Liao, Z.; Barker, R.; Foltynie, T.; Williams‐Gray, C.H.; Mason, S.; Winder‐Rhodes, S.; Breen, D.; Cummins, G.; Evans, J.; Corvol, J.‐C.; Brice, A.; Elbaz, A.; Mallet, A.; Vidailhet, M.; Bonnet, A.‐M.; Bonnet, C.; Grabli, D.; Hartmann, A.; Klebe, S.; Lacomblez, L.; Mangone, G.; Bourdain, F.; Brandel, J.‐P.; Derkinderen, P.; Durif, F.; Mesnage, V.; Pico, F.; Rascol, O.; Forlani, S.; Lesage, S.; Tahiri, K.; van Hilten, J.J.; Marinus, J.; Duong, K.; Dong, X.; Hutten, S.J.; Amr, S.S.; Shoulson, I.; Tanner, C.M.; Lang, A.E.; Nalls, M.A.
    Objective: We hypothesized that specific mutations in the β‐glucocerebrosidase gene (GBA) causing neuropathic Gaucher's disease (GD) in homozygotes lead to aggressive cognitive decline in heterozygous Parkinson's disease (PD) patients, whereas non‐neuropathic GD mutations confer intermediate progression rates. Methods: A total of 2,304 patients with PD and 20,868 longitudinal visits for up to 12.8 years (median, 4.1) from seven cohorts were analyzed. Differential effects of four types of genetic variation in GBA on longitudinal cognitive decline were evaluated using mixed random and fixed effects and Cox proportional hazards models. Results: Overall, 10.3% of patients with PD and GBA sequencing carried a mutation. Carriers of neuropathic GD mutations (1.4% of patients) had hazard ratios (HRs) for global cognitive impairment of 3.17 (95% confidence interval [CI], 1.60–6.25) and a hastened decline in Mini–Mental State Exam scores compared to noncarriers (p = 0.0009). Carriers of complex GBA alleles (0.7%) had an HR of 3.22 (95% CI, 1.18–8.73; p = 0.022). By contrast, the common, non‐neuropathic N370S mutation (1.5% of patients; HR, 1.96; 95% CI, 0.92–4.18) or nonpathogenic risk variants (6.6% of patients; HR, 1.36; 95% CI, 0.89–2.05) did not reach significance. Interpretation Mutations in the GBA gene pathogenic for neuropathic GD and complex alleles shift longitudinal cognitive decline in PD into “high gear.” These findings suggest a relationship between specific types of GBA mutations and aggressive cognitive decline and have direct implications for improving the design of clinical trials. Ann Neurol 2016;80:674–685
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    Preservation of Neuronal Number Despite Age-Related Cortical Brain Atrophy in Elderly Subjects Without Alzheimer Disease
    (Oxford University Press (OUP), 2008) Freeman, Stefanie H.; Kandel, Ruth; Cruz, Luis; Rozkalne, Anete; Newell, Kathy; Frosch, Matthew; Hedley-Whyte, E.; Locascio, Joseph; Lipsitz, Lewis; Hyman, Bradley
    Cerebral volume loss has long been associated with normal aging but whether this is due to aging itself or to age-related diseases including incipient Alzheimer disease (AD) is uncertain. To understand the changes that occur in the aging brain, we examined the cerebral cortex of 27 normal individuals ranging in age from 56 to 103 years. None fulfilled the criteria for the neuropathological diagnosis of AD or other neurodegenerative disease. Seventeen of the elderly participants had cognitive testing an average of 6.7 months prior to death. We used quantitative approaches to analyze cortical thickness, neuronal number, and density. Frontal and temporal neocortical regions had clear evidence of cortical thinning with age but total neuronal numbers in frontal and temporal neocortical regions remained relatively constant over a 50-year age range. These data suggest that loss of neuronal and dendritic architecture, rather than loss of neurons, underlies neocortical volume loss with increasing age in the absence of AD.
