Predicting Outcomes in Frail Older Community-Dwellers in Western Australia: Results from the Community Assessment of Risk Screening and Treatment Strategies (CARTS) Programme.

Understanding risk factors for frailty, functional decline and incidence of adverse healthcare outcomes amongst community-dwelling older adults is important to plan population-level health and social care services. We examined variables associated with one-year risk of institutionalisation, hospitalisation and death among patients assessed in their own home by a community-based Aged Care Assessment Team (ACAT) in Western Australia. Frailty and risk were measured using the Clinical Frailty Scale (CFS) and Risk Instrument for Screening in the Community (RISC), respectively. Predictive accuracy was measured from the area under the curve (AUC). Data from 417 patients, median 82 ± 10 years, were included. At 12-month follow-up, 22.5% (n = 94) were institutionalised, 44.6% (n = 186) were hospitalised at least once and 9.8% (n = 41) had died. Frailty was common, median CFS score 6/9 ± 1, and significantly associated with institutionalisation (p = 0.001), hospitalisation (p = 0.007) and death (p < 0.001). Impaired activities of daily living (ADL) measured on the RISC had moderate correlation with admission to long-term care (r = 0.51) and significantly predicted institutionalisation (p < 0.001) and death (p = 0.01). The RISC had the highest accuracy for institutionalisation (AUC 0.76). The CFS and RISC had fair to good accuracy for mortality (AUC of 0.69 and 0.74, respectively), but neither accurately predicted hospitalisation. Home assessment of community-dwelling older patients by an ACAT in Western Australia revealed high levels of frailty, ADL impairment and incident adverse outcomes, suggesting that anticipatory care planning is imperative for these patients.

Luteinizing hormone levels are positively correlated with plasma amyloid-beta protein levels in elderly men.

Dysregulation of the hypothalamic pituitary gonadal (HPG) axis during aging has been associated with increased risk of cognitive decline and developing dementia. Compared to controls, men with Alzheimer's disease (AD) have been shown to have lower serum testosterone levels and higher serum luteinizing hormone (LH) levels. As serum free testosterone concentration is negatively correlated with LH in older men, the independent contributions of these hormones to the pathogenesis of AD warrants further clarification. To explore this notion, we measured plasma amyloid-beta (Abeta), serum testosterone, serum LH and other biochemical parameters in 40 cognitively normal elderly men. Multiple linear regression analysis revealed that serum LH concentration is the only parameter that significantly correlates with plasma Abeta levels in these men (r=0.5, p=0.041). These results suggest that increased serum LH concentration, rather than lower serum free testosterone, is associated with the accumulation of Abeta in plasma. Larger, longitudinal human studies are needed to determine the significance of LH in the pathogenesis of AD.

Interaction between testosterone and apolipoprotein E epsilon4 status on cognition in healthy older men.

CONTEXT: Reduced testosterone levels have been implicated as a potential causative factor in cognitive decline with older age. Men who possess the apolipoprotein E (APOE) epsilon4 allele have an increased risk of developing Alzheimer's disease; however, no studies have examined whether the influence of testosterone on cognition in healthy older men may be modulated by this genetic predisposition. OBJECTIVE: The objective of the study was to investigate the association between serum testosterone concentrations and cognitive performance in healthy older men, taking into account APOE epsilon4 status. DESIGN: This was a cross-sectional study conducted from 2003 to 2004. SETTING: The study population consisted of community-dwelling males residing in Perth, Western Australia. PARTICIPANTS: Healthy men over 55 yr, free of cognitive impairment and dementia (n = 45), were included in the study. MAIN OUTCOME MEASURES: Participants had fasting early morning blood samples for testosterone and SHBG and were assessed for mood as well as indices of general cognition, verbal and visual memory, executive functioning, working memory, and attention. RESULTS: There was a significant interaction between calculated free testosterone (FT) and APOE epsilon4 on general cognition (P = 0.01) and executive functioning, working memory, and attention (P < 0.01). Higher levels of FT were associated with better general cognition in non-epsilon4 carriers (P = 0.01). By contrast, in epsilon4 carriers higher FT levels were associated with lower scores on tests of executive functioning, working memory, and attention (P = 0.02). In men at increased risk for Alzheimer's disease, higher testosterone levels were not associated with better cognitive function. CONCLUSIONS: Cross-sectional and prospective studies of testosterone and cognition in older men should take into account APOE epsilon4 status.

