Deaths due to dementia: An analysis of multiple-cause-of-death data.

This study analyzes multiple-cause-of-death information from over 113,000 death certificates of Canadians aged 65+ and identifies causes that are significantly likely and significantly unlikely to combine with dementia to cause death. For dementia as a mentioned cause and as the underlying cause of death, frequencies and rates of death were calculated. Dementia was mentioned on death certificates 2.4 times as often as it occurred as the underlying cause of death. Among the causes least associated with dementia were some cancers, chronic respiratory diseases and rheumatoid arthritis. Causes of death that rarely occur with dementia should be further investigated in terms of their potential role in preventing or delaying the onset of dementia. In particular, further study of the role of anti-inflammatory drugs and nicotine in reducing the risk of dementia is indicated. Causes positively associated with dementia largely reflect the physical deterioration it confers.

A simple method for estimating incidence from prevalence.

A two-state deterministic model is used to estimate the incidence of an irreversible disease from prevalence and mortality data. The method is simpler than those described previously. Diabetes and dementia are used as examples.

Marital status, dementia and institutional residence among elderly Canadians: the Canadian Study of Health and Aging.

The association between marital status and mortality is well known; marital status has also been related to morbidity. In this paper, we examine the importance of marital status in relation to the presence or absence of dementia and to institutional residence, using data from the Canadian Study of Health and Aging. Three groups are compared: married, single and previously married. We show that the age-standardized prevalence of dementia and the proportions of elderly Canadians living in institutions with and without dementia are highest among single people and are also high for those who were previously married. These associations hold true for both women and men, but the relation between marital status and institutionalization is much stronger for men. Possible explanations and implications for the future care of the elderly are discussed.

Risk factors, causality, and policy initiatives: the case of aluminum and mental impairment.

The question addressed is when can the evidence concerning a health issue be regarded as adequate to implement policy initiatives. The approach is illustrated by comparing evidence about the effects of cigarette smoking with evidence for the aluminum (Al) hypothesis (that Al contributes to mental impairment and especially to Alzheimer's Disease). The criteria for evaluating the evidence are based on the consistency and strength of the association between a putative risk factor and the relevant outcome variable, the likelihood that the relative risk represents a causal relationship, whether possible mechanisms are available, the number of persons affected, and the costs of modifying the risk factor.

Life expectancy and dementia in Canada: the Canadian study of health and aging.

Using the 1991 Canadian life table and estimates of the prevalence of dementia from the Canadian Study of Health and Aging, we have partitioned the expectation of life at age 65 into years spent in the community and in institutions, with and without different forms of dementia. The total expectation of life for women was 26% greater than that for men, but women's expectations of life with dementia and of life in institutions were more than twice the corresponding expectations for men. The difference between sexes was greater for Alzheimer's disease than for vascular and other types of dementia.

Speciation of aluminum in biological systems.

As a "hard", trivalent metal ion, Al3- binds strongly to oxygen-donor ligands such as citrate and phosphate. The aqueous coordination chemistry of Al is complicated by the tendency of many Al complexes to hydrolyze and form polynuclear species, many of which are sparingly soluble. Thus there is considerable variation among the Al stability constants reported for several important ligands. The complexity in the aqueous chemistry of Al has also affected Al toxicity studies, which have often utilized poorly characterized Al stock solutions. Serum fractionation studies show that most Al is protein bound, primarily to the serum iron transport protein transferrin. Albumin appears to play little, if any, role in serum transport. There is little agreement as to the speciation of the remaining low-molecular mass fraction of serum Al. The lability of the Al3+ion precludes the simple separation and identification of individual Al complexes. Computational methods are available for detailed computer calculations of the Al speciation in serum, but efforts in this area have been severely hampered by the uncertainties regarding the stability constants of the low molecular mass Al complexes with citrate, phosphate, and hydroxide. Specific recommendations for further research on Al speciation include: (1) Determine more accurate Al stability constants with critical low molecular mass ligands such as citrate and phosphate; (2) supplement traditional potentiometric studies on Al complexes with data from other techniques such as 27Al-NMR and accelerator mass spectrometry with 26Al; (3) develop new methods for generating reliable linear free energy relationships for Al complexation; (4) determine equilibrium and rate constants for Al binding to transferrin at 37 degrees C; (5) confirm the possible formation of low-molecular-mass Al-protein complexes following desferrioxamine therapy; (6) continue research efforts to incorporate kinetic considerations into the present equilibrium speciation calculations; (7) improve methods for preparing chemically well-defined stock solutions for toxicological studies; (8) incorporate more detailed speciation data into studies on Al toxicity and pharmacokinetics; and (9) incorporate more detailed speciation data into future epidemiological studies on the relationship between Al toxicity and various water quality parameters.

