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Biomedical subjects

Kenneth Rockwood

Publications and source records attributed to Kenneth Rockwood.

At least 55 records · Page 3Linked to original sources

Differential effects of lipid-lowering agents on human cholinesterases.

OBJECTIVES: Epidemiologic reports indicate that lipid-lowering agents (LLAs) protect against dementia. We hypothesized that LLAs might affect cholinergic systems. The effects of LLAs on the activity of cholinesterases were examined. DESIGN AND METHODS: Odds ratios and relative risks were calculated from clinical studies of LLAs and dementia and compared with their impacts on human cholinesterases. Representative LLAs were examined for their effects on the activity of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) using Ellman's assay. RESULTS: Epidemiological studies, but not clinical trials, showed lower odds of dementia in patients taking "statins". Comparison of LLAs indicated that "statins" most consistently produced apparent protection. Individual "statins" showed differential cholinesterase inhibition. Lovastatin and simvastatin significantly inhibited butyrylcholinesterase, while mevastatin, pravastatin and the "non-statins" did not. None of the LLAs inhibited acetylcholinesterase. CONCLUSIONS: Some "statins" inhibit butyrylcholinesterase. This inhibition suggests a possible means whereby "statins" could protect against dementia.

Cholinesterase Inhibitors↗

Changes with age in the distribution of a frailty index.

Models of human mortality include a factor that summarises intrinsic differences in individual rates of ageing, commonly called frailty. Frailty also describes a clinical syndrome of apparent vulnerability. In a representative, cross-sectional, Canadian survey (n = 66,589) we calculated a frailty index as the mean accumulation of deficits and previously showed it to increase exponentially with age. Here, its density function exhibited a monotonic change in shape, being least skewed at the oldest ages. Although the shape gradually changed, the frailty index was well fitted by a gamma distribution. Of note, the variation coefficient, initially high, decreased from middle age on. Being able to quantify frailty means that health risks can be summarised at both the individual and group levels.

Adult↗

Lending a helping eye: artists in residence at a memory clinic.

An artist-in-residence programme at the Capital Health Memory Clinic in Halifax, Canada, was established 6 years ago. The artists contribute to the clinic's academic mission by helping to describe how Alzheimer's disease treated by cholinesterase inhibitors is providing a better understanding of human cholinergic neurotransmission. The artists also contribute to the clinical programme by helping to establish a therapeutic ambience, and by allowing clinicians to see themselves through their patients' eyes. The artist programme has inspired a design initiative for the improvement of the physical environment for older patients, and has created a unique art collection that is becoming a resource for scholarship.

Alzheimer Disease↗

Prevalence, attributes, and outcomes of fitness and frailty in community-dwelling older adults: report from the Canadian study of health and aging.

BACKGROUND: Frailty and fitness are important attributes of older persons, but population samples of their prevalence, attributes, and outcomes are limited. METHODS: The authors report data from the community-dwelling sample (n = 9008) of the Canadian Study of Health and Aging, a representative, 5-year prospective cohort study. Fitness and frailty were determined by self-reported exercise and function level and testing of cognition. RESULTS: Among the community-dwelling elderly population, 171 per 1000 were very fit and 12 per 1000 were very frail. Frailty increased with age, so that by age 85 years and older, 44 per 1000 were very frail. The risk for adverse health outcomes increased markedly with frailty: Compared with older adults who exercise, those who were moderately or severely frail had a relative risk for institutionalization of 8.6 (95% confidence interval, 4.9 to 15.2) and for death of 7.3 (95% confidence interval, 4.7 to 11.4). These risks persist after adjustments for age, sex, comorbid conditions, and poor self-rated health. At all ages, men reported higher levels of exercise and less frailty compared with women. Decreased fitness and increased frailty were also associated with poor self-ratings of health (42% in the most frail vs 7% in the most fit), more comorbid illnesses (6 vs 3), and more social isolation (34% vs 29%). CONCLUSIONS: Fitness and frailty form a continuum and predict survival. Exercise influences survival, even in old age. Relative fitness and frailty can be determined quickly in a clinical setting, are potentially useful markers of the risk for adverse health outcomes, and add value to traditional medical assessments that focus on diagnoses.

