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Plasma biomarkers for Parkinson’s disease (PD) diagnosis that carry predictive value for cognitive impairment are valuable. We explored the relationship of Mini-Mental State Examination (MMSE) score with plasma biomarkers in PD patients and compared results to vascular dementia (VaD) and normal controls. The predictive accuracy of an individual biomarker on cognitive impairment was evaluated using area under the receiver operating characteristic curve (AUROC), and multivariate logistic regression was applied to evaluate predictive accuracy of biomarkers on cognitive impairment; 178 subjects (41 PD, 31 VaD and 106 normal controls) were included. In multiple linear regression analysis of PD patients, α-synuclein, anti-α-synuclein, α-synuclein/Aβ40 and anti-α-synuclein/Aβ40 were highly predictive of MMSE score in both full model and parsimonious model (R2 = 0.838 and 0.835, respectively) compared to non-significant results in VaD group (R2 = 0.149) and in normal controls (R2 = 0.056). Α-synuclein and anti-α-synuclein/Aβ40 were positively associated with MMSE score, and anti-α-synuclein, α-synuclein/Aβ40 were negatively associated with the MMSE score among PD patients (all Ps

Introduction: Little is known about the role of inflammation in the process of small vessel vascular dementia (VaD). Recently, the notion that small vessel VaD is caused solely by vascular pathology has been challenged by new evidence of concomitant breakdown of the blood-brain barrier and dysregulation of neuroinflammation in the white matter. Methods: We examined selected inflammatory cytokines and chemokines in the plasma from patients with small vessel VaD (n = 41) and from age-matched controls (n = 131) using multiplex bead-based assays. Participants were recruited from a memory disorder clinic and from a hospital or community. Results: When compared to controls, patients with small vessel VaD had a highly significant increase in the plasma interferon-γ-inducible protein 10 (IP-10) level (p < 0.0001) and a highly significant decrease in plasma macrophage inflammatory protein 1-beta (MIP-1β) level (p < 0.0001). We also observed a significant increase in patients’ levels of interleukin-10 (IL-10) (p = 0.022) as well as decreases in interleukin-8 (IL-8) (p = 0.004) and interleukin-7 (IL-7) (p = 0.011) when compared to age-matched controls. Conclusion: Both IP-10 and MIP-1β are macrophage-related chemokines. The significant differences between cases and controls suggest a potential role for macrophages in small vessel VaD neuroinflammation. Although it remains unclear whether there is a causal effect of their alteration for small vessel VaD, a better understanding of these molecules in the pathogenesis of small vessel VaD may lead to improved diagnosis and future treatment outcomes against this disease.

Graphical abstract, Vascular dementia (VaD) is a complex neurocognitive disorder secondary to a variety of cerebrovascular lesions. Numerous studies have shown that lipid metabolism is involved in the pathobiology of the disease. We examined the plasma lipid profiles in VaD, with the expectation of identifying reliable lipid biomarkers for VaD. 49 VaD patients and 48 healthy controls were recruited from Bankstown-Lidcombe Hospital in Sydney, Australia. Lipids were extracted by single phase 1-butanol/methanol, and untargeted analysis was performed by liquid chromatography coupled-mass spectrometry (LC–MS/MS). Univariate analysis of variance was used to examine the differences in lipid classes and individual lipids between VaD and control groups. In an independent sample of 161 subjects from the Older Australian Twins Study (OATS), elastic net penalization for the generalized linear model (Glmnet) and Random Forest were applied to the lipid levels to subcategorise the sample into vascular cognitive impairment and controls. Most lipids belonging to the classes of ceramides (Cer), cholesterol esters (ChE) and phospholipids were significantly lower in VaD plasma, while glycerides were elevated compared to controls. Levels of ChE, Cer and the two lipid classes together achieved the best accuracy in discriminating VaD from controls, with more than 80% accuracy. The probable VaD group in the OATS sample predicted by the lipid levels showed greater impairment in most cognitive domains, especially attention and processing speed and executive function from controls but did not differ in white matter hyperintensities and DTI measures. As a conclusion, plasma lipids levels, in particular Cer and ChE, are abnormal in VaD and may help discriminate them from healthy controls. Understanding the basis of these differences may provide insights into the pathobiology of VaD.

Easily accessible and accurate biomarkers can aid Parkinson's disease diagnosis. We investigated whether combining plasma levels of α-synuclein, anti-α-synuclein, and/or their ratios to amyloid beta-40 correlated with clinical diagnosis. The inclusion of amyloid beta-40 (Aβ40) is novel. Plasma levels of biomarkers were quantified with ELISA. Using receiver operating characteristic (ROC) curve analysis, levels of α-synuclein, anti-α-synuclein, and their ratios with Aβ40 were analyzed in an initial training set of cases and controls. Promising biomarkers were then used to build a diagnostic algorithm. Verification of the results of biomarkers and the algorithm was performed in an independent set. The training set consisted of 50 cases (age 65.2±9.3, range 44-83, female:male=21:29) with 50 age- and gender-matched controls (67.1±10.0, range 45-96 years; female:male=21:29). ROC curve analysis yielded the following area under the curve results: anti-α-synuclein=0.835, α-synuclein=0.738, anti-α-synuclein/Aβ40=0.737, and α-synuclein/Aβ40=0.663. A 2-step diagnostic algorithm was built: either α-synuclein or anti-α-synuclein was ≥2 times the means of controls (step-1), resulting in 74% sensitivity; and adding α-synuclein/Aβ40 or anti-α-synuclein/Aβ40 (step-2) yielded better sensitivity (82%) while using step-2 alone yielded good specificity in controls (98%). The results were verified in an independent sample of 46 cases and 126 controls, with sensitivity reaching 91.3% and specificity 90.5%. The algorithm was equally sensitive in Parkinson's disease of ≤5-year duration with 92.6% correctly identified in the training set and 90% in the verification set. With two independent samples totaling 272 subjects, our study showed that combination of biomarkers of α-synuclein, anti-α-synuclein, and their ratios to Aβ40 showed promising sensitivity and specificity.

