scholarly journals Intra-individual Variability in Prodromal Huntington Disease and Its Relationship to Genetic Burden

2015 ◽  
Vol 21 (1) ◽  
pp. 8-21 ◽  
Author(s):  
Mandi Musso ◽  
Holly James Westervelt ◽  
Jeffrey D. Long ◽  
Erin Morgan ◽  
Steven Paul Woods ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Disease Onset ◽  
Individual Variability ◽  
Effect Sizes ◽  
Motor Functioning ◽  
Single Measure ◽  
Timing Task ◽  
Neuropsychological Tasks ◽  
Genetic Burden ◽  
Task Variability

AbstractThe current study sought to examine the utility of intra-individual variability (IIV) in distinguishing participants with prodromal Huntington disease (HD) from nongene-expanded controls. IIV across 15 neuropsychological tasks and within-task IIV using a self-paced timing task were compared as a single measure of processing speed (Symbol Digit Modalities Test [SDMT]) in 693 gene-expanded and 191 nongene-expanded participants from the PREDICT-HD study. After adjusting for depressive symptoms and motor functioning, individuals estimated to be closest to HD diagnosis displayed higher levels of across- and within-task variability when compared to controls and those prodromal HD participants far from disease onset (FICV(3,877)=11.25; p<.0001; FPacedTiming(3,877)=22.89; p<.0001). When prodromal HD participants closest to HD diagnosis were compared to controls, Cohen’s d effect sizes were larger in magnitude for the within-task variability measure, paced timing (−1.01), and the SDMT (−0.79) and paced tapping coefficient of variation (CV) (−0.79) compared to the measures of across-task variability [CV (0.55); intra-individual standard deviation (0.26)]. Across-task variability may be a sensitive marker of cognitive decline in individuals with prodromal HD approaching disease onset. However, individual neuropsychological tasks, including a measure of within-task variability, produced larger effect sizes than an index of across-task IIV in this sample. (JINS, 2015, 21, 8–21)

scholarly journals Mechanistic within-host models of the asexual Plasmodium falciparum infection: a review and analytical assessment

2021 ◽  
Author(s):  
Flavia Camponovo ◽  
Tamsin E Lee ◽  
Jonathan Russell ◽  
Lydia Burgert ◽  
Jaline Gerardin ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Immune Escape ◽  
Clinical Symptoms ◽  
Disease Onset ◽  
Clinical Malaria ◽  
Individual Variability ◽  
Switching Dynamics ◽  
Underlying Mechanisms ◽  
Parasite Dynamics

Background: Malaria blood-stage infection length and intensity are important drivers of disease and transmission; however, the underlying mechanisms of parasite growth and the host's immune response during infection remain largely unknown. Over the last 30 years, several mechanistic mathematical models of malaria parasite within-host dynamics have been published and used in malaria transmission models. Methods: We identified mechanistic within-host models of parasite dynamics through a review of published literature. For a subset of these, we reproduced model code and compared descriptive statistics between the models using fitted data. Through simulation and model analysis, we compare and discuss key features of the models, including assumptions on growth, immune response components, variant switching mechanisms, and inter-individual variability. Results: The assessed within-host malaria models generally replicate infection dynamics in malaria-na&iumlve individuals. However, there are substantial differences between the model dynamics after disease onset, and models do not always reproduce late infection parasitemia data used for calibration of the within host infections. Models have attempted to capture the considerable variability in parasite dynamics between individuals by including stochastic parasite multiplication rates; variant switching dynamics leading to immune escape; variable effects of the host immune responses; or via probabilistic events. For models that capture realistic length of infections, model representations of innate immunity explain early peaks in infection density that cause clinical symptoms, and model representations of antibody immune responses control the length of infection. Models differed in their assumptions concerning variant switching dynamics, reflecting uncertainty in the underlying mechanisms of variant switching revealed by recent clinical data during early infection. Overall, given the scarce availability of the biological evidence there is limited support for complex models. Conclusions: Our study suggests that much of the inter-individual variability observed in clinical malaria infections has traditionally been attributed in models to random variability, rather than mechanistic disease dynamics. Thus, we propose that newly developed models should assume simple immune dynamics that minimally capture mechanistic understandings and avoid over-parameterisation and large stochasticity which inaccurately represent unknown disease mechanisms.