Aged↗

The estimation of relative fitness and frailty in community-dwelling older adults using self-report data.

BACKGROUND: While on average health declines with age, it also becomes more variable with age. As a consequence of this marked variability, it becomes more important as people age to have a means of summarizing health status, but how precisely to do so remains controversial. We developed one measure of health status, personal biological age, from a frailty index. The index itself is a count of deficits derived, in the first instance, from a clinical database. In our earlier investigations, personal biological age demonstrated a strong relationship with 6-year survival. Here we extend this approach to self-reported data. METHODS: This is a secondary analysis of community-dwelling people aged 65 years and older (n = 9008) in the Canadian Study of Health and Aging. The frailty index was calculated from 40 self-reported variables, representing symptoms, attitudes, illnesses, and function. Personal biological age was estimated for each individual as the age corresponding to the mean chronological age for the index value. Individual frailty (and the related construct of fitness) was calculated as the difference between chronological and personal biological age. RESULTS: The frailty index showed, on average, an exponential increase with age at an average rate of 3% per year. Although women, on average, demonstrate more frailty than men of the same chronological age, their survival chances are greater. The frailty index strongly correlated (Pearson r =.992 for women and.955 for men) with survival. CONCLUSIONS: A frailty index, based on self-report data, can be used as a tool for capturing heterogeneity in the health status of older adults.

Aged↗

The effects of MK-0677, an oral growth hormone secretagogue, in patients with hip fracture.

OBJECTIVES: To evaluate the effects of MK-0677, an orally active growth hormone (GH) secretagogue, on functional recovery from hip fracture in previously mobile older individuals. DESIGN: Placebo-controlled, randomized, double-blind trial. SETTING: Thirteen medical centers in England, Sweden, Denmark, Belgium, Switzerland, Canada, and the United States. Patients were recruited between 3 and 14 days postoperatively, or no more than 18 days postfracture, at acute care hospitals and rehabilitation centers. PARTICIPANTS: One hundred sixty-one hip-fracture patients were enrolled. Entry criteria included consenting hip-fracture patients who were aged 65 and older and who were ambulatory before their fracture, medically stable postoperatively, and mentally competent. Patients were excluded if they had multiple fractures or severe trauma, diabetes mellitus, cancer, uncontrolled hypertension, congestive heart failure, or total hip replacement in the involved extremity. INTERVENTION: Random assignment to 6 months of daily treatment with MK-0677 or placebo. Patients were followed for an additional 6 months after completion of therapy. MEASUREMENTS: Change from Week 6 to Week 26 in a panel of functional performance measures. Additional outcome measures included change in the Sickness Impact Profile for Nursing Homes (SIP-NH), the ability to live independently, and insulin-like growth factor I (IGF-I) levels. RESULTS: MK-0677 treatment increased serum IGF-I levels by 84% (95% confidence interval (CI)=63-107), compared with an increase of 17% (95% CI=8-28) on placebo. There were no significant differences between MK-0677 and placebo in improvement in functional performance measures or in the overall SIP-NH score. Although MK-0677 patients showed greater improvement relative to placebo in three of four lower extremity functional performance measures, in the physical domain of the SIP, and in the ability to live independently, these differences were not statistically significant. CONCLUSION: Although MK-0677 treatment increased serum IGF-I, it is uncertain whether clinically significant effects on physical function were achieved. Measuring function in clinical trials in hip-fracture patients is difficult because of the lack of validated outcome measures, high variability, and the lack of a baseline assessment. Present functional performance measures may not be sufficiently responsive for use as the primary endpoint of small intervention studies; alternatively, stimulation of GH may not result in significant functional improvement.