Objective The aim of this study was to evaluate the effectiveness and identify factors predictive of home discharge in a cohort of patients admitted to the residential Transitional Aged Care Program (r‐TACP) after a stay in an acute hospital. Methods A retrospective observational cohort study of patients admitted to a single r‐TACP unit between 1 January 2014 and 31 December 2017 was carried out. Baseline patient characteristics and discharge outcomes were analyzed. Results Three hundred sixty‐nine patients were admitted during the study period. The discharge outcomes were as follows: 68% returned home, 17% went onto residential care, 14% were readmitted to hospital, and 1% died. Factors associated with not returning home were increased age, increased comorbidities, and lower Barthel Index on admission to the r‐TACP. Conclusion Our r‐TACP is an effective program that successfully returns the majority (67.8%) of older patients home after an acute hospital admission. Older patients with greater comorbidities and poorer baseline functional status in our program were less likely to return home.

There is no gold standard screening tool available to assess post-stroke cognitive impairment (PSCI). PSCI is a common and under-recognised global problem in stroke patients that may eventually lead to post-stroke dementia (PSD). Two major issues in PSCI research include the lack of a clear-cut definition and a lack of highly specific and sensitive screening tools that accurately predict PSCI. To identify the most appropriate cognitive screening tool to be used in the diagnosis of PSCI. MEDLINE and “The Cochrane Library” were searched for articles published between January 2000 and August 2016 that contained the keywords “post-stroke cognitive impairment”, “post-stroke dementia” or “cognitive tools after stroke” or “cognitive impairment after stroke”. Abstracts were selected using predetermined inclusion and exclusion criteria, and full-text reviews were performed. Publications on cognitive screening tools and PSCI or PSD were pooled separately for the review process. A total of 22 publications discussing cognitive screening tools in PSCI and PSD were identified. Only two publications discussed the use of multidomain cognitive tools. Some publications reported that domain-specific cognitive screening tools had higher sensitivity and specificity when compared to commonly use cognitive screening tools such as the Montreal Cognitive Assessment (MOCA) and Mini-Mental State Examination (MMSE). The superiority of one available tool was not evident in studies that performed a meta-analysis. The Oxford Cognitive Screen (OCS), a multidomain tool, was found to be a better predictor of PSCI/PSD than the MOCA or MMSE. To date, the literature on PSCI has primarily focused on nonspecific cognitive screening tools, although there has been a recent move towards domain-specific screening tools. Multidomain screening tools such as the OCS may be better than existing tools in the diagnosis of PSD and PSCI.

Falls are very common among older people. Previous literature has reported a mean fall rate of 1.7 falls per person-year (range, 0.6–3.6) for those who live in nursing homes (Rubenstein et al, 1994) and a rate of 0.65 (range, 0.3–1.6) for those living in the community (Rubenstein, 2006). A more recent study of 70,000 falls in Bavarian nursing homes has reported a similar fall rate (1.6 per person-year), with the rate being higher among men (Rapp et al, 2012). The higher fall rate among older people in nursing homes compared to the rest of the community is expected, and falls are a major reason for admission into nursing homes. One non-injurious fall carries a 3.1 times relative risk of admission into a nursing home, while a fall accompanied by serious injuries is associated with a 10.2 times higher relative risk (Tinetti and Williams, 1997). Even though the majority of falls in nursing homes do not result in serious injury, 10–25% result in hospital admission and/or fractures (Vu et al, 2004). With such a high prevalence, falls, unsurprisingly, result in 81.5% of external (defined as premature, usually injury related and potentially preventable) causes of deaths among nursing home residents (Ibrahim et al, 2017).

To share our experience of establishing an acute outreach service to nursing homes and to evaluate the impact of such service on emergency department presentations, data were drawn from a pre-existing database from 2013 to 2017. Of the 986 acute patients treated in 12 nursing homes over a 23-month period, the acute geriatric outreach service was shown to be safe, with few adverse events (one allergic reaction) and 5.3% of patients required transfer to hospital. The acute service decreased emergency department presentation of nursing home patients by 10% compared to the subacute service (incidence rate ratio = 0.90; 95% confidence interval: 0.84-0.96; P = 0.001). Cost-benefit analysis showed for every $1 spent, a saving of $5 was realised.

Background COVID-19 pandemic has had a major impact globally, with older people living in aged care homes suffering high death rates. Objectives We aimed to compare the impact of initial government policies on this vulnerable older population between the UK and Australia during the first wave of attack. Methods We searched websites of governments in the UK and Australia and media outlets. We examined the key policies including the national lockdown dates and the distribution of some important resources (personal protective equipment and testing) and the effects of these initial policies on the mortality rates in the aged care homes during the first wave of attack of COVID-19. Results We found that both countries had prioritized resources to hospitals over aged care homes during the first wave of attack. Both countries had lower priority for aged care residents in hospitals (e.g. discharging without testing for COVID-19 or discouraging admissions). However, deaths in aged care homes were 270 times higher in the UK than in Australia as on 7 May 2020 (despite UK having a population only 2.5 times larger than Australia). The lower fatality rate in Australia may have been due to the earlier lockdown strategy when the total daily cases were low in Australia (118) compared to the UK (over 1000), as well as the better community viral testing regime in Australia. Conclusion In conclusion, the public health policy in Australia aimed towards earlier intervention with earlier national lockdown and more viral testing to prevent new cases. This primary prevention could have resulted in more lives being saved. In contrast, the initial policy in the UK focussed mainly on protecting resources for hospitals, and there was a delay in national lockdown intervention and lower viral testing rate, resulting in more lives lost in the aged care sector.

