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There are conflicting reports about the potential role of vitamin antioxidants in preventing and/or slowing the progression of various forms of cognitive impairment including Alzheimer’s disease (AD). We examined longitudinal data from the Canadian Study of Health and Aging, a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. Our primary objective was to examine the association between supplemental use of antioxidant vitamins and subsequent risk of significant cognitive decline (decrease in 3MS score of 10 points or more) among subjects with no evidence of dementia at baseline (n = 894). We also explored the relationship between vitamin supplement use and incident vascular cognitive impairment (VCI; including a diagnosis of vascular dementia, possible AD with vascular components and VCI but not dementia), dementia (all cases) and AD. After adjusting for potential confounding factors assessed at baseline, subjects reporting a combined use of vitamin E and C supplements and/or multivitamin consumption at baseline were significantly less likely (adjusted OR 0.51; 95% CI 0.29–0.90) to experience significant cognitive decline during a 5-year follow-up period. Subjects reporting any antioxidant vitamin use at baseline also showed a significantly lower risk for incident VCI (adjusted OR 0.34, 95% CI 0.13–0.89). A reduced risk for incident dementia or AD was not observed. Our findings suggest a possible protective effect for antioxidant vitamins in relation to cognitive decline but randomized controlled trials are required for confirmation.

Objectives: To determine whether baseline self-rated health (SRH) independently predicted survival in an older Canadian population and to investigate the role of cognition on the SRH-mortality relationship. Design: Population-based prospective cohort study. Setting: Ten Canadian provinces, community-based. Participants: A total of 8,697 community-dwelling participants aged 65 and older. Measurements: Self-reported measures of overall health, physical function, comorbidities, and demographic characteristics were obtained by interview. Cognitive ability was ascertained using the Modified Mini-Mental State Examination (3MS). Participants were followed for their survival status from the initial interview in 1991 until October 31, 1996. Results: Subjects with reports of poor SRH were significantly more likely to die during follow-up than those reporting good SRH, after adjusting for relevant covariates (adjusted hazard ratio (AHR)=1.38, 95% confidence interval (CI)=1.24–1.53). SRH was also related to other measures of health status across levels of cognitive impairment. SRH remained a significant predictor of mortality in subjects with mild to moderate cognitive impairment (AHR=1.26, 95% CI=1.01–1.59) but not in those with severe cognitive impairment (AHR=1.00, 95% CI=0.76–1.31). Conclusion: This study supports the utility of SRH assessments in predicting survival of individuals with mild to moderate cognitive impairment. The findings highlight the potential role of complex cognitive processes underlying the SRH-mortality relationship.

Objectives:We examined whether easily attainable variables were useful in predicting who became demented over a five year period and determined the rates of incident dementia for different categories of mild cognitive impairment.Methods:This was a cohort study of subjects recruited nationally in a population-based survey of Canadians 65 years and older (the Canadian Study of Health and Aging). After standardized clinical assessments, a subset of subjects (n=1782) was categorized as not demented at time one. Identical study methods allowed a reassessment of the cognitive status of surviving subjects (n=892) five years later.Results:Three baseline variables (Modified Mini Mental State (3MS) score, subject's age, and an informant's report of the presence of memory problems) were statistically significant predictors of the development of a dementia. An equation incorporating these three variables had a sensitivity of 79% and a specificity of 56% for predicting dementia among survivors at time two. An equation substituting the MMSE for the 3MS showed similar results. The various categories of mild cognitive impairment examined showed significantly different likelihoods for the subsequent development of a dementia. Some categories with a higher dementia risk were characterized by inclusion criteria requiring neuropsychological test scores that were greater than one standard deviation (SD) below the mean of age based normative data.Conclusion:In the absence of extensive laboratory, radiologic or neuropsychological tests, simple variables that can be easily determined in the course of a single clinical encounter were useful in predicting subjects with a higher risk of developing dementia. Attempts to use neuropsychological results to predict the development of dementia should look for significant impairments on age-standardized tests.

