The Community Assessment of Risk Instrument: Investigation of Inter-Rater Reliability of an Instrument Measuring Risk of Adverse Outcomes.

BACKGROUND: Frailty is increasingly common in community dwelling older adults and increases their risk of adverse outcomes. Risk assessment is implicit in the Aged Care Assessment Teams process, but few studies have considered the factors that influence the assessor's decision making or explored the factors that may contribute to their interpretation of risk. OBJECTIVE: to examine the inter-rater reliability of the Community Assessment of Risk Instrument (CARI), which is a new risk assessment instrument. DESIGN: A cohort study was used. SETTING AND PARTICIPANTS: A sample of 50 community dwelling older adults underwent comprehensive geriatric assessment by two raters: a geriatrician and a registered nurse. Procedure and measurements: Each participant was scored for risk by the two raters using the CARI. This instrument ranks risk of three adverse outcomes, namely i) institutionalisation, ii) hospitalisation and iii) death within the next year from a score of 1, which is minimal risk to 5, which is extreme risk. Inter-rater reliability was assessed with Gamma, Spearman correlation and Kappa statistics. Internal consistency was assessed with Cronbach's alpha. RESULTS: There were 30 female (mean age 82.23 years) and 20 male (mean age 81.75 years) participants. Items within domains showed good-excellent agreement. The gamma statistic was >0.77 on 6/7 Mental State items, 14/15 items in the Activities of Daily Living domain. In the Medical domain, 6/9 items had Gamma scores >0.80. The global domain scores correlated well, 0.88, 0.72 and 0.87. Caregiver network scores were 0.71, 0.73 and 0.51 for the three domains. Inter-rater reliability scores for global risk scales were 0.86 (institutionalisation) and 0.78 (death). The gamma statistic for hospitalisation was 0.29, indicative of lower inter-rater reliability. Cronbach's alpha was 0.86 and 0.83 for the Activities of Daily Living domain, 0.51 and 0.42 for the Mental state domain and 0.23 and 0.10 for the Medical state domain. CONCLUSIONS: Overall, the instrument shows good inter-rater reliability. Poor correlations on some items relate to poor communication of clinical data and variable interpretation based on professional background. Lack of internal consistency in the medical condition domain confirms the discrete nature of these variables.

Severe hypoglycaemia and cognitive impairment in older patients with diabetes: the Fremantle Diabetes Study.

AIMS/HYPOTHESIS: The aim was to investigate the relationship between severe hypoglycaemia and cognitive impairment in older patients with diabetes. METHODS: A sample of 302 diabetic patients aged >/=70 years was assessed for dementia or cognitive impairment without dementia in 2001-2002 and a subsample of non-demented patients (n = 205) was followed to assess cognitive decline. A history of severe hypoglycaemia was determined from self-reports, physician assessments and records of health service use for hypoglycaemia (HSH). Prospective HSH was determined up to 2006. Data analysis, including multiple logistic and Cox regression models, was used to determine whether: (1) there were cross-sectional associations between hypoglycaemia and cognitive status, (2) historical hypoglycaemia predicted cognitive decline, and (3) baseline cognitive status predicted subsequent HSH. RESULTS: There were significant cross-sectional associations between both cognitive impairment and dementia and hypoglycaemia. Independent risk factors for future HSH included dementia (hazard ratio 3.00, 95% CI 1.06-8.48) and inability to self-manage medications (hazard ratio 4.17, 95% CI 1.43-12.13). However, there were no significant associations between historical hypoglycaemia, incident HSH and cognitive decline. CONCLUSIONS/INTERPRETATION: Dementia is an important risk factor for hypoglycaemia requiring health service utilisation. We found no evidence that hypoglycaemia contributes to cognitive impairment in older patients with diabetes.

Predictors of cognitive impairment and dementia in older people with diabetes.