Fall prevention and management of behavioural and psychological symptoms of dementia (BPSD) in long-term care (LTC) facility is a major challenge. The objective of this systematic review is to assess the evidence of digital technology in their management. All studies of English-language excluding case-reports were eligible for review. Databases chosen were MEDLINE, EMBASE, Scopus, Web of Science and PSYCINFO from January 2000 to June 2020. Downs and Black checklist was used to check for risk of bias. Papers with a focus in LTC setting, using digital technology as intervention for older adults with dementia, and with measurable outcomes (outcomes that are quantified, not descriptive) were included in the final review. Seventeen original papers (8 RCTs, 8 quasi-experimental and 1 mixed method) were included. Three articles examining position-sensor technology for fall prevention showed mixed results. Two showed no difference and 1 showed small reduction in fall after alarm removal but the positive effect might be due to bias. Overall, the sample sizes were too small to draw meaningful conclusion. Fourteen studies (9 pet robots of which 8 were robotic seal/PARO) were identified for BPSD and results were mixed. Overall, PARO might have modest benefit in BPSD compared to usual care but might be no better than plush toy with more hallucinations or delusions seen in advanced dementia. However, the significant heterogeneity in methodology (intervention intensity, lack of record in psychoactive drug use), clinical tools used (different BPSD scales, different digital technologies) and variability in outcomes made it difficult to draw clear-cut conclusion. Studies involving other digital technologies are scarce and in pilot phases; hence, conclusion is premature. One limitation of the review was that only 9 out of 17 studies were of good quality. The limited research work in position-sensors meant insufficient evidence to prove efficacy for their use in LTC setting. The possible modest benefit of PARO in BPSD (e.g. in agitation, apathy or reduction in psychoactive drugs) was off-set by possible adverse events such as delusions or hallucinations in advanced dementia.The online version contains supplementary material available at 10.1007/s10433-021-00627-5.

Precision medicine and clinical relevance in older people.

Eighty consecutive Chinese patients diagnosed with Alzheimer disease were assessed for darkening of grey hair. Of the 62 eligible patients (mean age = 79.3 ± 7.9 years; male: female = 1:1.48), 24/62 (38.7%, 95%CI: 26.6 – 51.9) reported hair darkening after prolonged usage of cholinesterase inhibitor for at least 6 months. Of the 24 patients with hair darkening, 17 (70.9%) experienced hair darkening in the occipital region, 3 (12.5%) in the parietal region, 2 (8.3%) patients in the frontal region and 2 (8.3%) patients experienced hair darkening in multiple regions. Analysis of melanin concentration showed no significant difference between darkened hair of patients after prolonged drug use and the dark hair of controls (P = 0.381).

‘Fatigue and the older stroke patient’ explores with the help of a case vignette and a conceptual model, the complex field of fatigue after stroke. It looks at the definition of fatigue, assessment of fatigue in older stroke patients, mechanisms of fatigue, medical management, and psychological treatment of post-stroke fatigue. While fatigue is common after stroke, research into its management is in its infancy. With respect to the older person there is in particular a deficiency in research not only into fatigue management but also its nature and origins in this age group. Older people often have multiple medical comorbidities that can also cause fatigue and these need to be addressed appropriately. Nonetheless, clinically both psychological and medical management offer treatments that at the individual level may be worthwhile. Further rigorous empirical research particularly considering older people after stroke might assist in refining understanding and treatment of fatigue in this population.

Background Cerebral small vessel disease (CSVD) comprises a variety of disorders affecting small arteries and microvessels of the brain, manifesting as white matter hyperintensities (WMHs), cerebral microbleeds (CMBs), and deep brain infarcts. In addition to its contribution to vascular dementia (VaD), it has also been suggested to contribute to the pathogenesis of Alzheimer’s disease (AD). Method A systematic review of the literature available on Medline, Embase and Pubmed was undertaken, whereby CSVD was divided into WMHs, CMBs and deep brain infarcts. Biomarkers of AD pathology in the cerebrospinal fluid or plasma, or positron emission tomographic imaging for amyloid and/or tau deposition were used for AD pathology. Results A total of 4117 articles were identified and 41 articles met criteria for inclusion. These consisted of 17 articles on vascular risk factors for clinical AD, 21 articles on Aβ pathology and 15 articles on tau pathology, permitting ten meta-analyses. CMBs or lobar CMBs were associated with pooled relative risk (RR) of AD at 1.546, (95%CI 0.842–2.838, z = 1.41 p = 0.160) and 1.526(95%CI 0.760–3.063, z = 1.19, p = 0.235) respectively, both non-significant. Microinfarcts were associated with significantly increased AD risk, with pooled odds ratio OR at 1.203(95%CI 1.014–1.428, 2.12 p = 0.034). Aβ pathology was significantly associated with WMHs in AD patients but not in normal age-matched controls. The pooled β (linear regression) for total WMHs with CSF Aβ42 in AD patients was -0.19(95%CI -0.26–0.11, z = 4.83 p = 0.000) and the pooled r (correlation coefficient) for WMHs and PiB in the normal population was -0.10 (95%CI -0.11–0.30, 0.93 p = 0.351). CMBs were significantly associated with Aβ pathology in AD patients. The pooled standardized mean difference (SMD) was -0.453, 95%CI -0.697– -0.208, z = 3.63 p = 0.000. There was no significant relationship between the incidence of lacunes and levels of CSFAβ, with a pooled β of 0.057 (95%CI -0.050–0.163, z = 1.05 p = 0.295). No significant relationship was found between CMBs and the levels of CSFt-tau/CSFp-tau in AD patients (-0.014, 95%CI -0.556–0.529, z = 0.05 p = 0.960; -0.058, 95%CI -0.630–0.515, z = 0.20 p = 0.844) and cortical CMBs and CSF p-tau in the normal population (0.000, 95%CI -0.706–0.706, z = 0.00 p = 0.999). Conclusions Some CSVD markers were significantly associated with clinical AD pathology and may be associated with Aβ/tau pathology. WMHs and microinfarcts were associated with increased risk of AD. It remains unclear whether they precede or follow AD pathology.

