It is currently widely acknowledged that the natural history of PD includes a preclinical phase, and there are increasing efforts to identify markers that would allow the identification of individuals at risk for PD. Here, we discuss the issues related to defining at-risk populations for PD and review findings of current population-based cohorts that have reported potential biomarkers for PD, such as the Honolulu-Asia Aging Study (HAAS) and the PRIPS (Prospective Validation of Risk factors for the development of Parkinson Syndromes) study. We also discuss enriched risk cohorts designed to evaluate specificity and predictive value of markers exemplified by the PARS (Parkinson Associated Risk Study) and the TREND (Tübinger evaluation of Risk factors for the Early detection of NeuroDegeneration) study. Although there is still a long way to go, studies designed according to these concepts might eventually provide sufficient data to form the basis for future screening programs for PD risk to be applied at a population level.

Objectives To determine whether adhering to a healthy lifestyle in midlife may reduce the risk of dementia. Design Case-control study nested in a prospective cohort. Setting The Honolulu-Asia Aging Study on Oahu, Hawaii. Participants 3468 Japanese American men (mean age 52, 1965–1968) examined for dementia after 25 years. Measurements Men at low risk were defined as those with the following midlife characteristics: nonsmoking, body mass index <25.0 kg/m2, physically active, and having a healthy diet (based on alcohol, dairy, meat, fish, fruit, vegetables, cereals, and monounsaturated-to-saturated fat). Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for developing overall dementia, Alzheimer’s disease (AD), and vascular dementia (VaD), adjusting for potential confounders. Results Dementia was diagnosed in 6.4% of men (52.5% with AD, 35.0% with VaD). Examining the risk factors individually, BMI was most strongly associated with increased risk of overall dementia (OR, 1.87; 95% CI, 1.26–2.77; BMI >25.0 vs. <22.6 kg/m2). All of the individual risk factors except diet score were significantly associated with VaD, whereas none were significantly associated with AD alone. Men with all four low-risk characteristics (7.2% of cohort) had the lowest OR for overall dementia (OR, 0.36; 95% CI, 0.15–0.84), as compared to other men. There were no significant associations between the combined low-risk characteristics and the risk of AD alone. Conclusion Having a healthy lifestyle in midlife is associated with a lower risk of dementia in late life among Japanese American men.

Incident dementia is a major cause of driving cessation. Based on these data, we estimate that approximately 4% of male drivers aged 75 years and older nationwide (about 175,000 men) have dementia. This number will increase with the projected growth of drivers aged 75 years and older.

BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk.MethodsIn June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD.ResultsWe describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs.ConclusionsPD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.

Objectives-To determine the effect of walking on incident depressive symptoms in elderly Japanese-American men with and without chronic disease Design-Prospective cohort study Setting-The Honolulu-Asia Aging StudyParticipants-Japanese-American men aged 71 to 93 years at baseline Measurements-Physical activity was assessed by self-reported distance walked per day. Depressive symptoms were measured with an 11-question version of the Centers for Epidemiologic Studies Depression Scale (CES-D) at the 4th exam (n=3196) and again at the 7th exam 8 years later (1999-2000, n=1417). Presence of incident depressive symptoms was defined as CESD-11 score ≥ 9 or taking anti-depressants at Exam 7. Subjects with prevalent depressive symptoms at baseline were excluded. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author ManuscriptResults-Age adjusted 8-year incident depressive symptoms were 13.6%, 7.6% and 8.5% for low (< ¼ miles/day), intermediate (¼ to 1.5 miles/day) and high (> 1.5 miles/day) walking groups at baseline, p=0. Conclusion-Daily physical activity (≥¼ mile/day) is significantly associated with a lower risk for 8-year incident depressive symptoms in elderly Japanese-American men who do not have chronic disease at baseline.

Warren and Stead's (1) contention that disturbed renal function secondary to a diminished cardiac output is responsible for the following series of events-salt and water retention, increased blood and extracellular fluid volume, rise in venous pressure, edema-seemed to offer a rational explanation for some of the clinically observed phenomena. We therefore initiated a series of studies on patients with chronic congestive heart failure, using the clearance techniques of Smith and associates (2), in order to evaluate the relationship between the decreased sodium excretion in heart failure (3, 4) and renal blood flow, to determine the nature of the disturbance in renal function and the relationship, if any, between the altered renal dynamics and sodium retention. We later attempted to define some of the variables involved in the tubular transfer system for sodium as it obtains in the normal and in the cardiac patient. Since our studies began, Merrill (5) reported that the renal plasma flow was reduced to as little as 20 per cent and the filtration rate to 33 per cent of normal in chronic congestive failure. We have been able to confirm his findings of a decreased sodium excretion rate due to a diminished load presented to the tubules for reabsorption, and not to enhanced tubular reabsorption as suggested by earlier workers (3). EXPERIMENTAL PROCEDUREPatients with advanced chronic congestive failure due predominantly to rheumatic heart disease were the subjects. All had variable amounts of edema at rest. Members of the resident house staff and patients without heart failure or renal disease served as controls.The subjects were brought to the laboratory in a postabsorptive state. Each patient was given 300 to 600 cc. of water about 30 to 60 minutes before the test period.' This study was aided by a grant from the Martha M. Hall Foundation and the Committee on Scientific Research of the American Medical Association.2 Martha M. Hall Foundation Fellow in Medicine.Five controls were maintained on a special cardiac saltpoor diet (about 1.3 grams of sodium chloride daily), for 4 to 5 days before the studies were made. Most of the patients with congestive heart failure were maintained on the same diet (strict metabolic control was not attempted) and, in addition, all were taking digitalis.

Background/Objectives Previous studies have found that higher white blood cell count is associated with incident stroke. However, there are inconsistent results in the elderly and only a few studies have included differential white blood cell counts or Asian populations. We studied the association between total and differential white blood cell counts and incident stroke in an older Asian population. Design Prospective population-based study with 8 years of follow-up. Setting The Honolulu Heart Program, Oahu, Hawaii. Participants Three thousand, three hundred and forty-two Japanese-American men (ages 71–93 years) who were free of stroke and had baseline WBC counts in 1991–93. Measurements Participants were divided into quartiles of total and differential WBC counts for analysis, and were followed for incident stroke (all strokes [ALL-CVA], thromboembolic [TE-CVA] and hemorrhagic [HEM-CVA]) for eight years using data from a comprehensive hospital surveillance system. Results Age-adjusted incident ALL-CVA rates increased significantly with total WBC quartiles (7.68, 9.04, 9.26, 14.10, per 1,000 person years follow-up, respectively, p=0.001).Hazard ratios for ALL-CVA for each quartile of total and differential WBC counts were obtained using Cox regression, with the lowest quartile as the reference group. After full adjustment including age, cardiovascular risk factors, fibrinogen, prevalent CHD, cancer or COPD, and aspirin/NSAID use, hazard ratios in the highest quartiles of total WBC and neutrophil counts were 1.62 (95%CI=1.04–2.52, p=0.033) and 2.19 (95%CI=1.41–3.39, p<0.001)respectively. These significant associations were also seen for TE-CVA, but not for HEM-CVA. No significant associations were found between lymphocyte or monocyte counts and incident stroke or subtypes. Conclusion In elderly Japanese-American men, higher total WBC and neutrophil counts were independent predictors of overall stroke, as well as thromboembolic stroke.

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