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Biomedical subjects

K Rockwood

Publications and source records attributed to K Rockwood.

At least 19 recordsLinked to original sources

Goal setting and attainment in Alzheimer's disease patients treated with donepezil.

OBJECTIVES: To understand the treatment goals of Alzheimer's disease (AD) patients, carers, and physicians; to estimate whether clinically important goals are met during treatment with donepezil; and to compare a measure of goal attainment with standard measures used to evaluate AD treatment. METHODS: In a 12 month phase IV trial, 108 patients with mild to moderate AD, their primary carers, and treating physicians set goals assigned to five domains, using Goal Attainment Scaling (GAS) as the primary outcome. Goal attainment was assessed quarterly. GAS scores were correlated with standard outcomes, including the Alzheimer's Disease Assessment Scale-Cognitive (ADAS-cog), and the Clinician's Interview-Based Impression of Change-Plus (CIBIC-plus). RESULTS: Physicians set fewer goals (342, mean (SD) per patient=3 (1)) than patients/carers (855, mean=9 (3)), particularly in leisure (20% by physicians compared with 76% by patients/carers), and social interaction (24% versus 49%). Physicians observed statistically significant improvement in global goal attainment for six months, and patients/carers for nine months. Patients/carers described consistent goal attainment, whereas physicians observed variable effects, such as decline in cognition but improved social interaction and behaviour. Physician global GAS scores correlated highly with the CIBIC-plus at weeks 12 (r= -0.82) and 52 (r=-0.80), but not with the ADAS-cog (r=0.12 and r=-0.45, respectively). Patient/carer global GAS scores correlated moderately with the physician's CIBIC-plus (week 12 r=-0.51; week 52 r=-0.56), and nominally with the ADAS-cog. CONCLUSIONS: Patients/carers and physicians differ in their expectations and impressions of treatment effects. Clinically important changes correlated only modestly with psychometric tests. Attainment of treatment goals does not accord with a simplistic model in which successful AD treatment means that all declines uniformly improve.

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The effect of the living situation on the severity of dementia at diagnosis.

INTRODUCTION: Previous studies have shown that social determinants not directly involved in the disease process may be implicated in the timing of dementia diagnosis. This study explores the relationship between a patient's living situation and the severity of dementia at diagnosis. METHODS: Data were collected from the baseline interviews of 1,325 patients with cognitive decline enrolled in the Consortium for the Investigation of Vascular Impairment of Cognition study. Data collected included: age, sex, living situation and scores on the Mini-Mental State Examination (MMSE), Global Deterioration Scale (GDS), the Functional Rating Scale (FRS), the Disability Assessment for Dementia (DAD) scale and the Cumulative Illness Rating Scale (CIRS). Living situation was grouped as: (1) lives alone, (2) lives with spouse, (3) lives with child, relative or other and (4) lives in a nursing home. A general linear model univariate analysis was used to compare patients by their respective living situations for differences in mean scores on each of the 4 measures of dementia severity. RESULTS: Statistical analysis of both unadjusted data and data adjusted for age, sex and CIRS scores showed significant differences among the groups. Those who lived alone were diagnosed at an earlier stage (mean scores: MMSE 21.4, GDS 3.6, FRS 20.0, DAD 29.8) followed by those who lived with a spouse (mean scores: MMSE 20.5, GDS 3.7, FRS 20.4, DAD 28.0), those who lived with a child or other (mean scores: MMSE 19.3, GDS 3.9, FRS 22.5, DAD 24.9) and finally those who lived in a nursing home (mean scores: MMSE 15.2, GDS 4.8, FRS 27.5, DAD 16.9). CONCLUSION: Living situation is related to the severity of dementia at diagnosis. Primary care providers should have a low threshold for case-finding in older adults who live with family or friends.

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Screening for PS1 mutations in a referral-based series of AD cases: 21 novel mutations.

BACKGROUND: Mutations in the presenilin-1 gene (PS1) account for a majority of patients with early-onset familial AD. However, the clinical indications and algorithms for genetic testing in dementia are still evolving. METHODS: The entire open reading frame of the PS1 gene was sequenced in a series of 414 consecutive patients referred for diagnostic testing, including 372 patients with AD and 42 asymptomatic persons with a strong family history of AD. RESULTS: Forty-eight independent patients screened had a PS1 mutation including 21 novel mutations. In addition, 3% of subjects (11/413) had a known polymorphism, the Glu318Gly substitution. The majority of the mutations were missense substitutions but there were three insertions and Delta exon 10 mutation. With six exceptions (codons 35, 178, 352, 354, 358, and 365) most of the mutations occurred at residues conserved in the homologous PS2 gene or in PS1 of other species. CONCLUSIONS: Eleven percent of a referral-based series of patients with AD can be explained by coding sequence mutations in the PS1 gene. The high frequency of PS1 mutations in this study indicates that screening for PS1 mutations in AD is likely to be successful, especially when directed at patients with a positive family history with onset before 60 years (90% of those with PS1 mutations were affected by age 60 years). This will also have significance for the secondary identification of at-risk relatives who might be candidates for future prophylactic therapies for AD.