Objective: The study aimed to survey hospital staff knowledge of the application of the Mental Health Act 2007 (NSW) (MHA) and the Guardianship Act 1987 (NSW) (GA) in the care and treatment of older persons in a teaching hospital in Sydney. Method Over a two-month period in 2017, a survey questionnaire was distributed to staff involved in older persons’ care across the hospital. Results: The majority of the hospital staff demonstrated basic theoretical knowledge of both the GA (76%) and of the MHA (84.5%). Fewer (64.5%) appeared to understand the practical application of the MHA in the hypothetical clinical situations. An even lower proportion of staff appeared to understand the application of the GA either to obtain consent for medical treatment or to appoint a guardian through the Guardianship Division of the NSW Civil and Administrative Tribunal (NCAT). Conclusion: Although clinical staff of the hospital displayed fair knowledge and awareness about the application of the MHA and the GA to inpatient care of older adults, further education is necessary, particularly about the application of the GA. The authors suggest similar findings may occur at other New South Wales hospitals, which may raise concern and need for education.

In this mini-review, we summarize recent findings relating to the prion-like propagation of α-synuclein (α-syn) and the development of novel therapeutic strategies to target synucleinopathy in Parkinson’s disease (PD). We link the Braak’s staging hypothesis of PD with the recent evidence from in-vivo and in-vitro studies for the prion-like cell-to-cell propagation of α-syn (via exocytosis and endocytosis). The classical accumulation of aggregated α-syn in PD may result from an increased production or a failure in the mechanisms of clearance of α-syn. We discuss novel agents, currently in clinical trial for PD including the ones that impact the aggregation of α-syn and others that interfere with α-syn endocytosis as a means to target the progression of the disease.

Background Delirium is common after stroke and has significant negative impact on mortality, morbidity, cognitive function, and institutionalization. Despite these known effects, any impact of delirium on the emotional well-being of stroke survivors is unclear. Methods A post hoc analysis was performed on our prospective cohort study of 156 stroke patients. Hospital Anxiety and Depression (HAD) scale scores were compared between patients with delirium and patients without delirium at 1-month, 6-month, and 12-month post-stroke. Results Contrary to the negative impact of delirium on cognition and functional status, we did not discern any influence on HAD scale scores in the short to long term. The median scores of the HAD anxiety scale were 4 (interquartile range IQR 3) at 1 month, 5.5 (IQR 8.75) at 6 months, and 6 (IQR 5) at 12 months in the delirium group compared to 5 (IQR 7) at 1 month (p = 0.6), 4 (IQR 7) at 6 months (p = 0.4), and 6 (IQR 5.75) at 12 months (p = 0.9) in the non-delirium group, respectively. Similarly, the median scores of the HAD depression scale were 5 (IQR 4) at 1 month, 4 (IQR 6.5) at 6 months, and 3 (IQR 6) at 12 months in the delirium group compared to 6 (IQR 5.75) at 1 month (p = 0.9), 5 (IQR 7) at 6 months (p = 0.9), and 6 (IQR 5) at 12 months (p = 0.5) in the non-delirium group. Conclusion Delirium may not have a significant effect on the development of anxiety or depression after stroke which differs in its effect on cognitive function and functional status.

Vast changes have occurred in China in the last five years since the decision of the Chinese Government to reform its health system. Many district and community hospitals in the city have been converted into community health centers. The hospital-based doctors who used to work in these centers are being retrained to become general practitioners (GPs). The reform had encountered many problems. The community has not embraced the concept of general practice readily. Lack of fair remuneration and lack of recognition of the importance of the reform by bureaucrats of local government are other problems encountered. The Ministry of Health meanwhile has also introduced a system of retraining hospital-based doctors to become GPs. A medical education curriculum for GPs has been developed. A nationwide network of GP training centers is progressively being formed. The GP training program has also extended to undergraduate medical students. Despite the progress made, many difficulties remained especially in regional areas. The speed and quality of GP training in wealthy, developed places is better than poorer regional areas. The issuing of national license and registration examinations for GPs has not been synchronized with GP training, leading to uneven standard of GP practice. Staff morale is also poor due to the lack of chance for promotion and professional development. Although a number of strategies have been proposed to improve the situation, problems are enormous that China may welcome international collaboration.

Background The most effective and efficient model for providing organized stroke care remains uncertain. This study aimed to compare the effect of two models in a randomized controlled trial. Methods Patients with acute stroke were randomized on day one of admission to combined, co-located acute/rehabilitation stroke care or traditionally separated acute/rehabilitation stroke care. Outcomes measured at baseline and 90 days post-discharge included functional independence measure, length of hospital stay, and functional independence measure efficiency (change in functional independence measure score ÷ total length of hospital stay). Results Among 41 patients randomized, 20 were allocated co-located acute/rehabilitation stroke care and 21 traditionally separated acute/rehabilitation stroke care. Baseline measurements showed no significant difference. There was no significant difference in functional independence measure scores between the two groups at discharge and again at 90 days postdischarge (co-located acute/rehabilitation stroke care: 103·6 ± 22·2 vs. traditionally separated acute/rehabilitation stroke care: 99·5 ± 27·7; P = 0·77 at discharge; co-located acute/rehabilitation stroke care: 109·5 ± 21·7 vs. traditionally separated acute/rehabilitation stroke care: 104·4 ± 27·9; P= 0·8875 at 90 days post-discharge). Total length of hospital stay was 5·28 days less in co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (24·15 ± 3·18 vs. 29·42 ± 4·5, P = 0·35). There was significant improvement in functional independence measure efficiency score among participants assigned to co-located acute/rehabilitation stroke care compared with traditionally separated acute/rehabilitation stroke care (co-located acute/rehabilitation stroke care: median 1·60, interquartile range: 0·87–2·81; traditionally separated acute/rehabilitation stroke care: median 0·82, interquartile range: 0·27–1·57, P = 0·0393). Linear regression analysis revealed a high inverse correlation ( R2 = 0·89) between functional independence measure efficiency and time spent in the acute stroke unit. Conclusion This proof-of-concept study has shown that co-located acute/rehabilitation stroke care was just as effective as traditionally separated acute/rehabilitation stroke care as reflected in functional independence measure scores, but significantly more efficient as shown in greater functional independence measure efficiency. Co-located acute/rehabilitation stroke care has potential for significantly improved hospital bed utilization with no patient disadvantage.

