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Background: Family caregivers of people with dementia (FG-of-PWD) suffer from a high level of stress and depressive symptoms, which usually require different interventions at different stages. Although some standalone interventions such as behavioral activation (BA) and mindfulness practice (MP) have been shown to be potentially effective at reducing depressive symptoms, the best sequence and combination of these interventions for caregivers are unknown. This study aims to develop and identify a two-stage adaptive intervention with pre-specified rules guiding whether, how, or when to offer different interventions initially/over time to reduce depressive symptoms in FG-of-PWD. Methods: A sequential multiple assignment randomized trial (SMART) design will be adopted. 272 FG-of-PWD with mild to moderate depressive symptoms will be recruited from the community. Four two-stage embedded adaptive interventions involving behavioral activation and mindfulness practice with different sequences and dosages (e.g., 8 weeks of Behavioral Activation followed by booster sessions for responders, and 8 weeks of mindfulness practice for non-responders) will be assigned to the participants following a set of decision rules. The primary outcomes will be depressive symptoms, assessed after the second stage of the intervention. Other outcomes (e.g., positive aspect of caregiving and sleep quality) and time-points will also be assessed. The analyses will follow the intention-to-treat principle. In addition, several process indicators (e.g. engagement in meaningful activities and level of mindfulness) will also be assessed. Discussion: The traditional RCT design allows for the effectiveness of an intervention to be rigorously tested but provides limited data to develop “treatment strategies” that may involve a number of different interventions, dosages, or components. We propose using the SMART design to provide evidence of which intervention to provide initially, how to determine whether the first stage of the intervention is working or not, and which intervention to provide next if the first stage of the intervention is not working. The findings will have strong implications for the further development of psycho-social adaptive intervention in reducing the depressive symptoms among FC-of-PWD. Trial registration: ClinicalTrials.gov, NCT05634317

BACKGROUND Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterised by later life emergence of persistent neuropsychiatric symptoms. Our previous meta-analysis showed that MBI is prevalent among cognitively normal (CN), subjective cognitive impairment (SCI) and mild cognitive impairment (MCI) subjects. This study is to calculate the pooled prevalence of MBI domains among CN, SCI, and MCI subjects. METHODS A search of relevant literature published between 1 January 2003 and 6 August 2021 was conducted. Meta-analysis using a random effects model and meta-regression was performed. RESULTS Ten studies conducted among 12 067 subjects (9758 CN, 1057 SCI and 1252 MCI) with retrievable MBI domains data underwent meta-analysis, revealing pooled prevalence of affective dysregulation (AFD), impulse dyscontrol (IDS), decreased motivation (DMT), social inappropriateness (SIP) and abnormal perception/thought (APT) of 32.84% (95% CI 24.44-42.5%), 26.67% (95% CI 18.24-37.23%), 12.58% (95% CI 6.93-21.75%), 6.05% (95% CI 3.44-10.42%), and 2.81% (95% CI 1.67-4.69%) respectively. AFD and APT domains demonstrated ordinal increase in pooled prevalence from CN, SCI and MCI subgroups, but meta-regression demonstrated no significant difference in MBI domains prevalence among cognitive subgroups (in contrast to the significant increase in MBI prevalence from CN to SCI to MCI). The pooled prevalence of AFD and IDS are greater than that of DMT, SIP and APT among all cognitive subgroups. Several variables were found to explain the high heterogeneity. CONCLUSIONS AFD and IDS are the two most prevalent MBI domains and remain the same with cognitive deterioration. This finding is potentially relevant to clinical practice.

BACKGROUND AND PURPOSE The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer's disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. METHODS This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50-90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation, treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). RESULTS Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test-Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p

INTRODUCTION: Alzheimer’s disease (AD) and Lewy body dementia (LBD) are two common forms of dementia. There are still controversies regarding whether LBD patients have a worse clinical course than AD patients. METHODS: We retrospectively reviewed all biomarkers that supported AD and LBD patients presenting to the Memory Clinic of Queen Mary Hospital, Hong Kong, between 1 January 2008 and 30 December 2016. Diagnoses of AD and LBD were supported by clinical diagnostic criteria and biomarkers. LBD patients included those with dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD). Baseline demographics, presenting clinical features, degree of cognitive impairment and specified clinical outcomes were compared. RESULTS: We recruited 31 AD and 25 LBD patients (18 DLB, 7 PDD). When measured from disease onset, LBD patients were noted to have shorter overall survival (p = 0.02) with earlier occurrence of falls (p < 0.001), dysphagia (p < 0.001), pneumonia (p = 0.01), pressure injuries (p = 0.003) and institutionalisation (p = 0.03) than AD patients. Cox regression analyses showed that LBD predicted falls (hazard ratio [HR] 5.86, 95% confidence interval [CI] 2.29–15.01, p < 0.001), dysphagia (HR 10.06, 95% CI 2.50–40.44, p = 0.001), pressure injuries (HR 17.39, 95% CI 1.51–200.10, p = 0.02), institutionalisation (HR 2.72, 95% CI 1.12–6.60, p = 0.03) and death (HR 2.96, 95% CI 1.18–7.42, p = 0.02). CONCLUSION: LBD patients had shorter overall survival with earlier occurrence of pre-specified long-term events compared with AD patients. LBD also independently predicted pre-specified long-term events.