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    A Web-Based Normative Calculator for the Uniform Data Set (UDS) Neuropsychological Test Battery
    (BioMed Central, 2011) Shirk, Steven D; Weintraub, Sandra; Mitchell, Meghan B; Shaughnhessy, Lynn W; Sherman, Janet; Locascio, Joseph; Atri, Alireza
    Introduction: With the recent publication of new criteria for the diagnosis of preclinical Alzheimer's disease (AD), there is a need for neuropsychological tools that take premorbid functioning into account in order to detect subtle cognitive decline. Using demographic adjustments is one method for increasing the sensitivity of commonly used measures. We sought to provide a useful online z-score calculator that yields estimates of percentile ranges and adjusts individual performance based on sex, age and/or education for each of the neuropsychological tests of the National Alzheimer's Coordinating Center Uniform Data Set (NACC, UDS). In addition, we aimed to provide an easily accessible method of creating norms for other clinical researchers for their own, unique data sets. Methods: Data from 3,268 clinically cognitively-normal older UDS subjects from a cohort reported by Weintraub and colleagues (2009) were included. For all neuropsychological tests, z-scores were estimated by subtracting the raw score from the predicted mean and then dividing this difference score by the root mean squared error term (RMSE) for a given linear regression model. Results: For each neuropsychological test, an estimated z-score was calculated for any raw score based on five different models that adjust for the demographic predictors of SEX, AGE and EDUCATION, either concurrently, individually or without covariates. The interactive online calculator allows the entry of a raw score and provides five corresponding estimated z-scores based on predictions from each corresponding linear regression model. The calculator produces percentile ranks and graphical output. Conclusions: An interactive, regression-based, normative score online calculator was created to serve as an additional resource for UDS clinical researchers, especially in guiding interpretation of individual performances that appear to fall in borderline realms and may be of particular utility for operationalizing subtle cognitive impairment present according to the newly proposed criteria for Stage 3 preclinical Alzheimer's disease.
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    The technical reliability and biotemporal stability of cerebrospinal fluid biomarkers for profiling multiple pathophysiologies in Alzheimer’s disease
    (Public Library of Science, 2018) Trombetta, Bianca A.; Carlyle, Becky; Koenig, Aaron M.; Shaw, Leslie M.; Trojanowski, John Q.; Wolk, David A.; Locascio, Joseph; Arnold, Steven
    Objective: Alzheimer’s disease (AD) is a complex neurodegenerative disease driven by multiple interacting pathophysiological processes that ultimately results in synaptic loss, neuronal death, and dementia. We implemented a fit-for-purpose modeled approach to qualify a broad selection of commercially available immunoassays and evaluate the biotemporal stability of analytes across five pathophysiological domains of interest in AD, including core amyloid-β (Aβ) and tau AD biomarkers, neurodegeneration, inflammation/immune modulation, neurovascular injury, and metabolism/oxidative stress. Methods: Paired baseline and eight-week CSFs from twenty participants in a clinical drug trial for mild cognitive impairment (MCI) or mild dementia due to AD were used to evaluate sensitivity, intra-assay precision, inter-assay replicability, and eight-week biotemporal stability for sixty unique analytes measured with commercially available single- and multi-plex ELISA assays. Coefficients of variation (CV) were calculated, and intraclass correlation and Wilcoxon signed rank tests were applied. Results: We identified 32 biomarker candidates with good to excellent performance characteristics according to assay technical performance and CSF analyte biotemporal stability cut-off criteria. These included: 1) the core AD biomarkers Aβ1–42, Aβ1–40, Aβ1–38, and total tau; 2) non-Aβ, non-tau neurodegeneration markers NfL and FABP3; 3) inflammation/immune modulation markers IL-6, IL-7, IL-8, IL-12/23p40, IL-15, IL-16, MCP-1, MDC, MIP-1β, and YKL-40; 4) neurovascular markers Flt-1, ICAM-1, MMP-1, MMP-2, MMP-3, MMP-10, PlGF, VCAM-1, VEGF, VEGF-C, and VEGF-D; and 5) metabolism/oxidative stress markers 24-OHC, adiponectin, leptin, soluble insulin receptor, and 8-OHdG. Conclusions: Assays for these CSF analytes demonstrate consistent sensitivity, reliability, and biotemporally stability for use in a multiple pathophysiological CSF biomarker panel to profile AD. Their qualification enables further investigation for use in AD diagnosis, staging and progression, disease mechanism profiling, and clinical trials.