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PubMedDate not supplied

[Frail elderly in hemodialysis].

A new category of patients aged >75 yrs, namely the elderly, is now being freely admitted to hemodialysis (HD) and this category is becoming predominant. The absence of systematic studies makes this patient category almost indistinguishable from other categories, even though its peculiarity is now evident. At least 30-40% of individuals in this age bracket are expected to be dependent and/or frail, but the incidence of frailty is likely to be higher in the elderly undergoing HD. Due to severe physical and/or mental impairment and often because of strong social hardships, these patients rarely experience clinical stability and are dependent on third parties for their survival. Their care produces complex problems for welfare services and this has proved responsible for modifying the organization of renal care units. These repeated patient admissions to hospital are filling nephrology facilities, and the dialysis management -- mainly concerning outpatients -- requires a much greater use of facilities and staff than normal if compared to average dialysis patients. In 112 elderly patients consecutively admitted to the dialysis program over a period of 10 yrs, we identified 35 dependent or frail patients (31.2%), even taking into consideration only extreme degrees of infirmity. Dependence proved to be the only clinical parameter associated with survival (mortality at 6 months 23.6 vs. 10.6%, p<0.01; Kaplan-Meier survival curves, p<0.03 log-rank test), while comorbidities -- in particular cardiovascular -- that usually affect dialysis mortality rates, did not seem to be discriminating risk factors in the elderly. More precisely, with the confirmation of these data through wider case studies, the idea will be reinforced that, also in dialysis, the elderly must be constantly monitored for dependence and frailty, as is the case in any exclusively geriatric field. Prevention, as well as a therapeutic approach specifically modeled on these conditions, could help to improve the prognosis of this patient category, which is particularly difficult to deal with and is becoming predominant in dialysis units.

Activities of Daily Living↗

PubMed2003

Osteoporosis and health-related quality-of-life outcomes in the Alameda County Study population.

INTRODUCTION: The objective of this study was to identify physical and mental outcomes of osteoporosis that affect quality of life in women. METHODS: Data were from the Alameda County Study, a longitudinal study of health and mortality that since 1965 has followed a cohort of 6,928 American persons aged 16 to 94 years at baseline. Subjects for this analysis were women who survived until at least 1994 (N = 1,171). The variables analyzed as possible outcomes of osteoporosis included measures of physical health, quality of life, and mental health. Sequential logistic regression models were run, and associations were presented as odds ratios. RESULTS: After controlling for age, ethnicity, education, financial strain, and physical activity, subjects with osteoporosis in 1994 were more likely to report the following outcomes in 1999: frailty, difficulty with balance, weakness, problems with activities of daily living, fair/poor perceived health, never going out for entertainment, and not enjoying free time much. When controlling for chronic medical conditions, the odds ratios were reduced, but remained significant for difficulty with balance and weakness (odds ratio = 2.48) and problems with activities of daily living (odds ratio = 2.80). CONCLUSION: From this study, it appears that people with osteoporosis are at higher risk of developing problems with physical frailty and difficulties with activities of daily living, and may be at risk for reduced quality of life in terms of going out for entertainment and enjoying free time. Therefore, care should be taken to maintain the quality of life for people with osteoporosis by helping them to keep as physically functional as possible.

Adolescent↗

PubMed2005

The future profile of health promotion and disease prevention in Japan: based on the study of seniors over age 75.

OBJECTIVES: One of the serious challenges for Japanese healthcare is the aging population. Analysis of health evaluation data, especially of the elderly over 75 years, is considered very important. In view of this prolonged life expectancy in Japan, our government started the new campaign of Healthy Japan 21, of which details are described, and also we will demonstrate the general profile of our perspective cohort study program concerning the new elder citizens in Japan. METHODS AND RESULTS: Our group has started a health evaluation program for those apparently healthy new elder citizens over the age of 75. A ten-year cohort study is in progress, which is designed to accumulate health check-up data annually. The study collects information on physical well being, as well as information on the individual's lifestyle, and social, emotional and spiritual environment. Such health appraisal is of primary importance. Preliminary results will be demonstrated with their special implications in clinical and epidemiological significance. The degree of frailty of the individual was also carefully evaluated, so that we can learn about the QOL of the seniors in Japan. CONCLUSIONS: At the present stage, we can only report a part of our study including the mental and spiritual environments of the individual. This kind of outcome study will give us some insights concerning the natural progress of frailty in the apparently healthy elderly.

Aged↗

PubMed2005

[Molecular abnormality in aging: its contribution to clinical pathology].