Purpose This study examines the risk of all-cause and cardiac-related mortality associated with calcium channel blockers (CCBs) and other antihypertensives/diuretics compared with β-blockers among an elderly cohort. We explored variations in mortality risk according to CCB formulation, dose and duration of use. Methods Data are from the clinical sample of the Canadian Study of Health and Aging, a population-based prospective study of community and institutional residing persons aged 65+ years. The sample comprised 837 subjects without dementia and reporting use of 1+ antihypertensive/diuretic agents at baseline (1991) and with survival data during follow-up (1996). Results Risk of all-cause and cardiac-related mortality was significantly higher among nifedipine users (HR=1.85, 95%CI 1.12, 3.05 and HR=2.22, 95%CI 1.02, 4.84, respectively) compared with β-blocker users. After adjusting for covariates, the hazard ratios (95% confidence interval) for selected drug classes compared with β-blockers were: nifedipine HR=1.82 (1.09–3.04), diltiazem/verapamil HR=0.96 (0.58–1.60), loop diuretics HR=1.84 (1.21–2.82), ACE inhibitors HR=0.98 (0.54–1.78) and other diuretics/antihypertensives HR=1.10 (0.70–1.72). Among nifedipine users, mortality risk increased with average daily dose and with recent (≤6 months) initiation of therapy and remained significant for prolonged-acting formulations. Conclusions Older subjects exposed to the dihydropyridine calcium antagonist nifedipine had a significantly higher risk for all-cause and cardiac-related mortality during the 5-year follow-up than subjects using β-blockers. Copyright © 2000 John Wiley & Sons, Ltd.

Background. Many diseases have been identified as risk factors for disability in the elderly. This report contrasts disability in the old-old (85 years of age or older, 85+) with younger seniors (65-84 years of age) and examines whether diseases have an equivalent impact on the two groups. Methods. Subjects were 603 cognitively intact community residents 65 years of age and older from 10 Canadian provinces. The purpose of the analysis was to try to isolate the effects of age and nondementing disease on function. Frequency of disease and functional disabilities was calculated. Logistic regression was used to determine significant explanatory variables for moderate, severe, or total disability and for specific disabilities. Results. Nearly twice as many of the cognitively intact 85+ had functional disabilities compared to those 65-84 years of age. In the 85+, increaslng age was the only significant explanatory variable for moderate, severe, or total dis­ ability and for problems with walking, showering, shopping, getting to places out of walking distance, and preparing meals. Diseases were also significant explanatory variables for functional disabilities, particularly in the 65-84 age range. An increase in the proportion with functional disability was found with increasing age even in those without the relevant disease risk factors. Conclusions. Disease prevention would only be partially effective in avoiding disability in the very old because dis­ ability occurred even in those without explanatory disease.

Potential adverse outcomes (falls, impaired cognition, impaired self-care) of psychotropic (benzodiazepines, antidepressants, antipsychotics) and narcotic medication use were examined in a large sample of Canadians 65 years of age and older. We examined rates of reported falls, Digit Symbol Substitution Test (DSST) scores, and mean number of self-care impairments for those consuming psychotropic and/or narcotic drugs as compared to non-users. Use of psychotropic drugs and/or narcotics was associated with an increased prevalence of falls, lower DSST scores, and/or number of self-care difficulties. For example, in subjects who were cognitively normal, the frequency of falls was 60% greater in benzodiazepine users and 120% greater in users of antidepressants as compared to non-users. Adverse outcomes increased with the number of classes of psychotropic or narcotic medications used. These effects were most pronounced in cognitively normal subjects where the prevalence of falls increased from 13.9% in those consuming none of the medication classes to 42.6% for users of two or more classes. In subjects with mild dementia the use of these medications was not associated with any significant differences in the outcomes measured. Regression models showed that benzodiazepine, antidepressant, and narcotic use remained significant explanatory variables for potential adverse outcomes even after simultaneously considering the effects of several other variables. Although further work is necessary, our results suggest that individuals with better cognitive function may be at particular risk for adverse effects with use of these medications.

