Gait slowing as a predictor of incident dementia: 6-year longitudinal data from the Sydney Older Persons Study.

Current definitions for the preclinical phase of dementia focus predominantly on cognitive measures, with particular emphasis on memory and the prediction of Alzheimer's disease. Incorporation of non-cognitive, clinical markers into preclinical definitions may improve their predictive power. The Sydney Older Persons Study examined 6-year outcomes of 630 community-dwelling participants aged 75 or over at recruitment. At baseline, participants were defined as demented, cognitively intact or having a syndrome possibly representing the preclinical phase of Alzheimer's disease, vascular dementia, an extrapyramidal dementia or various combinations of the three. Those with cognitive impairment in combination with gait and motor slowing were the most likely to dement over the 6-year period (OR 5.6; 95% CI 2.5-12.6). This group was also the most likely to die (OR 3.3; 95% CI 1.6-6.9). White matter indices on MRI scanning were not consistently correlated with gait abnormalities. Simple measures of gait may provide useful clinical tools, assisting in the prediction of dementia. However, the underlying nature of these deficits is not yet known.

Effect of anti-inflammatory medications on neuropathological findings in Alzheimer disease.

BACKGROUND: There has been no analysis of brain tissue from longitudinally observed, cognitively tested patients to validate whether anti-inflammatory medications protect against the pathological changes of Alzheimer disease. OBJECTIVE: To investigate the role of anti-inflammatory medications in alleviating the pathological features of Alzheimer disease. DESIGN AND MAIN OUTCOME MEASURES: A 5-year postmortem tissue collection was performed after a case-control study of Alzheimer disease (approximately 90 [30%] of patients died during follow-up, of whom consent for autopsy was obtained in 44 [50%]). Cases were selected on the basis of (1) adequate clinical histories of nonsteroidal anti-inflammatory drug usage, (2) no neuropathological findings other than Alzheimer disease, and (3) no generalized sepsis at death. Variables analyzed included neuropsychological test scores and amount of tissue inflammation and Alzheimer-type pathological changes. Two-way analysis of variance was used to determine whether drug usage significantly affected these variables. SETTING: The Centre for Education and Research on Ageing and the Prince of Wales Medical Research Institute, Sydney, Australia. PATIENTS: Twelve patients with Alzheimer disease (5 taking anti-inflammatory drugs) and 10 nondemented controls (3 taking anti-inflammatory drugs) were selected (50% of available sample). RESULTS: Of the patients with Alzheimer disease, anti-inflammatory drug users performed better on neuropsychological test scores than did nonusers. However, there were no significant differences in the amount of inflammatory glia, plaques, or tangles in either diagnostic group. CONCLUSION: Long-term anti-inflammatory medications in patients with Alzheimer disease enhanced cognitive performance but did not alleviate the progression of the pathological changes. Arch Neurol. 2000.

Anti-inflammatory drugs protect against Alzheimer disease at low doses.

CONTEXT: Anti-inflammatory medications have an inverse association with Alzheimer disease (AD). OBJECTIVES: To examine at what doses this anti-inflammatory drug effect occurs and whether other medications and/or International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses affect the association. DESIGN: Subjects 75 years and older from a random population sample were classified by consensus using International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses. Drug associations with different types of dementia with and without the International Classification of Diseases, Ninth Revision, Clinical Modification diagnoses as well as dosage data were analyzed. SETTING: The Centre for Education and Research on Aging, Concord Hospital, Concord, Australia. PATIENTS: The Sydney Older Persons Study recruited 647 subjects (average age, 81 years). A total of 163 patients were given diagnoses placing them in different dementia categories and were compared with 373 control subjects. Of the patients with dementia, 78 had AD without vascular dementia, 45 had vascular dementia (permissive of other dementia diagnoses), and 40 had other dementia diagnoses (without AD or vascular dementia). MAIN OUTCOME MEASURES: Fifty drugs or drug groups were subjected to a 2 (drug used vs drug not used) x 4 (dementia and control groups) chi(2) analysis. Drugs with inverse associations were identified and potential confounders (logistic regression) and dosage data (exact small sample 1-tailed tests) analyzed. RESULTS: As expected, there was an inverse association between nonsteroidal anti-inflammatory drugs and aspirin (and unexpectedly angiotensin-converting enzyme inhibitors) and AD. This association was not observed with vascular dementia or any other diagnoses. Analysis showed no evidence for a dosage effect, ie, responses were equivalent for low and high doses. CONCLUSIONS: This study does not support a high-dose anti-inflammatory action of nonsteroidal anti-inflammatory drugs or aspirin in AD. Potential mechanisms for the beneficial effects of these medications are discussed.

The Australian Vietnam Veterans Health Study: I. study design and response bias.