scholarly journals Psychiatric and Cognitive Difficulties as Indicators of Juvenile Huntington Disease Onset in 29 Patients

2007 ◽  
Vol 64 (6) ◽  
pp. 813 ◽  
Author(s):  
Pascale Ribaï ◽  
Karine Nguyen ◽  
Valérie Hahn-Barma ◽  
Isabelle Gourfinkel-An ◽  
Marie Vidailhet ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Disease Onset ◽  
Cognitive Difficulties ◽  
Juvenile Huntington Disease

J01 Improving Prediction Of Huntington Disease Onset With Clinical And Imaging Measures: A 10-year Preopective Study Of Converters

2014 ◽  
Vol 85 (Suppl 1) ◽  
pp. A65-A65
Author(s):  
J. Paulsen ◽  
J. Long ◽  
C. Ross ◽  
D. Harrington ◽  
C. Erwin ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Disease Onset

scholarly journals Response to Therapeutic Sleep Deprivation: A Naturalistic Study of Clinical and Genetic Factors and Post-Treatment Depressive Symptom Trajectory

2018 ◽  
Author(s):  
Nina Trautmann ◽  
Jerome C. Foo ◽  
Josef Frank ◽  
Stephanie H. Witt ◽  
Fabian Streit ◽  
...  
Keyword(s):  
Depressive Symptom ◽  
Sleep Deprivation ◽  
Genetic Factors ◽  
Disease Onset ◽  
Depression Symptom ◽  
Healthy Controls ◽  
Biological Mechanisms ◽  
Global Improvement ◽  
Genetic Burden ◽  
The Impact

AbstractResearch has shown that therapeutic sleep deprivation (SD) has rapid antidepressant effects in the majority of depressed patients. Investigation of factors preceding and accompanying these effects may facilitate the identification of the underlying biological mechanisms. This exploratory study aimed to examine clinical and genetic factors predicting response to SD and determine the impact of SD on illness course. Mood and tiredness during SD were also assessed via visual analogue scales (VAS). Depressed inpatients (n = 78) and healthy controls (n = 15) underwent ~36hrs of SD. Response to SD was defined as a score of ≤2 on the Clinical Global Impression Scale for Global Improvement. Depressive symptom trajectories were evaluated for up to a month using self/expert ratings. Impact of genetic burden was calculated using polygenic risk scores for major depressive disorder. 72% of patients responded to SD. Responders and nonresponders did not differ in baseline self/expert depression symptom ratings, but mood subjectively measured by VAS scale differed. Response was associated with lower age (p = 0.007) and later age at life-time disease onset (p = 0.003). Higher genetic burden of depression was observed in non-responders than healthy controls. Up to a month post-SD, depressive symptoms decreased in both patients groups, but more in responders, in whom effects were sustained. The present findings suggest that re-examining SD with a greater focus on biological mechanisms will lead to better understanding of mechanisms of depression.

scholarly journals Diagnosis of Huntington Disease

2003 ◽  
Vol 49 (10) ◽  
pp. 1726-1732 ◽  
Author(s):  
Russell L Margolis ◽  
Christopher A Ross
Keyword(s):  
Huntington Disease ◽  
Clinical Presentation ◽  
Neurodegenerative Disorder ◽  
Diagnostic Testing ◽  
Disease Onset ◽  
Test Results ◽  
Genetic Test Results ◽  
Essential Components ◽  
Trinucleotide Expansion ◽  
Expansion Mutation

Abstract Background: Huntington disease (HD) is a rare, progressive, and fatal autosomal dominant neurodegenerative disorder, typically of adult onset. Methods: We reviewed the literature concerning the molecular diagnosis of HD. Results: The discovery of the genetic etiology of HD, a trinucleotide expansion mutation on chromosome 4p, has led to the development of increasingly reliable and valid diagnostic tests that can be applied to symptomatic patients, individuals at risk for HD but currently asymptomatic, fetuses, and embryos. However, the unstable nature of the HD mutation, the lack of effective treatments for HD, the mid-adulthood age of disease onset, and the existence of disorders with the same clinical presentation but different etiology all complicates diagnostic testing. Conclusion: Conscientious laboratory work, knowledgeable interpretation of genetic test results, and the availability of pre- and posttest counseling are essential components of HD diagnosis.