Can the controversy of the role of aluminum in Alzheimer's disease be resolved? What are the suggested approaches to this controversy and methodological issues to be considered?

Aluminum (Al) is unquestionably neurotoxic in both experimental animals and certain human diseases. Minute quantities injected intracerebrally into rabbits will induce severe neurological symptoms and neuropathological features of neurodegeneration. Hyper-aluminemia often develops in patients with renal failure being treated with intermittent hemodialysis on a chronic basis, and in severe cases results in an encephalopathy. Uremic adults and premature infants not on dialysis treatment also can develop encephalopathy due to Al toxicity, as is the case when large amounts of alum are used as a urinary bladder irrigant. There are many other examples of Al-induced neurotoxicity; however, the question as to whether Al presents a health hazard to humans as a contributing factor to Alzheimer's disease is still the subject of debate. Several lines of evidence are presented that have formed the basis of the debate concerning the possible pathogenic role for Al in Alzheimer's disease. Important evidence for an Al-Alzheimer's causal relationship is the observation by laser microprobe mass analysis (LMMS) of the presence of Al in neurofibrillary tangles, although there are conflicting data on the extent of the Al deposition. The relatively poor sensitivity of some of the analytical instruments available for these challenging in situ microanalyses could explain the discrepant results, although LMMS and perhaps secondary ion mass spectrometry (SIMS) appear to be sufficiently sensitive. Harmonization of the techniques is an essential next step. There is new evidence that exposure to Al from drinking water might result in cognitive impairment and an increased incidence of Alzheimer's disease. However, these epidemiological studies have inherent problems that must be scrutinized to determine if an association really does exist. An understanding of a possible enhanced bioavailability of Al in this type of exposure, versus other exposures such as antacid intake or industrial exposure, needs to be considered and explored. There has been one promising clinical trial of the treatment of Alzheimer's disease patients with the Al chelator desferrioxamine (DFO). Further studies are needed, and if confirmation is forthcoming then such data could also support an Al-Alzheimer's disease link as well as suggesting that DFO offers potential as a therapeutic agent. The possibility that iron might be the offending agent needs to be considered since DFO is a very strong iron chelator. The significance of Al-induced neurofibrillary degeneration in experimental animals should be assessed especially in light of new data showing that this model exhibits abnormally phosphorylated tau protein structures in the neuronal perikarya. Thus the key questions that must be answered before it can be asserted that Al possesses causal relationship to Alzheimer's disease, are as follows and are addressed in this present discussion: (1) Are there elevations of the concentration of Al in the brains of Alzheimer's disease patients? (2) Is there a relationship between environmental exposure to Al, particularly in drinking water, and an increased risk of Alzheimer's disease? (3) Is treatment with DFO a potentially useful therapeutic approach and to what extent might beneficial effects of DFO implicate Al in the etiology of Alzheimer's disease? (4) Are there similarities between the experimental animal studies and Alzheimer's disease particularly in the development of abnormal forms of tau seen in neurofibrillary tangles? (5) Does Al promote the deposition of the A beta peptide in Alzheimer's disease? (6) Does hyperaluminemia associated with long-term hemodialysis treatment induce neurofibrillary degeneration? If the answer to each of these six questions is yes, then does this assert that Al possesses a causal relationship to Alzheimer's disease? On the other hand, must all six be met to be able to make this assertion?

Further thoughts on the aluminum-Alzheimer's disease link.

UNLABELLED: STUDY OBJECTIVE AND METHOD: The results of studies on aluminum (Al) and Alzheimer's disease (AD) from groups in Newcastle, UK and Ontario, Canada were compared in order to explain why the former were unable to detect a link while the latter could, and to suggest alternative ways of examining the data. RESULTS: The Al concentrations in the Newcastle study were relatively small compared with the Ontario ones. When Al concentrations > 250 micrograms/l were used, the RRs were greater for AD than for other forms of dementia, and the RRs were lower for those under 75 years and greater at ages 85 years and over than at ages above 75 years. The relationship between dementia and Al concentrations was U or J shaped--there was a minimum at an Al concentration of 100 micrograms/l. Other constituents or properties such as silicic acid, fluoride, turbidity, iron, and pH all have an effect on the relationship. CONCLUSIONS: Analyses of the type reported from Newcastle can yield further information if they are extended to include multivariate analyses that take account of other water constituents which can affect the relationship between Al water concentrations and AD are carried out. The relationship between Al and dementia may be U or J shaped rather than linear. With regard to AD, the group aged less than 65 years is not the best one in which to explore a relationship. Lastly, it may be that a link with AD is most meaningful at relatively high Al water concentrations.

