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.

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.

Hippocampal size and memory function in the ninth and tenth decades of life: the Sydney Older Persons Study.

OBJECTIVES: The purpose of this study was to define magnetic resonance imaging (MRI) correlates of normal brain ageing, with the specific objective of investigating whether the size of the hippocampus is selectively correlated with age related memory performance in non-demented individuals in their ninth and tenth decades of life. METHODS: Hippocampal size was estimated using MRI based volumetry and qualitative visual assessment in 102 community dwelling individuals aged between 81 and 94 years. Participants were evaluated on a variety of clinical and experimental instruments, including a comprehensive neuropsychological test battery. All participants underwent neurological examination, an extensive medical history was obtained, and an informant confirmed details of each participant's functional ability. RESULTS: Both visual and volumetric hippocampal measures were identified as robust predictors of memory performance, even when the influence of age related illnesses and sociodemographic variables was accounted for. When the sample was reduced to include the most cognitively healthy participants who were rated by an informant as showing no evidence of cognitive decline, the left hippocampal measures remained significant predictors of delayed retention of verbal material. CONCLUSIONS: These findings suggest that hippocampal volumes are selectively correlated with memory functioning in both normal and successful ageing.

Preclinical syndromes predict dementia: the Sydney older persons study.

OBJECTIVES: To identify if preclinical syndromes for Alzheimer's disease, vascular dementia, and Parkinson's disease and related dementias exist. Identification of dementia at early or even preclinical stages has important implications for treatment. METHODS: A community dwelling sample of 647 subjects aged 75 and over at recruitment were followed up for a mean period of 3.19 years (range 2.61 to 4.51 years). Each subject was asked to participate in a medical assessment which included a standardised medical history examining both past and current health and medication usage; a neuropsychological battery (mini mental state examination, Reid memory test, verbal fluency, subsets of the Boston naming test and similarities, clock drawing and copied drawings) and physical examination. Preclinical syndromes for the three predominant dementias (Alzheimer's disease, vascular dementia and Parkinson's disease, and related dementias) and their combinations were defined using cognitive, motor, and vascular features. Their longitudinal outcome as defined by death and dementia incidence was examined. RESULTS: Preclinical syndromes affected 55.7% (n=299) of subjects. Preclinical syndromes showed a trend for an increased odds of death (odds ratio 1.72, p=0.056) and a significantly increased odds of developing dementia (odds ratio 4.81, p<0.001). Preclinical syndromes were highly sensitive, detecting 52 of 58 (89.7%) incident dementias. Two hundred and sixteen of 268 (80.6%) preclinical subjects did not show dementia over the 3 year period (positive predictive value 19.4%). Subjects defined as having a combination of cognitive, extrapyramidal, and vascular features were at greatest risk of progressing to dementia. CONCLUSIONS: Preclinical syndromes were sensitive and significant predictors of dementia. In view of their poor positive predictive value, the preclinical syndromes as defined in this study remain a research tool needing both definitional refinement and greater periods of observation. Multiple coexistent preclinical disorders resulted in a greater incidence of dementia, providing evidence for an additive role between multiple disorders.

The incidence of dementia in an Australian community population: the Sydney Older Persons Study.

OBJECTIVES: Limited Australian dementia incidence data are available. This study aimed to identify the incidence of dementia and its subtypes in an Australian community dwelling population. METHOD: A community dwelling sample of 647 subjects aged > or =75 years at recruitment were followed for a mean period of 3.2 years (range 2.6-4.5 years). The incidence of dementia (measured in person years at risk) was identified for different levels of severity of dementia, Alzheimer's disease and vascular dementia. RESULTS: Incidence figures were slightly higher than those previously reported. The incidence of dementia and of Alzheimer's disease increased with age but was not affected by gender. The incidence of vascular dementia was not affected by age. CONCLUSION: This study provides the largest body of data on the incidence of dementia in Australia, indicating a slightly higher incidence of dementia than previous reports. Further Australian data are required to confirm these findings.

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.

Medical-care costs associated with posttraumatic stress disorder in Vietnam veterans.

