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Biomedical subjects

I McDowell

Publications and source records attributed to I McDowell.

At least 19 recordsLinked to original sources

Oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency.

BACKGROUND: Vitamin B12 deficiency is common and rises with age. Most people with vitamin B12 deficiency are treated in primary care with intramuscular vitamin B12 which is a considerable source of work for health care professionals. Several case control and case series studies have reported equal efficacy of oral administration of vitamin B12 but it is rarely prescribed in this form, other than in Sweden and Canada. Doctors may not be prescribing oral formulations because they are unaware of this option or have concerns regarding effectiveness. OBJECTIVES: To assess the effectiveness of oral vitamin B12 versus intramuscular vitamin B12 for vitamin B12 deficiency. SEARCH STRATEGY: Searches were undertaken of The Cochrane Library, MEDLINE, EMBASE and Lilacs in early 2005. The bibliographies of all relevant papers identified using this strategy were searched. In addition we contacted authors of relevant identified studies and Vitamin B12 research and pharmaceutical companies to enquire about other published or unpublished studies and ongoing trials. SELECTION CRITERIA: Randomised controlled trials (RCTs) examining the use of oral or intramuscular vitamin B12 to treat vitamin B12 deficiency. DATA COLLECTION AND ANALYSIS: All abstracts or titles identified by the electronic searches were independently scrutinised by two reviewers. When a difference between reviewers arose, we obtained and reviewed a hard copy of the papers and made decisions by consensus. We obtained a copy of all pre-selected papers and two researchers independently extracted the data from these studies using piloted data extraction forms. The whole group checked whether inclusion and exclusion criteria were met, and disagreement was decided by consensus. The methodological quality of the included studies was independently assessed by two researchers and disagreements were brought back to the whole group and resolved by consensus. MAIN RESULTS: Two RCT's comparing oral with intramuscular administration of vitamin B12 met our inclusion criteria. The trials recruited a total of 108 participants and followed up 93 of these from 90 days to four months. High oral doses of B12 (1000 mcg and 2000 mcg) were as effective as intramuscular administration in achieving haematological and neurological responses. AUTHORS' CONCLUSIONS: The evidence derived from these limited studies suggests that 2000 mcg doses of oral vitamin B12 daily and 1000 mcg doses initially daily and thereafter weekly and then monthly may be as effective as intramuscular administration in obtaining short term haematological and neurological responses in vitamin B12 deficient patients.

Administration, Oral↗

Cognitive decline in high-functioning older adults: reserve or ascertainment bias?

The detection of mild cognitive impairment and dementia in high-functioning older adults can be difficult. It has also been observed that high-functioning persons show a lower prevalence of dementia than low-functioning persons. Three alternative explanations for this observation have been proposed in the literature: brain reserve capacity (BRC), cognitive reserve, and ascertainment bias. With data from a prospective, population-based study of incident dementia, the Canadian Study of Health and Aging (CSHA), we classified participants as being high- (HF) or low-functioning (LF) in three ways: educational and occupational attainment, and estimated premorbid IQ. We observed that fewer HF older adults were diagnosed with dementia after five years, which is in accordance with both the BRC and cognitive reserve models. Contrary to expectations, no difference on rate of memory deterioration was observed between those HF and LF persons who exhibited mild cognitive impairment at CSHA-1. However, HF persons who subsequently were diagnosed with dementia (CSHA-2) showed more rapid decline on five of the six memory measures over time than did LF persons diagnosed with dementia at CSHA-2. When performance on measures of memory functioning at CSHA-1 was examined for highly educated older adults, significantly more of those with dementia at CSHA-2 (n = 59) had scores falling within or below the average range in comparison to normative standards than those who continued to show no cognitive impairment (n = 145). Our findings suggest that the lower incidence of dementia for HF persons may be primarily the result of ascertainment bias, not underlying differences in brain or cognitive reserve.

Activities of Daily Living↗

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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Alzheimer's disease: insights from epidemiology.