During a survey of age-associated changes in the liver, we discovered a novel protein SMP30. SMP30 expression decreased with aging due to oxidative stress. We studied the effects of SMP30 on the plasma membrane calcium pump. SMP30 enhances its activity. This finding suggests that the decrease of SMP30 with aging induces cellular frailty and various injuries. This frailty is one of the critical factors in the development of senescence. To elucidate its role in senescence we established a knockout. Its life span was shorter than the wild type. The enzymatic functions of SMP30 have been reported. SMP30 is an organophosphatase. SMP30 is also gluconolactonase having natural substrates. This activity is associated with the pentose phosphate pathway and the ascorbic acid synthesis pathway. These findings indicate the pivotal role of SMP30. Another contribution of gerontology to clinical pathology is citrullination. Citrullinated proteins are the products of post-translational modification of the argine residues to citrulline, catalyzed by a peptidylarginine deiminase (PADs) in a calcium ion-dependent manner. We detected abnormal accumulation of citrullinated proteins in the Alzheimer disease (AD) hippocampus, but not in the normal brain. Two of the citrullinated proteins were identified as a vimentin and GFAP. Type II PAD expression was enhanced in the AD brain. Citrullinated protein could be a useful hallmark of organ injuries. The physiological aspect of citrullinated proteins was also recognized in epidermal differentiation. The normal epidermis contains citrullinated proteins but not the epidermis affected by psoriasis. This finding suggests that the citrullination is critical for skin differentiation. The findings observed in this aging study may contribute to clinical pathology.

Aging↗

PubMed2005

Clinical implications of the reduced activity of the GH-IGF-I axis in older men.

During the last decade, a significant body of evidence has accumulated, indicating that IGF-I might play a role in several pathological conditions commonly seen during aging, such as atherosclerosis and cardiovascular disease (CVD), cognitive decline, dementia, sarcopenia and frailty. A vascular protective role for IGF-I has been suggested because of its ability to stimulate nitric oxide production from endothelial and vascular smooth muscle cells. In cross sectional studies, low IGF-I levels have been associated with unfavorable CVD risk factors profile, such as atherosclerosis, abnormal lipoprotein levels and hypertension, while in prospective studies, lower IGF-I levels predict future development of ischemic heart disease. The fall in IGF-I levels with aging correlates with cognitive decline and it has been suggested that IGF-I plays a role in the development of dementia. IGF-I is highly expressed within the brain and is essential for normal brain development. IGF-I has anti-apoptotic and neuroprotective effects and promotes projection neuron growth, dendritic arborization and synaptogenesis. Collectively, these data are consistent with a causal link between the age-related decline in GH and IGF-I levels and cognitive deficits in older persons. Finally, there is evidence of a relationship between declining GH and IGF-I levels and age-related changes in body composition and physical function. However, few studies have documented a precise role of IGF-I in the development of sarcopenia, frailty and poor mobility. We have recently documented that serum IGF-I is significantly associated with measures of muscle strength and physical performance in men and to a lesser extent in women. In conclusion, IGF-I is a pleiotropic hormone that in older persons may positively affect the cardiovascular system, the central nervous system and physical function.

Aged↗

PubMedDate not supplied

[SOSIA classification of the frail elderly in nursing homes of region of Lombardy].

Since 2001, the region of Lombardy has accreditated nursing homes named R.S.A. "Residenza Sanitario-Assistenziale", which make up Italy's principal RSA network with the annual turnover of approximately 60,000 people. The most noteworthy element of the reform introduced is a concentration on resident's frailty rather than disability. This is assessed by using SOSIA, a form for intermediate observation of assistance. Residents are classified into eight classes of frailty, called isofrailty classes of SOSIA, which are differentiated by how compromised their motor and cognitive skills are, and by the presence of comorbidity. The study presents the methodology used to identify and estimate cut-offs of three indicators employed in SOSIA classification. It also discusses their characteristics versus other evaluation systems, such as Resource Utilization Group RUG-III and Autonomie Gerontologique--Groupes Iso-Resources AGGIR.

Activities of Daily Living↗

PubMed1995

Illness presentation in elderly patients.