BACKGROUND: The Australian Vietnam Veterans Health Study was set up to examine the post-war health of former soldiers 20 or more years after service and to examine the relation of combat exposure to physical and mental health. METHOD: A prospective cohort study of a simple random sample of 1000 male Australian Army Vietnam veterans used information gathered from Army records, from personnel interview and questionnaires. Military records were used to examine response bias by determining the differences between 641 interviewed veterans, 50 known deceased veterans and 309 non-respondents (including 48 refusers and 213 non-traceable). RESULTS: Differences were evident between respondents and non-respondents, with logistic regression modelling pointing to pre-enlistment employment, antisocial behaviour, intelligence and post-Vietnam AWOL (absent without leave) as the most important discriminants with non-respondents performing worse. Compared to respondents, deceased left school earlier, had higher rank in Vietnam and at discharge, had a higher overall number of charges but not a higher rate overall, and were less likely to have gone AWOL. Deceased also received more casualty reports than respondents and non-respondents, were better behaved during service, and were better emotionally adjusted than non-respondents. Respondents compared with the Australian population had equivalent or better current socioeconomic status. CONCLUSION: There seems little bias due to non-response, but deceased tend to come from and older cohort than in the other two groups.

The Australian Vietnam Veterans Health Study: II. self-reported health of veterans compared with the Australian population.

BACKGROUND: Self-reported physical health status of Australian Vietnam veterans was determined 20-25 years after the war and its relation to combat was investigated. METHOD: An epidemiological cohort study of a simple random sample of Army veterans posted to Vietnam between 1964 and 1972 was conducted with personal interviews using the Australian Bureau of Statistics Health Interview Survey questionnaire to compare veterans with the Australian population and a 21-item combat exposure index used to measure the relationship of combat to physical health. RESULTS: Veterans reported greater health service usage and more recent health actions than population expectations. They also reported excess health problems in almost all recent illness disease categories except endocrine conditions and cardiovascular conditions; only 6 of 37 chronic disease groups were not elevated compared to the population. Adjustment for non-response changed estimates only slightly. Combat exposure was significantly related to reports of recent and chronic mental disorders, recent hernia and chronic ulcer, recent eczema and chronic rash, deafness, chronic infective and parasitic disease, chronic back disorders and symptoms, signs and ill-defined conditions. CONCLUSION: Combat exposure may have significantly increased reports of only some health problems. A general position to complain as a result of psychological conditions due to combat is not consistent with the lack of relationship between combat and reports of physical conditions.

The Australian Vietnam Veterans Health Study: III. psychological health of Australian Vietnam veterans and its relationship to combat.

BACKGROUND: Self-reported psychiatric status of Australian Vietnam war veterans was determined 20-25 years after the war and its relation to combat was investigated. METHOD: A simple random sample of Australian Army Vietnam veterans was interviewed nationally using standardized interviews and self-completion tests to assess the prevalence of lifetime and current psychiatric illness and its relationship to combat. Army records were used to extract data on the cohort for use in regression-based adjustment for non-response. RESULTS: The conditions mainly affecting the Australian veterans were alcohol abuse or dependence, post-traumatic stress disorder, somatization disorder were significantly related to combat exposure but not with posting to a combat unit. Less than half of the current one-month diagnoses were related to combat, possibly because of low power conferred by the relative rarity of these conditions. CONCLUSIONS: The results confirm a range of psychological problems in former warriors may linger 20 or more years from their war exposure and may be directly affected by exposure to war trauma.

Evidence for association of anaemia with vascular dementia.

The present investigation aimed to examine associations of anaemia with dementia. Analysis of community-dwelling, elderly subjects characterized for different dementias failed to confirm a previously reported association of anaemia with Alzheimer's disease (AD) but revealed instead a significant association with vascular dementia (VAD). Nearly 45% of VAD subjects were anaemic, compared with 17% of controls. Close to one-third of all subjects with haemoglobin levels > 0.5 g/dl below reference anaemia levels had VAD. Co-existing VAD may explain previous links between AD and anaemia. The association was independent of age, dementia severity and a range of other factors including vitamin B 12 and folate levels. Anaemia can exacerbate focal cerebral ischaemia and could precipitate or amplify VAD symptoms in elderly subjects with vasculopathy.

Latent trait analysis of the Eysenck Personality Questionnaire.

This paper exhibits contemporary psychometric models of questionnaires with dichotomous items. Such as approach allows assessment of individual items in terms of precision of measurement in ways not previously available. This Latent Trait Model approach is used to analyse the responses of 3806 subjects to the Eysenck Personality Questionnaire (EPQ). Short forms, of 10 items length, are recommended; they are the best possible such short forms, in that they provide the most accurate possible measurement overall.

Help-seeking in Vietnam veterans: post-traumatic stress disorder and other predictors.