Introduction Cognitive impairment is common among patients on peritoneal dialysis (PD). We hypothesize that cognitive impairment has a negative impact on the outcome of patients on PD, especially with regard to peritonitis. Methods This was a single-center 2-year prospective cohort study involving 206 patients at 1 PD unit. Cognitive impairment was defined by the latest Hong Kong Montreal Cognitive Assessment Score (HK-MoCA) multiple cut-offs as determined by age and years of education. Eighty percent of patients had come back for interval HK-MoCA. The HK-MoCA was performed at baseline and after 1 year on PD. Potential risk factors for cognitive impairment and peritonitis were studied separately for the first and second year. Results For cognitive impairment at baseline, multivariate analyses showed that age (odds ratio [OR] 1.003, 95% confidence interval [CI] 1.003 – 1.065, p = 0.03), female sex (OR 3.57, 95% CI 1.60 – 7.97, p = 0.002), peripheral vascular disease (PVD) (OR 3.46, 95% CI 1.33 – 9.01, p = 0.01), and hemoglobin level (OR 0.60, 95% CI 0.43 – 0.84, p = 0.003) were statistically significant factors. For cognitive impairment at 1 year, multivariate analyses showed that age (OR 1.07, 95% CI 1.02 – 1.012, p = 0.007), female sex (OR 5.87, 95% CI 1.86 – 18.5, p = 0.003), and PVD (OR 3.68, 95% CI 1.07 – 12.84, p = 0.04) were statistically significant independent factors for cognitive impairment at 1 year. For self-care PD patients in the second year, patients with cognitive impairment had a higher rate of peritonitis and proportionately more patients suffered from both peritonitis and exit-site infection than non-cognitively impaired patients in the second year (0.50 vs 0.27 episodes per year, p = 0.048; 25% vs 7.2%, p = 0.049). Logistic regression showed that only HK-MoCA-defined cognitive impairment and HK-MoCA scores at 1 year were factors predicting peritonitis (risk ratio [RR] 3.2 [95% CI 1.03 – 9.95], p = 0.04 and RR 0.92 [95% CI 0.86 – 0.995], p = 0.04 respectively). Conclusions In summary, increasing age, female sex, anemia, and presence of PVD are risk factors for cognitive impairment in PD patients. Self-care PD with cognitive impairment at 1 year has a higher risk for PD-related peritonitis in the second year. Interval HK-MoCA assessment is recommended to detect cognitive impairment in our local PD patients.

Background This study investigated the differences in caregiver activity, caregiver burden, and awareness of both caregivers and patients with Alzheimer’s disease (AD) across different Asian locations. Methods This was a secondary analysis of a multi-national cohort study that aimed to assess caregiver activity and caregiver burden using the Caregiver Activity Scale (CAS) and Zarit Burden Interview (ZBI), respectively. Patients’ awareness of their dementia diagnosis was assessed by asking the following yes/no question: “Do you have dementia?” Caregivers’ awareness of the patient’s dementia diagnosis was assessed by asking the following yes/no question: “Does your patient have dementia?” Results In total, 524 caregivers of patients with AD from China, Hong Kong, South Korea, the Philippines, Singapore, Thailand, and Taiwan participated. The CAS and ZBI score were significantly different across most locations (p p = 0.033, respectively). Overall, 56.6% of caregivers and 37.5% of patients had awareness of the dementia diagnosis, and the proportion of patients and caregivers with awareness were also different between each location (all, p Conclusions Caregiving, caregiver burden, and the awareness of caregivers and patients were different across many Asian locations. With understanding of cultural differences, further public education on dementia could help increase the awareness of patients and caregivers and reduce caregiver burden. Trial registration ClinicalTrials.gov, NCT02262975. Registered 13 October 2014

