Chronic oral administration of adipoRon reverses cognitive impairments and ameliorates neuropathology in an Alzheimer's disease mouse model.

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 Aß-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 Aß 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 Aß 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.

Prevalence of mild behavioural impairment domains: a meta-analysis.

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.

Caregiving, care burden and awareness of caregivers and patients with dementia in Asian locations: a secondary analysis.

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 < 0.001 and 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 < 0.001). 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.

Prevalence of mild behavioural impairment: a systematic review and meta-analysis.

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.

Prevalence of hyperphagia in Alzheimer's disease: a meta-analysis.

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 < 0.001). CONCLUSIONS: Hyperphagia 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.

Effectiveness of interventions for co-residing family caregivers of people with dementia: Systematic review and meta-analysis.

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.

Association between high cumulative dose of benzodiazepine in Chinese patients and risk of dementia: a preliminary retrospective case-control study.

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 <1096 or ≥1096. Odds ratios and 95% confidence intervals were computed by multivariate analysis. RESULTS: The difference in exposure density between the dementia and control groups was statistically significant between prescribed daily doses <1096 and ≥1096 (P = 0.02). There were two multivariate analyses models; one factored in depression (model 1), and the other (model 2) did not. Model 2 showed a statistically significant association (odds ratio = 1.71, 95% confidence intervals = 1.02-2.89, P = 0.04) between benzodiazepine exposure density and dementia. CONCLUSION: High-dose benzodiazepine use may be associated with dementia in the Chinese population. Prospective studies are required.

Prevalence of CMMSE defined cognitive impairment among peritoneal dialysis patients and its impact on peritonitis.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 < 0.001), lower CMMSE (p < 0.001), and scored higher for age-adjusted Charlson Co-morbidity index (p < 0.001). Compared with self-care PD patients, assisted PD patients did not have higher rates exit site infection (p = 0.30) but had a trend of higher PD peritonitis (p = 0.07). CONCLUSION: CI is common among local PD patients. Overall, CI could not be identified as an independent risk factor for PD peritonitis. There is a higher prevalence of CI among assisted PD patients but helpers may not completely eliminate the risk of PD-related peritonitis.

A systematic review of familial Alzheimer's disease: Differences in presentation of clinical features among three mutated genes and potential ethnic differences.

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 < 0.001) and were more commonly affected by seizures, spastic paraparesis, myoclonus, and cerebellar signs (p < 0.001, p < 0.001, p = 0.003, and p = 0.002, respectively). Patients with PSEN2 mutations have a delayed AOO with longest disease duration and presented more frequently with disorientation (p = 0.03). Patients with amyloid precursor protein (APP) mutations presented more frequently with aggression (p = 0.02) and those with APP duplication presented more frequently with apraxia (p = 0.03). PSEN1 mutations before codon 200 had an earlier AOO than those having mutations after codon 200 (41.4 ± 8.0 years vs. 44.7 ± 8.7 years, p < 0.001). Because 42.9% of the mutations reported are novel, the mutation spectrum and clinical features in Asian FAD families could be different from that of whites. Asian patients with PSEN1 mutations presented more frequently with disorientation (p = 0.02) and personality change (p = 0.01) but less frequently with atypical clinical features. Asian patients with APP mutations presented less frequently with aphasia (p = 0.02). Thus, clinical features could be modified by underlying mutations, and Asian FAD patients may have different clinical features when compared with whites.

Comparisons of clinical symptoms in biomarker-confirmed Alzheimer's disease, dementia with Lewy bodies, and frontotemporal dementia patients in a local memory clinic.

BACKGROUND: There has been no previous Chinese study that differentiated the clinical symptoms among biomarker-confirmed Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). The objective of this study was to compare the cognitive, behavioural, and neuropsychiatric symptoms in biomarker-confirmed AD, DLB, and FTD patients. METHODS: We recruited 30 patients (14 AD, 7 DLB, 9 FTD) who presented to the memory clinic at Queen Mary Hospital from 1 January 2007 to 31 December 2013. AD was diagnosed according to the National Institution of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria with cerebrospinal fluid biomarkers (tau, phosphorylated tau, and amyloid ß-42) fulfilling locally determined cut-off values for AD. DLB was diagnosed based on the McKeith diagnostic criteria. The behavioural variant of FTD was diagnosed based on the revised diagnostic criteria proposed by the International bvFTD Criteria Consortium, and language variant FTD was diagnosed based on the latest published criteria. In addition, patients with DLB and FTD had typical imaging features on single-photon emission computed tomography or (18) fludeoxyglucose-positron emission tomography, either with or without Pittsburgh Compound B imaging, which supported their diagnoses. Data on patient characteristics including demographics, presenting clinical features, Mini-Mental State Examination, clinical dementia ratings, and neuropsychiatry inventory scores were collected. RESULTS: There were no differences in age, education level, dementia severity, and duration of symptoms before presentation among the three subgroups of patients. All patients had amnesia symptoms, which were not statistically significant. Apraxia was most common in AD. While 83% of the patients were affected by behavioural and neuropsychiatric symptoms of dementia, behavioural disinhibition and decline in executive function were most common in FTD patients. Recurrent hallucinations, fluctuation of consciousness, parkinsonism, and rapid eye movement sleep behaviour disorder were most common in DLB. CONCLUSION: Memory impairment and apathy are not useful discriminative symptoms in diagnosing AD, DLB, and FTD. Apraxia favours AD. Hallucinations, particularly well-formed visual hallucinations, favour DLB. Overall, behavioural and neuropsychiatric symptoms of dementia symptoms are common among the three groups of dementia patients.