Adult↗

Progression of impairment in patients with vascular cognitive impairment without dementia.

Little is known about progression, short of dementia, in vascular cognitive impairment. In the Canadian Study of Health and Aging, 149 participants (79.3 +/- 6.7 years; 61% women) were found to have vascular cognitive impairment, no dementia (CIND). After 5 years, 77 participants (52%) had died and 58 (46%) had developed dementia. Women were at greater risk of dementia (OR 2.1, 1.0 to 4.5). Of 32 participants alive without dementia, cognition had deteriorated in seven and improved in four. Half of those with vascular CIND developed dementia within 5 years, suggesting a target for preventive interventions.

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A reevaluation of the duration of survival after the onset of dementia.

BACKGROUND: Dementia shortens life expectancy; estimates of median survival after the onset of dementia have ranged from 5 to 9.3 years. Previous studies of people with existing dementia, however, may have underestimated the deleterious effects of dementia on survival by failing to consider persons with rapidly progressive illness who died before they could be included in a study (referred to as length bias). METHODS: We used data from the Canadian Study of Health and Aging to estimate survival from the onset of symptoms of dementia; the estimate was adjusted for length bias. A random sample of 10,263 subjects 65 years old or older from throughout Canada was screened for cognitive impairment. For those with dementia, we ascertained the date of onset and conducted follow-up for five years. RESULTS: We analyzed data on 821 subjects, of whom 396 had probable Alzheimer's disease, 252 had possible Alzheimer's disease, and 173 had vascular dementia. For the group as a whole, the unadjusted median survival was 6.6 years (95 percent confidence interval, 6.2 to 7.1). After adjustment for length bias, the estimated median survival was 3.3 years (95 percent confidence interval, 2.7 to 4.0). The median survival was 3.1 years for subjects with probable Alzheimer's disease, 3.5 years for subjects with possible Alzheimer's disease, and 3.3 years for subjects with vascular dementia. CONCLUSIONS: Median survival after the onset of dementia is much shorter than has previously been estimated.

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Physical activity and risk of cognitive impairment and dementia in elderly persons.

CONTEXT: Dementia is common, costly, and highly age related. Little attention has been paid to the identification of modifiable lifestyle habits for its prevention. OBJECTIVE: To explore the association between physical activity and the risk of cognitive impairment and dementia. DESIGN, SETTING, AND SUBJECTS: Data come from a community sample of 9008 randomly selected men and women 65 years or older, who were evaluated in the 1991-1992 Canadian Study of Health and Aging, a prospective cohort study of dementia. Of the 6434 eligible subjects who were cognitively normal at baseline, 4615 completed a 5-year follow-up. Screening and clinical evaluations were done at both waves of the study. In 1996-1997, 3894 remained without cognitive impairment, 436 were diagnosed as having cognitive impairment-no dementia, and 285 were diagnosed as having dementia. MAIN OUTCOME MEASURE: Incident cognitive impairment and dementia by levels of physical activity at baseline. RESULTS: Compared with no exercise, physical activity was associated with lower risks of cognitive impairment, Alzheimer disease, and dementia of any type. Significant trends for increased protection with greater physical activity were observed. High levels of physical activity were associated with reduced risks of cognitive impairment (age-, sex-, and education-adjusted odds ratio, 0.58; 95% confidence interval, 0.41-0.83), Alzheimer disease (odds ratio, 0.50; 95% confidence interval, 0.28-0.90), and dementia of any type (odds ratio, 0.63; 95% confidence interval, 0.40-0.98). CONCLUSION: Regular physical activity could represent an important and potent protective factor for cognitive decline and dementia in elderly persons.

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Pharmacotherapy of Alzheimer's disease: is there a need to redefine treatment success?

The traditional aim of Alzheimer's disease treatment in clinical trials has been to improve cognitive abilities. It has become increasingly clear, however, that other aspects are important in assessing treatment responses. A group of 10 physicians recently gathered to review the current criteria for assessing treatment success in Alzheimer's disease. While cognition has been previously viewed as the primary measure of efficacy, areas such as functional abilities, behaviour, caregiver burden, quality of life and resource utilization all need to be comprehensively assessed to fully evaluate treatment effects in patients with Alzheimer's disease, as well as their impacts on caregivers and society. Postponing or slowing decline in any of these areas may represent an important benefit and should be considered as an outcome measure in clinical trials, clinical practice and decision-making about healthcare budgets. Accepted instruments are available for assessing outcomes in each aspect of Alzheimer's disease, but they need to be selected carefully to provide valid, meaningful data. Some of the most frequently used outcome measures in Alzheimer's disease are reviewed. Using expanded criteria for treatment success and clinically relevant outcome measures, data from currently available studies show that cholinesterase inhibitors produce clinically meaningful long-term benefits in multiple domains in patients with Alzheimer's disease.