BACKGROUND: Atypical disease presentations, such as delirium, are associated with adverse health outcomes. They are also markers of frailty in elderly people, which is itself associated with adverse hospital outcomes. We investigated the relationship between frailty and atypical disease presentation in predicting adverse hospital outcomes and complications of the hospital course of elderly patients admitted to general medical services. METHODS: We conducted a cohort study in a large (800 beds) tertiary care university hospital. The prevalence of atypical disease presentations and the incidence of adverse hospital outcomes (death, nursing home admission, prolonged hospital stay, and failure to regain premorbid functional status) were studied in previously well and previously frail elderly patients. RESULTS: Patients were classified as being well or frail on the basis of the premorbid Barthel Index (well, score of > or = 95 [n = 76]; frail, score of < 95 [n = 117]). Frail elderly were older (80 vs 76 years), more often female (62% vs 46%), and less likely to be community dwelling (89% vs 99%). Atypical disease presentation was more common in the frail elderly (59% vs 25%; P < .001). Of those who presented atypically, the frail most often presented with delirium (61%) and the well presented with falls (37%) and delirium (32%). Of the frail elderly with atypical symptoms, 60% had adverse hospital outcomes compared with 32% of the well elderly who presented typically (P < .05). Logistic regression analysis showed that premorbid functional dependence (odds ratio, 2.48; 95% confidence interval, 1.17 to 5.22), atypical disease presentation (odds ratio, 2.37; 95% confidence interval, 1.20 to 4.67), and functional decline at admission (odds ratio, 5.64; 95% confidence interval, 2.37 to 13.44) were all independently predictive of poor hospital outcomes. By contrast, severity of disease, age, and sex did not confer an increased risk of adverse events. CONCLUSIONS: Premorbid functional dependency, atypical disease presentation, and functional decline on admission have independent impacts on adverse hospital outcomes. Assessment of each should be incorporated into the routine care of elderly patients.

Activities of Daily Living↗

PubMed1998

Sensitizing students to functional limitations in the elderly: an aging simulation.

BACKGROUND AND OBJECTIVES: Using activities of daily living (ADLs) and instrumental activities of daily living (IADLs) as a focus, faculty at Eastern Virginia Medical School provide an aging simulation exercise for a mandatory fourth-year clerkship in geriatrics. The specific aims of the simulation are to 1) experience the physical frailties of aging, 2) develop creative problem-solving techniques, 3) identify feelings regarding the experience of functional loss, and 4) develop proactive clinical approaches to the care of the elderly. METHODS: Students are assigned one of four diagnoses (Parkinson's disease, rheumatoid arthritis, advanced diabetes, or stroke) and are then impaired to simulate the frailties of the condition, using a variety of clothes, bindings, and other devices. In their "impaired states," they perform ADLs and IADLs, such as paying bills, organizing their pills, shopping, toileting, dressing, and eating. RESULTS: Evaluation results show the aging simulation to be the highest rated program in the clerkship. A pre- and post-course survey on attitudes toward the elderly showed a statistically significant improvement in students' attitudes toward the elderly following the course. CONCLUSIONS: Simulation exercises in aging are useful activities for helping students better understand the feelings and needs of the elderly.

Activities of Daily Living↗

PubMed1998

Posterior likelihood methods for multivariate survival data.

This article deals with the semiparametric analysis of multivariate survival data with random block (group) effects. Survival times within the same group are correlated as a consequence of a frailty random block effect. The standard approaches assume either a parametric or a completely unknown baseline hazard function. This paper considers an intermediate solution, that is, a nonparametric function that is reasonably smooth. This is accomplished by a Bayesian model in which the conditional proportional hazards model is used with a correlated prior process for the baseline hazard. The posterior likelihood based on data, as well as the prior process, is similar to the discretized penalized likelihood for the frailty model. The methodology is exemplified with the recurrent kidney infections data of McGilchrist and Aisbett (1991, Biometrics 47, 461-466), in which the times to infections within the same patients are expected to be correlated. The reanalysis of the data has shown that the estimates of the parameters of interest and the associated standard errors depend on the prior knowledge about the smoothness of the baseline hazard.

Bayes Theorem↗

PubMed2026

Identifying biomarkers of accelerated ageing in cancer patients from routine clinical data.