Aim Mild behavioural impairment (MBI) is a neurobehavioural syndrome characterized by emergent neuropsychiatric symptoms in later life. There has been no systematic review or meta-analysis on the prevalence of MBI. The main aim of the study is to calculate the pooled prevalence of MBI. Methods A search of the literature on MBI in mild cognitive impairment (MCI), cognitively normal (CN), and subjective cognitive impairment (SCI) and CN but at risk (CN-AR) subjects published between 1 January 2003 and 28 September 2020 was conducted. Meta-analysis using a random effects model was performed to determine the pooled estimate of the prevalence of MBI. Meta-regression was performed to identify factors contributing to the variance of prevalence rate. A systematic review was also performed to study the impact of MBI in cognitive outcomes and its correlation to the pathology and genetics of Alzheimer's disease. Results Eleven studies conducted among 15 689 subjects underwent meta-analysis, revealing the pooled prevalence of MBI to be 33.5% (95% confidence interval (CI): 22.6%-46.6%). Seven studies conducted among 1358 MCI subjects underwent meta-analysis, revealing the pooled prevalence to be 45.5% (95%CI: 36.1%-55.3%). Four studies conducted among 13 153 CN subjects underwent meta-analysis, revealing the pooled prevalence to be 17.0% (95%CI: 7.2%-34.9%). Five studies conducted among 1158 SCI or CN-AR subjects underwent meta-analysis, revealing the pooled prevalence to be 35.8% (95%CI: 21.4%-53.2%). A systematic review of 13 studies showed that MBI has a significant impact on cognitive deterioration and is associated with the pathology and genetics of Alzheimer's disease. Conclusions In MCI, CN, and SCI and CN-AR subjects, MBI is common. Our finding is potentially useful in planning future clinical trials.

CLU encoding clusterin, has been reported to associate with Alzherimer's disease (AD) by genome-wide association studies (GWAS) based on Caucasian populations. Our previous case-control study has independently confirmed the disease association of CLU in Chinese population. Since little is known about the underlying mechanism of CLU in AD, we have conducted this study to investigate whether the genetic impact of CLU polymorphisms on cognitive functioning is via serum lipid's dysfunction. Three GWAS previously published CLU polymorphisms including rs2279590, rs11136000 and rs9331888, were genotyped in 689 subjects. Serum levels of triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were measured and tested as mediators. Delayed Word Recall Test (DWRT) was used to evaluate subjects' memory performance. Multiple mediation analysis, a nonparametric procedure to create confidence interval, was performed according to Preacher and Hayes's Bootstrapping method. Our findings suggested significant correlation between CLU polymorphism and DWRT scores for rs11136000 (p = 0.045) after adjustment for age, gender, body mass index, and APOEe4 status, with borderline significant correlation for rs2279590 (p = 0.058). Both T allele of rs11136000 and A allele of rs2279590 were negatively correlated with serum TG levels (p = 0.003; p = 0.001, separately). Moreover, A allele of rs2279590 was positively correlated with serum HDL-C levels (p = 0.015). Consistent with our hypotheses, the genetic impact of CLU polymorphisms on memory performance were partially mediated through TG (rs11136000 95% CI [-0.099,-0.003] and rs2279590 95% CI [-0.104, −0.004]), but not through HDL-C and LDL-C. Our findings indicate CLU polymorphisms may modify AD susceptibility through lipid metabolic pathway.

Regarding a sexual difference in the prevalence of Alzheimer disease (AD), it has been found that women are more susceptible to developing this disease, which suggests the important role of sex steroid hormones, especially estrogen depletion during menopause. During the past 20 decades, abundant evidence has accumulated indicating the neuroprotective effects of estrogen on cognition and AD, of which the effects are partially mediated by estrogen receptors (ERs). Although findings from the Women's Health Initiative Memory Study discourages the clinical application of estrogen replacement therapy (ERT), studies based on both Caucasian and Asian populations have shown that polymorphisms in ESR1 encoding ERα and ESR2 encoding ERβ confer AD susceptibility in a gender-specific manner. Continuing exploration of novel polymorphisms in ER genes and biological elucidation of the function of those detected polymorphisms shows promise in developing new ERT in AD.

Aim To study the prevalence and risk factors of delirium and subsyndromal delirium (SSD) in Chinese older adults with acute medical illnesses. Methods A prospective cohort study was carried out in acute general medical wards in a university-affiliated hospital in Hong Kong. Patients were assessed by the confusion assessment method by geriatricians within 6 h after admission and classified into three mutually exclusive groups, namely delirium, SSD and those without both conditions. Predisposing factors and precipitating factors of delirium and SSD were retrieved from collateral information, clinical charts and electronic clinical records. Results A total of 575 patients with mean age of 80.8 years were recruited. A total of 73% of the patients did not have delirium, 15.8% of patients had delirium and 11.3% of patients had SSD. On multivariate analysis, patients with delirium or SSD were more likely to be current users of psychotropic medications, had hearing and visual impairment, had a major neurocognitive disorder as defined by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, and with a lower Barthel Index 20 points version than those without both conditions. Significant predisposing and precipitating factors of delirium included psychotropic medications, acute stroke and other causes of organic brain syndromes. Predisposing and precipitating factors of delirium and SSD were almost identical. Conclusions Delirium and SSD are common among Chinese older adults with acute medical illnesses, with a combined prevalence of delirium and SSD of 27%. Important precipitating and predisposing factors include psychotropic medications, acute ischemic stroke and other causes of organic brain syndromes. Geriatr Gerontol Int 2018; 18: 1625-1628.