Parkinson's disease (PD) is a multicentred neurodegenerative disorder characterised by the accumulation and aggregation of alpha-synuclein (α-syn) in several parts of the central nervous system. However, it is well established that PD can generate symptoms of constipation and other gastrointestinal problems and α-syn containing lesions have been identified in intestinal nerve cells. In this study, we show that α-syn can be taken up and accumulate in primary human foetal enteric neurons from the gastrointestinal tract and can be transferred between foetal enteric neurons. Impaired proteosomal/lysosomal degradation can promote the uptake and accumulation of α-syn in enteric neurons. Enteric neurons exposed to α-syn can also lead to impaired mitochondrial complex I activity, reduced mitochondrial function, and NAD(+) depletion culminating in cell death via energy restriction. These findings demonstrate neuron-to-neuron transmission of α-syn in enteric neurons, providing renewed evidence for Braak's hypothesis and the aetiology of PD.

Falls are a significant cause of morbidity and mortality in older people. There is an increased frequency of falls in older adults with cognitive impairment and dementia which may be due to impaired judgement of self capability to mobilise safely. This case control study assessed 53 Aged Care subjects aged 75+ years that were hospitalised post fall, from January 2008–December 2009, and compared these subjects’ responses to those of 26 non-fallers to a standard question: ‘While you are in the hospital, what would you do if you need to go to the toilet later?’ This hypothetical scenario question was designed to assess judgement based on self-toileting behaviour and mobility. The study group and control group were similar in age (83.9 ± 4.7 vs. 82.0 ± 4.6 years respectively, p = 0.081) but the study group had statistically lower MMSE results when compared to controls (median 23 vs. 26.5 respectively, p = 0.031). Impaired judgement, defined as an unsafe/inappropriate response to the scenario question, was significantly more prevalent in the study group (fallers) compared to the control group (non-fallers) (41.5 vs. 15.4 %, p = 0.020). Impaired judgement was also more common with lower MMSE scores with 80.9 % of unsafe/inappropriate responses given by participants with MMSE of ≤20. The authors suggest there may be an association between impaired judgement, evidenced by responses to a standardised question, and falls history in older subjects, particularly in those with cognitive impairment or dementia. Ultimately, this may lead to identification of people at increased risk of falls and possibly effective falls prevention strategies in this population.

Discovering genes following Medelian inheritance, such as autosomal dominant-synuclein and leucine-rich repeat kinase 2 gene, or autosomal recessive Parkin, P-TEN-induced putative kinase 1 gene and Daisuke-Junko 1 gene, has provided great insights into the pathogenesis of Parkinson’s disease (PD). Genes found to be associated with PD through investigating genetic polymorphisms or via the whole genome association studies suggest that such genes could also contribute to an increased risk of PD in the general population. Some environmental factors have been found to be associated with genetic factors in at-risk patients, further implicating the role of gene-environment interactions in sporadic PD. There may be confusion for clinicians facing rapid progresses of genetic understanding in PD. After a brief review of PD genetics, we will discuss the insight of new genetic discoveries to clinicians, the implications of ethnic differences in PD genetics and the role of genetic testing for general clinicians managing PD patients.

Vascular dementia (VaD) describes a combination of both cognitive and behavioural manifestations associated with variable brain lesions of vascular origin. While vascular risk factors have been implicated in VaD, the relationship is most evident when the factors are considered together and not individually. This review will examine the significance of the integrity of blood brain barrier (BBB) tight junction (TJ) proteins - occludin and claudins in the pathophysiology of VaD. Specifically, some of the genetic contributors to VaD, namely those responsible for the integrity of the BBB, will be reviewed in detail. Moreover, environmental factors will be considered in conjunction with these genes to examine how the interaction of environmental and genetic factors contributes to one's susceptibility to VaD.

Increasing evidence suggests an important role of alpha-synuclein (α-Syn) in the pathogenesis of Parkinson's disease (PD). The inter-neuronal spread of α-Syn via exocytosis and endocytosis has been proposed as an explanation for the neuropathological findings of PD in sub-clinical and clinical phases. Therefore, interfering the uptake of α-Syn by neurons may be an important step in slowing or modifying the propagation of the disease. The purposes of our study were to investigate if the uptake of α-Syn fibrils can be specifically interfered with monomeric β-Amyloid1-40 (Aβ40) and to characterise the core acting site of interference. Using a radioisotope-labelled uptake assay, we found an 80 % uptake reduction of α-Syn fibrils in neurons interfered with monomeric Aβ40, but not β-Amyloid1-42 (Aβ42) as compared to controls. This finding was further confirmed by enzyme-linked immunosorbent assay (ELISA) with α-Syn uptake reduced from about 80 % (Aβ42) to about 20 % (Aβ40) relative to controls. To define the region of Aβ40 peptide capable of the interference, we explored shorter peptides with less amino acid residues from both the C-terminus and N-terminus. We found that the interference effect was preserved if amino acid residue was trimmed to position 11 (from N-terminus) and 36 (from C-terminus), but dropped off significantly if residues were trimmed beyond these positions. We therefore deduced that the "core acting site" lies between amino acid residue positions 12-36. These findings suggest α-Syn uptake can be interfered with monomeric Aβ40 and that the core acting site of interference might lie between amino acid residue positions 12-36.

In this study, we aimed to determine the factors associated with recurrent falls in aged-care inpatients at a tertiary hospital, with a focus on the cognitive domains of recurrent fallers. We retrospectively examined the characteristics of 70 aged-care inpatients who sustained ≥ 2 falls; 269 patients who sustained 1 fall; and 69 non-fallers during their hospital admission. We also analyzed the available Mini-Mental State Examination (MMSE) scores and sub-scores of 37 recurrent fallers, 163 single fallers, and 37 non-fallers. The independent risk factors for recurrent falls were a history of dementia, stroke, or atrial fibrillation; and patients' hospital length of stay5 weeks. Protective factors were the patients' ability to speak English and a history of depression. Recurrent fallers had significantly lower MMSE scores than single fallers and non-fallers (17.3 ± 6.7, 20.2 ± 6.2, 24.0 ± 5.1, respectively, p0.01); and a larger proportion of recurrent fallers had MMSE18 than in the other two groups (54.1%, 34.4% and 10.8%, respectively, p0.01). In addition, patients with recurrent falls were more likely to have significantly lower scores in the 'registration', 'attention and calculation', 'recall' and 'praxis' domains of the MMSE than single fallers. The findings from this study suggest that cognitive impairment particularly affecting short-term memory, recall and visuospatial perception may contribute to recurrent falls in the inpatient population. Prospective studies to elucidate a causal relationship may be worthwhile.

