Browsing by Subject "longitudinal"

Now showing 1 - 5 of 5
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    Bayesian multivariate longitudinal model for immune responses to Leishmania: A tick-borne co-infection study
    (Wiley, 2023-09-20) Pabon-Rodriguez, Felix M.; Brown, Grant D.; Scorza, Breanna M.; Petersen, Christine A.; Biostatistics and Health Data Science, Richard M. Fairbanks School of Public Health
    While many Bayesian state-space models for infectious disease processes focus on population infection dynamics (eg, compartmental models), in this work we examine the evolution of infection processes and the complexities of the immune responses within the host using these techniques. We present a joint Bayesian state-space model to better understand how the immune system contributes to the control of Leishmania infantum infections over the disease course. We use longitudinal molecular diagnostic and clinical data of a cohort of dogs to describe population progression rates and present evidence for important drivers of clinical disease. Among these results, we find evidence for the importance of co-infection in disease progression. We also show that as dogs progress through the infection, parasite load is influenced by their age, ectoparasiticide treatment status, and serology. Furthermore, we present evidence that pathogen load information from an earlier point in time influences its future value and that the size of this effect varies depending on the clinical stage of the dog. In addition to characterizing the processes driving disease progression, we predict individual and aggregate patterns of Canine Leishmaniasis progression. Both our findings and the application to individual-level predictions are of direct clinical relevance, presenting possible opportunities for application in veterinary practice and motivating lines of additional investigation to better understand and predict disease progression. Finally, as an important zoonotic human pathogen, these results may support future efforts to prevent and treat human Leishmaniosis.
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    Examining the role of repeated test exposure over 12 months across ADNI protocols
    (Wiley, 2022) Hammers, Dustin B.; Duff, Kevin; Apostolova, Liana G.; Alzheimer's Disease Neuroimaging Initiative; Neurology, School of Medicine
    Objective: Changes to study protocols during longitudinal research may alter cognitive testing schedules over time. Unlike in prior Alzheimer's Disease Neuroimaging Initiative (ADNI) protocols, where testing occurred twice annually, participants enrolled in the ADNI-3 are no longer exposed to cognitive materials at 6 months. This may affect their 12-month performance relative to earlier ADNI cohorts, and potentially confounds data harmonization attempts between earlier and later ADNI protocols. Method: Using data from participants enrolled across multiple ADNI protocols, this study investigated whether test exposure during 6-month cognitive evaluation influenced scores on subsequent 12-month evaluation. Results: No interaction effects were observed between test exposure group and time at 12 months on cognitive performance. No improvements, and limited declines, were seen between baseline and 12-month follow-up scores on most measures. Conclusions: The 6-month testing session had minimal impact on 12-month performance in ADNI. Collapsing longitudinal data across ADNI protocols in future research appears appropriate.
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    NEURAL CORRELATES AND PROGRESSION OF SACCADE IMPAIRMENT IN PREMANIFEST AND MANIFEST HUNTINGTON DISEASE
    (2010-10-15) Rupp, Jason Douglas; Foroud, Tatiana; Conneally, P. Michael; Kareken, David A.; Saykin, Andrew J.; Wojcieszek, Joanne
    Huntington disease (HD) is an autosomal dominant disorder characterized by progressive decline of motor, cognitive, and behavioral function. Saccades (rapid, gaze-shifting eye movements) are affected before a clinical diagnosis of HD is certain (i.e. during the premanifest period of the disease). Fundamental questions remain regarding the neural substrates of abnormal saccades and the course of premanifest disease. This work addressed these questions using magnetic resonance imaging (MRI) and a longitudinal study of premanifest disease progression. Gray matter atrophy is a characteristic of HD that can be reliably detected during the premanifest period, but it is not known how such changes influence saccadic behavior. We evaluated antisaccades (AS) and memory guided saccades (MG) in premanifest and manifest HD, then tested for associations between impaired saccadic measures and gray matter atrophy in brain regions involved in these saccadic tasks. The results suggest that slowed vertical AS responses indicate cortical and subcortical atrophy and may be a noninvasive marker of atrophic changes in the brain. We also investigated the brain changes that underlie AS impairment using an event-related AS design with functional MRI (fMRI). We found that, in premanifest and manifest HD, blood oxygenation level dependent (BOLD) response was abnormally absent in the pre-supplementary motor area and dorsal anterior cingulate cortex following incorrect AS responses. These results are the first to suggest that abnormalities in an error-related response network underlie early disease-related saccadic changes, and they emphasize the important influence of regions outside the striatum and frontal cortex in disease manifestations. Though saccadic abnormalities have been repeatedly observed cross sectionally, they have not yet been studied longitudinally in premanifest HD. We found different patterns of decline; for some measures the rate of decline increased as individuals approached onset, while for others the rate was constant throughout the premanifest period. These results establish the effectiveness of saccadic measures in tracking premanifest disease progression, and argue for their use in clinical trials. Together, these studies establish the utility of saccade measures as a marker of HD neurodegeneration and suggest that they would be a valuable component of batteries evaluating the efficacy of neuroprotective therapies.
