Chapter 9 Repeat expansion diseases

Publication date: 2018 Source:Handbook of Clinical Neurology, Volume 147 Author(s): Henry Paulson More than 40 diseases, most of which primarily affect the nervous system, are caused by expansions of simple sequence repeats dispersed throughout the human genome. Expanded trinucleotide repeat diseases were discovered first and remain the most frequent. More recently tetra-, penta-, hexa-, and even dodeca-nucleotide repeat expansions have been identified as the cause of human disease, including some of the most common genetic disorders seen by neurologists. Repeat expansion diseases include both causes of myotonic dystrophy (DM1 and DM2), the most common genetic cause of amyotrophic lateral sclerosis/frontotemporal dementia (C9ORF72), Huntington disease, and eight other polyglutamine disorders, including the most common forms of dominantly inherited ataxia, the most common recessive ataxia (Friedreich ataxia), and the most common heritable mental retardation (fragile X syndrome). Here I review distinctive features of this group of diseases that stem from the unusual, dynamic nature of the underlying mutations. These features include marked clinical heterogeneity and the phenomenon of clinical anticipation. I then discuss the diverse molecular mechanisms driving disease pathogenesis, which vary depending on the repeat sequence, size, and location within the disease gene, and whether the repeat is translated into protein. I conclude with a brief clinical and genetic description ...
Source: Handbook of Clinical Neurology - Category: Neurology Source Type: research

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Background: Bright light treatment is a therapeutic intervention mainly used to treat sleep and circadian disturbances in Alzheimer ’s disease (AD) patients. Recently, a handful of studies also focused on the effect on cognition and behavior. Conflicting findings are reported in the literature, and no definite conclusions have been drawn about its specific therapeutic effect.Summary: The aim of this review is to provide a critical evaluation of available evidence in this field, highlighting the specific characteristics of effective bright light treatment. Eligible studies were required to assess at least one of the f...
Source: Dementia and Geriatric Cognitive Disorders - Category: Geriatrics Source Type: research
Conclusions: The VRTC exercise posed a protective effect for some cognitive and physical functions in older adults with CI. The more engaging the program, the greater the improvement in the cognitive performance.Dement Geriatr Cogn Disord 2018;46:358 –370
Source: Dementia and Geriatric Cognitive Disorders - Category: Geriatrics Source Type: research
Conclusion: Our findings support an association between neuroaxonal injury and delirium. The correlation between serum and CSF NFL supports the use of NFL as a blood biomarker in future delirium studies.Dement Geriatr Cogn Disord 2018;46:346 –357
Source: Dementia and Geriatric Cognitive Disorders - Category: Geriatrics Source Type: research
CONCLUSIONS:: These findings suggest that the repetitive behaviors in bvFTD are repetitive impulsions, possibly from specific involvement of frontostriatal-anterior temporal pathology. PMID: 30537913 [PubMed - as supplied by publisher]
Source: Journal of Neuropsychiatry and Clinical Neurosciences - Category: Psychiatry Tags: J Neuropsychiatry Clin Neurosci Source Type: research
Authors: Martins AP, Prado LGR, Lillo P, Mioshi E, Teixeira AL, de Souza LC Abstract OBJECTIVE:: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with prominent motor symptoms. Patients with ALS may also manifest frontal behavior symptoms and cognitive decline, including impairment in facial emotion recognition. The authors aimed to investigate whether deficits in emotion recognition were associated with frontal behavior symptoms in ALS. METHODS:: Participants were patients with probable or definite sporadic ALS (N=21; male:female ratio, 11:10; median age, 62 years; median disease duration, 3 ...
Source: Journal of Neuropsychiatry and Clinical Neurosciences - Category: Psychiatry Tags: J Neuropsychiatry Clin Neurosci Source Type: research
Authors: Lavretsky H PMID: 30538073 [PubMed - as supplied by publisher]
Source: The American Journal of Geriatric Psychiatry - Category: Psychiatry Tags: Am J Geriatr Psychiatry Source Type: research
The objective of this study was to examine whether reduced awareness of memory deficits in individuals with dementia is associated with more frequent need for Medicare home health care services. METHODS: Cross-sectional analyses were conducted in a multicenter, clinic-based cohort. In total, 192 participants diagnosed with dementia and their informants were independently asked whether or not the participant demonstrated cognitive symptoms of dementia related to memory and word-finding. Participant self-awareness was measured as the discrepancy between participant and caregiver report of these symptoms. Annual Medicare ...
Source: Alzheimer Disease and Associated Disorders - Category: Psychiatry Tags: Alzheimer Dis Assoc Disord Source Type: research
Gaze stabilization during head movements is provided by the vestibulo-ocular reflex (VOR). Clinical assessment of this reflex is performed using the video Head Impulse Test (vHIT). To date, the influence of different fixation distances on VOR gain using the vHIT has not been explored. We assessed the effect of target proximity on the horizontal VOR using the vHIT. Firstly, we assessed the VOR gain in 18 healthy subjects with 5 viewing target distances (150, 40, 30, 20, and 10 cm). The gain increased significantly as the viewing target distance decreased. A second experiment on 10 subjects was performed in darkness whilst t...
Source: Audiology and Neurotology - Category: Audiology Source Type: research
(Reuters Health) - - Mental engagement through problem-solving games like crossword puzzles, sudoku and brain teasers may not offset cognitive losses due to age-related dementia, a new study suggests.
Source: Reuters: Health - Category: Consumer Health News Tags: healthNews Source Type: news
Authors: Hatabe Y, Shibata M, Ohara T, Oishi E, Yoshida D, Honda T, Hata J, Kanba S, Kitazono T, Ninomiya T Abstract BACKGROUND: The association between decline in handgrip strength from midlife to late-life and dementia is unclear. METHODS: Japanese community-dwellers without dementia aged 60 to 79 (i.e., individuals in late-life; mean age, 68 years) were followed for 24 years (1988-2012) (n=1,055); 835 of them had participated in a health examination in 1973-1974 (mean age, 53 years), and these earlier data were used for the midlife analysis. Using a Cox proportional hazards model, we estimated the risk confe...
Source: Journal of Epidemiology - Category: Epidemiology Tags: J Epidemiol Source Type: research
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