This study investigated factors predicting help-seeking from the Department of Veterans' Affairs (DVA) by Vietnam veterans. Data used were from a national Australian survey of Vietnam veterans' health (n = 641) conducted between July 1990 and April 1993. The survey involved current clinical assessments and retrospective questionnaires, supplemented with health and service records retrieved from the DVA and Army personnel files. Measures included the 1989-90 Australian Bureau of Statistics Health Survey questionnaire, and mental health, sociodemographic and operational deployment history questionnaires. For both current and lifetime diagnoses of post-traumatic stress disorder, a third of the veterans with the disorder had never obtained any health care entitlement from the DVA. Other than physical and mental problems, which accounted for the greatest proportion of the help-seeking odds, significant factors predicting help-seeking included factors such as: predeployment personality, combat exposure, the veterans' own attitudes towards their deployment, experiences during deployment, experiences during repatriation and membership of ex-service organisations. These findings on how post-traumatic stress disorder and other health problems relate to help-seeking patterns could help in developing prevention and care programs for stress disorder.

Item bias in the Center for Epidemiologic Studies Depression Scale: effects of physical disorders and disability in an elderly community sample.

The Center for Epidemiologic Studies Depression Scale (CES-D) is frequently used in studies of elderly individuals. One controversy regarding its use turns on the issue of whether the effect of physical disorder on the CES-D total score reflects genuine effects on depression or item-level artifacts. The present article addresses this issue using medical examination data from 506 community-dwelling individuals aged 75 or older. A form of structural equation modeling, the MIMIC model, is used, enabling the effect of a physical disorder on CES-D total score to be partitioned into bias and genuine depression components. The results show substantial physical disorder-related artifacts with the CES-D total score. Caution is required in the use of CES-D (and possibly other) depression scales in groups in which physical disorders are present, such as in elderly individuals.

Health habits and risk of cognitive impairment and dementia in old age: a prospective study on the effects of exercise, smoking and alcohol consumption.

Previous research has yielded inconsistent results on the effects of exercise, smoking and alcohol use on cognitive impairment and dementia in old age. We analysed data from the Sydney Older Persons Study to see if these health habits were associated with cognitive functioning, dementia or Alzheimer's disease. Health habits were assessed in Wave 1 of the study, when the subjects were aged 75 years or over. Three years later, the subjects were tested for cognitive functioning and clinically examined for dementia and Alzheimer's disease. The analysis was restricted to the 327 subjects examined in Wave 2 who were non-demented in Wave 1. There were few significant associations between health habits and cognitive performance and these were not found consistently across cognitive measures. No associations were found with dementia or Alzheimer's disease. While these health habits do not affect risk for dementia and cognitive impairment in the very elderly, who are at highest risk for these disorders, we cannot discount a role at younger ages.

Alcohol consumption in a community sample of older people.

OBJECTIVE: To examine the prevalence and pattern of alcohol use among community-living elderly Australians. METHODS: A survey was conducted of randomly selected non-institutionalised people aged 75 years and older living in the inner western suburbs of Sydney. Personal interviews by trained interviewers covered background demographic information and self-reported alcohol use. RESULTS: 72% of men and 54% of women drank alcohol. The median usual daily volume of ethanol consumed by drinkers was 10 grams for men and 1.3 grams for women. However 11% of male drinkers and 6% of female drinkers consumed at defined hazardous or harmful levels. CONCLUSIONS AND IMPLICATIONS: Although a sizeable majority of these older people were either non-drinkers or very light drinkers, a small but important proportion drank in the hazardous to harmful range. Despite increasing evidence of the health benefits of alcohol consumption it remains important to be alert for potentially harmful alcohol use among older people.

Posttraumatic stress disorder and other predictors of health care consumption by Vietnam veterans.

A total of 641 randomly selected Australian veterans of the Vietnam War were interviewed about their use of health care in the previous two weeks to determine what factors contributed to health care consumption. Seventy-three variables were examined by univariate linear regression and then grouped into seven categories relating to age, physical and mental health, predisposition to posttraumatic stress disorder (PTSD), deployment and repatriation experiences, and membership in veterans groups. PTSD was associated with an additional cost of $79 in health care for the two-week period. Each physical diagnosis was associated with an additional $28. Alcohol consumption was not related to health care costs. Other important variables contributing to costs were depression, educational status, the quality of the repatriation experience, and social support.

Screening for dementia using an informant interview.

