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Biomedical subjects

Chris MacKnight

Publications and source records attributed to Chris MacKnight.

16 recordsLinked to original sources
PubMed2006

Disease progression in vascular cognitive impairment: cognitive, functional and behavioural outcomes in the Consortium to Investigate Vascular Impairment of Cognition (CIVIC) cohort study.

BACKGROUND AND PURPOSE: Empirical studies to clarify the outcomes in Vascular Cognitive Impairment (VCI) are needed. We compared cognitive, functional, and behavioural outcomes in patients with VCI to patients with no cognitive impairment (NCI), and Alzheimer's disease (AD). METHODS: Secondary analysis of the Consortium to Investigate Vascular Impairment of Cognition (CIVIC), a multi-centre Canadian memory clinic 30-month cohort study. RESULTS: Of 1347 patients, 938 were eligible for follow-up, of whom 239 (24.5%) were lost and 29 (3%) had died. Of the remaining 697 patients, 125 had NCI, 229 had VCI, and 343 had AD at baseline. Compared to people with NCI, of whom 20-40% showed progression based on cognitive and functional measures, those with VCI were more likely to progress (50-65%), as were people with AD (50-80%) (p<0.01). More people with VCI showed progression of affective symptoms (30%) than those with NCI (12%) or AD (15% p<0.01). Progression of impaired judgment (rated clinically) in VCI (15%) was similar to AD (11%) but more common than in NCI (4%, p<0.01). CONCLUSIONS: Most people with VCI show readily detectable progression by 30 months. Depressive symptoms were more common and more progressive in VCI than in Alzheimer's disease, whereas clinical evidence of progressive executive dysfunction was common in both AD and VCI.

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PubMed2006

Attainment of treatment goals by people with Alzheimer's disease receiving galantamine: a randomized controlled trial.

BACKGROUND: Although cholinesterase inhibitors have produced statistically significant treatment effects, their clinical meaningfulness in Alzheimer's disease is disputed. An important aspect of clinical meaningfulness is the extent to which an intervention meets the goals of treatment. METHODS: In this randomized controlled trial, patients with mild to moderate Alzheimer's disease were treated with either galantamine or placebo for 4 months, followed by a 4-month open-label extension during which all patients received galantamine. The primary outcome measures were Goal Attainment Scaling (GAS) scores from assessments by clinicians and by patients or caregivers of treatment goals set before treatment and evaluated every 2 months. Secondary outcome measures included the cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS-cog), the Clinician's Interview-based Impression of Change plus Caregiver Input (CIBIC-plus), the Disability Assessment for Dementia (DAD) and the Caregiving Burden Scale (CBS). To evaluate treatment effect, we calculated effect sizes (as standardized response means [SRMs]) and p values. RESULTS: Of 159 patients screened, 130 (mean age 77 [standard deviation (SD) 7.7]; 63% women) were enrolled in the study (64 in the galantamine group and 66 in the placebo group); 128 were included in the analysis because they had at least one post-baseline evaluation. In the intention-to-treat analysis, the clinician-rated GAS scores showed a significantly greater improvement in goal attainment among patients in the galantamine group than among those in the placebo group (change from baseline score 4.8 [SD 9.6]) v. 0.9 [SD 9.5] respectively; SRM = 0.41, p = 0.02). The patient- caregiver-rated GAS scores showed a similar improvement in the galantamine group (change from baseline score 4.2 [SD 10.6]); however, because of the improvement also seen in the placebo group (2.3 [SD 9.0]), the difference between groups was not statistically significant (SRM = 0.20, p = 0.27). Of the secondary outcome measures, the ADAS-cog scores differed significantly between groups (SRM = -0.36, p = 0.04), as did the CIBIC-plus scores (SRM = -0.40, p = 0.03); no significant differences were in either the DAD scores (SRM = 0.28, p = 0.13) or the CBS scores (SRM = -0.17, p = 0.38). INTERPRETATION: Clinicians, but not patients and caregivers, observed a significantly greater improvement in goal attainment among patients with mild to moderate Alzheimer's disease who were taking galantamine than among those who were taking placebo.

