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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 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.

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

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.

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

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.

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

Objective This study investigated the improvement in the accuracy of diagnosis of dementia subtypes among Chinese dementia patients who underwent [18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography ((18)FDG PET) with or without carbon 11-labelled Pittsburgh compound B ((11)C-PIB). Methods This case series was performed in the Memory Clinic at Queen Mary Hospital, Hong Kong. We reviewed 109 subjects (56.9% were female) who received PET with or without (11)C-PIB between January 2007 and December 2014. Data including age, sex, education level, Mini-Mental State Examination score, Clinical Dementia Rating scale score, neuroimaging report, and pre-/post-imaging clinical diagnoses were collected from medical records. The agreement between the initial and post-PET with or without (11)C-PIB dementia diagnosis was analysed by the Cohen's kappa statistics. Results The overall accuracy of initial clinical diagnosis of dementia subtype was 63.7%, and diagnosis was subsequently changed in 36.3% of subjects following PET with or without (11)C-PIB. The rate of accurate initial clinical diagnosis (compared with the final post-imaging diagnosis) was 81.5%, 44.4%, 14.3%, 28.6%, 55.6% and 0% for Alzheimer's disease, dementia with Lewy bodies, frontotemporal dementia, vascular dementia, other dementia, and mixed dementia, respectively. The agreement between the initial and final post-imaging dementia subtype diagnosis was only fair, with a Cohen's kappa of 0.25 (95% confidence interval, 0.05-0.45). For the 21 subjects who underwent (11)C-PIB PET imaging, 19% (n=4) of those with Alzheimer's disease (PIB positive) were initially diagnosed with non-Alzheimer's disease dementia. Conclusions In this study, PET with or without (11)C-PIB brain imaging helped improve the accuracy of diagnosis of dementia subtype in 36% of our patients with underlying Alzheimer's disease, dementia with Lewy bodies, vascular dementia, and frontotemporal dementia.

BACKGROUND The efficacy of influenza vaccination in older nursing home residents is frequently overestimated due to frailty selection bias. Limited data exist to examine this issue. METHODS We conducted a prospective cohort study from December 2009 to November 2010 to evaluate the efficacy of influenza vaccination in old nursing home residents with respect to their functional status. Participants were stratified according to the Barthel Index (BI) into good functioning (GF; BI > 60), intermediate functioning (IF; BI = 5-60), and poor functioning (PF; BI = 0). Participants were vaccinated by monovalent H1N1 2009 and trivalent seasonal influenza vaccinations (H1N1-TIV), TIV alone, or remained unvaccinated by choice. The associations between all-cause mortality, vaccination efficacy, and functional status were examined. RESULTS A total of 711 older nursing home residents were enrolled (GF group: N = 230; IF group: N = 246; PF group: N = 235). At 12 months, H1N1-TIV recipients had the lowest all-cause mortality, whereas unvaccinated residents had the highest all-cause mortality in all three functional status groups. In the comparison between H1N1-TIV recipients and TIV alone recipients, the hazard ratios (HRs) of all-cause mortality were lower in the GF group and higher in the PF group (GF group: HR 0.30 [0.07-0.95], p < .05; IF group: HR 0.40 [0.18-0.86], p < .05; PF group: HR 0.53 [0.28-0.99], p < .05). The same observation was found in comparison between other vaccination statuses (H1N1-TIV vs unvaccinated and TIV alone vs unvaccinated). CONCLUSIONS Influenza vaccination was associated with reduced all-cause mortality in older nursing home residents with different functional statuses. Vaccine efficacy in reducing mortality declined with increasingly impaired functional status.

Objectives The objectives of the present study were to describe the knowledge and preferences of Hong Kong Chinese older adults regarding advance directives and end-of-life care decisions, and to investigate the predictors of preferences for advance directive and community end-of-life care in nursing homes. Methods This was a cross-sectional survey conducted in 140 nursing homes in Hong Kong. A total of 1600 cognitively normal Chinese older adults were recruited. Information on demographics, social, medical diseases, preferences of end-of-life care decisions, and advance directives were collected by face-to-face questionnaire interviews. Results The mean age of the participants was 82.4 years; 94.2% of them would prefer to be informed of the diagnosis if they had terminal diseases and 88.0% preferred to have their advance directives regarding medical treatment in the future. Approximately 35% would prefer to die in their nursing homes. The significant independent predictors for the preference of advance directive included asking for relatives' advice, wishing to be informed of their terminal illness diagnoses, absence of stroke, and having no problems in self-care in European Quality of Life–5 Dimensions. For the preference for community end-of-life care and dying in nursing homes, the independent predictors included older age, not having siblings in Hong Kong, Catholic religion, nonbeliever of traditional Chinese religion, not receiving any old age allowance, lower Geriatric Depression Scale score, and being residents of government-subsidized nursing homes. Conclusions Most of our cognitively normal Chinese nursing home older adults prefer having an advance directive, and one-third of them would prefer to die in nursing homes.