Dementia and age at death.

The objective of this paper is to investigate changes in dementia mortality, as recorded on death certificates in Canada. Use is made of data available at Statistics Canada for the period 1990-1991. During this period there have been appreciable changes over time in the ages at death and in the percentage of death certificates that mention dementia. This increase in mortality associated with dementia can be explained, in large part, by an increased tendency for dementia to be listed as an underlying cause of death on the death certificate. Also, the median ages at death of persons in Canada for the period 1990-1991, for whom dementia is recorded as the underlying cause of death, are similar to or greater than the ages at death reported for all other causes of death but excluding dementia. Because those who have dementia are living longer, there is an increase in the number of people with dementia (prevalence of dementia); this has important implications concerning public policy on health and aging. We discuss the significance of these changes with respect to the future prevalence of dementia.

Disability among older people: United States and Canada.

Data from two national surveys of community-dwelling people 55 years of age and over are the basis of tables presenting 25 measures of disability for each country. The report includes discussions of similarity and differences between the countries, methods used to make the data comparable, and limitations on interpretation of the data.

Concerning the role of aluminum in causing dementia.

Topics outlined in an earlier paper by Eichhorn are expanded, with particular emphasis on the implications of the associations between aluminum (Al) concentrations and various indications of mental impairment. These associations represent the main thrust of the evidence that Al is a contributory cause for some forms of dementia. Of particular interest are the more recently observed associations between Al concentrations in drinking (finished) water and various indications of mental impairment, and the relevance of other water quality variables such as silica, fluoride, and pH. Various unresolved questions are also identified.

A suggested mechanism for aluminum biotoxicity.

Following earlier work on the relevance of silica (SiO2) and fluoride (F) to the biotoxicity of aluminum (Al), it is shown that relatively high risks of a measure of mental impairment are frequently associated with relatively low SiO2 and F in the drinking water available in different parts of Ontario. Also, because of a negative association between SiO2 and F concentrations in the treated water available in different municipalities, a low SiO2 concentration can account for the observed association involving high F concentrations, and low F concentrations can similarly account for associations involving high SiO2 concentrations. In the light of these observations, the biotoxic effects at low Al concentrations can be explained by assuming that interactions occur with membranes. Such interactions may be less likely at higher SiO2 and F concentrations, because at these concentrations, interactions between Al-, SiO2- and F-containing species are more important. Generally, the various associations with a measure of mental impairment can be explained on the assumption that F exerts a protective effect against the biotoxic effects of Al, as does SiO2 under certain conditions, but the effects of SiO2 only become important at higher SiO2 concentrations. The results from this and other studies suggest that the neurotoxic effects of Al depend on other water constituents. The results also indicate that absorption through the lung or skin, rather than through the stomach or the bowel, can better explain the reported associations.

The relationship between aging and disease: geriatric ideology and myths of senility.

An ongoing debate in gerontology concerns the relationship between aging and disease. Goodwin, as part of a discussion on the importance of geriatric ideology, argues that age-related disorders like senile dementia of the Alzheimer's type (SDAT) should be regarded as an aging process, while others suggest it is more appropriate to consider it as a disease. This paper comments on the arguments presented by Goodwin and develops these by providing a review of the underlying assumptions concerning aging and disease. The policy relevance and implications for future research are also outlined.

Factors associated with self-reported use and non-use of assistive devices among impaired elderly residing in the community.

We report an analysis of data from the Health and Activity Limitation Survey (HALS) pertaining to the use of assistive devices. The focus is on elderly people reporting an impairment who did not use assistive devices. The degree of impairment, type of impairment, and socio-demographic variables were analyzed for their association with non-use of assistive devices. The non-use of assistive devices was often found to be consistently and strongly correlated for women who report social isolation, less education and who reside in rural areas, suggesting that these groups could be the target for policy initiatives.

A log-linear relationship between reported impairments and age: implications for the multistage hypothesis.

The relationship of mortality rates with age can be represented by a log-linear (Gompertz-type) plot and also, slightly less satisfactorily, by a log-log plot. Similar relationships are observed for incidence rates for a number of specific diseases. For a case where the log-log plot seems preferable, a multistage model is often invoked to explain this relationship. This study investigated the relationship between rates of various impairments and age. Both log-linear and log-log plots of data from the HALS study are compared. Because impairment rates are essentially prevalence rates, models explaining linearity in these plots are different from those used for incidence rates; however, a multistage model with independent events occurring simultaneously may apply.