Data collected as part of the Canadian Study of Health and Aging were analyzed to determine whether physiological changes associated with Alzheimer's disease are common to other types of dementia and are related more to the severity of cognitive impairment. We found that blood pressure and body mass index decreased with increasing dementia severity in both probable Alzheimer's disease and vascular dementia. There were no differences in mean random blood glucose levels or serum osmolarities between types or stages of dementia. We conclude that certain 'hypometabolic' features are associated with dementia severity and are not unique to Alzheimer's disease.

Complementary medicine is frequently utilized for a variety of chronic health problems. We evaluated its use among patients attending a Canadian dementia clinic. Using a telephone survey, we inquired about the use of alternative therapy, including nutritional supplements, herbal remedies, and chelation therapy, for problems with cognition. Only 9.6% of our patient population used complementary medicine as a treatment for cognitive problems. A further 29% used complementary medicines for general health promotion. While higher use might have been anticipated because of the limited conventional therapies available, we did not find a high prevalence of consumption of alternative medicine for cognitive problems. Knowledge of the use of these therapies is still important and should not be neglected. A nonjudgmental inquiry into all therapies being used (for whatever reason) should be part of the assessment of any patient with suspected dementia.

We report on the prevalence of primitive reflexes (PR) and their association with cognitive, behavioural, functional and clinical characteristics in 2914 Canadians 65 years and older. Data were collected as part of the Canadian Study of Health and Aging (1990-92) and included individuals living in the community and in institutions. PR were more commonly found in demented subjects. Demented subjects with prehensile PR (i.e. grasp, traction, suck) had significantly more functional and behavioural problems and were more severely demented. The presence of any PR increased the likelihood of other neurological findings (e.g. bradykinesia). Vascular dementia (VD) cases were more likely to have unilateral primitive PR than probable Alzheimer's disease (Pro AD) and Parkinson's dementia (PD) cases. PD cases were more likely to have glabellar and traction responses. While more common among the demented, PR lacked sufficient sensitivity to be an early diagnostic tool for dementia. Prehensile PR may help to define particular types or severity of dementia.

Five hundred and fifty-three patients were referred to a Canadian dementia clinic for standardized evaluation. The majority (83.5%) had a dementia with Alzheimer’s disease (AD) accounting for 89% of dementias. Patients with probable AD who were followed for five years had variable rates of progression, increased mortality (37.1%, 2.5 times the expected rate) and a high rate of institutionalization (79%). Simple demographic (age) and social factors (marital status) were strong predictors for institutionalization. It was extremely difficult at presentation to predict the rate of progression. The prevalence of AD in autopsied cases was 62.5%. Clinic patients were younger, had milder dementias, and were more likely to have AD than patients identified in the course of a contemporaneous population-based dementia prevalence study.

To determine whether baseline self-rated health (SRH) independently predicted survival in an older Canadian population and to investigate the role of cognition on the SRH-mortality relationship.Population-based prospective cohort study.Ten Canadian provinces, community-based.A total of 8,697 community-dwelling participants aged 65 and older.Self-reported measures of overall health, physical function, comorbidities, and demographic characteristics were obtained by interview. Cognitive ability was ascertained using the Modified Mini-Mental State Examination (3MS). Participants were followed for their survival status from the initial interview in 1991 until October 31, 1996.Subjects with reports of poor SRH were significantly more likely to die during follow-up than those reporting good SRH, after adjusting for relevant covariates (adjusted hazard ratio (AHR)=1.38, 95% confidence interval (CI)=1.24-1.53). SRH was also related to other measures of health status across levels of cognitive impairment. SRH remained a significant predictor of mortality in subjects with mild to moderate cognitive impairment (AHR=1.26, 95% CI=1.01-1.59) but not in those with severe cognitive impairment (AHR=1.00, 95% CI=0.76-1.31).This study supports the utility of SRH assessments in predicting survival of individuals with mild to moderate cognitive impairment. The findings highlight the potential role of complex cognitive processes underlying the SRH-mortality relationship.

