Integrated whole transcriptome and DNA methylation analysis identifies gene networks specific to late-onset Alzheimer’s disease

Previous transcriptome studies observed disrupted cellular processes in late-onset Alzheimer\u27s disease (LOAD), yet it is unclear whether these changes are specific to LOAD, or are common to general neurodegeneration. In this study, we address this question by examining transcription in LOAD and comparing it to cognitively normal controls and a cohort of disease controls. Differential transcription was examined using RNA-seq, which allows for the examination of protein coding genes, non-coding RNAs, and splicing. Significant transcription differences specific to LOAD were observed in five genes: C10orf105, DIO2, a lincRNA, RARRES3, and WIF1. These findings were replicated in two independent publicly available microarray data sets. Network analyses, performed on 2,504 genes with moderate transcription differences in LOAD, reveal that these genes aggregate into seven networks. Two networks involved in myelination and innate immune response specifically correlated to LOAD. FRMD4B and ST18, hub genes within the myelination network, were previously implicated in LOAD. Of the five significant genes, WIF1 and RARRES3 are directly implicated in the myelination process; the other three genes are located within the network. LOAD specific changes in DNA methylation were located throughout the genome and substantial changes in methylation were identified within the myelination network. Splicing differences specific to LOAD were observed across the genome and were decreased in all seven networks. DNA methylation had reduced influence on transcription within LOAD in the myelination network when compared to both controls. These results hint at the molecular underpinnings of LOAD and indicate several key processes, genes, and networks specific to the disease

Smoking, dementia and cognitive decline in the elderly, a systematic review.

Background. Nicotine may aid reaction time, learning and memory, but smoking increases cardiovascular risk. Cardiovascular risk factors have been linked to increased risk of dementia. A previous meta-analysis found that current smokers were at higher risk of subsequent dementia, Alzheimers disease, vascular dementia and cognitive decline. Methods. In order to update and examine this further a systematic review and meta-analysis was carried out using different search and inclusion criteria, database selection and more recent publications. Both reviews were restricted to those aged 65 and over. Results. The review reported here found a significantly increased risk of Alzheimers disease with current smoking and a likely but not significantly increased risk of vascular dementia, dementia unspecified and cognitive decline. Neither review found clear relationships with former smoking. Conclusion. Current smoking increases risk of Alzheimers disease and may increase risk of other dementias. This reinforces need for smoking cessation, particularly aged 65 and over. Nicotine alone needs further investigation. © 2008 Peters et al; licensee BioMed Central Ltd

A REVIEW ON ALZHEIMERS DISEASE AND ITS CONCEPTS IN AYURVEDA

Alzheimers disease is the form of dementia and usually occur in the old age. In Alzheimers disease death of brain cells leads to memory loss. Modern science says Aβ (amyloid beta) is causative agent of Alzheimers disease and also some infections, toxins and metabolic disorders. The cholinergic deficiency in this disease is responsible for most of the short term memory which leads to progressive loss of memory, deterioration of all intellectual functions, increases apathy, decreases speech function, disorientation and gait irregularities. Modern science have explained symptomatic treatment which may lead to adverse effects. Ayurveda has explained Alzheimers disease under Vatavyadhi which may be cause due to imbalance of Vatadosha. Ayurveda has mentioned some herbs which are said as tonics for nervous system and memory enhancers which not only act on brain cells but whole nervous system. Exact mechanism of these drugs is not clear but some of them have valuable compounds that show their roles on pharmacological activities. Yoga and meditation is most helpful in disorders related to nervous system. According to research patients who performed meditation and yoga those had less atrophy in parts of the brain. This review article helps to know about Alzheimers disease in modern and Ayurvedic view and some individual herbs and some new things which play a very crucial role in Alzheimers disease

Empirically Defining Trajectories of Late-Life Cognitive and Functional Decline

Background: Alzheimer’s disease (AD) is associated with variable cognitive and functional decline, and it is difficult to predict who will develop the disease and how they will progress. Objective: This exploratory study aimed to define latent classes from participants in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database who had similar growth patterns of both cognitive and functional change using Growth Mixture Modeling (GMM), identify characteristics associated with those trajectories, and develop a decision tree using clinical predictors to determine which trajectory, as determined by GMM, individuals will most likely follow. Methods: We used ADNI early mild cognitive impairment (EMCI), late MCI (LMCI), AD dementia, and healthy control (HC) participants with known amyloid-β status and follow-up assessments on the Alzheimer’s Disease Assessment Scale - Cognitive Subscale or the Functional Activities Questionnaire (FAQ) up to 24 months postbaseline. GMM defined trajectories. Classification and Regression Tree (CART) used certain baseline variables to predict likely trajectory path. Results: GMM identified three trajectory classes (C): C1 (n = 162, 13.6%) highest baseline impairment and steepest pattern of cognitive/functional decline; C3 (n = 819, 68.7%) lowest baseline impairment and minimal change on both; C2 (n = 211, 17.7%) intermediate pattern, worsening on both, but less steep than C1. C3 had fewer amyloid- or apolipoprotein-E ɛ4 (APOE4) positive and more healthy controls (HC) or EMCI cases. CART analysis identified two decision nodes using the FAQ to predict likely class with 82.3% estimated accuracy. Conclusions: Cognitive/functional change followed three trajectories with greater baseline impairment and amyloid and APOE4 positivity associated with greater progression. FAQ may predict trajectory class

Factors underpinning caregiver burden in frontotemporal dementia differ in spouses and their children

The objectives of this observational study were to (1) compare spousal and child caregiver burden; (2) compare co-resident and live-out child caregiver burden; and (3) investigate factors influencing spousal and child caregiver burden. Data was collected from 90 caregivers of people with frontotemporal degeneration (FTD) recruited from the Frontotemporal Dementia Research Group (Frontier) at Neuroscience Research, Australia. Of this caregiver group, 43 were spousal caregivers and 47 were child caregivers. Caregiver burden and emotional state were evaluated using the short Zarit Burden Interview and the short version of the Depression, Anxiety and Stress Scale-21. The Social Network Index was applied to ascertain the social network of the caregiver, while the Intimate Bond Measure was used to evaluate the current quality of the relationship between the caregiver and the person with dementia. The Frontotemporal Dementia Rating Scale was used to assess severity of dementia. Spousal and child caregivers experienced similar levels of burden, depression, anxiety, and stress, regardless of disease severity. Co-resident child caregivers had smaller social networks and greater burden than live-out caregivers. Dementia severity was key in spousal caregiver burden, whereas caregiver depression was most important in child caregiver burden. Child and spousal caregivers of individuals with FTD share similar levels of burden, influenced by different factors. Future interventions need to account for these differences