Androgen deficiency in the ageing male (ADAM) was proposed to characterize a symptom cluster of decrease in sexual function and strength, dysphoria and osteopenia in ageing men with decreased levels of androgens. Unlike menopause, literature on the topic is scarce and focuses mainly on the physiological aspects of the problem. However, men with ADAM also face a milieu of psychosocial stressors which may adversely affect their mental health. It is pertinent to examine ADAM within a psychological context. This study aims to determine the prevalence of symptoms of ADAM among Chinese men, and to examine their relationship with psychological distress and quality of life. A cross-sectional design was employed with standardized questionnaires to assess symptoms of ADAM and related psychological factors. The ADAM questionnaire, Hospital Anxiety and Depression Scale, Perceived Stress Scale, General Health Questionnaire and Short Form Health Survey-12 were administered to a community sample of 311 Chinese men (aged 40-80) attending a family medicine clinic in Hong Kong. Demographic information was also collected. A total of 87.8% of the sample was screened ADAM positive using the ADAM questionnaire. Age, duration of marriage, occupation, household income and physical health were found to be significantly associated with ADAM status. ADAM positive individuals were found to have higher anxiety and depression scores, higher stress level, higher psychiatric morbidity and poorer physical and mental quality of life compared with their ADAM negative counterparts. Symptoms of ADAM are prevalent among the Chinese. ADAM positivity as measured by the ADAM questionnaire is associated with poorer psychological well-being and quality of life in the ageing population. Further research and clinical attention to the psychological needs of this population is warranted.

Recent linkage and association studies have implicated the chromosome 12p13 locus as possibly harboring genetic variants predisposed to Alzheimer’s disease (AD). We attempted to replicate this association in a Chinese data set comprised of 256 AD cases and 264 age-matched normal controls. A total of 14 single nucleotide polymorphisms (SNPs) were examined. Single marker association revealed the two SNPs in NCAPD2 (rs7311174 and rs2072374) as showing nominal significant p values (p = 0.0491 and 0.0116, respectively). Haplotype analysis found LD block one to be significantly associated with AD (global p = 0.0250). Haplotypes CGGATG and CAGTCG were also significantly associated with AD (p = 0.0498 and p = 0.0482, respectively). These genetic analyses provide evidence that the chromosome 12p13 locus is associated with AD in Chinese.

Background. A 10-question screening questionnaire for androgen deficiency in aging men (ADAM) was reported in previous white but not Chinese populations. We therefore investigated the validity of a Chinese version of the Saint Louis University ADAM questionnaire to screen for androgen deficiency in Chinese men. Methods. This was a cross-sectional study. Seven hundred ninety-six ambulatory community-based Chinese men, 18‐ 89 years old, were recruited from October 2003 through June 2006. Self-administered Chinese ADAM questionnaire and morning blood samples for serum total testosterone (TT) and bioavailable testosterone (BT) levels were collected from all participants. Low serum BT levels (androgen deficiency) were defined as ,5 th percentile of serum BT levels in young healthy Chinese men (18‐29 years). Results. The Chinese ADAM questionnaire had good internal consistency (Cronbach a ¼ 0.74) and test‐retest reliability (Pearson correlation coefficient, r ¼ 0.86; p , .001, two-tailed). As a screening test for low serum BT levels, the Chinese ADAM questionnaire has a high sensitivity of 88% but low specificity of 32%. In 6 of the 10 questions, the mean serum BT levels were significantly lower in those who answered positively than in those who answered negatively. Using a cut-off score of � 2, a six-question short Chinese ADAM questionnaire demonstrated sensitivity, specificity, and positive and negative predictive values of 86%, 40%, 46%, and 82%, respectively. Conclusion. We have validated a full Chinese version and developed a shortened version of the ADAM questionnaire, and demonstrated that they are sensitive but not specific screening tests for androgen deficiency in Chinese men.