Background/aim Occupational therapists and health practitioners commonly provide interventions to family caregivers of people with dementia with the aim of relieving burden, depression, and disruptions in health and social support. To date, the effects of multicomponent interventions specifically targeting these four important outcomes has not been established. The aim of this study was to evaluate the effectiveness of multicomponent interventions on four outcomes for co-residing family caregivers of people with dementia. Methods A comprehensive database search of the literature was performed using CINAHL, MEDLINE, PubMed, PsycINFO, OTseeker, EMBASE and the Cochrane library. Randomised control trials (RCTs) that included multicomponent interventions for co-residing family caregivers addressing burden, depression, health and social support were selected. Relevant articles were critically reviewed and study results were synthesised. Meta-analysis was conducted separately. Results Twenty-two of 358 retrieved studies were selected, with 15 studies being included in the meta-analyses. The multicomponent interventions identified were comprised of a range of different individual strategies. Significant effective results were found for all four specified outcomes. Conclusions Many types of multicomponent interventions appear beneficial on all of the four specified outcomes. The literature presents a trend that multicomponent interventions consisting of a combination of counselling, support groups, education, stress and mood management or telephone support are important strategies within an effective multicomponent intervention.

BACKGROUND Unlike other behavioural and psychological symptoms of dementia, hyperphagia is less recognized among patients with Alzheimer's disease (AD). The prevalence of hyperphagia varies among studies, but there has been no systematic review or meta-analysis. METHODS An extensive search on the literature on hyperphagia in AD published between 1 January 1980 and 30 October 2017 was conducted. Data on the prevalence were retrieved. Meta-analysis with a random effect model was performed to determine the pooled estimate of prevalence. Meta-regression analysis was performed based on study characteristics, population demographics, or condition information. RESULTS Results from 20 studies were extracted. Twenty-six reported cases of hyperphagia were identified. The mean age of onset was 70.7 ± 8.9 years, with a male predominance (68.4%). Hyperphagia occurred in all stages of AD. Only eight studies reported the prevalence of hyperphagia. Meta-analysis showed a pooled prevalence of hyperphagia of 18.6%. Publication bias may have been present. Meta-regression showed that ethnicity accounted for the variance among studies (coefficient: -1.247 (95% confidence interval: -1.978 to -0.516), R2 analogue: 0.77, P

Background Evidence describing the association between high-dose benzodiazepine use and dementia has been conflicting. Most previous studies involved Caucasian populations, with only limited data on Chinese subjects. Possible differences exist between Chinese and Caucasian populations with regard to metabolism and prescription practice. This study aimed to assess the association between high-dose benzodiazepine use and dementia in a Chinese population. Method A retrospective case–control study was carried out in all public hospitals under the Hong Kong Hospital Authority Hong Kong West Cluster between 2000 and 2015. The study recruited 273 Chinese adults (91 cases, 182 controls) aged 75 and over, with at least 6 years of follow-up data. Each dementia case was matched with two controls according to sex, age group, and duration of follow-up. The number of patients with benzodiazepine ever-use and the exposure density based on the prescribed daily doses were assessed. Prescribed daily doses were categorized as either

Objectives To investigate whether genetic variations on the estrogen metabolic pathway would be associated with risk of Alzheimer's disease (AD). Design Cross-sectional study. Setting Individuals were recruited at the Memory Clinic, Queen Mary Hospital, Hong Kong. Participants Chinese individuals with (n = 426) and without (n = 350) AD. Measurements All subjects underwent a standardized cognitive assessment and genotyping of four candidate genes on the estrogen metabolic pathway (estrogen receptor α gene (ESR1), estrogen receptor β gene (ESR2), cytochrome P450 19A1 gene (CYP19A1), cytochrome P450 11A1 gene (CYP11A1)). Results Apart from consistent results showing an association between apolipoprotein (APO)E and AD, strong evidence of disease associations were found for polymorphisms in ESR2 and CYP11A1 based on the entire data set. For ESR2, significant protective effects were found for A alleles of rs4986938 (permuted P = .02) and rs867443 (permuted P = .02). For CYP11A1, significant risk effects were found for G alleles of rs11638442 (permuted P = .03) and rs11632698 (permuted P = .03). Stratifying subjects according to APOE e4 status, their genetic effects continued to be significant in the APOE e4-negative subgroup. Associations between CYP11A1 polymorphisms (rs2279357, rs2073475) and risk of AD were detected in women but not men. Further gene-level analysis confirmed the above association between ESR2 and CYP11A1, and pathway-level analysis highlighted the genetic effect of the estrogen metabolic pathway on disease susceptibility (permuted pathway-level P = .03). Conclusion Consistent with previous biological findings for sex steroid hormones in the central nervous system, genetic alterations on the estrogen metabolic pathway were revealed in the Chinese population. Confirmation of these present findings in an independent population is warranted to elucidate disease pathogenesis and to explore the potential of hormone therapy in the treatment of AD.