The aim of this study was to evaluate changes in benzodiazepine use over time, and the association between benzodiazepine use and select outcomes.A five-year longitudinal cohort study in subjects 65 years of age and older.Select urban communities and institutions across Canada with senior citizens.Subjects who were first seen in 1990 to 1991, recontacted in 1996, and agreed to undergo a second clinical examination. Mortality rates were based on the initial 2914 subjects enrolled.Number and type of medications used. Outcomes (mortality, incident institutionalization, change in cognition, depression, function, self-rated health) associated with benzodiazepine use. Logistic regression to predict outcomes and pattern of benzodiazepine use.Mean number of medications being taken by senior citizens increased to 5.8 from 3.9. The proportion of subjects using benzodiazepines at time 1 and time 2 was similar (26.4% versus 25.2%). Affect, self-rated health, cognition, function and incident institutionalization were significantly associated with benzodiazepine use. Subjects with a depressed mood were more likely to be prescribed a benzodiazepine (37%) than an antidepressant (26.9%).Benzodiazepines were associated with a number of adverse outcomes. The relative benefits and risks of benzodiazepine use in an older population should be re-examined.

Recent epidemiologic studies have shown an association between low serum folate levels and risk of vascular disease, including stroke and various types of vascular cognitive impairment. We examined data from the Canadian Study of Health and Aging (CSHA), a population-based, prospective 5-year investigation of the epidemiology of dementia among Canadians aged 65+ years. The risk of an adverse cerebrovascular event (including vascular dementia, vascular cognitive impairment, or fatal stroke) during follow-up, was assessed according to serum folate quartiles among subjects with no evidence of dementia at baseline (n = 369). After adjusting for certain covariates, including cardiovascular disease and nutritional indices, education, smoking and baseline cognitive status, the risk estimate for an adverse cerebrovascular event associated with the lowest folate quartile compared with the highest quartile was OR 2.42 (95% CI 1.04–5.61). Results from stratified analyses also showed that relatively low serum folate was associated with a significantly higher risk of an adverse cerebrovascular event among female (OR 4.02, 95% CI 1.37–11.81) but not male (OR 1.02, 95% CI 0.25–4.13) subjects. Among the total sample, there was a consistent trend toward poorer health and cognitive outcomes during follow-up (including mortality, cognitive decline and dementia) among those in the lowest folate quartile compared with the highest quartile. Low serum folate levels are independently associated with a significantly higher risk of an adverse cerebrovascular event, including vascular dementia and stroke death, among older, cognitively vulnerable persons.

This report describes a population of individuals with dementia living alone in the community. Data were collected as part of the Canadian Study of Health and Aging (CSHA). We found that one third of the subjects in the CSHA sample with a dementia residing in the community lived alone. Whether their identified informal caregiver had thought about institutionalization was an important factor in actual short-term (2-year) institutionalization and appeared to be influenced by living arrangements. Caregivers of those living alone provided less hands-on assistance, experienced less burden, and were less likely to be depressed than those living with the demented person, but were more likely to have considered institutionalization. Presumably, this was driven by concerns about safety and support. How to support the growing numbers of individuals with dementia living alone in the community will be a significant challenge. Copyrightz1999S.KargerAG,Basel

Objective: to report on the relationship between serum folate levels and the prevalence of stroke, peripheral vascular disease, cognitive problems and short-term mortality in elderly people. Setting and participants: 1171 subjects whose serum folate was determined as part of their clinical examination in the Canadian Study of Health and Aging, a population study of individuals 65 years and older. Methods: cross-sectional analysis compared relationships between serum folate levels and clinical features; longitudinal analysis examined mortality at follow-up by folate status at the time of the clinical examination. Results: membership in the lowest quartile for serum folate was associated with an increased likelihood of stroke. Those with low folate levels were more likely to be demented, institutionalized and depressed. In the cognitively impaired but not demented group, those with low folate levels scored lower on the Modified Mini Mental State and had more short-term memory problems. Conclusions: low folate level was a significant explanatory variable for stroke. Low folate levels were common in all types of dementia and were associated with a history of weight loss, lower body mass index and lower serum albumin concentrations. This may reflect the reduced ability of cognitively impaired individuals to eat adequately.