A meta-analysis of the neuropsychological sequelae of HIV infection

2002 ◽  
Vol 8 (3) ◽  
pp. 410-424 ◽  
Author(s):  
MARK REGER ◽  
ROBERT WELSH ◽  
JILL RAZANI ◽  
DAVID J. MARTIN ◽  
KYLE B. BOONE
Keyword(s):  
Cognitive Functioning ◽  
Disease Progression ◽  
Cognitive Deficits ◽  
Meta Analysis ◽  
Effect Sizes ◽  
Disease Stage ◽  
Information Processing Speed ◽  
Motor Functioning ◽  
Neuropsychological Sequelae ◽  
Large Motor

This meta-analysis summarizes the broad spectrum of neuropsychological research on HIV disease across a sample of 41 primary studies and an aggregate of 8,616 participants for 10 major neuropsychological ability areas. Analyses of the course of cognitive decline within and across Centers for Disease Control classifications reveals statistically significant cognitive deficits from asymptomatic HIV to AIDS. Effect sizes (Cohen, 1988) were calculated to reflect between-group (asymptomatic, symptomatic, AIDS) differences in each neuropsychological domain. Relatively small effect sizes were obtained for the asymptomatic (0.05–0.21) patients, and generally small to moderate effect sizes were obtained for symptomatic (0.18–0.65) HIV+ patients, with motor functioning exhibiting the greatest effects in this later disease stage. The most notable deficits in cognitive functioning were found in the AIDS group with moderate (attention and concentration) to large (motor functioning) effect sizes with values ranging from 0.42–0.82. Comparison of cognitive functioning as a function of disease progression revealed that motor functioning, executive skills, and information processing speed were among the cognitive domains showing the greatest decline from early to later stages of HIV. These findings indicate that cognitive deficits in the early stages of HIV are small and increase in the later phases of the illness, and that specific patterns of cognitive deficits can be detected with disease progression. These results and their clinical utility are further discussed. (JINS, 2002, 8, 410–424.)

scholarly journals MicroRNAs in CSF as prodromal biomarkers for Huntington disease in the PREDICT-HD study

Neurology ◽  
2017 ◽  
Vol 90 (4) ◽  
pp. e264-e272 ◽  
Author(s):  
Eric R. Reed ◽  
Jeanne C. Latourelle ◽  
Jeremy H. Bockholt ◽  
Joli Bregu ◽  
Justin Smock ◽  
...  
Keyword(s):  
Huntington Disease ◽  
Disease Onset ◽  
Low Risk ◽  
Csf Biomarkers ◽  
Gene Expansion ◽  
False Discovery ◽  
Medium Risk ◽  
Study Participants ◽  
Risk Categories ◽  
Hd Gene

ObjectiveTo investigate the feasibility of microRNA (miRNA) levels in CSF as biomarkers for prodromal Huntington disease (HD).MethodsmiRNA levels were measured in CSF from 60 PREDICT-HD study participants using the HTG protocol. Using a CAG–Age Product score, 30 prodromal HD participants were selected based on estimated probability of imminent clinical diagnosis of HD (i.e., low, medium, high; n = 10/group). For comparison, participants already diagnosed (n = 15) and healthy controls (n = 15) were also selected.ResultsA total of 2,081 miRNAs were detected and 6 were significantly increased in the prodromal HD gene expansion carriers vs controls at false discovery rate q < 0.05 (miR-520f-3p, miR-135b-3p, miR-4317, miR-3928-5p, miR-8082, miR-140-5p). Evaluating the miRNA levels in each of the HD risk categories, all 6 revealed a pattern of increasing abundance from control to low risk, and from low risk to medium risk, which then leveled off from the medium to high risk and HD diagnosed groups.ConclusionsThis study reports miRNAs as CSF biomarkers of prodromal and diagnosed HD. Importantly, miRNAs were detected in the prodromal HD groups furthest from diagnosis where treatments are likely to be most consequential and meaningful. The identification of potential biomarkers in the disease prodrome may prove useful in evaluating treatments that may postpone disease onset.Clinicaltrials.gov identifierNCT00051324.

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