AIMS/HYPOTHESIS: Diabetes is associated with an increased risk of dementia but the reasons for this association are unclear because there are many potential mechanisms. We explored the relative contribution of diabetes-related variables as predictors of dementia in older individuals with diabetes. METHODS: Survivors, aged > or =70 or more, were recruited from an existing observational cohort study 7.6 +/- 1.0 years after baseline, when they underwent a comprehensive assessment of diabetes, complications and cardiovascular risk factors. Dementia, probable Alzheimer's disease and cognitive impairment without dementia were diagnosed clinically. Logistic regression modelling determined independent predictors of cognitive diagnoses. RESULTS: Of 302 participants, aged 75.7 +/- 4.6 years, 28 (9.3%) had dementia (16 with probable Alzheimer's disease) and 60 (19.9%) had cognitive impairment without dementia. The major independent longitudinal predictors of dementia were older age (per decade; odds ratio 4.0, 95% CI 1.59-10.10), diabetes duration (for each 5 years; odds ratio 1.69, 95% CI 1.24-2.32), peripheral arterial disease (odds ratio 5.35, 95% CI 2.08-13.72) and exercise (which was protective; odds ratio 0.26, 95% CI 0.09-0.73). For Alzheimer's disease, diabetes duration was an independent predictor in addition to age and diastolic blood pressure. The results of the cross-sectional analyses were similar with respect to diabetes duration and peripheral arterial disease. CONCLUSIONS/INTERPRETATION: Peripheral arterial disease is a strong independent risk factor for dementia in diabetes. After adjustment for a wide range of potential risk factors, diabetes duration remains independently associated with dementia and probable Alzheimer's disease, indicating that factors not measured in this study may be important in the pathogenesis of dementia in diabetes.

Neurological soft signs are associated with APOE genotype, age and cognitive performance.

Neurodegeneration is associated with increased frequency of neurological soft signs (NSS). We designed the present study to investigate the association between NSS and subjective memory complaints, cognitive function and apolipoprotein E genotype in a community-dwelling sample of volunteers participating in an ongoing longitudinal program investigating predictors of cognitive decline. NSS were found to be associated with apolipoprotein E (APOE) epsilon4 genotype (p = 0.015), age (p = 0.012) and poor cognitive performance, as assessed by the Mini Mental State Examination (p = 0.053). There was no significant difference between subjects with and without memory complaints in relation to the frequency of NSS (p = 0.130). The association with age and the APOE epsilon4 genotype suggests that the systematic investigation of NSS may contribute to identify subjects at risk of clinically significant cognitive decline in later life.

Relationship between testosterone, sex hormone binding globulin and plasma amyloid beta peptide 40 in older men with subjective memory loss or dementia.

In a group of 28 older men with either subjective memory loss or dementia, serum total testosterone and sex hormone binding globulin (SHBG) correlated inversely with plasma levels of amyloid beta peptide 40 (Abeta40, r=-0.5, P=0.01 and r=-0.4, P=0.04, respectively). Calculated free testosterone was also inversely correlated (r=-0.4, P=0.03), and all three relationships remained statistically significant after allowing for age. A similar but non-significant trend was seen with dehydroepiandrosterone sulphate (DHEAS), and neither luteinising hormone (LH) nor estradiol correlated with Abeta40. These data demonstrate that lower androgen levels are associated with increased plasma Abeta40 in older men with memory loss or dementia, suggesting that subclinical androgen deficiency enhances the expression of Alzheimer's disease-related peptides in vivo. An inverse correlation exists between SHBG and Abeta40, warranting further investigation.

APOE-epsilon4 and APOE -491A polymorphisms in individuals with subjective memory loss.