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PubMed2005

Clinical and radiographic subtypes of vascular cognitive impairment in a clinic-based cohort study.

BACKGROUND AND PURPOSE: There is a need for empirical studies to define criteria for vascular cognitive impairment (VCI) subtypes. In this paper, we report the predictive validity of a subtype classification scheme based on clinical and radiographic features. METHODS: Nine Canadian memory clinics participated in the Consortium to Investigate Vascular Impairment of Cognition. This cohort consisted of 1347 patients, of whom 324 had VCI, and was followed for up to 30 months. RESULTS: Clinical and neuroimaging features defined three subtypes: vascular cognitive impairment, no dementia, (n=97), vascular dementia (n=101) and mixed neurodegenerative/vascular dementia (n=126). Any ischemic lesion on neuroimaging increased the odds (odds ratio=9.31; 95% confidence interval 6.46, 13.39) of a VCI diagnosis. No VCI subtype, however, was associated with a specific neuroimaging abnormality. Compared to those with no cognitive impairment, patients with each VCI subtype had higher rates of death and institutionalization (hazard ratio for combined adverse events=6.08, p<0.001). CONCLUSIONS: Both clinical features and radiographic features help establish a diagnosis of VCI. The outcomes of VCI subtypes, however, are more strongly associated with clinical features than with radiographic ones.

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PubMed2005

A global clinical measure of fitness and frailty in elderly people.

BACKGROUND: There is no single generally accepted clinical definition of frailty. Previously developed tools to assess frailty that have been shown to be predictive of death or need for entry into an institutional facility have not gained acceptance among practising clinicians. We aimed to develop a tool that would be both predictive and easy to use. METHODS: We developed the 7-point Clinical Frailty Scale and applied it and other established tools that measure frailty to 2305 elderly patients who participated in the second stage of the Canadian Study of Health and Aging (CSHA). We followed this cohort prospectively; after 5 years, we determined the ability of the Clinical Frailty Scale to predict death or need for institutional care, and correlated the results with those obtained from other established tools. RESULTS: The CSHA Clinical Frailty Scale was highly correlated (r = 0.80) with the Frailty Index. Each 1-category increment of our scale significantly increased the medium-term risks of death (21.2% within about 70 mo, 95% confidence interval [CI] 12.5%-30.6%) and entry into an institution (23.9%, 95% CI 8.8%-41.2%) in multivariable models that adjusted for age, sex and education. Analyses of receiver operating characteristic curves showed that our Clinical Frailty Scale performed better than measures of cognition, function or comorbidity in assessing risk for death (area under the curve 0.77 for 18-month and 0.70 for 70-month mortality). INTERPRETATION: Frailty is a valid and clinically important construct that is recognizable by physicians. Clinical judgments about frailty can yield useful predictive information.

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PubMed2004

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.

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PubMed2004

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.

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PubMed2003

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↗
PubMed2003

The Consortium to Investigate Vascular Impairment of Cognition: methods and first findings.

