Parkinson disease is a progressive neurodegenerative disorder that affects approximately 6 million people worldwide and more than one-half million individuals in the United States.¹ Parkinson disease–associated morbidity and mortality in the United States contribute $6 billion to health care costs annually.² Incidence of Parkinson disease is expected to increase over the next decade, but neither a cure nor a treatment is available that has been proven to slow progression. Identification and development of effective therapies for slowing progression of Parkinson disease is a research priority.

Background: Research-based exercise interventions improve health-related quality of life (HRQL) and mobility in people with Parkinson’s disease (PD). Objective: To examine whether exercise habits were associated with changes in HRQL and mobility over two years. Methods: We identified a cohort of National Parkinson Foundation Quality Improvement Initiative (NPF-QII) participants with three visits. HRQL and mobility were measured with the Parkinson’s Disease Questionnaire (PDQ-39) and Timed Up and Go (TUG). We compared self-reported regular exercisers (≥2.5 hours/week) with people who did not exercise 2.5 hours/week. Then we quantified changes in HRQL and mobility associated with 30-minute increases in exercise, across PD severity, using mixed effects regression models. Results: Participants with three observational study visits ( n = 3408) were younger, with milder PD, than participants with fewer visits. After 2 years, consistent exercisers and people who started to exercise regularly after their baseline visit had smaller declines in HRQL and mobility than non-exercisers ( p < 0.05). Non-exercisers worsened by 1.37 points on the PDQ-39 and a 0.47 seconds on the TUG per year. Increasing exercise by 30 minutes/week was associated with slower declines in HRQL (–0.16 points) and mobility (–0.04 sec). The benefit of exercise on HRQL was greater in advanced PD (–0.41 points) than mild PD (–0.14 points; p < 0.02). Conclusions: Consistently exercising and starting regular exercise after baseline were associated with small but significant positive effects on HRQL and mobility changes over two years. The greater association of exercise with HRQL in advanced PD supports improving encouragement and facilitation of exercise in advanced PD.

Background: Identifying predictors of conversion to Alzheimer’s disease (AD) is critically important for AD prevention and targeted treatment. Objective: To compare various clinical and biomarker trajectories for tracking progression and predicting conversion from amnestic mild cognitive impairment to probable AD. Methods: Participants were from the ADNI-1 study. We assessed the ability of 33 longitudinal biomarkers to predict time to AD conversion, accounting for demographic and genetic factors. We used joint modelling of longitudinal and survival data to examine the association between changes of measures and disease progression. We also employed time-dependent receiver operating characteristic method to assess the discriminating capability of the measures. Results: 23 of 33 longitudinal clinical and imaging measures are significant predictors of AD conversion beyond demographic and genetic factors. The strong phenotypic and biological predictors are in the cognitive domain (ADAS-Cog; RAVLT), functional domain (FAQ), and neuroimaging domain (middle temporal gyrus and hippocampal volume). The strongest predictor is ADAS-Cog 13 with an increase of one SD in ADAS-Cog 13 increased the risk of AD conversion by 2.92 times. Conclusion: Prediction of AD conversion can be improved by incorporating longitudinal change information, in addition to baseline characteristics. Cognitive measures are consistently significant and generally stronger predictors than imaging measures.

Purpose: Prediction of patients at highest risk for ipsilateral breast tumor recurrence (IBTR) after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The aim of our study was to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center to predict for risk of IBTR in patients with DCIS from our institution. Patients and Methods: We retrospectively identified 794 patients with a diagnosis of DCIS who had undergone local excision from 1990 through 2007 at the MD Anderson Cancer Center (MDACC). Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients who had complete data. Results: There was a marked difference with respect to tumor grade, prevalence of necrosis, initial presentation, final margins, and receipt of endocrine therapy between the two cohorts. The biggest difference was that more patients received radiation in the MDACC cohort (75% at MDACC v 49% at MSKCC; P < .001). Follow-up time in the MDACC cohort was longer than in the MSKCC cohort (median 7.1 years v 5.6 years), and the recurrence rate was lower in the MDACC cohort (7.9% v 11%). The median 5-year probability of recurrence was 5%, and the median 10-year probability of recurrence was 7%. The nomogram for prediction of 5- and 10-year IBTR probabilities demonstrated imperfect calibration and discrimination, with a concordance index of 0.63. Conclusion: Predictive models for IBTR in patients with DCIS who were treated with local excision are imperfect. Our current ability to accurately predict recurrence on the basis of clinical parameters alone is limited.

Purpose: American Joint Committee on Cancer (AJCC) staging is used to determine breast cancer prognosis, yet patient survival within each stage shows wide variation. We hypothesized that differences in biology influence this variation and that addition of biologic markers to AJCC staging improves determination of prognosis. Patients and Methods: We identified a cohort of 3,728 patients who underwent surgery as the first intervention between 1997 and 2006. A Cox proportional hazards model, with backward stepwise exclusion of factors and stratification on pathologic stage (PS), was used to test the significance of adding grade (G), lymphovascular invasion (L), estrogen receptor (ER) status (E), progesterone receptor (PR) status, combined ER and PR status (EP), or combined ER, PR, and human epidermal growth factor receptor 2 status (M). We assigned values of 0 to 2 to these disease-specific survival (DSS) –associated factors and assessed six different staging systems: PS, PS + G, PS + G L, PS + G E, PS + G EP, and PS + G M. We compared 5-year DSS rates, Akaike's information criterion (AIC), and Harrell's concordance index (C-index) between systems. Surveillance, Epidemiology, and End Results data were used as the external validation cohort (n = 26,711). Results: Median follow-up was 6.5 years, and 5-year DSS rate was 97.4%. The PS + G E status staging system was most precise, with a low AIC (1,931.9) and the highest C-index (0.80). PS + G E status was confirmed to stratify outcomes in internal bootstrapping samples and the external validation cohort. Conclusion: Our results validate an improved breast cancer staging system that incorporates grade and ER status. We recommend that biologic markers be incorporated into revised versions of the AJCC staging system.