There was no long-term clinical study on galantamine in Alzheimer's disease (AD) in the Asian population. The objectives of this study were to evaluate the efficacy of galantamine on cognitive function, daily functioning, behavioural symptoms and its safety in Chinese AD patients. This was a 2-year open-label clinical trial. The inclusion criteria were patients with probable AD by the NINCDS-ADRDA criteria. A historical control group (n = 19) of AD patients with no galantamine or other cholinesterase inhibitor therapy was employed. In the galantamine group, 33 and 32 subjects had completed a 1-year and 2-year follow up, respectively. Within the galantamine group and at a 6-month follow up, the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADAS-cog score) showed an improvement of 2.9 +/- 1.18 (p = 0.019, paired t-test) but remained the same at 1 and 2 years. The Alzheimer's Disease Cooperative Study-Activities of Daily Living Inventory (ADCS-ADL) deteriorated by 4.31 +/- 2.06 (p = 0.044, paired t-test) at 6 months but showed no significant decline at 1 and 2 years vs. baseline. The Neuropsychiatric Inventory (NPI) score also showed a significant deterioration of 5 +/- 1.99 (p = 0.017, paired t-test) at 6 months, 8.06 +/- 1.97 (p < 0.001, paired t-test) at 1 year and 7.31 +/- 1.76 at 2 years. Comparison between the two groups showed a statistically significant improvement in the 1-year ADAS-cog score but decline in the NPI score in the galantamine vs. control groups. Adverse effects were commonly mild. In Chinese mild-moderate AD patients, galantamine showed beneficial effects mainly on the cognitive function.

Cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease (AD), especially Aβ42/t-tau and Aβ42/p-tau, showed high diagnostic sensitivities and specificities. But significant interassay and interlaboratory variabilities hinder the widespread clinical applications of CSF biomarkers. The objective of this study was to validate the diagnostic accuracy of AD-CSF-Index in our local Chinese patients with AD compared to nondemented controls. A total of 36 patients, which included 24 patients with AD and 12 nondemented controls, were recruited. Chinese patients with AD showed higher mean AD-CSF-Indices than nondemented controls (AD = 1.25-1.3, normal = 0.62-0.63; P < .001). The AD-CSF-indices have a high sensitivity and specificity of 86.4% to 90.9% and 83.3%, respectively, in differentiating patients with AD from nondemented controls. After selecting the patients with “pure AD” and “pure normal” controls, the AD-CSF-indices have a high sensitivity and specificity of 94.1% and 90%, respectively, in differentiating patients with AD from nondemented controls. Most importantly, our AD-CSF-indices cutoff was highly similar to that reported in Western studies.

Objective. The objective of the present study was to investigate the impact of incident falls on the balance, gait, and Activities of Daily Living functioning in community-dwelling older adults. Methods. This was a population-based, 1-year prospective cohort study in older adults. We performed baseline assessment of potential predictors, the 1-year occurrence of falls, and then 1-year reassessment of the following outcome measures: the Barthel Index (BI), Lawton's Instrumental Activities of Daily Living (IADL) scale, gait speed, and Tinetti Balance and Gait Evaluation's total mobility score (TMS). At 1 year of follow-up, participants who had declined by >/=1 standard deviation (SD) below the baseline mean value of each outcome measure were classified as "decliners." Results. Of the 1517 participants, 93.5% (n = 1419) completed the 1-year follow-up reassessment of BI and IADL. For gait speed and TMS, respectively, 88.2% (n = 1338) and 88.3% (n = 1339) completed the 1-year outcome assessment. Fallers, particularly recurrent fallers, experienced significantly greater 1-year declines in the four functional measures. Multivariate logistic regression analyses showed that an incident fall was a significant independent predictor for decliners in the BI, Lawton's IADL score, gait speed, and TMS after adjustment of all significant confounding factors. The relative risks of an incident fall as an independent predictor for decliners in the BI, IADL score, gait speed, and TMS were 2.4 (95% confidence interval [CI], 1.4-4.0; p =.01), 2.9 (95% CI, 1.7-5.2; p