The vulnerability of older people to serious underlying medical illness and adverse effects of psychotropics means that the safe and effective treatment of severe agitation can be lifesaving, the primary management goals being to create a safe environment for the patient and others, and to facilitate assessment and treatment. We review the literature on acute sedation and provide practical guidelines for the management of this problem addressing a range of issues, including aetiology, assessment, pharmacological and non-pharmacological strategies, restraint and consent. The assessment of the agitated older patient must include concurrent assessment of the likely aetiology of, the risks posed by, and the risks/benefits of management options for, the agitation. A range of environmental modifications and non-pharmacological strategies might be implemented to maximize the safety of the patient and others. Physical restraints should only be considered after appropriate assessment and trial of alternative management and if the risk of restraint is less than the risk of the behaviour. Limited evidence supports a range of pharmacological options from traditional antipsychotics to atypical antipsychotics and benzodiazepines. It is advised to start low and go slow, using small increments of dose increase. Medical staff are frequently called to sedate agitated older patients in hospital settings, often after hours, with limited access to relevant medical information and history. Safe and effective management necessitates adequate assessment of the aetiology of the agitation, exhausting all non-pharmacological strategies, and resorting to pharmacological and/or physical restraint only when necessary, judiciously and for a short-term period, with frequent review and the obtaining of consent as soon as possible.

Whiting R, Shen Q, Hung WT, Cordato D, Chan DKY. Predictors for 5-year survival in a prospective cohort of elderly stroke patients. Acta Neurol Scand: 2011: 124: 309–316. © 2011 John Wiley & Sons A/S. Objectives – To examine predictors for 5-year survival in elderly stroke patients. Materials and Methods – Prospective cohort study of 186 consecutive acute stroke patients aged ≥65 years admitted to Bankstown-Lidcombe Hospital, Australia 03/2002 to 03/2003. All subjects were followed up in 2007/8, at 5 years post-stroke, for outcome measures. Logistic regression analysis was performed to predict 5-year survival using covariables, including functional status, age, stroke type and severity and vascular risk factors. Patients lost to follow-up (n = 20) were excluded from the analyses. Results – One hundred patients (60%) were dead at study end. Predictors for survival in final logistic regression model were as follows: Glasgow Coma Scale (GCS) on admission (OR 1.49, 95%CI 1.1–2.0, P = 0.01), preadmission functional independence measure (FIM) score (OR 1.04, 95%CI 1.0–1.1, P = 0.01), age (OR 0.93, 95%CI 0.87–0.98, P = 0.01) and atrial fibrillation (OR 0.43, 95% CI 0.19–0.95, P = 0.04). For 5-year survivors, mean Modified Rankin Scale was 3.1 ± 1.5, total FIM score 85 ± 32, mini-mental state examination (MMSE) 22 ± 8 and Hospital Anxiety and Depression (HAD) scores 5.4 ± 3.4 and 5.2 ± 3.9, respectively. FIM cognition score was significantly lower at 5 years when compared to baseline (24 ± 8 vs 29 ± 8, P

SummaryOR 0.790.980.870.830.750.330.51 0.8 0.2 0.4 0.6 0.8 1 1.2 Study A-Z trial (4)PROVE-IT (5)IDEAL (6)SPARCL (7)TNT (8)SAGE (9)JUPITER (10) SummaryOR 0.880.860.770.590.790.720.53 0.74 0.5 0.6 0.7 0.8 0.9 1 Study A-Z trial (4)PROVE-IT (5)IDEAL (6)SPARCL (7)TNT (8)SAGE (9)JUPITER (10) SummaryOR 0.740.780.980.790.790.390.83 0.84 0.2 0.4 0.6 0.8 1 1.2 Liver enzyme elevation Treatment discontinuation due to side effects Study A-Z trial (4)PROVE-IT (5)IDEAL (6)TNT (8)SAGE (9)JUPITER (10)Summary OR 1.190.892.431.390.840.981.2 1 1.5 2 2.5 Study A-Z trial (4)PROVE-IT (5)IDEAL (6)TNT (8)SAGE (9)JUPITER (10)Summary OR 2.4 3.0 8.8 6.819.8 1.44 51015 2025 AB C Stroke events DEFigure 2. Odds ratios for statin treatment effects and safety. (A) Stroke events, (B) Major coronary events, (C) Cardiovascu-lar ⁄coronary heart deaths, (D) Liver enzyme elevation, and (E) Treatment discontinuation because of side effects. Table 3 Meta-analysis of safety data on statin treatmentStudyLiver enzyme elevation* Treatment discontinuation due to side effectsLess Intensive Intensive Odds Ratios(95% confidenceintervals)Less Intensive Intensive Odds Ratios(95% confidenceintervals)Events (%) Events (%) Events (%) Events (%)A-Z trial (4) 8 (0.4) 19 (0.8) 2.35 (1.03–5.38) 34 (1.5) 41 (1.8) 1.19 (0.75–1.88)PROVE-IT (5) 23 (1.1) 69 (3.3) 3.01 (1.87–4.85) 681 (33.0) 638 (30.4) 0.89 (0.78–1.01)IDEAL (6) 7 (0.2) 61 (1.4) 8.84 (4.04–19.35) 186 (4.2) 426 (9.6) 2.43 (2.04–2.91)SPARCL (7) NA NA NA NA NA NATNT (8) 9 (0.2) 60 (1.2) 6.75 (3.35–13.62) 265 (5.3) 360 (7.2) 1.39 (1.18–1.64)SAGE (9) 1 (0.2) 19 (4.3) 19.76 (2.63–148.23) 103 (23.1) 90 (20.2) 0.84 (0.61–1.16)JUPITER (10) 17 (0.2) 23 (0.3) 1.35 (0.72–2.54) 1377 (15.5) 1352 (15.2) 0.98 (0.90–1.06)ALL studies included 65 (0.1) 251 (0.5) 3.96 (2.08–7.53) 2646 (3.8) 2907 (6.3) 1.20 (0.88–1.64)Exclude JUPITER 48 (0.1) 228 (0.8) 4.96 (2.73–9.01) 1269 (3.0) 1555 (5.5) 1.25 (0.82–1.92)Exclude SPARCL and JUPITER NA NA*Defined by an elevation in AST or ALT levels of more than three times upper limit of reference range.