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    Telomere Shortening in the Alzheimer’s Disease Neuroimaging Initiative Cohort
    (IOS Press, 2019-09-03) Nudelman, Kelly N. H.; Lin, Jue; Lane, Kathleen A.; Nho, Kwangsik; Kim, Sungeun; Faber, Kelley M.; Risacher, Shannon L.; Foroud, Tatiana M.; Gao, Sujuan; Davis, Justin W.; Weiner, Michael W.; Saykin, Andrew J.; Initiative for the Alzheimer’s Disease Neuroimaging; Medical and Molecular Genetics, School of Medicine
    BACKGROUND: Although shorter telomeres have been associated with Alzheimer’s disease (AD), it is unclear whether longitudinal change in telomere length is associated with AD progression. OBJECTIVE: To investigate the association of telomere length change with AD diagnosis and progression. METHODS: In 653 individuals from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort, T/S ratio (telomere vs. single copy gene), a proxy of telomere length, was measured for up to five visits per participant (N=1918 samples post-QC) using quantitative PCR (qPCR). T/S ratio was adjusted for batch effects and DNA storage time. A mixed effects model was used to evaluate association of telomere length with AD diagnostic group and interaction of age and diagnosis. Another mixed effects model was used to compare T/S ratio changes pre- to post-conversion to MCI or AD to telomere change in participants with stable diagnoses. RESULTS: Shorter telomeres were associated with older age (Effect Size (ES)=−0.23) and male sex (ES=−0.26). Neither baseline T/S ratio (ES=−0.036) nor T/S ratio change (ES=0.046) differed significantly between AD diagnostic groups. MCI/AD converters showed greater, but non-significant, telomere shortening compared to non-converters (ES=−0.186). CONCLUSIONS: Although AD compared to controls showed small, non-significant effects for baseline T/S ratio and T/S ratio shortening, we did observe a larger, though still non-significant effect for greater telomere shortening in converters compared to non-converters. Although our results do not support telomere shortening as a robust biomarker of AD progression, further investigation in larger samples and for subgroups of participants may be informative.
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    Within-Person Associations Among Self-Perceptions of Memory, Depressive Symptoms, and Activity Participation in Older Adults
    (Oxford, 2020) Hill, Nikki L.; Mogle, Jacqueline; Bhargava, Sakshi; Bratlee-Whitaker, Emily; Wion, Rachel K.; Sweeder, Logan; Sliwinski, Martin; Barnes, Lisa L.; School of Nursing
    Background and Objectives Self-perceptions of memory problems may impact older adults’ mood as well as their activity participation, thereby negatively affecting health and well-being. We examined within-person associations among self-reported memory, depressive symptoms, as well as physical, social, and cognitive activity participation in older adults without cognitive impairment. Research Design and Methods Samples were drawn from the Einstein Aging Study (EAS), National Health and Aging Trends Study (NHATS), Rush Memory and Aging Project (MAP), and Minority Aging Research Study (MARS), with over 8,000 participants (65+ years) included across data sets. In a series of coordinated analyses, multilevel structural equation modeling was used to examine within-person relationships over periods of up to 20 years. Results Across EAS, NHATS, and MAP/MARS samples, we found that older adults’ self-perceptions of memory did not directly covary with activity participation over time. However, we did find an indirect association in NHATS such that within-person changes in depressive symptoms were associated with changes in self-reported memory, and these contributed to lower physical as well as social activity participation. Discussion and Implications Older adults’ activity participation is important for health, but maximizing engagement requires understanding potentially impeding factors. We found some evidence that as self-perceptions of memory change over time, associated depressive symptoms may contribute to lower activity participation. Inconsistent findings across data sets, however, suggest future research is needed to understand individual characteristics that may influence these relationships.