Human Immunodeficiency Virus Infection in Huntington’s Disease is Associated with an Earlier Age of Symptom Onset
Authors: Schultz, Jordan L. | Nopoulos, Peg C. | Gonzalez-Alegre, Pedro
Article Type: Research Article
Abstract: Background: Huntington Disease (HD) and human immunodeficiency virus (HIV) are both associated with neurodegeneration in the cerebral cortex and striatum. The rate of striatal degeneration is a known predictor of symptom onset in HD indicating a potential neurobiological link between HD and HIV. Objective: To determine if the presence of pre-existing HIV infection would trigger a significantly earlier age of symptom onset (ASO) in HD-mutation carriers when compared to non-infected HD subjects. Methods: This was a retrospective analysis of the Enroll-HD database that included participants with a CAG repeat of at least 36. Participants with HD and a comorbidity of …HIV that was diagnosed prior to their reported ASO were identified and compared to participants with HD who did not have HIV. An ANCOVA analysis was performed to investigate the differences in ASO between the HIV and non-HIV groups. Sex, drug use, and CAG repeat number were used as covariates. Results: The average ASO of HD subjects with previous HIV infection (n = 8) was 9.1 years earlier than non-HIV infected HD subjects (n = 3259) [F (1, 3267) =10.05, p = 0.002]. Despite low numbers of participants in the HIV group, the calculated effect size of this difference was 1.07. Conclusion: The known neurobiological changes caused by HIV seem to hasten the ASO in patients with HD. These results may enhance our understanding of the neuropathology of HD in a way that will help with the identification of novel targets for future therapies. Show more
Keywords: Huntington’s disease, symptom onset, Enroll-HD, human immunodeficiency virus
DOI: 10.3233/JHD-180287
Citation: Journal of Huntington's Disease, vol. 7, no. 2, pp. 163-166, 2018
Quantifying the Onset of Unintended Weight Loss in Huntington’s Disease: A Retrospective Analysis of Enroll-HD
Authors: Ogilvie, Amy C. | Nopoulos, Peg C. | Schultz, Jordan L.
Article Type: Research Article
Abstract: Background: Unintended weight loss and decreased body mass indexes (BMIs) are common symptoms of individuals with manifest HD. It is unknown at what point during disease progression weight loss starts to accelerate relative to a healthy individual’s weight and when recommended interventions should be initiated to have the strongest impact on patient care. Objective: The objective of this study was to identify a point in time relative to age at motor onset when the decline in weight in HD starts to accelerate relative to a non-HD population. The relationship between initiation of weight loss interventions and changes in weight loss …was also explored. Methods: Participants from the fifth version of the Enroll-HD study were identified for this research. Linear mixed-effects piecewise regression models were used to estimate the point in time relative to the reported age of motor onset in which BMI started to decline in participants with HD compared to healthy non-HD controls. A post-hoc descriptive analysis was performed to look at when nutritional supplements and swallow therapy were initiated in participants with HD relative to motor onset. Results: BMI decline in the HD group began to accelerate compared to controls approximately 5.7 years after the reported age of motor onset (95% CI: 4.7–6.9). The average initiation times of swallow therapy and nutritional supplements were 7.7 years (SD = 5.5 years) and 6.7 years (SD = 6.5 years) after motor onset, respectively. Conclusion: Our findings suggest a potential point for intervention of nutrition programs or therapies used to prevent future weight loss. Show more
Keywords: Huntington’s disease, disease progression, body-weight trajectory, weight loss
DOI: 10.3233/JHD-210488
Citation: Journal of Huntington's Disease, vol. 10, no. 4, pp. 485-492, 2021
The Neurodevelopmental Hypothesis of Huntington’s Disease
Authors: van der Plas, Ellen | Schultz, Jordan L. | Nopoulos, Peg C.
Article Type: Review Article
Abstract: The current dogma of HD pathoetiology posits it is a degenerative disease affecting primarily the striatum, caused by a gain of function (toxicity) of the mutant mHTT that kills neurons. However, a growing body of evidence supports an alternative theory in which loss of function may also influence the pathology.This theory is predicated on the notion that HTT is known to be a vital gene for brain development. mHTT is expressed throughout life and could conceivably have deleterious effects on brain development. The end event in the disease is, of course, neurodegeneration; however the process by which that occurs may …be rooted in the pathophysiology of aberrant development. To date, there have been multiple studies evaluating molecular and cellular mechanisms of abnormal development in HD, as well as studies investigating abnormal brain development in HD animal models. However, direct study of how mHTT could affect neurodevelopment in humans has not been approached until recent years. The current review will focus on the most recent findings of a unique study of children at-risk for HD, the Kids-HD study. This study evaluates brain structure and function in children ages 6–18 years old who are at risk for HD (have a parent or grand-parent with HD). Show more
Keywords: Brain development, Huntington’s disease, children at risk for HD, MRI
DOI: 10.3233/JHD-200394
Citation: Journal of Huntington's Disease, vol. 9, no. 3, pp. 217-229, 2020
COVID-19 Case Fatality and Alzheimer’s Disease
Authors: Zhang, Qiang | Schultz, Jordan L. | Aldridge, Georgina M. | Simmering, Jacob E. | Kim, Youngcho | Ogilvie, Amy C. | Narayanan, Nandakumar S.
Article Type: Short Communication
Abstract: Previous studies have identified dementia as a risk factor for death from coronavirus disease 2019 (COVID-19). However, it is unclear whether Alzheimer’s disease (AD) is an independent risk factor for COVID-19 case fatality rate. In a retrospective cohort study, we identified 387,841 COVID-19 patients through TriNetX. After adjusting for demographics and comorbidities, we found that AD patients had higher odds of dying from COVID-19 compared to patients without AD (Odds Ratio: 1.20, 95%confidence interval: 1.09–1.32, p < 0.001). Interestingly, we did not observe increased mortality from COVID-19 among patients with vascular dementia. These data are relevant to the evolving COVID-19 pandemic.
Keywords: Alzheimer’s disease, case fatality, Coronavirus disease 2019 (COVID-19), dementia with Lewy bodies, frontotemporal dementia, Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), vascular dementia
DOI: 10.3233/JAD-215161
Citation: Journal of Alzheimer's Disease, vol. 84, no. 4, pp. 1447-1452, 2021