This first edition of “Aging Medicine” marks the birth of a new journal in the field of Geriatrics and Gerontology. It serves as a timely reminder to focus on research opportunities in this field, shedding light on where research effort is best directed. Clinicians often need to make adjustments when applying investigative or study results to older patients because many investigative results of older patients vary from the general population and many therapeutic studies exclude older patients for a variety of reasons. For instance, it is well known that antinuclear antibody (ANA) is a sensitive test for rheumatological conditions such as systemic lupus erythematosus. Therefore, many clinicians and laboratories would proceed with testing extractable nuclear antigen (ENA) when ANA is positive. However, in many older persons, ANA is modestly increased and may not necessarily reflect a disease process and so automatic request for ENA is unjustified. Furthermore, many older patients have multiple medical comorbidities and such patients are usually excluded from therapeutic trials. Therefore, when considering treatments, clinicians would often have to weigh up the benefits—especially if the benefit is only found in the longer term—against the side effects that treatments may bring in the shorter term. This is because many older patients’ life expectancy is limited by their medical comorbidities and may not survive to enjoy the long‐term benefits if treated. Such complex considerations may not be required in the younger population without medical comorbidities. Hence, the guidelines of treatments found in the literature are not always generalizable to our older population.

An increasing body of research suggests that a number of immune mechanisms play a role in degenerative pathways in Parkinson's disease (PD). In the current work we investigated a posited humoral immune response in this disorder. Sera from PD patients exhibited a significantly enhanced absorbance response on a novel ELISA for anti-melanin antibodies, compared to sera from age-matched control subjects. The enhanced ELISA absorbance response was specific for catecholamine-based melanins and was unrelated to antiparkinsonian dopaminergic medication. Further, the absorbance response was significantly and negatively correlated with disease duration. These data suggest that a specific humoral anti-melanin antibody response is present in PD and is more active in early disease. While the contribution of this novel immune response to the initiation and progression of this disorder is unclear, this finding supports the hypothesis that specific immune responses occurring in PD may respond to therapeutic interventions in this disorder.

STUDY OBJECTIVE - Nested case-control study aimed to assess the quality of life of community dwelling participants aged 65 years or over with newly diagnosed Essential Tremor (ET). METHODS AND RESULTS - Thirty-two participants with newly diagnosed ET and 32 age and gender matched controls were administered the Rand-SF36 quality of life questionnaire. Medical co-morbidities were also assessed in the two groups. Results - Participants with ET had significantly lower scores in the physical function, role limitation because of physical function, role limitation as a result of emotional problem, pain, and energy/vitality subscales of the Rand-SF36 when compared with controls. CONCLUSIONS - Older patients with newly diagnosed ET have poorer quality of life than their community dwelling counterparts without ET.

Summary Objective To review the severe acute respiratory syndrome (SARS) epidemic in Beijing using basic epidemiological principles omitted from the original analysis. Study design Analysis of Prospective surveillance data for Beijing collected during the outbreak. Methods Surveillance data were reclassified according to World Health Organization criteria. Cases previously excluded without date of onset of illness were included in the epidemic curve from estimates using the average time between date of onset and date of hospitalization for cases with both dates. Cases who failed to give a contact history were now included; 7% ( n = 5 ) of cases during the import phase and 61% ( n = 365 ) during the peak phase. Previously excluded cases were included for plotting on an epidemic curve, and basic spot mapping for distribution of cases was used from attack rates recalculated for age, gender, occupation, residential location, date of onset of illness and demographics. Results The spot map effectively illustrated clusters by residency, with the inner-city sustaining the highest attack rate (33.42 per 100,000), followed by an easterly distribution 5–30 km away (21.62 per 10,000), and lowest in districts 60–160 km away (9.21 per 100,000). The new epidemic curve shows the outbreak commencing 10 days earlier than initially reported, with a three-fold greater increase in cases during the escalation phase than previously estimated. Conclusion In hindsight, the investigation of the Beijing SARS would have benefited from the use of spot maping as an essential outbreak tool for early identification of specific geographical area(s) for quarantining. If a spot map of incidence density rates was used during the early phase of the outbreak, the inner city might have been identified as a major risk factor requiring rapid quarantining. Contact history became uncommon as the outbreak progressed, suggesting that hospitals were over-burdened or pathogenesis and environment risk factors changed, strengthening the usefulness of early spot mapping and the need to modify risk factors included as contact history as the epidemic progresses.

Mutations in the parkin gene are the major cause of autosomal recessive early-onset forms of Parkinson's disease (PD). As reduced parkin expression might also affect the clinical course of idiopathic PD we investigated the effect of a low expressing allele in the parkin promoter region on the age at disease onset (AAO). Patients with PD (n=175) fulfilling standard diagnostic criteria were recruited by experienced neurologists at two movement disorders clinics in Sydney and Brisbane, Australia. DNA was extracted from whole blood and the -258 T/G polymorphism genotyped using PCR/RFLP. AAO effects were analysed using univariate ANOVA, binomial logistic regression modelling and Kaplan-Meier survival analysis. Subjects with the GG genotype (n=10, mean AAO=46.2+/-11.5 (S.D.) years) had a significantly lower mean AAO compared to the common TT genotype (n=104, mean AAO=56.1+/-12.7, p=0.02). There was no difference in mean AAO between the TT and TG individuals (n=61, mean AAO=55.3+/-11.6). Stratifying the sample by median AAO (55 years) revealed that the GG genotype was over-represented in the early-onset group (n=9, OR=18.6, 95% CI=1.41-245.3, p=0.03). We speculate that reduced expression of normal parkin protein may result in an early manifestation of PD symptoms.