Circulating adiponectin (APN) levels decrease with age and obesity. On the other hand, a reduction in APN levels is associated with neurodegeneration and neuroinflammation. We previously showed that aged adiponectin knockout (APN-/-) mice developed Alzheimer's like pathologies, cerebral insulin resistance, and cognitive impairments. More recently, we also demonstrated that APN deficiency increased Aβ-induced microglia activation and neuroinflammatory responses in 5xFAD mice. There is compelling evidence that deregulated insulin activities or cerebral insulin resistance contributes to neuroinflammation and Alzheimer's disease (AD) pathogenesis. Here, we demonstrated that APN levels were reduced in the brain of AD patients and 5xFAD mice. We crossbred 5xFAD mice with APN-/- mice to generate APN-deficient 5xFAD (5xFAD;APN-/-). APN deficiency in 5xFAD mice accelerated amyloid loading, increased cerebral amyloid angiopathy, and reduced insulin-signaling activities. Pharmacokinetics study demonstrated adipoRon (APN receptor agonist) was a blood-brain barrier penetrant. AdipoRon improved neuronal insulin-signaling activities and insulin sensitivity in vitro and in vivo. Chronic adipoRon treatment improved spatial memory functions and significantly rescued neuronal and synaptic loss in 5xFAD and 5xFAD;APN-/- mice. AdipoRon lowered plaque and Aβ levels in AD mice. AdipoRon also exerted anti-inflammatory effects by reducing microglial and astrocytes activation as well as suppressing cerebral cytokines levels. The microglial phagocytic activity toward Aβ was restored after adipoRon treatment. Our results indicated that adipoRon exerts multiple beneficial effects providing important therapeutic implications. We propose chronic adipoRon administration as a potential treatment for AD.

Table S1. LipiDiDiet trial adverse events in participants randomly assigned to Souvenaid or control [9]. (DOCX 13 kb)

Background Mild cognitive impairment (MCI) among an aging global population is a growing challenge for healthcare providers and payers. In many cases, MCI is an ominous portent for dementia. Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a personalized care plan including lifestyle modifications to reduce the impact of modifiable risk factors (for example, blood pressure control and increased physical activity), cognitive training, dietary advice, and nutritional support. Souvenaid is a once-daily drink containing a mixture of precursors and cofactors (long-chain omega-3 fatty acids, uridine, choline, B vitamins, vitamin C, vitamin E, and selenium), which was developed to support the formation and function of neuronal membranes and synapses. Healthcare providers, patients, and carers require expert advice about the use of Souvenaid. Methods An international panel of experts was convened to review the evidence and to make recommendations about the diagnosis and management of MCI, identification of candidates for Souvenaid, and use of Souvenaid in real-world practice. This article provides a summary of the expert opinions and makes recommendations for clinical practice and future research. Summary of opinion Early diagnosis of MCI requires the use of suitable neuropsychological tests combined with a careful clinical history. A multimodal approach is recommended; dietary and nutritional interventions should be considered alongside individualized lifestyle modifications. Although single-agent nutritional supplements have failed to produce cognitive benefits for patients with MCI, a broader nutritional approach warrants consideration. Evidence from randomized controlled trials suggests that Souvenaid should be considered as an option for some patients with early Alzheimer’s disease (AD), including those with MCI due to AD (prodromal AD). Conclusion Early and accurate diagnosis of MCI provides a window of opportunity to improve the outcomes using a multimodal management approach including lifestyle risk factor modification and consideration of the multinutrient Souvenaid. Electronic supplementary material The online version of this article (10.1186/s13195-019-0528-6) contains supplementary material, which is available to authorized users.