The effectiveness of an informant interview as a screening and assessment instrument for dementia was evaluated in a community survey of 398 people aged 78 or over. Participants received a battery of neuropsychological tests and were diagnosed for dementia by Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV; American Psychiatric Association, 1994) criteria. Informants were independently interviewed about changes in everyday cognitive functioning over the previous five years. A factor analysis of the 31 items from the informant interview showed a large general factor. A long 31-item scale was constructed, as well as a short 12-item scale. The long scale had a sensitivity of 89% and a specificity of 89% for detecting dementia, while the short scale had a sensitivity of 83% and a specificity of 87%. Correlations with subtests of the neuropsychological battery ranged between .4 and .7. The informant scales were less affected by premorbid ability and education than was the Mini-Mental State Examination (MMSE).

Common factor models of validity and reliability for use with ordinal data in k x k tables.

Three common factor models are proposed for the analysis of k x k ordinal data arising from test validity or reliability situations. These models represent an extension of the polychoric correlation model and item response theory. Identification is complete in the most usual reliability situation, where data from only two indicators (raters) are available. Full maximum likelihood estimation is available together with associated informative deviance tests and goodness-of-fit tests, examples of which are provided.

Predicting memory performance in normal ageing using different measures of hippocampal size.

A number of different methods have been employed to correct hippocampal volumes for individual variation in head size. Researchers have previously used qualitative visual inspection to gauge hippocampal atrophy. The purpose of this study was to determine the best measure(s) of hippocampal size for predicting memory functioning in 102 community-dwelling individuals over 80 years of age. Hippocampal size was estimated using magnetic resonance imaging (MRI) volumetry and qualitative visual assessment. Right and left hippocampal volumes were adjusted by three different estimates of head size: total intracranial volume (TICV), whole-brain volume including ventricles (WB+V) and a more refined measure of whole-brain volume with ventricles extracted (WB). We compared the relative efficacy of these three volumetric adjustment methods and visual ratings of hippocampal size in predicting memory performance using linear regression. All four measures of hippocampal size were significant predictors of memory performance. TICV-adjusted volumes performed most poorly in accounting for variance in memory scores. Hippocampal volumes adjusted by either measure of whole-brain volume performed equally well, although qualitative visual ratings of the hippocampus were at least as effective as the volumetric measures in predicting memory performance in community-dwelling individuals in the ninth or tenth decade of life.

Comparing white matter lesions on T2 and FLAIR MRI in the Sydney Older Persons Study.

There is suggestion that magnetic resonance imaging (MRI) fluid-attenuated inversion recovery (FLAIR) sequence may be more accurate than T2 images in detecting white matter lesions (WML) in older people. Comparative ratings of these two image sequences have not been directly investigated in very old individuals to date. We compared the ratings of periventricular and deep WML on these two sequences in a sample of 111 community dwellers (mean age 85.5 years) using semiquantitative methods. Periventricular WML were as commonly detected on T2 as on FLAIR but were more severely rated on the latter sequence. No such bias was observed for the deep WML. With one exception, correlations between the two sets of measures were significant at the P < 0.001 level (range: 0.34-0.75). Intrarater reliability coefficients were moderate to excellent for most ratings. These results suggest that ratings performed on T2-weighted images to detect WML in very old individuals are very comparable with those performed on FLAIR images although FLAIR may allow a finer grading of periventricular lesions. Absence of FLAIR does not preclude the identification of WML in this population. These findings have clinical and epidemiological relevance where the acquisition of supplementary MRI data may not always be possible.

Statistical diagnosis and the influence of diagnostic error.

The optimal class of rules for allocating subjects, on the basis of an observable symptom profile, to sick or well states is based on the likelihood-ratio scale. This scale is estimated from a training set where the symptoms and true disease status are simultaneously measured. In the important case where true disease status is unavailable and only a "noisy" diagnosis can be performed, it is shown that exactly the same optimal class of allocation rules is obtained. This is true under very general assumptions of diagnostic error. Special cases are examined, providing insight into the dynamics of such diagnostic error. In particular, the conditions under which sensitivity, specificity, and the overall correct classification rate are underestimates of the true quantities are investigated.

Confounding confounding.

Miettinen and Cook (Am J Epidemiol 1981;114:593-603) postulate that confounding is a result of exposure-strata dependence in the joint source population, irrespective of the effective parameter used. Boivin and Wacholder (Am J Epidemiol 1985;121:152-8) postulate that confounding is dependent on the additive structure of the crude effect parameter. Both of these conflicting principles are at variance with the familiar definition in terms of parameter bias. It is argued that the change-in-parameter definition is the only fundamental definition.

Can categorical and dimensional views of psychiatric illness be distinguished?

Bimodality in a distribution of symptoms is often claimed to be convincing evidence that a disorder is categorical, a discrete disease entity, rather than the extreme on a continuous dimension. However, using concepts from contemporary psychometric theory it is shown that bimodality can arise from the dimensional viewpoint. In fact, contrary to the usual belief, bimodality would be expected to occur in many research contexts if the dimensional alternative were correct.