Falls are a common problem in the elderly. A common error in their management is that injury from the fall is treated, without finding its cause. Thus a proactive approach is important to screen for the likelihood of fall in the elderly. Fall assessment usually includes a focused history and a targeted examination. Timed up-and-go test can be performed quickly and is able to predict the likelihood of fall. Evidence-based fall prevention interventions include multi-component group or home-based exercises, participation in Tai Chi, environmental modifications, medication review, management of foot and footwear problems, vitamin D supplementation, and management of cardiovascular problems. If possible, these are best implemented in the form of multifactorial intervention. Bone health enhancement for residential care home residents and appropriate community patients, and prescription of hip protectors for residential care home residents are also recommended. Multifactorial intervention may also be useful in a hospital and residential care home setting. Use of physical restraints is not recommended for fall prevention.

Background: Coagulation disorders are seen in cancer patients, but it is not clear whether cancer predisposes stroke patients to unique characteristics. The aim of the study was to investigate risk factors, pattern,etiology and outcome in stroke patients with cancer. Methods: A retrospective review of all ischemic stroke (IS) patients with cancer (n = 56) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted and comparison made to age- and gender-matched noncancer IS patients admitted to the same hospital during the same period. Results: Vascular risk factors and stroke pattern were comparable in cancer and noncancer groups. Poststroke thrombotic episodes (myocardial infarction, deep vein thrombosis or pulmonary emboli) were more common in the cancer group than in the noncancer group (11 vs. 0%, p = 0.031). Depression was also more common in the cancer group than in the noncancer group (14 vs. 2%, p = 0.039). There was a tendency for more patients in the cancer group to die in hospital (30 vs. 14%, p = 0.078). Conclusions: Coagulation disorders were more likely to be seen in stroke cancer patients, and patients with cancer tended to have a higher in-hospital poststroke mortality. Larger sample size studies may identify further differences in the characteristics of stroke patients with cancer.

Objective – To investigate risk factors, stroke pattern and outcome in stroke patients with cancer. Methods – A retrospective review of all stroke patients with cancer (n = 69) admitted to Bankstown-Lidcombe Hospital, Sydney, Australia, between January 1999 and December 2004 was conducted, and comparison made to age- and gender-matched non-cancer stroke patients admitted to the same hospital during the same period. Results – Vascular risk factors did not significantly differ between cancer and non-cancer groups. There was a trend towards greater risk of intracerebral haemorrhage in the cancer group vs the non-cancer group. Previous deep vein thrombosis was more common, and prothrombin time and activated partial thromboplastin time were prolonged in the cancer group vs the non-cancer group. More patients died in hospital in the cancer group vs the non-cancer group. Conclusions – Coagulation disorders are more likely to be seen in stroke patients with cancer, and patients with cancer have a higher in-hospital post-stroke mortality.

OBJECTIVES: To evaluate the incidence of stroke, riskfactors for stroke, and outcomes in elderly stroke patientswith delirium.DESIGN: Cohort study with 12-month follow-up.SETTING: Bankstown-Lidcombe Hospital, a 450-bedteaching hospital of the University of New South Wales,Sydney, Australia.PARTICIPANTS: One hundred fifty-six stroke patientsaged 65 and older recruited over 1 year.MEASUREMENTS: Incidence of delirium (defined in ac-cordance with Diagnostic and Statistical Manual of MentalDisorders, Fourth Edition, criteria) within 3 days post-stroke, length of hospital stay, discharge destination, short-andlong-termmortality,FunctionalIndependenceMeasure(FIM)scores,andMini-MentalStateExamination(MMSE)scores.RESULTS: Thirty-nine (25%) elderly stroke patients haddelirium within 3 days after stroke. Logistic regressionanalysis found that older age (P5.04), hemorrhagic stroke(P5.02), metabolic disorders (P5.003), dementia pre-stroke(P5.02),GlasgowComaScale(GCS)scorelessthan15 on admission (Po.001), and inability to lift both armson admission (P5.03) were independent predisposing fac-tors for delirium. Patients who had a cardioembolic stroke(odds ratio (OR)55.58) or total anterior circulation in-farction (OR53.42) were also more likely to develop de-lirium. Patients with delirium were associated with higher6- and 12-month mortality (Po.05), lower 12-month FIMand MMSE scores, and a higher 12-month institutionali-zation rate.CONCLUSION: Delirium occurred frequently in acutestroke patients aged 65 and older. Factors independentlyassociated with delirium included old age, intracerebralhemorrhage, metabolic factors, prestroke dementia, initialGCS less than 15, and inability to lift both arms onadmission. Patients with delirium had higher long-termmortality and a worse functional outcome. J Am GeriatrSoc 54:1192–1198, 2006.Key words: stroke; delirium; incidence; risk factor; mor-tality

To improve elderly patients' understanding and safe usage of their medications. English-speaking hospital inpatients aged > or =65 years were recruited. They were self-medicating at home with at least 1 regular medication and had a Mini-Mental State Examination (MMSE) score of at least 20 out of 30. The patients were taught medication details on 3 consecutive days. The patients' medication knowledge was recorded before education and again at a home visit after discharge from hospital. Patient medication knowledge before education showed that participants knew 50% of brand names, dosage and times, 55% of medication purpose, and 15% of major side effects. At follow-up home visits, the relevant figures improved significantly to 90%, 85%, and 25%, respectively (P < or = .05). Similar improvement occurred in the 2 patient groups with an MMSE score of 20 to 24 and 25 to 30 (P = .03). This simple, practical, nursing-staff-conducted program worked well in a hospital setting and resulted in improved medication knowledge, even in patients with mild cognitive impairment.