INTRODUCTION: Cancer and ageing have a bidirectional relationship: age is the strongest risk factor for cancer, and cancer and treatments can accelerate ageing. Therefore, biological age can differ from chronological age; biomarkers are needed to stratify interventions to minimise accelerated ageing. METHODS: PhenoAge was calculated from routine blood test results of patients attending a Geriatric Oncology clinic. PhenoAgeAccel was the residual from a regression of PhenoAge against age. RESULTS: Data were available for 173 patients (62% male). Mean PhenoAge was higher than age (84.3 (12.6) vs 76.2 (7.24), p < 0.001), though the two were correlated (r = 0.579, p < 0.001). Unlike age, PhenoAge and PhenoAgeAccel were associated with one-year mortality (PhenoAge OR=1.083, 95% CI: 1.038-1.136; PhenoAgeAccel OR=1.096, 95% CI: 1.047-1.155). PhenoAge correlated with Clinical Frailty Score and Timed Up and Go (CFS: Rs=0.31, p < 0.001; TUG: Rs=0.25, p < 0.005); there were no correlations with age. PhenoAgeAccel correlated with the number of CGA interventions made (Rs=0.17, p < 0.05), unlike age and PhenoAge. Patients with diabetes mellitus had a higher PhenoAgeAccel compared to those without (3.40 vs -1.71, p = 0.002). In patients receiving systemic anti-cancer treatment, patients with PhenoAgeAccel calculated pre-treatment had less age acceleration than those with PhenoAgeAccel calculated post-treatment, both overall (2.18 vs -2.87; p = 0.048) and in matched samples (n = 21, 7.76 vs -2.87, p < 0.001). CONCLUSIONS: PhenoAgeAccel is a greater predictor of risk than chronological age in older people with cancer. This makes it a promising biomarker to stratify patients for holistic geriatric assessment, dose reductions, or future geroprotective measures which could be integrated within electronic healthcare record systems.

Humans↗

PubMed2025

Multiomic clocks to predict phenotypic age in mice.

Biological age refers to a person's overall health in aging, as distinct from their chronological age. Diverse measures of biological age, referred to as "clocks," have been developed in recent years and enable risk assessments and an estimation of the efficacy of longevity interventions in animals and humans. Although most clocks are trained to predict chronological age, clocks have been developed to predict more complex composite biological age outcomes, at least in humans. These composite outcomes can be made up of a combination of phenotypic data, chronological age, and disease or mortality risk. Here, we develop the first such composite biological age measure for mice: the mouse phenotypic age model (Mouse PhenoAge). This outcome is based on frailty measures, complete blood counts, and mortality risk in a longitudinally assessed cohort of male and female C57BL/6 mice. We then develop clocks to predict Mouse PhenoAge, based on multiomic models using metabolomic and DNA methylation data. Our models accurately predict Mouse PhenoAge, and residuals of the models are associated with remaining lifespan, even for mice of the same chronological age. These methods offer novel ways to accurately predict mortality in laboratory mice, thus reducing the need for lengthy and costly survival studies.

Animals↗

PubMed2026

Epidemiology, diagnosis, and surgical management of urolithiasis in older adults: overview from EAU endourology.

PURPOSE OF REVIEW: Population ageing is changing everyday urological practice. The number of older adults is increasing, and urology already treats a patient population that is, on average, older than the general population. Consequently, older adults with urolithiasis represent a core part of contemporary endourological practice. Given this, a focused review of the available evidence is valuable to inform clinical practice. RECENT FINDINGS: A peak in stone disease can occur in older adults who may also be less likely to present with the classical features of renal colic. As such, delayed or missed diagnosis may carry greater clinical consequences. Although the literature remains relatively limited, ureteroscopy, shock wave lithotripsy, and percutaneous nephrolithotomy remain feasible options in appropriately selected older adults. In this group in particular, broader health associations merit consideration, as the presence of urolithiasis in older adults may reflect overall health status in later life. SUMMARY: The burden of urolithiasis in older adults is increasing and now represents a routine component of everyday clinical practice. Clinical presentation may differ from that seen in younger "index" patients, and complications may have a greater impact on recovery and function. Management should therefore be individualized, taking into account comorbidity, frailty, functional status, and the patient's own priorities.

Humans↗

PubMed2026

Aging and Reproductive Cancers: An Integrative View on Cell-Free DNA and Transposable Elements.

