Macrophage- and Microglia-Related Chemokines Are Associated with Small Vessel (White Matter) Vascular Dementia: A Case-Control Study.

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-1ß) 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-1ß 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.

COVID-19 in aged care homes: a comparison of effects initial government policies had in the UK (primarily focussing on England) and Australia during the first wave.

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.

Re-pigmentation of hair after prolonged cholinesterase inhibitor therapy in a Chinese population.

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).

Staff awareness of the application of Mental Health and Guardianship Legislation in the care of hospitalised older persons.

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.

The association between dietary patterns, plasma lipid profiles, and inflammatory potential in a vascular dementia cohort.

Background: Inflammation and altered lipid dyshomeostasis have been implicated in the pathogenesis of Alzheimer's disease and vascular dementia. Objective: To determine if there are any associations between dietary patterns, plasma lipid profiles, and inflammatory potential in a vascular dementia cohort. Methods: One hundred fifty participants (36 subjects with Vascular Dementia and 114 healthy controls) from two Australian teaching hospitals completed a cross-sectional survey examining their dietary and lifestyle patterns. Each participant's diet was further evaluated using the Empirical Dietary Inflammatory Index. Some participants also donated blood samples for lipidomic analysis. Results: After adjusting for age, education, and socioeconomic status, participants with vascular dementia tend to have higher lipid profiles, do less exercise, and engage less frequently in social interaction, educational, or reading activities. They also tend to consume more deep-fried food and full-fat dairy compared to control subjects. However, there was no difference in Empirical Dietary Inflammatory Index between the two groups after adjusting for age, education, and socioeconomic status. Conclusion: Our findings suggest a graded inverse association between healthy lifestyle factors and vascular dementia.

Developing a self-reported tool on fall risk based on toileting responses on in-hospital falls.

The aim of this cohort study was to determine the predictive value of a 2-item self-reported questionnaire regarding in-hospital toileting behavior for predicting falls in older inpatients and to compare its performance with an existing state-based falls assessment scale. Between May 28, 2009 and January 30, 2010, we assessed aged care inpatients for risk of falls using the standard STRATIFY fall screening tool and the 2-item self-reported questionnaire developed for this study. The participants were then followed up, with the primary outcome being the occurrence of falls. Results indicated that participants who were unable to answer the 2-item questionnaire appropriately or sensibly were 14.1 times (confidence interval [CI]: 4.4-45, p <. 001) to 17.0 times (CI: 6.7-43, p < .001) more likely to fall than those who gave an appropriate negative or positive answer. Participants who were assessed to be at high risk of falls on the STRATIFY scale were 9.5 times (odds ratio: 9.5, CI: 1.3-72, p = .03) more likely to fall than those who were low risk. In conclusion, a simple bedside questionnaire regarding patients' toileting behavior with a careful appraisal of answers for appropriate and inappropriate answers may be used as a quick screening tool of fall risk.

A pilot randomized controlled trial of WeiNaoKang (SaiLuoTong) in treating vascular dementia.

Objective: WeiNaoKang (or SaiLuoTong) is an herbal formula consisting of ginkgo, ginseng, and saffron. Our objective was to investigate if WeiNaoKang could improve cognitive function and cerebral perfusion in patients suffering from vascular dementia. Methods: A 16-week randomized double-blind, placebo-controlled trial was carried out in the setting of a memory disorder clinic at a single center. Patients with vascular dementia diagnosed clinically but supported by imaging and other investigations were invited to participate. The diagnoses were based on the National Institute of Neurological Disorders and Stroke/Association Internationale pour la Recherche et l'Enseignement en Neurosciences (NINDS-AIREN) criteria. An independent blinded assessor evaluated the effects of the formula. Intervention group was compared to the control group. A subgroup of participants was randomly chosen for further evaluation of cerebral perfusion by single photon emission computed tomography scans post-treatment. Results: Both groups were comparable in age (mean = 74 ± 7.2 years in the placebo group and 75 ± 7.4 in the intervention group) and in other demographics. Sixty-two participants were included in final analysis. Alzheimer's Disease Assessment Scale - Cognitive Portion (ADAS-cog) was the primary outcome. By week 16, the mean ADAS-cog reduced from 24.48 to 20.30 (mean reduction = 4.18) for those in the treatment group, and from 18.98 to 17.81 (mean reduction = 1.18) for those in the placebo group. The difference in mean reduction of ADAS-cog was -3.00 (95% confidence interval [CI] = -4.910 to -1.100) in favor of the treatment group. Secondary outcomes of activities of daily living and quality of life measures also showed significant difference. In the perfusion scan analysis, the difference in the change in cerebral blood flow (t-scores) pre- and post-treatment between the intervention group (n = 7) and the placebo group (n = 11) was statistically significant (P < 0.001). Conclusion: In this randomized, double-blind placebo-controlled trial, we demonstrated significant differences in improvement in cognitive function and activities of daily living. The clinical improvement is corroborated with improvement in cerebral perfusion in a subset of participants.

Plasma biomarkers inclusive of α-synuclein/amyloid-beta40 ratio strongly correlate with Mini-Mental State Examination score in Parkinson's disease and predict cognitive impairment.