Study Objective: To describe a population that was categorized as "cognitively impaired not demented" (CIND) and to examine the utility of some of the proposed criteria for describing this degree of cognitive impairment. Design: Population-based prevalence study of dementia in those subjects who were 65 years and older. Setting: Community and institutional settings in Canada. Subjects: Individuals who underwent a clinical evaluation (N=2914). Intervention: Initial screening with the Modified Mini-Mental State Examination (3MS) to identify potential cognitive impairment; the 3MS was followed by a detailed clinical examination to confirm the presence of dementia and to determine the probable cause. Clinical examinations were performed on all those subjects who were residing in institutions, those in the community with a 3MS score less than 78, and a sample of those in the community with a 3MS score of 78 or more. Neuropsychological testing was performed as part of the clinical examination when the 3MS score was 50 or more. At the conclusion of the assessment, subjects were categorized as being cognitively normal, CIND, and demented. Measurements: Frequency of a diagnosis of CIND; demographical, cognitive, and functional characteristics of cognitively normal and CIND subjects and those with early and late dementia; and proportion of subjects who were CIND and met the proposed criteria. Results: Subjects who were categorized as CIND were common and fell between cognitively normal subjects and those with dementia in terms of age, 3MS score, general intellectual function, and performance of daily activities. Because of the restrictive inclusion and exclusion criteria, the proposed criteria for cognitive impairment described only 30% of our subjects who were CIND. Conclusions: Subjects who were categorized as CIND appeared to be distinct from and intermediate between subjects with dementia and cognitively normal subjects. Most individuals did not meet the criteria that were evaluated for describing this group. While the various criteria that were evaluated may accurately define a select subset of cognitively impaired individuals, the natural history and prognosis of such groups, currently unknown, may not be generalizable to the larger population of subjects who are CIND. Further work is needed to clearly define this group, and longitudinal studies are required to determine an outcome.

We report on the prevalence of dementia in Canadians age 85 years and older. The purpose of this study was to determine whether the prevalence of dementia continued to increase in the very old, and to define the types of dementia and their relative proportions in this age group. We collected data as part of the Canadian Study of Health and Aging (1990 to 1992), which consisted of a sample of 1,835 subjects from a population of 283,510 Canadians who were 85 years of age and older residing in the community or in institutions. The prevalence of dementia in the 85 years and older group was 28.5%, more than twice that of the 75- to 84-years cohort. The prevalence of dementia of 23% in the 85- to 89-years sample (n = 1,332) increased to 40% in the 90 to 94 years group (n = 371) and, in the 95 years and older sample (n = 104), reached 58%. Overall, Alzheimer's disease (AD; probable or possible) accounted for 75% of all dementias; a vascular etiology alone accounted for 13% of dementias. The proportion of clinically diagnosed AD cases to vascular dementia cases increased significantly after age 65 and was higher in the 85+ group than in a younger cohort (65 to 84 years).

ROGERS, R. C., L. A. LIHOLTZ AND E. M. EBLY. Nonidet P40 and the retrograde transport of horseradish peroxidase in undamaged visceral nerves . BRAIN RES. BULL. 8 (6) 775–776, 1982.—The cell bodies of origin of peripheral nerves, in particular visceral nerves, are often difficult to identify using standard horseradish peroxidase (HRP) methods. The non-ionic surfactant Nonidet-P40, when applied to intact peripheral nerve along with HRP, allows the investigator to examine the neurons of origin of the nerve without cutting the fibers or injecting label into its peripheral terminal field.