Aging is one of the strongest risk factors for cancer, and its impact is particularly evident in malignancies of the reproductive system. Ovarian, endometrial, cervical, vulvar, prostate, and penile cancers are mainly diagnosed in older adults and often show different clinical and biological features compared with the same tumors in younger patients. Aging is associated with hormonal changes, immune decline, epigenetic alterations, and accumulation of DNA damage, all of which contribute to cancer development and progression. At the same time, many older patients have frailty and multiple comorbidities, which can limit the use of screening programs and invasive diagnostic procedures. This often leads to delayed diagnosis and worse outcomes. Cell-free DNA (cfDNA) is a minimally invasive biomarker that can be obtained from blood samples and provides molecular information on both tumor and host tissues. Circulating DNA reflects tumor-specific alterations but is also influenced by aging-related changes in DNA release, fragmentation, and methylation. For this reason, aging must be considered when cfDNA-based biomarkers are applied in clinical practice. In this review, we describe how aging influences the biology of reproductive system cancers and how these processes are mirrored in cfDNA profiles. We focus on the clinical use of cfDNA for cancer detection and monitoring in older and fragile patients. Special attention is given to repetitive elements in cfDNA, which are strongly affected by aging and tumor-related epigenetic changes and can be detected with high sensitivity even when the tumor fraction is low. We propose an integrative mechanistic framework in which age-related epigenetic and genomic changes influence both tumor biology and cfDNA composition, with transposable elements acting as a central link between aging and cancer.

Humans↗

PubMed1998

Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age.

BACKGROUND: Change in body weight is a potentially modifiable risk factor for hip fracture in older women but, to our knowledge, its relationship to risk in older men has not been reported previously. OBJECTIVE: To investigate the effects of weight loss and weight gain from age 50 years to old age on the risk of hip fracture among elderly men. METHODS: The association between weight change and risk of hip fracture was studied in a cohort of 2413 community-dwelling white men aged 67 years or older from 3 sites of the Established Populations for Epidemiologic Study of the Elderly. RESULTS: The older men in this study, observed for a total of 13620 person-years during the 8 years of follow-up, experienced 72 hip fractures, yielding an overall incidence rate of 5.3 per 1000 person-years. Extreme weight loss (> or =10%) beginning at age 50 years was associated in a proportional hazards model with increased risk of hip fracture (relative risk, 1.8; 95% confidence interval, 1.04-3.3). Weight loss of 10% or more was associated with several indicators of poor health, including physical disability, low mental status score, and low physical activity (P<.05). Weight gain of 10% or more beginning at age 50 years provided borderline protection against the risk of hip fracture (relative risk, 0.4; 95% confidence interval, 0.1-1.00). CONCLUSIONS: Despite differences between older men and women in the incidence of and risk factors for hip fracture, weight history is also an important determinant of the risk of hip fracture among older men. Weight loss of 10% or more beginning at age 50 years increases the risk of hip fracture in older white men; weight gain of 10% or more decreases the risk of hip fracture. The relationship between extreme weight loss and poor health suggests that weight loss is a marker of frailty that may increase the risk of hip fracture in older men. Physicians should include weight history in their assessment of the risk of hip fracture among older men.

Aged↗

PubMed2000

Hospital readmissions as a measure of quality of health care: advantages and limitations.

We reviewed the recent literature on hospital readmissions and found that most of them are believed to be caused by patient frailty and progression of chronic disease. However, from 9% to 48% of all readmissions have been judged to be preventable because they were associated with indicators of substandard care during the index hospitalization, such as poor resolution of the main problem, unstable therapy at discharge, and inadequate postdischarge care. Furthermore, randomized prospective trials have shown that 12% to 75% of all readmissions can be prevented by patient education, predischarge assessment, and domiciliary aftercare. We conclude that most readmissions seem to be caused by unmodifiable causes, and that, pending an agreed-on method to adjust for confounders, global readmission rates are not a useful indicator of quality of care. However, high readmission rates of patients with defined conditions, such as diabetes and bronchial asthma, may identify quality-of-care problems. A focus on the specific needs of such patients may lead to the creation of more responsive health care systems for the chronically ill.

Humans↗

PubMed2005

A prospective study of anemia status, hemoglobin concentration, and mortality in an elderly cohort: the Cardiovascular Health Study.