The accurate clinical diagnosis of Alzheimer's disease can only be made with a high degree of certainty in specialized centres. The identification of predictive or diagnostic genetic factors may improve accuracy of disease prediction or diagnosis. One major genetic risk factor, the epsilon4 allele of the apolipoprotein E gene, is universally recognised. We have recently shown that the A allele of the apolipoprotein E, -491A/T promoter polymorphism is also an important risk factor for Alzheimer's disease in an Australian population. We designed the present study to investigate the association between apolipoprotein E genotype, -491A/T polymorphism, plasma apoE levels and the subjective experience of memory decline among 98 subjects and 49 age, gender and education-matched normal controls. An increased frequency of the epsilon4 allele of apolipoprotein E was significantly associated with the 'memory complainers' group (OR = 2.35, P = 0.02) as was the A allele of the -491A/T polymorphism (OR = 2, P = 0.02). Among all subjects, only seven individuals were homozygous for both of these alleles, and six of these seven individuals belonged to the 'memory complainers' group. This sub-group also had relatively elevated plasma apolipoprotein E levels (P < 0.01) and tended to score lower on the Mini-Mental State Examination (MMSE) and Cambridge Cognition Test. These data suggest that the epsilon4 allele of apolipoprotein E and the -491A allele are over-represented among individuals who complain of memory difficulties. Follow-up studies should clarify whether these genotypes and phenotypes are useful in the prediction and/or diagnosis of Alzheimer's disease.

Association between presenilin-1 Glu318Gly mutation and familial Alzheimer's disease in the Australian population.

Mutations in the presenilin-1 (PS-1) gene on chromosome 14 account for the majority of early-onset familial Alzheimer's disease (FAD) cases. To date, more than 90 mutations have been identified and, while most of these mutations are completely penetrant, the Glu318Gly mutation has been suggested to be partially penetrant. These findings indicate that it may play a similar role to apolipoprotein E (APOE)-epsilon4 by acting as a genetic risk factor for AD. In the current study, a total of 682 subjects were tested to assess the frequency of the Glu318Gly mutation in AD in the Australian population. The Glu318Gly mutation was identified in six sporadic late-onset AD patients, four FAD patients (unrelated) and in nine control subjects. The frequency of this mutation was highest in the familial AD group (8.7%) and lowest in control subjects (2.2%). When the mutation frequencies were compared, we found a statistically significant difference between the latter two groups (Fisher's exact test, P < 0.05). The genotype frequency of the Glu318Gly mutation in all AD cases and controls in the Australian population was 2.8%. This frequency is comparable to that observed for the Dutch population (3.2%), but not for the Finnish population (6.8% and 6.0%) or the Spanish population (5.3%). These findings show that the frequency of the Glu318Gly mutation is increased in FAD patients, suggesting a potential role as a genetic risk factor contributing to the pathogenesis of familial AD.

Clinical characteristics of individuals with subjective memory loss in Western Australia: results from a cross-sectional survey.

Subjective memory complaint is common in later life. Its relationship to future risk of dementia is unclear, although many reports have found a positive association. We designed the present cross-sectional survey to investigate the clinical features associated with subjective memory impairment. One hundred and eight volunteers and 38 non-complainers acting as age-matched controls were recruited. Eleven subjects with memory complaints were excluded because of prior stroke or low MMSE score. The CAMCOG was used to measure cognition; complainers had significantly lower scores (p<0.001). Univariate analysis showed that complainers had greater prevalence of depression, anxiety, insomnia, psychotic phenomenon, difficulties with ADL and word-finding difficulties. The frequency distribution of the apolipoprotein E epsilon4 allele was similar for both groups (p=0.469). Logistic regression analysis indicated that CAMCOG scores (p=0.002) and word-finding difficulty (p=0.002) were independently associated with memory complaints. These results show that memory complainers have worse cognitive performance than non-complainers and support the findings of other studies that suggest that subjective memory loss may be a reliable indicator of cognitive decline.

Advance directives affecting medical treatment choices.

Advance directives theoretically enhance individual autonomy and facilitate treatment decision making at the end of life. There is little empirical evidence to support this, however. Based on a national postal survey of 2172 randomly selected medical practitioners (response rate 73%), this paper examines the effect advance medical directives have on (a) treatment prescribing for terminally ill people and (b) the degree of difficulty practitioners experience in making treatment choices. A hypothetical patient with Alzheimer's disease and an acute life-threatening illness was presented with and without an advance directive. With a directive, respondents were more uniform in their choice of treatment, with 86% choosing as the patient had requested. Difficulty with decision making was also less with the directive, 31% vs 45% with no directive. The data indicate that advance directives do affect practitioners' treatment choices in favor of patient wishes and reduce the difficulty practitioners may experience in making them.