There are great diversities of clinical phenotypes among the various familial Alzheimer's disease (FAD) families. We aimed to systematically review all the previously reported cases of FAD and to perform comparisons between Asian and white patients. In this regard, we collected individual-level data from 658 pedigrees. We found that patients with presenilin 1 (PSEN1) mutations had the earliest age of onset (AOO; 43.3 ± 8.6 years, p

INTRODUCTION Patients with familial Alzheimer's disease are being increasingly reported in Hong Kong. The objectives of this study were to report the clinical features of these patients, and to compare them with those with biomarker-confirmed sporadic late-onset Alzheimer's disease. METHODS All symptomatic Chinese patients with familial Alzheimer's disease who attended Queen Mary Hospital, Memory Clinic between January 1998 and December 2016 were included. Information about clinical features, baseline Mini-Mental State Examination score, and presenting cognitive symptoms or atypical clinical features were collected. Their clinical features were compared with those of 12 patients with sporadic late-onset Alzheimer's disease with cerebrospinal fluid biomarker evidence of Alzheimer's disease and 14 patients with late-onset Alzheimer's disease and positive amyloid loading on Pittsburgh compound B imaging. RESULTS There were three families with familial Alzheimer's disease among whom eight family members were affected. The mean (± standard deviation) age of onset and the Mini-Mental State Examination score were 48.4 ± 7.7 years and 7.9 ± 9.2, respectively. Compared with the sporadic late-onset Alzheimer's disease patients, those with familial Alzheimer's disease had an earlier age of onset and presentation (both P

Peritoneal dialysis (PD) exchange procedure is complex. Patients with cognitive impairment (CI) may require assistance. We studied the prevalence of CI among PD patients, its impact on PD-related peritonitis and the outcome of assisted PD. Cantonese version of Mini-Mental State examination (CMMSE) was performed in 151 patients newly started on PD. Data on patient characteristics including demographics, co-morbidities, blood parameters, medications, and number of PD-related peritonitis in the first 6 months were collected. 151 subjects were recruited. The age of studied patients was 60 ± 15.0 years, and 45 % were female. The prevalence of CI was 13.9 % using education-adjusted cut-off of CMMSE. Patients older than 65-year-old, female, and lower education level were independent risk factors for CI (OR 9.27 p = 0.001, OR 14.84 p = 0.005, and OR 6.10 p = 0.009, respectively). Age greater than 65-year old is an independent risk factor for PD-related peritonitis but CI was not. Patients requiring assisted PD were of older age (p

Unlike other behavioural and psychological symptoms of dementia, hyperphagia is less recognized among patients with Alzheimer's disease (AD). The prevalence of hyperphagia varies among studies, but there has been no systematic review or meta-analysis.An extensive search on the literature on hyperphagia in AD published between 1 January 1980 and 30 October 2017 was conducted. Data on the prevalence were retrieved. Meta-analysis with a random effect model was performed to determine the pooled estimate of prevalence. Meta-regression analysis was performed based on study characteristics, population demographics, or condition information.Results from 20 studies were extracted. Twenty-six reported cases of hyperphagia were identified. The mean age of onset was 70.7 ± 8.9 years, with a male predominance (68.4%). Hyperphagia occurred in all stages of AD. Only eight studies reported the prevalence of hyperphagia. Meta-analysis showed a pooled prevalence of hyperphagia of 18.6%. Publication bias may have been present. Meta-regression showed that ethnicity accounted for the variance among studies (coefficient: -1.247 (95% confidence interval: -1.978 to -0.516), RHyperphagia occurs in all stages of AD. In this meta-analysis of eight published studies, the prevalence of hyperphagia was 18.6%. In view of the possible publication bias, a large-scale study on hyperphagia is recommended in the future.

Introduction Lewy body dementia includes dementia with Lewy bodies and Parkinson's disease dementia. There have been limited clinical studies among Chinese patients with Lewy body dementia. This study aimed to review the presenting clinical features and identify risk factors for complications including falls, dysphagia, aspiration pneumonia, pressure sores, and mortality in Chinese patients with Lewy body dementia. We also wished to identify any difference in clinical features of patients with Lewy body dementia with and without an Alzheimer's disease pattern of functional imaging. Methods We retrospectively reviewed 23 patients with Lewy body dementia supported by functional imaging. Baseline demographics, presenting clinical and behavioural and psychological symptoms of dementia, functional and cognitive assessment scores, and complications during follow-up were reviewed. Patients with Lewy body dementia were further classified as having an Alzheimer's disease imaging pattern if functional imaging demonstrated bilateral temporoparietal hypometabolism or hypoperfusion with or without precuneus and posterior cingulate gyrus hypometabolism or hypoperfusion. Results The pre-imaging accuracy of clinical diagnosis was 52%. In 83% of patients, behavioural and psychological symptoms of dementia were evident. Falls, dysphagia, aspiration pneumonia, pressure sores, and death occurred in 70%, 52%, 26%, 26%, and 30% of patients, respectively with corresponding event rates per person-years of 0.32, 0.17, 0.18, 0.08, and 0.10. Patients with aspiration pneumonia compared with those without were more likely to have dysphagia (100% vs 35%; P=0.01). Deceased patients with Lewy body dementia, compared with alive patients, had a higher (median [interquartile range]) presenting Clinical Dementia Rating score (1 [1-2] vs 0.5 [0.5-1.0]; P=0.01), lower mean (± standard deviation) baseline Barthel index (13 ± 7 vs 18 ± 4; P=0.04), and were more likely to be prescribed levodopa (86% vs 31%; P=0.03). Patients with Lewy body dementia with an Alzheimer's disease pattern of functional imaging, compared with those without the pattern, were younger at presentation (mean ± standard deviation, 73 ± 6 vs 80 ± 6 years; P=0.02) and had a lower Mini-Mental State Examination score at 1 year (15 ± 8 vs 22 ± 6; P=0.05). Conclusions Falls, dysphagia, aspiration pneumonia, and pressure sores were common among patients with Lewy body dementia. Those with an Alzheimer's disease pattern of functional imaging had a younger age of onset and lower 1-year Mini-Mental State Examination score.

