Differential blood miRNA expression in brain amyloid imaging-defined Alzheimer's disease and controls.

BACKGROUND: Peripheral blood microRNAs (miRNA) have been identified as potential biomarkers for Alzheimer's disease (AD). Study results have generally been inconsistent and limited by sample heterogeneity. The aim of this study is to establish candidate blood miRNA biomarkers for AD by comparing differences in miRNA expression between participants with brain amyloid imaging-defined AD and normal cognition. METHODS: Blood RNA was extracted from a subset of participants from the Australian Imaging Biomarkers Lifestyle Study of Ageing cohort (AIBL) with brain amyloid imaging results. MiRNA profiling was performed using small RNA sequencing on 71 participants, comprising 40 AD with high brain amyloid burden on imaging (amyloid positive) and 31 cognitively normal controls with low brain amyloid burden (amyloid negative). Cross-sectional comparisons were made between groups to examine differential miRNA expression levels using Fisher's exact tests. Replication of results was undertaken using a publicly available dataset of blood miRNA data of AD and controls. In silico analysis of downstream messenger RNA targets of candidate miRNAs was performed to elucidate potential biological function. RESULTS: After quality control, 816 miRNAs were available for analysis. There were 71 significantly differentially expressed miRNAs between the AD and control groups (p < 0.05). Two of these miRNAs, miR-146b-5p and miR-15b-5p, were also significant in the replication cohort. Pathways analysis showed these miRNAs to be involved in innate immune system and regulation of the cell cycle, respectively, both of which have relevance to AD pathogenesis. CONCLUSION: Blood miR-146b-5p and miR15b-5p showed consistent differential expression in AD compared to controls. Further replication and translational studies in strictly phenotyped cohorts are needed to establish their role as biomarkers for AD to have clinical utility.

Circulating microRNAs as Biomarkers of Alzheimer's Disease: A Systematic Review.

BACKGROUND: In recent years, microRNAs (miRNA), a class of non-coding RNA known to regulate protein expression post-transcriptionally, have been recognized as novel biomarkers of diseases. OBJECTIVE: In this systematic review, we identify miRNAs that are differentially expressed in Alzheimer's disease (AD) and/or mild cognitive impairment (MCI) and evaluate their accuracy as potential blood biomarkers. METHODS: Eligible studies of miRNAs in peripheral blood distinguishing patients with AD or MCI from cognitively normal controls were identified through standardized search strategies in Medline, PubMed, and Embase. MiRNAs that were differentially expressed were identified and where available their sensitivity and specificity for AD or MCI extracted from the retrieved studies. RESULTS: Eighteen studies investigated the diagnostic value of miRNAs as peripheral biomarkers of AD/MCI. Twenty miRNAs were significantly upregulated and 32 miRNAs downregulated in AD compared to controls in ten AD studies. Nine miRNAs were consistently dysregulated in more than one study. Of the 8 MCI studies, only one miRNA, miR-132, was consistently upregulated in three independent studies. Of the studies that reported diagnostic accuracy data, the majority of miRNA panels and individual miRNAs had a sensitivity and specificity greater than 0.75. CONCLUSION: Individual studies suggest that miRNAs can differentiate patients with AD/MCI from cognitively normal controls with modest accuracy. However, the literature is constrained by methodological differences between studies, with few studies assessing the same miRNAs. To become potential biomarkers for AD, further studies with standardized study designs for replication and validation are required. Results from this review may help researchers select candidate miRNAs for further investigation.

Therapeutic effects of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms.