While a complete understanding of the pathogenesis of Alzheimer's disease (AD) remains elusive, many conclusions can be drawn from the numerous epidemiological studies undertaken to date. Prevalence and incidence estimates show consistency, following a roughly exponential pattern with a doubling of both parameters roughly every five years after age 65. Roughly 7% of the population aged 65 and over has AD. The clinical course of the disease is reasonably well established and mortality rates rise with increasing levels of cognitive deficit. Four risk factors for AD are firmly established: increasing age, the presence of the apolipoproteinE-epsilon4 allele, familial aggregation of cases, and Down's syndrome. Numerous other associations have been shown in some studies, but not in others. For example, women generally appear at higher risk than men, as do people with lower levels of education; depression is probably prodromal; head injury is an established risk factor, and may interact with the apoE gene; several occupational exposures appear hazardous, and exposure to aluminum in the water supply confers excess risk. Hypertension and other vascular symptoms appear to predispose to AD, which is now seen as nosologically closer to vascular dementia than was previously believed. Several apparently protective factors have been identified, although preventive trials based on these have so far shown minimal effectiveness. The use of non-steroidal anti-inflammatory drugs to treat arthritis is associated with a reduced risk of AD, as is estrogen use by post-menopausal women. Physical activity appears beneficial, as does a diet with high levels of vitamins B6, B12 and folate. while red wine in moderate quantities appears protective. This review concludes with a discussion of the strengths and limitations of current epidemiological methods for studying Alzheimer's disease.

Age Factors↗

An overview of the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging is a multicenter, population-based cohort study of dementia with a sample of 10,263 participants aged 65 or over. Field work began in 1991, and a follow-up study was undertaken in 1996-97. The present article describes the origins and objectives of the study, provides an overview of its design, organization, and data collection methods, and offers a brief summary of the main results.

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Study sampling in the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging drew representative samples of people aged 65 or over from the community and institutions across Canada. The sample was designed to provide regional and national prevalence estimates for dementia by age and sex. Thirty-six sampling areas were used in a stratified cluster design with optimal allocation; sampling weights were developed to provide population estimates. The sample included 9,008 people aged 65 or over from the community, and 1,255 from institutions. This report describes the sampling procedures, the methods used to recruit people to the study and participation rates, the characteristics of the resulting sample, and the way in which sample weights should be used.

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Data collected in the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging collected data focusing on the epidemiology of dementia, using interviews and questionnaires, clinical and neuropsychological examinations, physical measurements and blood collection, and access to public records such as death certificates, from people 65 and over in community (N = 9,008) institutional settings (N = 1,255). The study produced 12 data sets, including community health interviews, clinical and neuropsychological assessments, risk factor questionnaires, and caregiver interviews. This report describes the data collection and processing procedures, summarizes the content of each data set, and outlines the information collected in sufficient detail to permit its suitability for secondary analyses to be scrutinized.

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Study organization in the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging was a complex undertaking that faced management challenges not encountered by smaller-scale projects. The study followed 10,263 elderly people in 18 study centers spanning six time zones; it was administered in two languages, and over 70 investigators were involved. The data collected from each participant were not fixed, but varied according to the results of earlier testing. The data could include a screening interview, a self-completed risk factor questionnaire, an interview with a relative, a clinical examination, neuropsychological testing, blood samples, and neuroimaging. This report describes the approach taken to organize the study, to track participants, and to monitor adherence to the study protocol. It also describes the human organizational aspects, including systems for staff training, for communicating among study centers, and for coordinating the publication of results. The discussion proposes some guiding principles for administering multicenter studies.

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Correlates of nonparticipation in the Canadian Study of Health and Aging.