Treatment decision-making at the end of life: a survey of Australian doctors' attitudes towards patients' wishes and euthanasia.

OBJECTIVE: To examine factors that influence medical practitioners' treatment decisions for patients with life-threatening or terminal illnesses. DESIGN: Postal survey, conducted between September and November 1995, of a self-administered questionnaire, describing four clinical case scenarios, to a random sample of 2172 Australian doctors in all States and Territories. Respondents were asked to prescribe treatment for the patients described in the scenarios. Patients' characteristics varied in terms of mental competence, illness severity, prognosis, the presence of advance directives, request for assisted death, and sociodemographic factors. The respondents' sociodemographic and medical training characteristics were also obtained. SETTING: Random national sample of all active medical practitioners. PARTICIPANTS: Hospital trainees, general practitioners, physicians, palliative care practitioners and surgeons were surveyed. A response rate of 73% was achieved. MAIN OUTCOME MEASURES: Frequency of prescription of supportive, acute or intensive treatment for patients in the four clinical scenarios based on respondents' sex, religion, medical training and country of medical degree. RESULTS: Three main findings were: (i) doctors did not make consistent decisions, but their decisions varied systematically by sociodemographic and medical training factors; (ii) doctors generally adhered to patient and family wishes when these were known; (iii) doctors did not generally adhere to a patient's request for assisted death. CONCLUSION: Treatment provided is significantly determined by the individual characteristics of the doctor and not solely by the nature of the medical problem. Participation in the informed-consent process and in the preparation of advance health care directives would enable practitioners to be familiar with patient and family wishes and could reduce variations of treatment related to sociodemographic and medical training factors. Stronger empirical data on the way that treatment decisions are made could provide the basis for an informed euthanasia policy.

Hypothyroidism: does treatment cure dementia?

Demented individuals are traditionally investigated for potentially reversible causes. Hypothyroidism is generally accepted as being a condition that, if identified and treated, may be associated with improvement in mental state. A literature search was carried out to determine if data exist to show that this is so. Analysis of 2781 cases from studies of etiology in dementia revealed only one case of reversible dementia due to hypothyroidism. Problems associated with interpretation of previous reports include lack of acceptable criteria for diagnosis of dementia and inadequate follow-up. A randomized controlled trial will be needed to resolve this issue.

Clinical significance of primitive reflexes in Alzheimer's disease.

STUDY OBJECTIVE: To establish the relationship between cognition, behavior, function, and clinical characteristics on the one hand, and the presence of primitive reflexes (PR) (pout, snout, palmomental and grasp) in patients with Alzheimer's disease (AD). DESIGN: Cross-sectional survey. SETTING: Secondary care geriatric practice specializing in the assessment of cognitive impairment. SUBJECTS: 136 consecutive patients presenting with AD. MEASUREMENTS: PR were assessed in standardized fashion by a single clinician. Cognitive function was measured using the Standardized Mini-Mental Status Examination, activities of daily living (ADL) and instrumental activities of daily living (IADL) were measured using the Lawton scale, and behavior was measured using the Behavioural Problem Checklist. RESULTS: There was no difference in age or duration of dementia in those with and without PR, nor was there any difference in cognitive function. Despite this, patients with PR showed a greater degree of functional limitation and dysfunctional behavior. There was also a higher incidence of rigidity, gait abnormalities, and apraxia in patients with PR. CONCLUSIONS: Patients with primitive reflexes had more severe impairment in ADL function and dysfunctional behavior for an equal level of cognitive function.

Malignant paraganglioma causing bilateral pleural effusions.

A male patient presented with dyspnea due to a large left pleural effusion, and pleural biopsy revealed a malignant paraganglioma. Raised urinary catecholamine levels confirmed a functioning tumour. Aggressive local spread occurred which did not respond to cytotoxic chemotherapy. The primary site of the tumour was most likely the aorticosympathetic chain.