Context: Information processing requires a series of mental operations from encoding to storage and retrieval. A large number of studies have examined the retrieval process, but less attention has been paid to the encoding process. Evidence Acquisition: The aims of this paper were to provide an overview of perceptual and semantic encoding processes as well as identify and compare the structural and functional changes in the memory encoding process of young and old adults. A review of encoding was conducted based on findings from two recent memory encoding studies and a literature search on memory encoding. It included studies published from January 1980 to December 2013 and appeared in the databases of CINAHL, MEDLINE, AMED, Journals@Ovid and the ISI Web of Science. Results: Five stages of encoding were identified. They were: 1) early perceptual processing; 2) prelexical feature detection and early lexical processing; 3) initial selection of information from competing information for processing in the working memory; 4) semantic, syntactic, or lexical processing; and 5) updating of working memory with the newly created item representation and elaborate processing. Perceptual encoding appears to be modulated by sensory cortices, in which stimuli are initially perceived and processed, whereas semantic encoding involves the left prefrontal cortex temporal regions by both verbal and nonverbal stimuli. Conclusions: Early perceptual processing and the selection of information processes associated with memory encoding are comparable between young and old adults. However, they showed differences in semantic processing, updating of working memory, and elaborate processing. These differences might be due to reduced volume and functional capacity of the hippocampus and frontal lobes, shrinkage in the white matter and its associated tracts, as well as inability of the aging brain to produce levels of dopamine comparable to its previous levels.

The integrity of structural connectivity in a functional brain network supports the efficiency of neural processing within relevant brain regions. This study aimed to quantitatively investigate the short- and long-range fibers, and their differential roles in the lower cognitive efficiency in aging and dementia. Three groups of healthy young, healthy older adults and patients with Alzheimer's disease (AD) participated in this combined functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study on prospective memory (PM). Short- and long-range fiber tracts within the PM task engaged brain networks were generated. The correlation between the fMRI signal change, PM performance and the DTI characters were calculated. FMRI results showed that the PM-specific frontal activations in three groups were distributed hierarchically along the rostrocaudal axis in the frontal lobe. In an overall PM condition generally activated brain network among the three groups, tractography was used to generate the short-range fibers, and they were found impaired in both healthy older adults and AD patients. However, the long-range fiber tracts were only impaired in AD. Additionally, the mean diffusivity (MD) of short-range but not long-range fibers was positively correlated with fMRI signal change and negatively correlated with the efficiency of PM performance. This study suggests that the disintegrity of short-range fibers may contribute more to the lower cognitive efficiency and higher compensatory brain activation in healthy older adults and more in AD patients.

High-dose recombinant human GH (rhGH) has been shown to improve the nutritional status of malnourished older adults. It is uncertain whether low-dose rhGH is effective and whether its effect on nutritional status will lead to any improvement in physical function. There is also no data on the outcome after a short course of rhGH treatment. The objectives of this study were to determine the efficacy of low-dose rhGH treatment for 4 weeks in malnourished elderly patients, its effect on physical functions, and the intermediate term outcome after a 4-week rhGH treatment. The study design was a randomized, placebo-controlled, double-blind trial conducted in a university teaching hospital. The patients were 19 medically stable malnourished elderly subjects. Intervention in the rhGH group was as follows: rhGH (Saizen, Serono, Switzerland) 0.09 IU/kg body weight (BW) 3 times weekly were given together with appropriate dietary intervention as prescribed by the dietitian. In the placebo group, equal volumes of norma...

Background. The incidence of falls among older hospitalized patients is higher than that of community-dwelling older persons. Prevention is important, but factors associated with these falls are less well studied than falls occurring in the community or nursing homes. Methods. This study was conducted in an acute-care general hospital in Hong Kong. During November 1995 to March 1997, all older inpatients who fell during hospitalization were assessed by a geriatrician, a physiotherapist, and an occupational therapist. A standardized protocol to study the clinical and performance-oriented functional factors was employed. A sex- and age-matched hospital control was recruited for each case. In total, 51 cases and controls (mean ages 77.8 ± 7.3 years and 77.5 ± 7.0 years, respectively) were studied. Results. Among the multiple clinical and functional risk factors for falls identified, lower limb weakness (i.e., power less than MRC grade 4 in one or both lower limbs) and poor tandem walk ability emerged as two significant predictive factors for falls in the hospital. The overall classification accuracy of fallers and nonfallers was 79%. The sensitivity was 84% and specificity was 75%. Clinical factors were the underlying causes for the lower limb weakness and poor tandem walk performance. Conclusions. Among clinical and functional risk factors for falls in the older medical patient, lower limb weakness and poor tandem walk ability were most predictive. Falls prevention programs in hospitals should employ these two tests as screening instruments.