BACKGROUND: Anemia is viewed as a negative prognostic factor in the elderly population; its independent impact on survival is unclear. METHODS: Baseline hemoglobin quintiles and anemia, as defined by the World Health Organization criteria, were assessed in relation to mortality in the Cardiovascular Health Study, a prospective cohort study with 11.2 years of follow-up of 5888 community-dwelling men and women 65 years or older, enrolled in 1989-1990 or 1992-1993 in 4 US communities. RESULTS: A total of 1205 participants were in the lowest hemoglobin quintile (<13.7 g/dL for men; <12.6 g/dL for women), and 498 (8.5%) were anemic (<13 g/dL for men; <12 g/dL for women). A reverse J-shaped relationship with mortality was observed; age-, sex-, and race-adjusted hazard ratios (95% confidence interval [CI]) in the first and fifth quintiles, compared with the fourth quintile, were 1.42 (95% CI, 1.25-1.62) and 1.24 (95% CI, 1.09-1.42). After multivariate adjustment, these hazard ratios were 1.33 (95% CI, 1.15-1.54) and 1.17 (95% CI, 1.01-1.36). The demographic- and fully-adjusted hazard ratios of anemia for mortality were 1.57 (95% CI, 1.38-1.78) and 1.38 (95% CI, 1.19-1.54). Adjustment for causes and consequences of anemia (renal function, inflammation, or frailty) did not reduce associations. CONCLUSIONS: Lower and higher hemoglobin concentrations and anemia by World Health Organization criteria were independently associated with increased mortality. The World Health Organization criteria did not identify risk as well as a lower hemoglobin value. Additional study is needed on the clinically valid definition for and causes of anemia in the elderly and on the increased mortality at the extremes of hemoglobin concentrations.

Age Factors↗

PubMed2006

Obesity, physical activity, and mortality in a prospective chinese elderly cohort.

BACKGROUND: In older people, it is unclear whether obesity relates to mortality, which calls into question its etiologic role in disease and its public health relevance. This apparent lack of relationship in older people could be an artifactual result of their diverse health states. METHODS: We used Cox regression analysis to determine whether the effect of body mass index (BMI) (calculated as weight in kilograms divided by the square of height in meters) or physical activity on mortality varied with health status in a prospective cohort study of Chinese people 65 years or older enrolled from 1998 to 2000 at all of the 18 Elderly Health Centers of the Hong Kong Government Department of Health. Health status was categorized into 5 morbidity groups using a 12-item index covering illnesses, medications, frailty, and smoking. RESULTS: After a mean follow-up of 4.1 years, there were 3819 deaths in 54 088 subjects (96.5% successful follow-up). The effect of BMI on mortality varied with baseline health status (P<.001). In the healthiest group, obese people (BMI >/=25) had higher mortality (adjusted hazard ratio [HR], 1.54; 95% confidence interval [CI], 1.02-2.33), but in the unhealthiest group they had lower mortality (HR, 0.55; 95% CI, 0.49-0.63) compared with subjects of normal weight. Daily physical activity was associated with lower mortality compared with inactivity in the unhealthiest group (HR, 0.70; 95% CI, 0.61- 0.81) but not in the healthiest group. CONCLUSIONS: In the elderly, the relationship between obesity and mortality varies according to the underlying health status. In those with poor health status, obesity is associated with better outcome, whereas in those with initially good health status, obesity is associated with worse outcome.

Aged↗

PubMed2005

Sudden uncontrollable somnolence and medication use in Parkinson disease.

BACKGROUND: Episodes of sudden uncontrollable somnolence have been reported in patients with Parkinson disease (PD) receiving dopamine agonists, including pramipexole and ropinirole, but controversy persists concerning their nature, severity, and frequency. OBJECTIVES: To quantify the risk of sudden uncontrollable somnolence in patients taking specific PD medications and to define its predictors. METHODS: We contacted 929 patients with PD and administered a 45- to 60-minute interview addressing medication use, adverse events, and the patient's clinical status in the preceding 6 months. Their physicians completed record reviews detailing their clinical histories and drug regimens. The outcome of interest in this case-control study was an episode of somnolence that was uncontrollable, severe, and inappropriate, such as while driving or engaged in social activity. For multiple events, the first was chosen as the index event. For each case, we sampled control time from all respondents who had no event as of the index time for that case. Multiple logistic regression was used to adjust for potential confounders. RESULTS: Episodes of uncontrollable somnolence were reported by 22% of all respondents. After controlling for age, sex, PD duration and severity, frailty, and other medication use, we found that patients receiving a dopamine agonist (pramipexole, ropinirole, or pergolide) were nearly 3-fold as likely to have episodes of sudden uncontrollable somnolence (odds ratio, 2.8; 95% confidence interval, 1.8-4.2) compared with all other PD medication users. Similar risks were seen for the 3 agents, pramipexole, ropinirole, and pergolide, each compared with levodopa alone (odds ratio, 2.2, 1.8, and 2.1, respectively), with a clear dose-response relationship for each. No increase in risk was seen with any other drugs studied. CONCLUSIONS: Dopamine agonists widely used for the management of PD significantly increase the risk of sudden uncontrollable somnolence in a dose-related manner. Greater attention to this potentially serious adverse effect will be necessary to improve the safety of use of this important category of PD drugs.

Adult↗