scholarly journals Central Cognitive Processing Speed Is an Early Marker of Huntington's Disease Onset

2020 ◽  
Vol 8 (1) ◽  
pp. 100-105
Author(s):  
Jody Corey‐Bloom ◽  
McKenna E. Williams ◽  
Ilex Beltran‐Najera ◽  
Andrea I. Mustafa ◽  
Chase M. Snell ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Disease Onset ◽  
Early Marker ◽  
Cognitive Processing Speed

scholarly journals Neuroimaging, Urinary, and Plasma Biomarkers of Treatment Response in Huntington’s Disease: Preclinical Evidence with the p75NTR Ligand LM11A-31

2021 ◽  
Author(s):  
Danielle A. Simmons ◽  
Brian D. Mills ◽  
Robert R. Butler III ◽  
Jason Kuan ◽  
Tyne L. M. McHugh ◽  
...  
Keyword(s):  
Mouse Model ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Treatment Response ◽  
Diffusion Tensor ◽  
Disease Onset ◽  
Therapeutic Effects ◽  
Plasma Cytokine ◽  
Cytokine Levels ◽  
Pharmacodynamic Biomarkers

AbstractHuntington’s disease (HD) is caused by an expansion of the CAG repeat in the huntingtin gene leading to preferential neurodegeneration of the striatum. Disease-modifying treatments are not yet available to HD patients and their development would be facilitated by translatable pharmacodynamic biomarkers. Multi-modal magnetic resonance imaging (MRI) and plasma cytokines have been suggested as disease onset/progression biomarkers, but their ability to detect treatment efficacy is understudied. This study used the R6/2 mouse model of HD to assess if structural neuroimaging and biofluid assays can detect treatment response using as a prototype the small molecule p75NTR ligand LM11A-31, shown previously to reduce HD phenotypes in these mice. LM11A-31 alleviated volume reductions in multiple brain regions, including striatum, of vehicle-treated R6/2 mice relative to wild-types (WTs), as assessed with in vivo MRI. LM11A-31 also normalized changes in diffusion tensor imaging (DTI) metrics and diminished increases in certain plasma cytokine levels, including tumor necrosis factor-alpha and interleukin-6, in R6/2 mice. Finally, R6/2-vehicle mice had increased urinary levels of the p75NTR extracellular domain (ecd), a cleavage product released with pro-apoptotic ligand binding that detects the progression of other neurodegenerative diseases; LM11A-31 reduced this increase. These results are the first to show that urinary p75NTR-ecd levels are elevated in an HD mouse model and can be used to detect therapeutic effects. These data also indicate that multi-modal MRI and plasma cytokine levels may be effective pharmacodynamic biomarkers and that using combinations of these markers would be a viable and powerful option for clinical trials.

scholarly journals Differential Diagnosis of Chorea—HIV Infection Delays Diagnosis of Huntington’s Disease by Years

2021 ◽  
Vol 11 (6) ◽  
pp. 710
Author(s):  
Jannis Achenbach ◽  
Simon Faissner ◽  
Carsten Saft
Keyword(s):  
Hiv Infection ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Disease Onset ◽  
Diagnostic Delay ◽  
Depression Scale ◽  
Cag Repeat ◽  
Psychiatric Disease ◽  
Disease Manifestation ◽  
Cross Sectional

Background: There is a broad range of potential differential diagnoses for chorea. Besides rare, inherited neurodegenerative diseases such as Huntington’s disease (HD) chorea can accompany basal ganglia disorders due to vasculitis or infections, e.g., with the human immunodeficiency virus (HIV). The clinical picture is complicated by the rare occurrence of HIV infection and HD. Methods: First, we present a case suffering simultaneously from HIV and HD (HIV/HD) focusing on clinical manifestation and disease onset. We investigated cross-sectional data regarding molecular genetic, motoric, cognitive, functional, and psychiatric disease manifestation of HIV/HD in comparison to motor-manifest HD patients without HIV infection (nonHIV/HD) in the largest cohort of HD patients worldwide using the registry study ENROLL-HD. Data were analyzed using ANCOVA analyses controlling for covariates of age and CAG repeat length between groups in IBM SPSS Statistics V.25. Results: The HD diagnosis in our case report was delayed by approximately nine years due to the false assumption that the HIV infection might have been the cause of chorea. Out of n = 21,116 participants in ENROLL-HD, we identified n = 10,125 motor-manifest HD patients. n = 23 male participants were classified as suffering from HIV infection as a comorbidity, compared to n = 4898 male non-HIV/HD patients. Except for age, with HIV/HD being significantly younger (p < 0.050), we observed no group differences regarding sociodemographic, genetic, educational, motoric, functional, and cognitive parameters. Male HIV/HD patients reported about a 5.3-year-earlier onset of HD symptoms noticed by themselves compared to non-HIV/HD (p < 0.050). Moreover, patients in the HIV/HD group had a longer diagnostic delay of 1.8 years between onset of symptoms and HD diagnosis and a longer time regarding assessment of first symptoms by the rater and judgement of the patient (all p < 0.050). Unexpectedly, HIV/HD patients showed less irritability in the Hospital Anxiety and Depression Scale (all p < 0.05). Conclusions: The HD diagnosis in HIV-infected male patients is secured with a diagnostic delay between first symptoms noticed by the patient and final diagnosis. Treating physicians therefore should be sensitized to think of potential alternative diagnoses in HIV-infected patients also afflicted by movement disorders, especially if there is evidence of subcortical atrophy and a history of hyperkinesia, even without a clear HD-family history. Those patients should be transferred for early genetic testing to avoid further unnecessary diagnostics and improve sociomedical care.