Correlates of nonparticipation in the community interview component of the Canadian Study of Health and Aging and their impact on bias in the results were analyzed. Characteristics of study subjects, their habitats, and encouragement techniques were analyzed to identify correlates of variation in response rates across the 18 study centers. Refusal rates from 14% to 41% varied by age, gender, city size, number of subjects and length of time for enrollment, and method of approach. Cognitively impaired subjects had higher refusal rates which affected prevalence estimates. At one study site, efforts to "convert" subjects who initially refused to participate in the survey were successful with 26% of those who were recontacted.

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Estimating antemortem cognitive status of deceased subjects in a longitudinal study of dementia.

There was a five-year delay between the two waves of the Canadian Study of Health and Aging during which 2,982 participants died. Their cognitive status before death should be taken into account in estimating the incidence of dementia in the cohort. Information concerning antemortem cognitive status was available from death certificates and from an interview with a close relative of the decedent at the CSHA-2 follow-up. The interview included a direct question on whether the person had been diagnosed with dementia and questions covering cognitive signs and symptoms from which we formed an algorithm to predict probability of dementia. These sources of information were validated using a small sample of study participants who died within five months of undergoing the CSHA clinical examination. Sensitivity of the death certificate and the question regarding diagnosis of dementia was low (33% and 44%), although their specificity was very high. Accordingly, we combined these with the predictive algorithm to form an overall estimate of the probability of antemortem dementia. This raised the sensitivity to 82% (specificity 93%).

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Development and validation of an indicator of support for community-residing older Canadians.

Lack of social support is an important risk factor for disability, psychiatric illness, cognitive impairment, institutionalization, and mortality. Social networks are also important for the caregiving and emotional support that elderly people need to allow them to function well in the community. This article details the development and validation of an index of the instrumental support available to older community residents in the Canadian Study of Health and Aging (CSHA). Preliminary item review, internal consistency, and exploratory factor analysis were carried out on a random half of the sample. The second half of the sample was used for cross-validation; internal consistency, exploratory factor analysis, and item response theory analysis were carried out. The final scale had six items; alpha internal consistency was 0.76 and IRT reliability was 0.85. A one-factor solution was most easily interpretable. IRT analyses showed that the scale was homogeneous and that most items were highly discriminating. The instrumental support scale also had a high correlation with size of social network; it was related to marital status and gender, and predicted institutionalization between the two phases of the study.

Activities of Daily Living↗

Effects of screening errors and differential mortality on the estimation of the incidence of dementia in the Canadian Study of Health and Aging.

The Canadian Study of Health and Aging produced an estimate of the incidence of dementia among elderly Canadians by following up, after 5 years, the undemented found in an initial prevalence survey. Initial and follow-up estimates could be biased by false-negative error in the screening tool used for subjects living in the community, and by erroneous classification of subjects who died in the interim. Here, we use a deterministic model to quantify those possible biases. We conclude that, using the estimates of the errors from control samples, the incidence among community subjects would be overestimated by 15%, and the incidence among the institutional subjects would be underestimated by 37%. The overall incidence would be underestimated by 14%. Most of the bias can be attributed to inaccuracies in the classification of deaths.

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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↗

Incidence and outcomes of diabetes mellitus in elderly people: report from the Canadian Study of Health and Aging.

BACKGROUND: The epidemiology of diabetes in elderly people is not well understood. The purpose of this study was to estimate the incidence of diabetes mellitus among elderly people in Canada and the relative risks of death and admission to an institution among elderly diabetic patients. METHODS: The study was a secondary analysis of data for a community-dwelling sample from the Canadian Study of Health and Aging, a nationwide representative cohort study of 9008 elderly people (65 years of age or older at baseline) in Canada. Diabetes was identified primarily by self-reporting, and a clinician's diagnosis and the presence of treatments for diabetes were used to identify diabetic patients who did not report that they had the condition. RESULTS: The reliability of self-reported diabetes (the kappa statistic) was 0.85. The estimated annual incidence of diabetes was 8.6 cases per thousand for elderly Canadians. Incidence decreased with age, from 9.5 for subjects 65-74 years of age, to 7.9 for those 75-84 years of age and then to 3.1 for those 85 years of age and older. Diabetes was associated with death (relative risk 1.87, 95% confidence interval 1.59-2.19) and admission to an institution (relative risk 1.58, 95% confidence interval 1.28-1.94). INTERPRETATION: Diabetes mellitus is common among elderly people, but the incidence declines among the very old.