Activities of Daily Living↗

The association between antiulcer medication and initiation of cobalamin replacement in older persons.

As chronic use of antiulcer medications might predispose older persons to cobalamin deficiency, we studied participants (> 65 years) in the clinical examination of the Canadian Study of Health and Aging to test the association between the use of an antiulcer medication (histamine-2 blocker or proton pump inhibitor) at baseline with initiation of cobalamin replacement during the 5 year follow-up period. Of 1054 eligible subjects, 125 (11.7%) were taking an antiulcer medication at baseline. At follow-up, 49 (4.6%) had started cobalamin replacement. Antiulcer medication use at baseline was significantly associated with the initiation of cobalamin therapy (odds ratio 2.56, 95% confidence interval 1.30-5.05), even after adjusting for age, gender and institutional residence (odds ratio 2.61, 95% confidence interval 1.31-5.23). There is an independent association between the use of antiulcer medication and initiation of cobalamin therapy. While the relationship is not unambiguously causal, this finding underscores the need for judicious prescribing of antiulcer medications for older persons.

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Butyrylcholinesterase and cognitive function.

Butyrylcholinesterase (BuChE) is expressed in brain structures involved in cognition, but the effect of selective BuChE inhibitors on human cognitive function is unknown. We report a patient whose cognitive function deteriorated following a reduction and improved following reinstitution of ethopropazine, a selective BuChE inhibitor. We suggest that, because neurons expressing BuChE may be involved in cognition, there is merit to further evaluation of selective BuChE inhibitors in treating cognitive dysfunction.

Adult↗

Defining parkinsonism in the Canadian Study of Health and Aging.

This study sought an operational definition of parkinsonism in elderly people (n = 2,914) who underwent a clinical examination in the Canadian Study of Health and Aging (CSHA). Parkinsonism was defined as having two of the following features: (1) bradykinesia of face or limbs, (2) resting tremor, (3) rigidity, and (4) abnormality of gait and posture. The association of parkinsonism with other parkinsonian-related features (prior diagnosis of Parkinson's disease, use of drugs with extrapyramidal side effects, and use of antiparkinsonian medications) and variables not expected to be related to parkinsonism (stroke and Hachinski score > 5) was determined. Parkinsonism was identified in 337 people (11.6%). It was significantly more likely with other parkinsonian-related characteristics, and was not associated with a history of stroke, but was slightly higher among those subjects with a Hachinski score > 5. Posture and gait abnormalities were significantly associated with other parkinsonian-related variables, but were also more common among subjects with stroke-related features. When the gait and posture disturbance category was excluded as a parkinsonian sign, the narrower definition was more specific but less sensitive in detecting cases with a clinical diagnosis of Parkinson's disease. Despite limitations, the approach presented in this article is a valid method to operationalize parkinsonism from the dataset.

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Assessing hypertension in the Canadian Study of Health and Aging.

We investigated the self-report hypertension variables in the CSHA, recorded in the screening questionnaire and the Self-Administered Risk Factor (SARF) questionnaire. The two questions showed high agreement (phi coefficient 0.83). Each was modestly but significantly associated with other simultaneous reports of heart disease and stroke, and with subsequent mortality. Only the SARF asked questions about treatment; controlling for treatment effects, five-year survival was longest among those with no hypertension and no treatment (mean survival time 1,645 days; 95% CI 1,632 to 1,658), and shortest for those with no reported hypertension who were receiving "antihypertensive" medications presumably prescribed for other cardiovascular disease (mean survival time 1,496 days; 95% CI 1,457 to 1,535). The SARF questions incorporating high blood pressure and treatment appear preferable to assess the risks associated with hypertension.

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Use of the chronic disease score to measure comorbidity in the Canadian Study of Health and Aging.

Most older adults have multiple chronic diseases. Consideration of these conditions can improve the performance of statistical models in epidemiological analyses. The Chronic Disease Score (CDS) is a measure of comorbidity derived from medication usage, which may have some advantages over measures derived from other sources. The calculation of the CDS from data contained in the Canadian Study of Health and Aging (CSHA) is described. This measure can be used to estimate comorbidity within the CSHA database.

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Estimating the prevalence of dementia in elderly people: a comparison of the Canadian Study of Health and Aging and National Population Health Survey approaches.