BACKGROUND: The Consortium to Investigate Vascular Impairment of Cognition (CIVIC) is a Canadian, multi-centre, clinic-based prospective cohort study of patients with Vascular Cognitive Impairment (VCI). We report its organization and the impact of diagnostic criteria on the study of VCI. METHODS: Nine memory disability clinics enrolled patients and recorded their usual investigations and care. A case report form included all vascular dementia (VaD) individual criteria for each of four sets (National Institute of Neurological Disorders and Stroke (NINDS-AIREN), Alzheimer's Disease Diagnostic Treatment Centers (ADDTC), the ICD-10 Classification of Mental and Behavioural Disorders (ICD-10), and the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV)) of consensus-based diagnostic criteria and for the Hachinski Ischemia Score (HIS). Investigators, having completed the case report form, were asked to make a clinical judgement about the cognitive diagnosis based on the best available information, including neuroimaging. RESULTS: Of 1,347 patients (mean age 72 years; 56% women), 846 (63%) were diagnosed with dementia and 324 (24%) were diagnosed with VCI. The proportion of patients diagnosed with VaD by the diagnostic criteria was: 23.9% (n = 322) by DSM-IV, 10.2% (n = 137) by HIS, 4.3% (n = 58) by ICD-10, 3.8% (n = 51) by ADTCC, and 3.6% (n = 48) by NINDS-AIREN. Judged against a clinical diagnosis of VaD, the sensitivity/specificity of each was: DSM-IV (0.77/0.80); HIS (0.41/0.92); ICD-10 (0.29/0.98); ADTCC (0.24/0.98); NINDS-AIREN (0.42/0.995). Compared with a clinical diagnosis of VCI, sensitivities were lower for the diagnostic criteria, reflecting the exclusion of patients who did not have dementia. CONCLUSIONS: Consensus-based criteria for VaD omit patients who do not meet dementia criteria that are modeled on Alzheimer's disease. Even for patients who do, the proportion identified with VaD varies widely. Criteria based on empirical analyses need to be developed and validated.

Adult↗
PubMed2002

The accumulation of deficits with age and possible invariants of aging.

This paper extends a method of apprising health status to a broad range of ages from adolescence to old age. The "frailty index" is based on the accumulation of deficits (symptoms, signs, disease classifications) as analyzed in the National Population Health Survey, a representative Canadian population sample (n = 81,859). The accumulation of deficits has both an age-independent (background) component and an age-dependent (exponential) component, akin to the well-known Gompertz-Makeham model for the risk of mortality. While women accumulate more deficits than men of the same age, on average, their rate of accumulation is lower, so the difference in the level of deficits between men and women decreases with age. Two possible invariants of the process of accumulation of deficits were found: (1) the age at which the average proportion of deficits coincides for men and women is 94 years, which closely matches the species-specific lifespan in humans (95 +/- 2); (2) the value of the frailty index (proportion of deficits), which corresponds to that age (0.18). The similarity between mortality kinetics and the accumulation of deficits (frailty kinetics), and the coincidence of the time parameters in the frailty and mortality models make it possible to express mortality risk in terms of accumulated deficits. This provides a simple and accessible tool that might have potential in a number of biomedical applications.

Aged↗
PubMed2002

Use of lipid-lowering agents, indication bias, and the risk of dementia in community-dwelling elderly people.

BACKGROUND: Recent reports suggest a possibly protective effect for statins in patients with Alzheimer disease. This association could be due to indication bias, i.e., people who elect to take lipid-lowering agents (LLAs) may be healthier than those who do not, so that it may be these other health factors that explain their lower risk of dementia. OBJECTIVES: To examine the association between the use of LLAs and dementia, adjusting for other markers of health, and to investigate factors associated with LLA use. DESIGN: A cohort study of LLA use and a case-control study of dementia in relation to LLA use, in a secondary analysis of the Canadian Study of Health and Aging. SETTING: A nationally representative population-based survey of Canadians 65 years and older. PARTICIPANTS: To examine features associated with statin use, we evaluated data on 2305 people for whom health information, drug use, and cognitive status were known. To examine the relationship between LLA use and dementia, we selected incident cases of dementia (n = 492, of whom 326 had Alzheimer disease) that occurred between the first and second waves of the study. Control subjects were 823 persons examined during the first and second phases of the Canadian Study of Health and Aging who had no cognitive impairment. RESULTS: Use of LLAs was significantly (P<.001) more common in younger (65-79 years) than in older (> or = 80 years) people. It was not associated with other factors indicating a healthy lifestyle, but was associated with a history of smoking and hypertension. Use of statins and other LLAs reduced the risk of Alzheimer disease in subjects younger than 80 years, an effect that persisted after adjustment for sex, educational level, and self-rated health (odds ratio, 0.26; 95% confidence interval, 0.08-0.88). There was no significant effect in subjects 80 years and older. CONCLUSIONS: While the possibility of indication bias in the original observations cannot be excluded, it was not demonstrated in LLA use in this study. Lipid-lowering agent use was associated with a lower risk of dementia, and specifically of Alzheimer disease, in those younger than 80 years. Further research is warranted.