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Prevalence and outcomes of vascular cognitive impairment. Vascular Cognitive Impairment Investigators of the Canadian Study of Health and Aging.

OBJECTIVE: To assess the importance of vascular cognitive impairment and its three subgroups (cognitive impairment, no dementia; vascular dementia; and AD with a vascular component) to the prevalence and burden of cognitive impairment in elderly people. BACKGROUND: Vascular lesions may produce a spectrum of cognitive changes. Omitting elderly patients whose cognitive impairment falls short of dementia (vascular cognitive impairment, no dementia) may give a falsely low indication of the prevalence and burden of disease. To test this proposition, we compared the rates of adverse outcomes for patients with no cognitive impairment, vascular cognitive impairment (and its subgroups), and probable AD. METHODS: The Canadian Study of Health and Aging is a prospective cohort study of 10,253 randomly selected community-dwelling and institution-dwelling respondents aged 65 years or older. In the community, all participants (n = 9,008) were screened for cognitive impairment; those who screened positive and a sample of those who screened negative received a clinical assessment (n = 1,659). All patients living in institutions received a clinical assessment (n = 1,255). Participants were reassessed 5 years after the original survey. RESULTS: Vascular cognitive impairment without dementia was the most prevalent form of vascular cognitive impairment among those aged 65 to 84 years. Rates of institutionalization and mortality for those with vascular cognitive impairment were significantly higher than those of people who had no cognitive impairment, and the mortality rate for patients with vascular cognitive impairment was similar to that of patients with AD. CONCLUSIONS: Failure to consider vascular cognitive impairment without dementia underestimates the prevalence of impairment and the risk for adverse outcomes associated with vascular cognitive impairment.

Age Distribution↗

Prediction of probable Alzheimer disease in patients with symptoms suggestive of memory impairment. Value of the Mini-Mental State Examination.

BACKGROUND: The Mini-Mental State Examination (MMSE) is a widely used diagnostic tool for dementia. Its use as a predictive indicator of probable Alzheimer disease (AD) has not been established. OBJECTIVES: To determine the accuracy of the MMSE in predicting emergent AD in a sample of patients who were referred because of symptoms suggestive of memory problems and to determine whether an abbreviated version of the MMSE could be developed that would be as accurate as the full MMSE in predicting emergent AD. DESIGN: Inception cohort of participants with symptoms suggestive of memory impairment by their family physicians were given baseline assessments, including MMSE. After 2 years, the participants' conditions were diagnosed following the standard criterion for AD. Diagnosticians were blind to baseline scores. SETTING AND PARTICIPANTS: One hundred eighty-three community-residing participants were referred by their family physicians to a university teaching hospital research investigation. After baseline screening, 165 participants were included in the study who did not have dementia and had no identifiable cause for memory impairment. After 2 years, 29 participants met criteria for AD, 98 did not develop dementia, 18 developed vascular lesions or non-AD dementia, and 20 did not return. MAIN OUTCOME MEASURE: Diagnostic classification of AD or no evidence of dementia. RESULTS: Logistic regression model was significant. At a cutoff score of 24 or less, sensitivity was 31%; specificity, 96%; with a likelihood ratio of 7.75. A reduced model of 2 subtests was identified with a sensitivity of 41%; specificity, 98%; with a likelihood ratio of 20.70. CONCLUSIONS: Results suggest that the full or abbreviated MMSE is useful in predicting emergent AD in patients with positive test results. However, it is not recommended for use as a screening or diagnostic instrument since a negative test result did not rule out emergent AD. It is recommended as a tool to identify those needing closer monitoring.

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