OBJECTIVE: Cerebrolysin is a nootropic drug with unique neurotrophic activities directly affecting cerebral neurons. This study evaluated the efficacy and safety of cerebrolysin added to risperidone in patients with schizophrenia dominated by negative symptoms. METHODS: The trial was a double-blind, placebo-controlled, parallel-group design. A total of 109 patients who met the DSM-IV diagnostic criteria for schizophrenia were randomly assigned to cerebrolysin (cerebrolysin plus risperidone, n=55) or placebo (risperidone only, n=54) groups. Intravenous infusions of 30 ml cerebrolysin or placebo were given once daily from Monday to Friday for 4 weeks. Efficacy was assessed with measurements including the Positive and Negative Symptoms Scale (PANSS), Wechsler Memory Scale (WMS), modified Chinese Wechsler Adult Intelligence Scale (mWAIS). and Clinical Global Impression (CGI). RESULTS: Patients in both groups demonstrated improvements in psychiatric symptoms and cognitive and memory performance as assessed by PANSS, mWAIS, and WMS over the trial. There was no difference in rates of change in the PANSS total score or negative score between the two treatment groups. Patients treated with cerebrolysin showed significantly greater improvements in cognitive and memory function from week 2. No severe treatment adverse events were observed in either group. The frequency of adverse events was comparable between the two groups at the end of the treatment. CONCLUSION: Cerebrolysin added to risperidone did not augment the efficacy of risperidone in treating the psychotic symptoms of schizophrenia patients over an 8-week trial. Cerebrolysin at 30 ml per day as an adjunctive treatment was safe and may improve cognitive and memory functions of patients with schizophrenia dominated by negative symptoms.

Future research on dementia relating to culturally and linguistically diverse communities.

About one in five older Australians were born overseas. However, there has been very little information published in Australia or internationally about dementia in persons from culturally and linguistically diverse (CALD) backgrounds. This limits our ability to plan for and provide evidence-based medical care, social care and aged care services to persons from CALD backgrounds. This paper describes challenges to conducting CALD dementia research; these include sampling, having valid instruments and costs. Nine key research recommendations in the areas of epidemiology, community knowledge, carers, service delivery, screening and assessment, medical management, residential aged care and minority CALD reached by consensus by an expert group are presented. The paper closes with some strategies to encourage CALD research. The material presented here will provide guidance for future research endeavours.

Differences in psychological morbidity among Australian and Chinese caregivers of persons with dementia in residential care.

OBJECTIVE: The aim of the present study was to determine the effects of culture on caregiver psychological morbidity among informal caregivers of institutionalised persons with dementia in three different populations: (1) Shanghai, (2) Australian-Chinese and (3) Australian mainstream (non-Chinese). METHODS: Caregivers and residents with dementia were recruited from (1) a dementia hospital in Shanghai, (2) three ethno-specific Chinese nursing homes in Sydney and (3) four mainstream nursing homes in Sydney. Psychological morbidity was assessed using the Geriatric Depression Scale, mental health component (MHC) of the RAND-36 Health Status Inventory and a guilt scale. RESULTS: There were no significant differences between the three groups as measured by the guilt scale and MHC. Shanghai caregivers had higher mean depression scores than Australian-Chinese caregivers (p < 0.001), who in turn had higher mean depression scores than Australian mainstream caregivers (p = 0.015). Higher depression scores were found to be inversely associated with the caregiver's education level and physical health status, and associated with increased frequency of nursing home visits, but not with levels of behavioural and psychological symptoms of dementia (BPSD). CONCLUSION: Levels of depression in caregivers of institutionalised persons with dementia differ by culture and country of residence.

A pilot study of differences in behavioral and psychological symptoms of dementia in nursing home residents in Sydney and Shanghai.

BACKGROUND: There are limited cross-cultural studies of behavioral and psychological symptoms of dementia (BPSD). The aim of the present study was to increase understanding of the effects of culture on BPSD by comparing the rates of BPSD in nursing home residents across three residential facility types: (1) mainstream nursing homes in Sydney, (2) ethno-specific Chinese nursing homes in Sydney, and (3) a long-term high care facility in Shanghai known as a dementia hospital. METHODS: 149 residents and their caregivers voluntarily participated in this study. The rates and levels of BPSD were assessed by interviewing staff with the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH). Clinical interviews using the Mini-mental State Examination (MMSE) and Global Deterioration Scale (GDS) were conducted with residents to assess dementia severity. RESULTS: The mean NPI-NH total score for the sample was 28.5 (SD = 17.2) with no significant differences across the three facility types. Comparison of NPI-NH subscales showed residents from the ethno-specific Chinese facilities had lower rates of hallucinations than Shanghai residents (p = 0.003), but no differences from those in mainstream facilities. Shanghai residents had lower frequencies of disinhibition and irritability than ethno-specific Chinese residents (p = 0.003, p = 0.004 respectively), but no differences with mainstream residents. CONCLUSION: The prevalence of BPSD does not differ among nursing home populations of different cultural backgrounds. Longitudinal community studies among different cultural groups would better elucidate the effects of culture on BPSD at different stages of dementia.