Aim The objective of the present study was to investigate the reliability and the validity of the Cantonese Chinese Montreal Cognitive Assessment (MoCA) as a brief screening tool of amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) in Southern Chinese older adults. Methods Cognitively normal, aMCI and AD Cantonese-speaking Chinese older adults were recruited from a memory clinic and the community. The English MoCA was translated into Cantonese Chinese and then back-translated. We then evaluated the content validity, reliability, sensitivity and specificity of the Chinese Cantonese MoCA. Results We recruited 115 cognitively normal controls, 87 aMCI and 64 AD patients. Only education was positively correlated with the Cantonese MoCA score (r = 0.46, P

Aim A U-shaped relationship between body mass index (BMI) and all-cause mortality has been reported, but there are few studies examining the association between BMI and cause-specific mortality and hospitalization. We carried out a longitudinal study to examine these associations in Chinese older adults with multiple comorbidities, which could provide a reference for the recommended BMI in this population. Methods From 2004 to 2013, a retrospective cohort of Chinese older adults was selected from a geriatric day hospital in Hong Kong. They were divided into groups according to their BMI: BMI 30. Other assessments included medical, functional, cognitive, social and nutritional assessment. Results A total of 1747 older adults (mean age 80.8 ± 7.1 years, 44.1% male, 46.1% living in nursing homes, Charlson Comorbidity Index 2.0 ± 1.6) with a median follow up of 3.5 years were included. Older adults with BMI 24–28 had the lowest all-cause, infection-related and cardiovascular mortality (P

Increasing lines of evidence support that testosterone may have neuroprotective effects. While observational studies reported an association between higher bioavailable testosterone or brain testosterone levels and reduced risk of Alzheimer’s disease (AD), there is limited understanding of the underlying neuroprotective mechanisms. Previous studies demonstrated that testosterone could alleviate neurotoxicity induced byβ-amyloid (Aβ), but these findings mainly focused on neuronal apoptosis. Since synaptic dysfunction and degeneration are early events during the pathogenesis of AD, we aim to investigate the effects of testosterone on oligomeric Aβ-induced synaptic changes. Our data suggested that exposure of primary cultured hippocampal neurons to oligomeric Aβcould reduce the length of neurites and decrease the expression of presynaptic proteins including synaptophysin, synaptotagmin, and synapsin-1. Aβalso disrupted synaptic vesicle recycling and protein folding machinery. Testosterone preserved the integrity of neurites and the expression of presynaptic proteins. It also attenuated Aβ-induced impairment of synaptic exocytosis. By using letrozole as an aromatase antagonist, we further demonstrated that the effects of testosterone on exocytosis were unlikely to be mediated through the estrogen receptor pathway. Furthermore, we showed that testosterone could attenuate Aβ-induced reduction of HSP70, which suggests a novel mechanism that links testosterone and its protective function on Aβ-induced synaptic damage. Taken together, our data provide further evidence on the beneficial effects of testosterone, which may be useful for future drug development for AD.