Activities of Daily Living↗

Assessment of individual risk of death using self-report data: an artificial neural network compared with a frailty index.

OBJECTIVES: To evaluate the potential of an artificial neural network (ANN) in predicting survival in elderly Canadians, using self-report data. DESIGN: Cohort study with up to 72 months follow-up. SETTING: Forty self-reported characteristics were obtained from the community sample of the Canadian Study of Health and Aging. An individual frailty index score was calculated as the proportion of deficits experienced. For the ANN, randomly selected participants formed the training sample to derive relationships between the variables and survival and the validation sample to control overfitting. An ANN output was generated for each subject. A separate testing sample was used to evaluate the accuracy of prediction. PARTICIPANTS: A total of 8,547 Canadians aged 65 to 99, of whom 1,865 died during 72 months of follow-up. MEASUREMENTS: The output of an ANN model was compared with an unweighted frailty index in predicting survival patterns using receiver operating characteristic (ROC) curves. RESULTS: The area under the ROC curve was 86% for the ANN and 62% for the frailty index. At the optimal ROC value, the accuracy of the frailty index was 70.0%. The ANN accuracy rate over 10 simulations in predicting the probability of individual survival mean+/-standard deviation was 79.2+/-0.8%. CONCLUSION: An ANN provided more accurate survival classification than an unweighted frailty index. The data suggest that the concept of biological redundancy might be operationalized from health survey data.

Aged↗

Operationalizing a frailty index from a standardized comprehensive geriatric assessment.

OBJECTIVES: To construct and validate a frailty index (FI) that is clinically sensible and practical for geriatricians by basing it on a routinely used comprehensive geriatric assessment (CGA) instrument. DESIGN: Secondary analysis of a 3-month randomized, controlled trial of a specialized mobile geriatric assessment team. SETTING: Rural Nova Scotia. Participants were seen in their homes. PARTICIPANTS: Frail older adults, of whom 92 were in the intervention group and 77 in the control group. MEASUREMENTS: A standard CGA form that accounts for impairment, disability, and comorbidity burden was scored and summed as a frailty index (FI-CGA). The FI-GCA was stratified to describe three levels of frailty. Patients were followed for up to 12 months to determine how well the index predicted adverse outcomes (institutionalization or mortality, whichever came first). RESULTS: The three levels of frailty were mild (FI-CGA 0-7), moderate (FI-CGA 7-13), and severe (FI-CGA>13). Demographic and social traits were similar across groups, but greater frailty was associated with worse function (r=0.55) and mental status (r=0.33). Those with moderate and severe frailty had a greater risk of adverse outcomes than those with mild frailty (unadjusted hazard ratio=1.9 and 5.5, respectively). There was no difference between frailty groups in mean 3-month goal-attainment scaling scores. Intrarater reliability was 0.95. CONCLUSION: The FI-CGA is a valid, reliable, and sensible clinical measure of frailty that permits risk stratification of future adverse outcomes.

Aged↗

Canadian Cardiovascular Society Consensus Conference 2002: Management of heart disease in the elderly patient.

Cardiovascular disease is a major health issue for the elderly patient. Many diagnostic, therapeutic and ethical issues are specific for the the older adult with heart disease. The Canadian Cardiovascular Society 2002 Consensus Conference provides recommendations for the most frequently encountered cardiac problems in the elderly patient. A common theme of the recommendations is the need to apply the best evidence based medicine together with an assessment of frailty, comorbidity and quality of life. A major goal of the conference was to identify treatments that are not optimally used in the older patient.

Aged↗

Comparison of machine learning techniques with classical statistical models in predicting health outcomes.