Sequential multiple assignment randomised controlled trial protocol for developing an adaptive intervention to improve depressive symptoms among family caregivers of people with dementia.

OBJECTIVES: Family caregivers of people with dementia (FC-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 behavioural 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 prespecified 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 randomised trial 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 BA and MP of different sequences and dosages (eg, 8 weeks of BA followed by booster sessions for responders and 8 weeks of MP for non-responders) will be assigned to the participants following a set of decision rules. The primary outcomes will be depressive symptoms (measured using the Patient Health Questionnaire-9), assessed after the second stage of the intervention. Other outcomes, such as positive aspects of caregiving (measured using the Positive Aspects of Caregiving Scale), sleep quality (measured using the Pittsburgh Sleep Quality Index) and time points will also be assessed. The analyses will follow the intention-to-treat principle. Several process indicators (eg, engagement in meaningful activities and level of mindfulness) will also be assessed. The findings will have strong implications for the further development of psychosocial adaptive interventions to reduce depressive symptoms among FC-of-PWD. ETHICS AND DISSEMINATION: This study has received ethical approval from the Human Research Ethics Committee at The Hong Kong Polytechnic University (HSEARS20211223001). The findings will be presented at academic conferences and submitted to peer-reviewed journals for publication. TRIAL REGISTRATION NUMBER: NCT05634317.

MicroRNA-128 suppresses tau phosphorylation and reduces amyloid-beta accumulation by inhibiting the expression of GSK3ß, APPBP2, and mTOR in Alzheimer's disease.

INTRODUCTION AND AIMS: Alzheimer's disease (AD) is characterized by the abnormal accumulation of hyperphosphorylated tau proteins and amyloid-beta (Aß) peptides. Recent studies have shown that many microRNAs (miRNAs) are dysregulated in AD, and modulation of these miRNAs can influence the development of tau and Aß pathology. The brain-specific miRNA miR-128, encoded by MIR128-1 and MIR128-2, is important for brain development and dysregulated in AD. In this study, the role of miR-128 in tau and Aß pathology as well as the regulatory mechanism underlying its dysregulation were investigated. METHODS: The effect of miR-128 on tau phosphorylation and Aß accumulation was examined in AD cellular models through miR-128 overexpression and inhibition. The therapeutic potential of miR-128 in AD mouse model was assessed by comparing phenotypes of 5XFAD mice administered with miR-128-expressing AAVs with 5XFAD mice administered with control AAVs. Phenotypes examined included behavior, plaque load, and protein expression. The regulatory factor of miR-128 transcription was identified through luciferase reporter assay and validated by siRNA knockdown and ChIP analysis. RESULTS: Both gain-of-function and loss-of-function studies in AD cellular models reveal that miR-128 represses tau phosphorylation and Aß secretion. Subsequent investigations show that miR-128 directly inhibits the expression of tau phosphorylation kinase GSK3ß and Aß modulators APPBP2 and mTOR. Upregulation of miR-128 in the hippocampus of 5XFAD mice ameliorates learning and memory impairments, decreases plaque deposition, and enhances autophagic flux. We further demonstrated that C/EBPα transactivates MIR128-1 transcription, while both C/EBPα and miR-128 expression are inhibited by Aß. CONCLUSION: Our findings suggest that miR-128 suppresses AD pathogenesis, and could be a promising therapeutic target for AD. We also find a possible mechanism underlying the dysregulation of miR-128 in AD, in which Aß reduces miR-128 expression by inhibiting C/EBPα.

Continuous use of antipsychotics and its association with mortality and hospitalization in institutionalized Chinese older adults: an 18-month prospective cohort study.

