Objective: Age at onset of diagnostic motor manifestations in Huntington disease (HD) is strongly correlated with an expanded CAG trinucleotide repeat. The length of the normal CAG repeat allele has been reported also to influence age at onset, in interaction with the expanded allele. Due to profound implications for disease mechanism and modification, we tested whether the normal allele, interaction between the expanded and normal alleles, or presence of a second expanded allele affects age at onset of HD motor signs. Methods:We modeled natural log-transformed age at onset as a function of CAG repeat lengths of expanded and normal alleles and their interaction by linear regression. Results:An apparently significant effect of interaction on age at motor onset among 4,068 subjects was dependent on a single outlier data point. A rigorous statistical analysis with a wellbehaved dataset that conformed to the fundamental assumptions of linear regression (e.g., constant variance and normally distributed error) revealed significance only for the expanded CAG repeat, with no effect of the normal CAG repeat. Ten subjects with 2 expanded alleles showed an age at motor onset consistent with the length of the larger expanded allele. Conclusions:Normal allele CAG length, interaction between expanded and normal alleles, and presence of a second expanded allele do not influence age at onset of motor manifestations, indicating that the rate of HD pathogenesis leading to motor diagnosis is determined by a completely dominant action of the longest expanded allele and as yet unidentified genetic or environmental factors. Neurology ® 2012;78:690-695

The purpose of this randomized controlled trial was to determine if increasing hours of selfmanagement rehabilitation had increasing benefits for health-related quality of life (HRQOL) in Parkinson's disease beyond best medical treatment, if effects persisted at two and six months follow-up, and if targeted compared to non-targeted HRQOL domains responded more to rehabilitation. Participants on best medication therapy were randomized to one of three conditions for six weeks intervention: 0 hrs of rehabilitation; 18 hrs of clinic group rehabilitation plus 9 hrs of attention control social sessions; and 27 hrs of rehabilitation, with 18 in clinic group rehabilitation and 9 hrs of rehabilitation designed to transfer clinic training into home and community routines. Results (N = 116) showed that at six weeks there was a beneficial effect of increased rehabilitation hours on HRQOL measured with the Parkinson's Disease Questionnaire-39 summary index (eta = .23, CI = .05 -.40, p =.01). Benefits persisted at follow-up. The difference between 18 and 27 hrs was not significant. Clinically relevant improvement occurred at a greater rate for 18 and 27 hrs (54% improved) than for 0 hrs (18% improved), a significant 36% difference in rates (95% CI = 20% to 52% difference). Effects were largest in two targeted domains: communication and mobility. More concerns with mobility and activities of daily living at baseline predicted more benefit from rehabilitation. KeywordsClinical trials Randomized controlled (CONSORT agreement); Health-related Quality of life; Parkinson's disease/Parkinsonism; Rehabilitation Health-related quality of life (HRQOL) is one's perceived health and well-being in personally valued domains of daily life.1 , 2 Parkinson's disease (PD) symptoms compromise HRQOL by making it difficult to participate in valued activities and roles of home and NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript community life. Yet individuals who feel mastery over life activities and maintain participation in them experience less depression and more well-being.3 , 4 Effective management of PD begins with considering the person's HRQOL and promoting a sense of control in valued life domains that realistically are within the person's capacity to influence. 5 , 6 Our meta-analyses of previous studies found rehabilitation to improve performance in mobility and self-care activities in 25% more individuals with PD compared to control conditions.7 -9 Recent studies have strengthened the evidence that rehabilitation benefits HRQOL.10 -12 Few of these studies implemented well-defined interventions and tested effects with randomized controlled trials, and fewer yet attempted to test varying intensities of rehabilitation.13 Consequently we developed a specific, best practice rehabilitation intervention and used a randomized-controlled trial to test the effects of differing rehabilitation intensities on health-related quality of life.An interdisciplinary team of physical, occupational, and speech therapists ...

Controversy persists about the etiology of Parkinson's disease (PD). Pesticides, herbicides, well-water consumption, head injury, and a family history of PD have been reported as risk factors for PD. The purpose of this study was to (1) investigate the impact of environmental factors on PD risk (2) estimate the chronology, frequency, and duration of those exposures associated with PD; and (3) investigate the effects of family history on PD risk. One-hundred and forty PD cases were recruited from Boston University Medical Center. The control group was composed of 147 friends and in-laws of PD patients. Environmental, medical, and family history data were obtained by structured interview from each participant for events recalled prior to PD onset for cases, or corresponding censoring age for controls (mean age = 56 years of age for each group). A traditional stratified analysis, adjusting for birth cohort and sex, was employed. Four factors were associated with increased risk for PD: (1) head injury (OR=6.23, confidence interval [CI]: 2.58-15.07); (2) family history of PD (OR=6.08, CI: 2.35-15. 58); (3) family history of tremor (OR=3.97, CI: 1.17-13.50); and (4) history of depression (OR=3.01, CI: 1.32-6.88). A mean latency of 36. 5 (SE=2.81) years passed between the age of first reported head injury and PD onset. A mean latency of 22 (SE=2.66) years passed between the onset of the first reported symptoms of depression and onset of PD. Years of education, smoking, and well-water intake were inversely associated with PD risk. PD was not associated with exposure to pesticides or herbicides. These findings support the role of both environmental and genetic factors in the etiology in PD. The results are consistent with a multifactorial model. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 88:742-749, 1999.