Background: Age-related osteoporosis may be associated with inefficient intestinal calcium absorption and bone remodeling. Objective: We investigated the pathogenesis of age-related osteoporosis in Chinese women with habitual low calcium intakes. Design: We studied the response of intestinal calcium absorption, calcitropic hormones, and biochemical bone markers to graded dietary calcium deprivation. Results: The osteoporotic subjects (n = 25) had higher urinary calcium excretion (P < 0.05) and lower plasma 1,25-dihydroxyvitamin D concentrations (P < 0.02) than did age-matched control women (n = 25). Parathyroid hormone was not significantly different from that in age-matched control women but was significantly higher than in young women (n = 15, P < 0.05). Fractional 45 Ca absorption was

Our patient (II2; Fig. 1) presented at 51 years of age, with a 1-year history of memory impairment. She also suffered from anomia, spatial disorientation, and apathy. During her clinical course, she also developed generalized epilepsy with tonic-clonic seizures which were controlled with phenytoin. Initial physical examination was unremarkable. Mini-Mental State Examination (MMSE) was 14/30. Vitamin B12, folate, thyroid function test, and Venereal Disease Research Laboratory test were normal. A computed tomography (CT) brain scan showed bilateral medial temporal lobes atrophy. Single photon emission CT (SPECT) showed hypoperfusion over the bilateral frontal and temporoparietal lobes. She fulfilled the National Institute of Neurological Communicative Disorders and Stroke-Alzheimer Disease and Related Disorders Association (NINCDS-ADRDA) diagnostic criteria of Alzheimer’s disease (AD). Initially, there was no apparent family history of early onset AD (EOAD).

In view of the paucity of data on cerebrospinal fluid (CSF) biomarkers in Chinese patients, we evaluated the validity of tau, phosphorylated tau 181 (p-tau-181), amyloid β 42 (Aβ42), and Aβ40 proteins in Chinese patients with Alzheimer’s disease (AD). We recruited 24 patients with AD, 12 nondemented controls, and 12 patients with non-AD dementia. We found the CSF levels of Aβ42, tau, p-tau, Aβ42–tau, and Aβ42–p-tau ratios, except the Aβ40 protein level, were significantly different among the 3 groups of patients. Patients with AD had higher levels of CSF tau and p-tau but lower levels of Aβ42 proteins, Aβ42–tau, and Aβ42–p-tau ratios than the nondemented controls. In the diagnosis of AD versus nondementia, the sensitivity and specificity of the ratios of Aβ42–tau and Aβ42–p-tau were 96% and 83% versus 92% and 83%, respectively. Only the Aβ42–p-tau ratio showed satisfactory sensitivity and specificity in the diagnosis of AD versus other dementia.

Cerebrospinal fluid (CSF) Aβ42, total tau and phosphorylated tau (p-tau) are well-defined diagnostic markers for Alzheimer’s disease (AD). There has been no previous report of the use of these markers in the diagnosis of AD in patients with chronic kidney disease (CKD). We would like to report our preliminary findings on these biomarkers in three patients with renal failure. One patient with a clinical diagnosis of AD showed elevated CSF tau, p-tau 181, and decreased Aβ42 levels, within a similar range as in local Chinese AD patients without renal impairment. The other two delirious patients, who did not have a clinical diagnosis of AD, showed normal CSF biomarkers. We found that the diagnosis of AD with CSF biomarkers appears to be useful in renal failure patients. But our results need to be confirmed in a larger study, comparing these CSF biomarkers in AD vs. non-AD patients with concomitant CKD.

We report a 32 year-old Chinese lady with history of tetralogy of Fallot, presented to us with chest pain due to hypocalcemia secondary to hypoparathyroidism. With her dysmorphic facial features and intellectual disability 22q11.2 deletion was suspected and confirmed by genetic study. Clinicians should consider the diagnosis of DiGeorge syndrome in adult patient with past medical history of congenital heart disease, facial dysmorphism, intellectual disability and primary hypoparathyroidism.

Background Vitamin D is essential for Ca absorption, prevention of falls and fracture, and maintenance of muscle strength and balance. Lack of awareness of the importance of vitamin D in bone health is common in Asia. Objective To define key statements, objectives and actions for improving osteoporosis management and vitamin D inadequacy in Asia. Results and conclusion This declaration was jointly produced by specialists at the Asia Metaforum on the Role of Vitamin D and the Management of Osteoporosis, held in September 2006 in Hong Kong, to define actions to prevent vitamin D insufficiency in Asia. Although developed specifically for Asia, some or all of these statements may be applicable to other regions of the world.