OBJECTIVE: This study examined the relationship between medical-care costs of Vietnam veterans and predictor factors, including posttraumatic stress disorder (PTSD). METHOD: We merged medical-care cost data from the Department of Veterans' Affairs and the Health Insurance Commission with data from an epidemiological study of 641 Australian Vietnam veterans. Posttraumatic stress disorder and other factors were examined as predictors of medical-care cost using regression analysis. RESULTS: We found that a diagnosis of PTSD was associated with medical costs 60% higher than average. Those costs appeared to be partly associated with higher treatment costs for physical conditions in those with PTSD and also related mental health comorbidities. Major predictors of medical-care cost were age ($137 per year for each 5-year increase in age) and number of diagnoses reported ($81 to $112 per year for each diagnosis). Mental health factors such as depression ($14 per year for each symptom reported) and anxiety ($27 per year for each symptom reported) were also important predictors. CONCLUSIONS: The findings indicate that, however they are incurred, high healthcare and, presumably, also economic and personal costs are associated with PTSD. There is an important social obligation as well as substantial economic reasons to deal with these problems. From both perspectives, continued efforts to identify and implement effective prevention and treatment programs are warranted.

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.

Motor function and disability in the dementias.

Epidemiological and neuropathological series have identified three predominant dementing processes; Alzheimer's disease (AD), vascular dementia (VaD) and dementia associated with Lewy bodies (termed Parkinson's disease dementia (PDD) in this paper). While each has its own distinguishing features and by definition all impact upon day to day functioning, no random community derived sample has examined clinical features as defined by gait and balance abnormalities and compared disability ratings of the three dementias simultaneously. Six hundred and forty-seven community dwelling subjects participated in the Sydney Older Persons Study and of these 537 participated in a medical assessment. Of these 537,482 informants rated disability. Gait and balance abnormalities of the three major dementias were identified and the association of the dementias with disability examined. The three major dementias showed evidence of both slowing and ataxia in gait and balance tests. This was maximal in those with PDD. Similarly, all showed evidence of disability that was maximal in those with PDD. In conclusion, this study has identified that gait abnormalities are present in all three dementias to a varying degree. It is hypothesised that the varying levels of disability observed are a consequence of the varying levels of motor impairment, resulting in greater levels of disability in those with PDD.

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.

Distress experienced by participants during an epidemiological survey of posttraumatic stress disorder.

We examined the potential for epidemiological studies of mental disorders, specifically of posttraumatic stress disorder (PTSD), to cause further harm to participants involved. Of 1,000 randomly selected Australian Vietnam veterans, 641 agreed to participate in an epidemiological survey. Participants were asked about distress experienced during the interview when traumatic events were raised. Significant distress attributed to the interview was reported by 75.3% of those with current PTSD, 56.5% of those with past PTSD, and 20.6% of those with no PTSD diagnosis. Distress did not affect participants' use of medical services following the interview nor did it affect their willingness to continue participating in the study. We concluded that research interviews about PTSD may cause short-term distress, but found no evidence of long-term harm.

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.

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.

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.

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.

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.

Postwar experiences and treatment-seeking behavior in a community counselling setting.

Previous research investigating the impact of postwar experiences on Vietnam veterans has focused on veteran morbidity. This emphasis has meant that the impact of these factors on treatment-seeking behavior has received little empirical attention. This study examined the association between postwar factors and treatment-seeking behavior in a sample of 692 Australian Vietnam veterans. Logistic regression analyses were used to compute the odds ratios associated with postwar experiences and self-referral to a community-based counselling service. Results suggest that veterans who reported experiencing negative feelings toward others when they first arrived home were more likely to seek treatment. Other factors, such as a veteran's perception of societal attitudes and the reception they received, were not associated with treatment-seeking behavior.

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).

Clinical diagnoses and disability of cognitively impaired older persons as predictors of stress in their carers.

BACKGROUND: Aspects of the caring relationship are often promoted as more important than the clinical features of the care recipient in predicting caregiver wellbeing. However, studies of consequences of caring for cognitively impaired people seldom include detailed measures of the diagnostic profile and disability of the care recipient. METHODS: Ninety community-living elderly persons with cognitive impairment were clinically assessed for severity on a range of illnesses. Their disability was examined via informant reports. Informants (88% of whom were primary carers) provided information on the behaviour and personality of the subject and reports of their own (informant) wellbeing. Using multiple regression, features of the subjects' clinical profile (severity of diseases, disability, behavioural problems and personality change) were examined as predictors of informant wellbeing. After controlling for subject clinical profile, we explored the additional associations between informant stress measures and other descriptors of the subject, caregiver and their relationship. RESULTS: The subjects' clinical characteristics, in particular disability and disturbed behaviour, were strong predictors of caregiver wellbeing, accounting for most of the explained variance. After control for the subjects' clinical profile, few of the sociodemographic, caregiver or relationship variables examined had any influence on caregiver outcome measures. The exceptions were caregiver time demands, older subject age and self-identification as primary carer. Coresidence was not associated with caregiver distress. CONCLUSION: Clinical characteristics of the care recipient are determinants of caregiver wellbeing, while socio-demographic, caregiver and relationship characteristics are less influential.