BACKGROUND: Previous meta-analyses have suggested that antipsychotics are associated with increased mortality in dementia patients with behavioral and psychological symptoms (BPSD). Subsequent observational studies, however, have produced conflicting results. In view of this controversy and the lack of any suitable pharmacological alternative for BPSD, this study aimed to investigate the relationship between continuous use of antipsychotics and mortality as well as hospitalizations in Chinese older adults with BPSD residing in nursing homes. METHODS: This was a prospective cohort study conducted in nursing homes in the Central & Western and Southern Districts of Hong Kong from July 2009 to December 2010. Older adults were stratified into the exposed group (current users of antipsychotics) and control group (non-users). Demographics, comorbidity according to the Charlson Comorbidity Index (CCI), Barthel Index (BI(20)), Abbreviated Mental Test (AMT), and vaccination status for pandemic Influenza A (H1N1) 2009, seasonal influenza and pneumococcus were collected at baseline. Subjects were followed up at 18 months. All-cause mortality and all-cause hospitalizations were recorded. RESULTS: 599 older adults with dementia from nine nursing homes were recruited. The 18-month mortality rate for the exposed group was 24.1% while that for control group was 27.5% (P = 0.38). The exposed group also had a lower median rate of hospitalizations (56 (0-111) per 1000 person-months vs 111 (0-222) per 1000 person-months, median (interquartile range), p<0.001). CONCLUSIONS: The continuous use of antipsychotics for BPSD does not increase mortality among Chinese older adults with dementia living in nursing homes. Furthermore, our results show that the use of antipsychotics can lead to decreased hospitalizations.

Effects of age, education and gender in the Consortium to Establish a Registry for the Alzheimer's Disease (CERAD)-Neuropsychological Assessment Battery for Cantonese-speaking Chinese elders.

BACKGROUND: The Consortium to Establish a Registry for Alzheimer's Disease Neuropsychological Assessment Battery (CERAD-NAB) offers information on the clinical diagnosis of Alzheimer's disease (AD) and gives a profile of cognitive functioning. This study explores the effects of age, education and gender on participants' performance on eight subtests in the Chinese-Cantonese version of the CERAD-NAB. METHODS: The original English version of the CERAD-NAB was translated and content-validated into a Chinese-Cantonese version to suit the Hong Kong Chinese population. The battery was administered to 187 healthy volunteers aged 60 to 94 years. Participants were excluded if they had neurological, medical or psychiatric disorders (including dementia). Stepwise multiple linear regression analyses were performed to assess the relative contribution of the demographic variables to the scores on each subtest. RESULTS: The Cantonese version of CERAD-NAB was shown to have good content validity and excellent inter-rater reliability. Stepwise multiple regression analyses revealed that performances on seven and four out of eight subtests in the CERAD-NAB were significantly influenced by education level and age, respectively. Age and education had significant effects on participants' performance on many tests. Gender also showed a significant effect on one subtest. CONCLUSIONS: The preliminary data will serve as an initial phase for clinical interpretation of the CERAD-NAB for Cantonese-speaking Chinese elders.

Discontinuation Rate of Newly Prescribed Donepezil in Alzheimer's Disease Patients in Asia.

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<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. CONCLUSIONS: In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.

Association between alcohol consumption and cognitive impairment in Southern Chinese older adults.

BACKGROUND: There is limited data on the effects of alcohol consumption on cognitive impairment in Chinese populations. OBJECTIVES: To investigate the association between alcohol consumption and the risk of cognitive impairment in Southern Chinese older adults in Hong Kong. METHOD: This was a cross-sectional study of 314 Chinese older participants, aged 65 years or over. Participants' socio-demographic, co-morbid diseases, alcohol drinking habits, and Mini Mental State Examination (MMSE) for cognitive function were obtained by a face-to-face interview. Participants were categorized into normal cognitive and cognitively impaired groups by education-adjusted MMSE cut-off scores. RESULT: The mean (SD) age of the participants was 79.9 (6.5) years. The average weekly alcohol consumption in the cognitively impaired group was significantly higher than that of the normal cognition group [mean (SD): 861.89 (673.03) versus 241.21 (276.26) grams per week respectively; p < 0.001, t-test]. Drinkers with light to moderate alcohol consumption were associated with higher MMSE scores than non-drinkers and heavy drinkers. Logistic regression analyses showed that heavy drinkers (> 400 g alcohol for men and > 280 g for women) were associated with an increased risk of cognitive impairment (OR = 4.99, 95%CI = 1.8-13.82), while light drinkers and moderated drinkers (< 400 g for men and < 280 g for women) were associated with reduced risks (OR = 0.32, 95%CI = 0.12-0.86; OR = 0.17, 95%CI = 0.06-0.51, respectively). Exercise and age were independent protective and risk factors respectively. CONCLUSION: Heavy alcohol consumption is associated with an increased risk of cognitive impairment while light to moderate alcohol consumption is associated with reduced risk among Southern Chinese older adults in Hong Kong.

Chinese patients with Lewy body dementia had shorter survival and developed complications earlier than those with Alzheimer's disease.

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.

Associations between CLU polymorphisms and memory performance: The role of serum lipids in Alzheimer's disease.

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 APOEε4 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.