scholarly journals Decline in cognitive processing speed as a mediator of verbal decline in HIV

1999 ◽  
Vol 14 (1) ◽  
pp. 131-132 ◽  
Author(s):  
D. J. Hardy ◽  
C. H. Hinkin ◽  
P. Satz ◽  
W. G. v. Gorp
Keyword(s):  
Cognitive Processing ◽  
Processing Speed ◽  
Cognitive Processing Speed

C04 Protein coding tandem repeat in TCERG1 modifies huntington’s disease onset

2021 ◽  
Author(s):  
Sergey Lobanov ◽  
Branduff McAllister ◽  
Mia McDade-Kumar ◽  
Jong-Min Lee ◽  
Marcy MacDonald ◽  
...  
Keyword(s):  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Tandem Repeat ◽  
Disease Onset ◽  
Protein Coding

Impaired cognitive processing speed in type 1 diabetic patients who had severe/recurrent hypoglycaemia

2018 ◽  
Vol 32 (11) ◽  
pp. 1040-1045 ◽  
Author(s):  
Stefano Bortolotti ◽  
Lisa Zarantonello ◽  
Ambra Uliana ◽  
Nicola Vitturi ◽  
Sami Schiff ◽  
...  
Keyword(s):  
Cognitive Processing ◽  
Processing Speed ◽  
Diabetic Patients ◽  
Type 1 Diabetic Patients ◽  
Cognitive Processing Speed ◽  
Recurrent Hypoglycaemia

scholarly journals Cortical circuit alterations precede disease onset in Huntington’s disease mice

2018 ◽  
Author(s):  
Johanna Neuner ◽  
Elena Katharina Schulz-Trieglaff ◽  
Sara Gutiérrez-Ángel ◽  
Fabian Hosp ◽  
Matthias Mann ◽  
...  
Keyword(s):  
Motor Cortex ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Primary Motor Cortex ◽  
Disease Onset ◽  
Single Neurons ◽  
Two Photon ◽  
Layer 2 ◽  
Cortical Circuit

AbstractHuntington’s disease (HD) is a devastating hereditary movement disorder, characterized by degeneration of neurons in the striatum and cortex. Studies in human patients and mouse HD models suggest that disturbances of neuronal function in the neocortex play an important role in the disease onset and progression. However, the precise nature and time course of cortical alterations in HD have remained elusive. Here, we use chronicin vivotwo-photon calcium imaging to monitor the activity of single neurons in layer 2/3 of the primary motor cortex in awake, behaving R6/2 transgenic HD mice and wildtype littermates. R6/2 mice show age-dependent changes in neuronal activity with a clear increase in activity at the age of 8.5 weeks, preceding the onset of motor and neurological symptoms. Furthermore, quantitative proteomics demonstrate a pronounced downregulation of synaptic proteins in the cortex, and histological analyses in R6/2 mice and HD patient samples reveal reduced inputs from parvalbumin-positive interneurons onto layer 2/3 pyramidal cells. Thus, our study provides a time-resolved description as well as mechanistic details of cortical circuit dysfunction in HD.Significance statementFuntional alterations in the cortex are believed to play an important role in the pathogenesis of Huntington’s disease (HD). However, studies monitoring cortical activity in HD modelsin vivoat a single-cell resultion are still lacking. We have used chronic two-photon imaging to investigate changes in the activity of single neurons in the primary motor cortex of awake presymptomatic HD mice. We show that neuronal activity increases before the mice develop disease symptoms. Our histological analyses in mice and in human HD autopsy cases furthermore demonstrate a loss inhibitory synaptic terminals from parvalbimun-positive interneurons, revealing a potential mechanism of cortical circuit impairment in HD.

Simultaneous and Successive Syntheses: A Factor Analysis of Speed of Information Processing

1978 ◽  
Vol 46 (3_suppl) ◽  
pp. 1167-1172 ◽  
Author(s):  
Ronald F. Jarman ◽  
Larry W. Krywaniuk
Keyword(s):  
Factor Analysis ◽  
Information Processing ◽  
Cognitive Processing ◽  
Processing Speed ◽  
Motor Speed ◽  
Parallel Processes ◽  
Speed Of Information Processing ◽  
Different Types ◽  
Grade 3 ◽  
Cognitive Processing Speed

A set of tasks was devised to measure different types of speed of information processing. These tasks were administered to a sample of 87 children in Grade 3, and the data were factor analyzed. The results indicated three factors, which were interpreted as simultaneous and successive cognitive processing speed and motor speed. The significance of these results was discussed in terms of current research on human abilities and serial and parallel processes.

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