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/Aß40 and anti-α-synuclein/Aß40 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/Aß40 were positively associated with MMSE score, and anti-α-synuclein, α-synuclein/Aß40 were negatively associated with the MMSE score among PD patients (all Ps < 0.005). In the AUROC analysis, anti-α-synuclein (AUROC = 0.788) and anti-α-synuclein/Aß40 (AUROC = 0.749) were significant individual predictors of cognitive impairment. In multivariate logistic regression, full model of combined biomarkers showed high accuracy in predicting cognitive impairment (AUROC = 0.890; 95%CI 0.796-0.984) for PD versus controls, as was parsimonious model (AUROC = 0.866; 95%CI 0.764-0.968). In conclusion, simple combination of biomarkers inclusive of α-synuclein/Aß40 strongly correlates with MMSE score in PD patients versus controls and is highly predictive of cognitive impairment.

Digital care technologies in people with dementia living in long-term care facilities to prevent falls and manage behavioural and psychological symptoms of dementia: a systematic review.

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. Supplementary Information: The online version contains supplementary material available at 10.1007/s10433-021-00627-5.

Strong Predictive Algorithm of Pathogenesis-Based Biomarkers Improves Parkinson's Disease Diagnosis.

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 (Aß40) 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 Aß40 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/Aß40=0.737, and α-synuclein/Aß40=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/Aß40 or anti-α-synuclein/Aß40 (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 Aß40 showed promising sensitivity and specificity.

Precision medicine and clinical relevance in older people.

Precision medicine and clinical relevance in older people.

Effectiveness and analysis of factors predictive of discharge to home in a 4-year cohort in a residential transitional care unit.

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.

Mini-review on initiatives to interfere with the propagation and clearance of alpha-synuclein in Parkinson's disease.

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.

Delirium post-stroke: short- to long-term effect on anxiety and depression compared to effect on cognition.

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.

Paraoxonase 1 gene Q192R polymorphism affects stroke and myocardial infarction risk.

OBJECTIVES: Paraoxonase (PON1), an enzyme associated with high-density lipoprotein (HDL) particles, inhibits oxidation and atherogenesis. We sought to investigate the association of the PON1 Q192R polymorphism with stroke and heart disease. DESIGN AND METHODS: In a case control study, we genotyped 242 ischemic stroke, 231 myocardial infarction (MI), and 310 healthy control subjects, all Chinese. RESULTS: R-containing genotypes (R+) were associated with vascular disease, OR = 1.5, P = 0.03. RR was increased in MI patients who were either smokers (OR = 3.1, P = 0.01), male, or younger than 60. R+ but not RR genotypes were increased in stroke patients, particularly large artery type (OR = 2.6 and P = 0.02 for R+, OR = 1.0 for RR) or among smokers. The relative dearth of RR in stroke might be due to earlier MI or death in at-risk people, such as smokers. R+ genotypes were increased with stroke in hypertensive (OR = 2.1, P = 0.02) but not normotensive (OR = 1.0) subjects. CONCLUSIONS: PON1 192R+ genotypes were associated with stroke and MI, particularly in subsets of patients, in patterns suggesting a possible survivor effect.

Effect of MDR1 haplotype on risk of Parkinson disease.

BACKGROUND: MDR1, a multidrug transporter, encodes a P-glycoprotein that regulates the bioavailability of xenobiotics and is highly expressed at the blood-brain-barrier. Two single nucleotide polymorphisms (SNPs) (e21/2677[G/T/A] and e26/3435[C/T]) in the MDR1 gene can lead to differences in MDR1 expression and function. Specific MDR1 alleles of the 2 SNPs are positively selected among ethnic Chinese but not in the white population. OBJECTIVE: To determine whether specific haplotypes formed by SNPs e21/2677 and e26/3435 may protect against Parkinson disease (PD) among ethnic Chinese in Hong Kong. DESIGN: Case-control study. SETTING: Tertiary referral centers in Hong Kong. SUBJECTS: One hundred eighty-five patients with PD and 206 control subjects. INTERVENTIONS: The two SNPs were amplified in a single multiplex polymerase chain reaction. Five other SNPs that span 100 kilobases of the gene were also analyzed. MAIN OUTCOME MEASURES: Haplotypes frequencies, degree of haplotype association with the disease status, and estimated odds ratio for each haplotype with associated 95% confidence intervals. RESULTS: In addition to 2677 G-->T/A (exon 21) and 3435 C-->T (exon 26), the other SNPs that were analyzed were -41 A-->G (intron -1), -145 C-->G (exon 1), -129 T-->C (exon 1), 1236 T-->C (exon 12), and 4036 A-->G (exon 28). Haplotypes containing SNPs e21/2677 and e26/3435 were found to be significantly associated with risk of PD. In particular, the 2677T-3435T haplotype was strongly associated with a reduced risk of PD (P<.001; chi(2) = 14.521; odds ratio, 0.33; 95% confidence interval, 0.19-0.59). CONCLUSIONS: An MDR1 haplotype containing SNPs e21/2677T and e26/3435T protects against PD in ethnic Chinese, compatible with the observation of a recent positive selection of the T alleles of these 2 SNPs in this ethnic population.