Objectives: Increasing evidence has demonstrated that vascular risk factors (VRFs) contribute to cognitive impairment in the elderly population. Prevention and administration of VRFs can be a vital strategy for delaying cognitive impairment. This study aimed to determine the impact of VRFs on cognitive function of the aged people from Chongqing, Southwest China. Methods: A total of 597 participants (≥60 years) from hospital and community population were enrolled in the cross-sectional study. Participants were screened for hypertension, coronary heart disease (CHD), and cerebrovascular disease (CVD). Blood pressure (BP) and blood lipid were also measured. Cognitive function was assessed with Mini-Mental State Examination and Clinical Dementia Rating. Logistic regression analysis was used to look for VRFs impacting mild cognitive impairment (MCI). Then we investigated the relationship between different types of vascular diseases and MCI. Results: A total of 457 participants showed normal cognitive function and 140 participants showed MCI. After adjusting for age, gender, and education, logistic regression analysis demonstrated that hypertension, CHD, systolic BP, total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) were independently associated with MCI; however, CVD, diastolic BP, triglyceride, and high-density lipoprotein cholesterol were not associated with MCI. Moreover, vascular diseases significantly contributed to MCI compared with no vascular disease; however, no significant difference in incident MCI was found among different combinations of vascular diseases. Conclusions: Hypertension, CHD, TC, and LDL-C are independent risk factors for MCI. Moreover, patients with vascular diseases have a higher risk of MCI; however, the amount of vascular diseases does not increase the risk of MCI.

Magnetic resonance spectroscopy (MRS) can explore aging at a molecular level. In this study, we investigated the relationships between regional concentrations of metabolites (such as choline, creatine, myo-inositol, and N-acetyl-aspartate) and normal aging in 30 cognitively normal subjects (15 women and 15 men, age range 22–82, mean = 49.9 ± 18.3 years) using quantitative proton magnetic resonance spectroscopy. All MR scans were performed using a 3 T scanner. Point resolved spectroscopy was used as the volume selection method for the region-of-interest and the excitation method for water suppression. Single voxel spectroscopy with short echo time of 39 ms and repetition time of 2,000 ms was employed. Single voxels were placed in the limbic regions, i.e., anterior cingulate cortex (ACC), posterior cingulate cortex (PCC), and left and right hippocampi. Cerebrospinal fluid normalization and T1 and T2 correction factors were implemented in the calculation of absolute metabolite concentrations. A standardized T1W 3D volumetric fast field echo and axial T2-weighted fast spin-echo images were also acquired. Our results showed significant positive correlation of choline (r = 0.545, p = 0.002), creatine (r = 0.571, p = 0.001), and N-acetyl-aspartate (r = 0.674, p

Aim The aim of the present study was to investigate the preference and willingness-to-pay (WTP) of older Chinese adults for community end-of-life care in a nursing home rather than a hospital. Methods A total of 1540 older Chinese adults from 140 nursing homes were interviewed. Four hypothetical questions were asked to explore their preferences for end-of-life care. Using a discrete choice approach, specific questions explored acceptable trade-offs between three attributes: availability of doctors onsite, attitude of the care staff and additional cost of care per month. Results Approximately 35% of respondents preferred end-of-life care in the nursing home, whereas 23% of them would consider it in a better nursing home. A good attitude of staff was the most important attribute of the care site. Respondents were willing to pay an extra cost of US$5 (HK$39) per month for more coverage of doctor's time, and US$49 (HK$379) for a better attitude of staff in the nursing home. The marginal WTP for both more coverage of doctor's time and better attitude of staff amounted to US$54 (HK$418). Respondents on government subsidy valued the cost attribute more highly, as expected, validating the hypothesis that those respondents would be less willing to pay an additional cost for end-of-life care. Conclusions Older Chinese adults living in nursing homes are willing to pay an additional fee for community end-of-life care services in nursing homes. Both the availability of the doctor and attitudes of nursing home staff are important, with the most important attribute being the staff attitudes. Geriatr Gerontol Int 2013; 14: 273–284.

This is a study on prospective memory (PM) and the PM interference effect in normal and pathological aging. One hundred and seven subjects, including 41 healthy young adults, 40 non-demented older adults and 26 patients with mild Alzheimer's disease (AD) participated in this study using a laboratory event-based PM task. PM task performance was comparable between the non-demented older and young adults, but impaired in the AD patients. The PM interference effect increased progressively from the healthy young adults, the non-demented older adults, to the AD patients. Path analysis revealed that the possible mechanism mediating the increased PM interference was the slow motor processing speed in normal aging, while it was the slow verbal speed in pathological aging. It is suggested that different neuropsychological mechanisms may underpin the affected performance of PM task in normal and pathological aging.

Autosomal dominant familial Alzheimer's disease accounts for 0.5% of all Alzheimer's disease. A familial Alzheimer's disease Chinese family, with 7 affected family members, underwent PSEN1 screening in 3 affected family members. A heterozygous novel missense mutation in the PSEN1 gene c.1156T>A, altering phenylalanine to isoleucine at codon 386, was identified. Because the change occurred in conserved domains of this gene and cosegregated with affected family members, this change may have a mutagenic and probably pathogenic effect.