Related Experiment Video
Updated: Jun 20, 2026
09:06
Whole-brain Segmentation and Change-point Analysis of Anatomical Brain MRI—Application in Premanifest Huntington's Disease
Published on: June 9, 2018
Progression in prediagnostic Huntington disease
Jason Rupp1, Tanya Blekher, Jacqueline Jackson
1Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN 46202-5251, USA.
Journal of Neurology, Neurosurgery, and Psychiatry
|September 4, 2009
Summary
Individuals at risk for Huntington disease (HD) show varying rates of cognitive and motor decline before diagnosis. Those closer to their estimated onset date experience faster progression in some measures.
Area of Science:
- Neuroscience
- Genetics
- Neurology
Background:
- Huntington disease (HD) is a progressive neurodegenerative disorder.
- Early detection of decline in at-risk individuals is crucial for understanding disease trajectory.
Purpose of the Study:
- To investigate the longitudinal changes in neurocognitive, psychomotor, and oculomotor functions in individuals at risk for Huntington disease.
- To compare the rates of decline between individuals with the CAG expansion (CAG+) and normal controls (NC), and to differentiate progression based on proximity to estimated onset.
Main Methods:
- 106 individuals at risk for HD were assessed twice over approximately 2.5 years.
- Participants were categorized into normal controls (NC), CAG+ individuals near estimated onset (near), and CAG+ individuals far from estimated onset (far).
- Repeated measures models and analysis of covariance were used to analyze longitudinal performance differences.
Main Results:
- The CAG+ group showed significant decline in movement time, tapping speed, and memory-guided task performance, with faster progression closer to estimated onset.
- Longitudinal progression differed significantly between the three groups (NC, near, far).
- The 'near' group exhibited faster progression than NC for most measures, while comparisons between NC and 'far' groups were inconsistent.
Conclusions:
- Prediagnostic Huntington disease progression varies, with some measures showing accelerated decline as onset approaches.
- Other measures indicate a consistently faster rate of decline in CAG+ individuals compared to normal controls throughout the prediagnostic period.
Related Concept Videos
01:21Huntington Disease l: Introduction
Huntington disease or HD is a progressive, fatal neurodegenerative disorder inherited in an autosomal dominant pattern.PathophysiologyIt is caused by expansion of the CAG trinucleotide repeat in the HTT gene on chromosome 4 (4p16.3), producing an abnormal huntingtin protein with an expanded polyglutamine tract. This misfolded protein disrupts cellular function, leading to neuronal death. Normal alleles have ≤26 repeats, 27–35 are intermediate (risk of expansion), 36–39 show reduced penetrance,...
01:24Parkinson Disease ll: Pathophysiology
Parkinson disease (PD) is a progressive neurodegenerative disorder primarily affecting movement, with additional non-motor features. Its pathophysiology involves complex interactions among genetic susceptibility, environmental exposures, and cellular dysfunction, including dopaminergic neuron loss, protein aggregation, and mitochondrial impairment.Selective NeurodegenerationA key feature is the degeneration of dopaminergic neurons in the substantia nigra pars compacta, leading to reduced...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
01:29Alzheimer Disease l: Introduction
Alzheimer disease is a chronic, progressive, and irreversible neurodegenerative disorder and the most common cause of dementia in older adults. It leads to gradual neuronal loss, causing cognitive decline, behavioral changes, and loss of functional independence.Risk Factors and EtiologyThe disease is multifactorial. Age is the strongest risk factor, with prevalence doubling every 5 years after age 65. Genetic factors include mutations in genes such as APP, PSEN1, and PSEN2, which are associated...
01:23Alzheimer Disease ll: Pathophysiology
Alzheimer disease involves structural changes in the brain that begin long before symptoms appear. The most distinctive features are extracellular neuritic plaques and intracellular neurofibrillary tangles.Neuritic plaques form in the cerebral cortex and around blood vessels. These plaques contain a dense core of beta-amyloid (Aβ)—a toxic protein fragment that clumps outside neurons. The core is surrounded by damaged neuronal extensions, as well as reactive astrocytes and microglia. Abnormal...