Several machine learning techniques (multilayer and single layer perceptron, logistic regression, least square linear separation and support vector machines) are applied to calculate the risk of death from two biomedical data sets, one from patient care records, and another from a population survey. Each dataset contained multiple sources of information: history of related symptoms and other illnesses, physical examination findings, laboratory tests, medications (patient records dataset), health attitudes, and disabilities in activities of daily living (survey dataset). Each technique showed very good mortality prediction in the acute patients data sample (AUC up to 0.89) and fair prediction accuracy for six year mortality (AUC from 0.70 to 0.76) in individuals from epidemiological database surveys. The results suggest that the nature of data is of primary importance rather than the learning technique. However, the consistently superior performance of the artificial neural network (multi-layer perceptron) indicates that nonlinear relationships (which cannot be discerned by linear separation techniques) can provide additional improvement in correctly predicting health outcomes.

Aged↗

Variations in case definition affect prevalence but not outcomes of mild cognitive impairment.

OBJECTIVE: To examine the prevalence estimates and 5-year outcomes of various case definitions of mild cognitive impairment (MCI). METHODS: The authors examined 1,790 adults 65 years of age or older who completed neuropsychological and clinical assessments in the Canadian Study of Health and Aging, a 5-year, representative, prospective cohort study. RESULTS: The most commonly used case definition of MCI yielded a population prevalence estimate of 1.03% (95% CI 0.66 to 1.40). Eliminating the requirements for subjective memory complaints and intact instrumental activities of daily living (IADL) increased the prevalence to 3.02% (CI 2.40 to 3.64). Five-year outcomes, including the risk of death, institutionalization, and dementia, were not distinctly different for various case definitions of MCI, but all were at increased risk of institutionalization (RR 2.3 to 5.2) and dementia (RR 9.3 to 19.7). Regardless of the case definition, most people with MCI developed dementia, chiefly Alzheimer disease (AD). Still, for each case definition, almost one third were considered to have no cognitive impairment after 5 years. CONCLUSIONS: Memory complaints and intact IADL may be unnecessary requirements for a case definition of MCI in population-based samples. The MCI criteria identify people at increased risk of AD, but the potential for improvement of a substantial proportion of those with MCI needs to be acknowledged.

Aged↗

The feasibility of performing resistance exercise with acutely ill hospitalized older adults.

BACKGROUND: For older adults, hospitalization frequently results in deterioration of mobility and function. Nevertheless, there are little data about how older adults exercise in the hospital and definitive studies are not yet available to determine what type of physical activity will prevent hospital related decline. Strengthening exercise may prevent deconditioning and Pilates exercise, which focuses on proper body mechanics and posture, may promote safety. METHODS: A hospital-based resistance exercise program, which incorporates principles of resistance training and Pilates exercise, was developed and administered to intervention subjects to determine whether acutely-ill older patients can perform resistance exercise while in the hospital. Exercises were designed to be reproducible and easily performed in bed. The primary outcome measures were adherence and participation. RESULTS: Thirty-nine ill patients, recently admitted to an acute care hospital, who were over age 70 [mean age of 82.0 (SD= 7.3)] and ambulatory prior to admission, were randomized to the resistance exercise group (19) or passive range of motion (ROM) group (20). For the resistance exercise group, participation was 71% (p = 0.004) and adherence was 63% (p = 0.020). Participation and adherence for ROM exercises was 96% and 95%, respectively. CONCLUSION: Using a standardized and simple exercise regimen, selected, ill, older adults in the hospital are able to comply with resistance exercise. Further studies are needed to determine if resistance exercise can prevent or treat hospital-related deterioration in mobility and function.

Clinical Trial↗

Help available--phenomenological models for research on aging.

In "Help Wanted: Physiologists for Research on Aging," George Martin challenged the scientific community to find better means of tackling aging of the whole organism. Although initiatives such as those proposed by Martin would be most welcome, we propose an additional means by which scientists can take into account the integrative response of the organism and its changes over time. This method consists of systematizing facts that cannot necessarily be explained by considering those facts in isolation.

Aging↗

Five-year follow-up of cognitive impairment with no dementia.