Age Factors↗
PubMed2002

The mortality rate as a function of accumulated deficits in a frailty index.

In a representative Canadian population survey (n=66589) the proportion of accumulated deficits in a frailty index showed a linear relationship with mortality in a log-log plot, such that the mortality rate was a power-law function of the frailty index. Represented in this way, the frailty index readily summarizes individual differences in health status. The exponent and amplitude parameters of the power function are gender specific, reflecting that while, on average, women accumulate more deficits than men of the same age, their risk of mortality is lower. The dependence of the mortality rate on the frailty index points to the merit of the index as a simple and accessible tool for estimating individual risks of mortality.

Adolescent↗
PubMed2002

Diabetes mellitus and the risk of dementia, Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging.

BACKGROUND: Conflicting results have been reported about the status of diabetes mellitus as a risk for Alzheimer's disease. We investigated the relationship between diabetes and incident dementia (including Alzheimer's disease and vascular cognitive impairment) in a 5-year longitudinal study. METHODS: Secondary analysis of the Canadian Study of Health and Aging, a representative cohort study of dementia in older Canadians. RESULTS: 5,574 subjects without cognitive impairment at baseline participated in 5-year follow-up. Diabetes mellitus at baseline was associated with incident vascular cognitive impairment (RR: 1.62; 95% CI: 1.12-2.33) and its subtypes, vascular dementia (RR: 2.03; 95% CI: 1.15-3.57), and vascular cognitive impairment not dementia (RR: 1.68; 95% CI: 1.01-2.78). Diabetes was not associated with mixed Alzheimer's/vascular dementia (RR: 0.87; 95% CI: 0.34-2.21), incident Alzheimer's disease (RR: 1.30; 95% CI: 0.83-2.03) or all dementias (RR: 1.26; 95% CI: 0.90-1.76). CONCLUSIONS: Despite increased recognition of the role of vascular factors in Alzheimer's disease, we did not find an association between diabetes and incident Alzheimer's disease, even though diabetes was associated with incident vascular cognitive impairment.

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PubMedDate not supplied

Undertreatment of osteoporosis in residents of nursing homes: population-based study with use of the Systematic Assessment of Geriatric Drug Use via Epidemiology (SAGE) database.

OBJECTIVE: To determine the proportion of nursing home residents >65 years of age with osteoporosis who were receiving antiosteoporosis pharmacotherapy and to identify the predictors of administration of such drugs. METHODS: We identified 29,357 patients with osteoporosis documented on the Minimum Data Set collected on residents of all nursing home facilities in 5 states during the period from 1992 through 1996. A multiple logistic regression model was used for analysis, with the dependent variable being use of any antiosteoporosis drug. RESULTS: Among the nursing home residents with osteoporosis, 25% received antiosteoporosis drugs. Women were more likely than men to receive antiosteoporosis drugs (adjusted odds ratio [OR], 1.41; 95% confidence interval [CI], 1.26 to 1.57). Both increasing age and level of cognitive impairment were inversely related to receipt of antiosteoporosis drugs. A history of fracture or falls was not predictive of use of such drugs. Treatment was less likely for nursing home residents with > or = 6 medical conditions (OR 0.55, 95% CI 0.51 to 0.59); those admitted to a nursing home from a hospital (OR 0.86, 95% Cl 0.80 to 0.92); and those with a terminal prognosis (OR 0.60,95% CI 0.42 to 0.87). CONCLUSION: The majority of nursing home residents with osteoporosis in this study did not receive drug therapy for this disabling and treatable disease. Although acceptable reasons may exist in some of these residents,others--especially the oldest old--may not be receiving adequate care.

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