The Canadian Study of Health and Aging (CSHA) and the National Population Health Survey (NPHS) collected data on the prevalence of dementia in differing fashions. The CSHA used a two-stage method with objective testing and expert judgment, and the NPHS used self-report and proxy data. The present report compares estimates of prevalence and the methodology for ascertainment in the two surveys. The more detailed approach of the CSHA offers the more valid means of estimating prevalence and providing data on subtypes, and can be used in naturalhistory studies. TheNPHSmeasures, including a self/proxy report of diagnosed dementia and a derived cognitive measure, are not sufficiently valid for useful inferences to be made. However, the NPHS method can be improved through supplementation with data on functional disability, providing age group-specific point estimates closer to the CSHA's estimates of cognitive impairment and dementia from the community sample. Future waves of the NPHS may wish to include objective cognitive function measures as a cost-efficient and more accurate method of estimating the prevalence of the dementia syndrome without attempting to estimate the prevalence of particular causes of that syndrome.

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Reliability and validity of questions about exercise in the Canadian Study of Health and Aging.

Regular exercise in elderly people has beneficial health effects. We examined exercise frequency and intensity from the Canadian Study of Health and Aging Risk Factor Questionnaire (RFQ). The reliability and validity of these two questions individually, and when combined to form a scale, are reported. Agreement between the self-administered RFQ and an interviewer-administered Add-on Study was examined using intraclass correlations, which were 0.80 for frequency (95% CI 0.77-0.82, p < .001) and 0.75 for intensity (95% CI 0.71-0.78, p = .012). Individuals reporting high levels of exercise frequency, intensity, and a combination of the two showed a smaller proportion of adverse health markers than those reporting no regular exercise. Predictive validity assessed by Cox proportional hazards modeling of mortality showed that the high and moderate levels of frequency, intensity, and combined exercise groups differed significantly (all p < .001) from the no exercise group. We have found that these exercise questions, though simple, appear reliable and valid. The finding that even comparatively crude exercise questions can demonstrate an important relationship to death suggests that the signal for exercise is a strong one, and future studies should seek to better examine mechanisms by which exercise benefit is conferred.

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Measurement of the influence of the physical environment on adverse health outcomes: technical report from the Canadian Study of Health and Aging.

A paucity of information exists to characterize the relationship between the health status of elderly people and their physical environment. The Canadian Study of Health and Aging (CSHA) is a multicenter study of the distribution of dementia among community-dwelling and institutionalized Canadians aged 65 years and older. The study also provides the opportunity to examine issues such as the physical environment which may be related to the health of elderly people. Six items were used to assess the cleanliness, neatness, and maintenance of the inside and outside of the homes of 8,134 community-dwelling individuals. Data were also obtained to evaluate cognition, physical health, and functional capacity. Five years after the original survey, information pertaining to subsequent institutionalization and/or mortality was obtained. A significant relationship was found between classification of physical environment and the outcomes of institutionalization and mortality. The likelihood of both adverse outcomes was notably higher for individuals living in a "less than ideally maintained environment" compared to an "ideally maintained environment." Limitations of the six items used to assess the physical environment and ways in which to improve the sensitivity of the items, consequently avoiding measurement bias, are discussed.

Activities of Daily Living↗

The Canadian Study of Health and Aging: organizational lessons from a national, multicenter, epidemiologic study.

The Canadian Study of Health and Aging was a large, multidisciplinary, national core study--with a number of "add-on" investigations--of the epidemiology of dementia and the health of older people. This structure was a fiscally prudent way to balance between mandated and investigator-initiated inquiry. In hindsight, several important features of the study would be repeated. Future studies might profitably consider a longer funding period for analysis, and a more strategic approach to in-depth, supplementary studies.

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Sleep disturbances and mortality: results from the Canadian Study of Health and Aging.

OBJECTIVES: To cross-validate, in a secondary analysis, the observation that daytime sleepiness is associated with an increased risk of death. DESIGN: Prospective cohort study. SETTING: Canada, a nationally representative sample of people age 65 and older. PARTICIPANTS: Nine thousand and eight community-dwelling participants in the Canadian Study of Health and Aging. MEASUREMENTS EXPOSURES: self-reported sleep disturbances. OUTCOMES: Cox hazard ratios (HRs) for death. RESULTS: The unadjusted analysis showed a small increased risk of death from daytime sleepiness (HR = 1.89; 95% confidence interval (CI) = 1.44-2.46), but this finding did not persist in a multivariate model adjusted for age, depression, cognition, comorbid illness, and function. CONCLUSION: Daytime sleepiness itself is not associated with an increased risk of death when other factors are taken into account. Daytime sleepiness may be a proxy for other morbid conditions and therefore for overall tiredness.

Activities of Daily Living↗