CONTEXT: The importance of early identification of dementia has prompted numerous investigations of mild cognitive impairment and the preclinical stages of progressive degenerative disorders. To date, there is limited information from large-scale studies regarding outcomes of persons specifically identified with cognitive impairment but no dementia (CIND). OBJECTIVES: To investigate outcomes for persons with no cognitive impairment (NCI) or CIND, focusing on its etiologic subcategories, from the Canadian Study of Health and Aging (CSHA) and to examine the predictive validity of a set of core features thought to be early manifestations of subsequent dementia. DESIGN: Five-year, longitudinal follow-up of all persons without dementia examined during the first phase of the CSHA in 1991. SETTING: Community and institutional settings. PARTICIPANTS: Population-based sample of 883 persons with NCI and 801 persons with CIND at the first phase of the CSHA. At follow-up, 517 persons with NCI (59%) and 327 persons with CIND (41%) were alive and received clinical diagnoses. MAIN OUTCOME MEASURES: Mortality, institutionalization, and clinical diagnoses using the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition criteria for dementia. RESULTS: Persons with CIND were more likely than those with NCI to die (49% vs 30%), to be admitted to facility care (29% vs 14%), or to receive diagnoses of dementia (47% vs 15%) at follow-up. Those subsequently diagnosed as having dementia were more likely to have had impaired memory, informant-reported change in memory, and functional impairment at baseline. CONCLUSIONS: Persons with CIND were more likely to have a negative outcome than persons with NCI during a 5-year interval. This was true across etiologic subcategories and suggests that the use of specific diagnostic criteria sets does not improve our identification of those who develop dementia compared with a broader, more inclusive approach. More factors contributed to the prediction of all forms of dementia than to AD, but the most accurate prediction was for those who remained dementia free.

Aged↗

Techniques for knowledge discovery in existing biomedical databases: estimation of individual aging effects in cognition in relation to dementia.

New interest is being expressed in the systematic application of modeling techniques to existing datasets. Under the rubric of Knowledge Discovery in Databases (KDD) large databases are being exploited for commercial and scientific purposes. This article reviews the development and applications of KDD techniques to dementia, using the longitudinal Canadian Study of Health and Aging dataset. KDD has demonstrated usefulness at the group level. For example, as in the course of functional impairment between Alzheimer's disease and no cognitive impairment suggest damage control-protection mechanisms for the former compared with noncompensated random accumulation of deficits for the latter. At the individual level, KDD suggests that more precise diagnosis seems possible as well as individual life expectancy prediction. Biomedical databases appear to hold the potential for novel insights when explored by systematic modeling.

Aged↗

Responsiveness of goal attainment scaling in a randomized controlled trial of comprehensive geriatric assessment.

BACKGROUND AND OBJECTIVE: Frail elderly patients have complex problems that require a multidimensional assessment and a range of treatment goals. Goal Attainment Scaling (GAS) measures multiple, individualized goals, but its responsiveness in comparative clinical trials has not been established. METHODS: We assessed the responsiveness of GAS in a randomized, controlled trial of an interdisciplinary Mobile Geriatric Assessment Team (MGAT) in 265 rural frail older adults. Sensitivity to change was compared with standard measures; clinical meaningfulness was assessed in relation to a patient and a blinded physician global measure. RESULTS: At 3 months follow-up, GAS was the most responsive measure (standardized response mean 1.22, Norman's responsiveness statistic 0.58) compared with the Barthel Index (1.13, 0.46), Physical Self-Maintenance Scale (0.10, 0.16, 0.02), Instrumental Activities of Daily Living (0.23, 0.00), and modified Spitzer Quality of Life Index (-0.04, 0.00). CONCLUSIONS: Only GAS detected clinically important change associated with the MGAT intervention in these frail elderly patients. Clinometric measures can offer a responsive means of evaluating complex interventions.

Aged↗