Association between the presenilin-1 mutation Glu318Gly and complaints of memory impairment.

Presenilin-1 mutations account for nearly 50% of all early-onset familial cases of Alzheimer's disease. Most of these mutations are completely penetrant, although the recently described Glu318Gly substitution seems to have only partial penetrance. These findings suggest that the Glu318Gly mutation may work as a genetic risk factor for Alzheimer's disease. We designed the present study to investigate the frequency of this mutation among non-demented volunteers with subjective memory impairment (n = 58) and controls (n = 66). Four (6.8%) subjects with complaints of memory problems, but no controls, carried this mutation. The presence of the Glu318Gly mutation was associated with significantly lower cognitive performance when compared to controls (P = 0.011). However, there was no significant association between the presence of the mutation and the cognitive performance of individuals within the memory complainers group. Follow-up studies should clarify whether the Glu318Gly mutation increases the risk of cognitive decline in later life.

A cross-sectional community study of serum iron measures and cognitive status in older adults.

The relationship of iron status with cognition and dementia risk in older people is contentious. We have examined the longitudinal relationship between serum ferritin and cognition in 800 community-dwelling Australians 60 years or older. Iron studies (serum iron, transferrin saturation, serum ferritin) were performed in 1994/5 and 2003/4 and clinical and cognitive assessments were conducted in 2003/4 for 800 participants of the Busselton Health Study. All participants completed the Cambridge Cognitive test (CAMCOG). Those with CAMCOG scores <84 underwent expert clinical review for cognitive disorders, including the Clinical Dementia Rating scale. Mean serum iron (18.3 micromol/l) and transferrin saturation (28.5%) in 2003/4 did not differ significantly from 1994/5 whereas mean serum ferritin decreased from 162 microg/l in 1994/5 to 123 microg/l in 2003/4, possibly reflecting aging or dietary changes. No relationships were observed between serum iron or transferrin saturation and presence or absence of dementia (p> 0.05). In participants without dementia (n=749), neither serum ferritin in 1994/5 or 2003/4 nor change in serum ferritin between these times was related to total CAMCOG or executive function scores, with or without adjustment for gender, age, National Adult reading test, or stroke history (all p> 0.05). No relationships were observed between ferritin and cognition for participants with possible or probable dementia (n=51). All participants identified as HFE C282Y homozygous or with serum ferritin >1,000 ng/ml had normal CAMCOG scores. We conclude abnormal body iron stores (low or high) are unlikely to have clinically significant effects on cognition or dementia risk in community-dwelling older people.

Predictors of cognitive decline in older individuals with diabetes.

OBJECTIVE: The purpose of this study was to determine longitudinal predictors of cognitive decline in older individuals with diabetes who did not have dementia. RESEARCH DESIGN AND METHODS: Cognitive assessments were performed in 205 subjects with diabetes (mean age 75.3 years) and repeated a median 1.6 years later. The sample was drawn from an existing cohort study, and data on diabetes, cardiovascular risk factors, and complications were collected 7.6 +/- 1.1 years before and at the time of the initial cognitive assessment. Cognitive status was defined using the Clinical Dementia Rating (CDR) scale, and cognitive decline was defined by change in CDR. RESULTS: The sample included 164 subjects with normal cognition (CDR 0) and 41 with cognitive impairment without dementia (CDR 0.5). At follow-up, 33 (16.1%) had experienced cognitive decline (4 new cases of dementia and 29 cognitive impairment without dementia). Only educational attainment predicted cognitive decline from the data collected 7.6 years before cognitive assessment. Univariate predictors of cognitive decline at the time of the first cognitive assessment included age, education, urinary albumin-to-creatinine ratio (ACR), and treatment with either ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs). With multiple logistic regression controlling for age and education, cognitive decline was predicted by natural logarithm ACR (odds ratio 1.37 [95% CI 1.05-1.78], P = 0.021), whereas treatment with either ACEIs or ARBs was protective (0.28 [0.12-0.65], P = 0.003). CONCLUSIONS: In this sample of older patients with diabetes, microalbuminuria was a risk factor for cognitive decline, whereas drugs that inhibit the renin-angiotensin system were protective. These observations require confirmation because of their considerable potential clinical implications.