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In these last few years, there has been a growing consensus in Europe and beyond on the need of increasing research on neurodegenerative diseases including Alzheimer's disease and other related dementias. The societal impact and financial consequences of these diseases are already being felt and will continue to grow with the projected rise in the elderly population. Currently, there are over 35 million individuals with dementia worldwide, a figure that will treble by the year 2050. It has been estimated that formal and informal dementia care costs a total of €445 billion (2009 data),' equivalent to 1 % of the global gross domestic product. It is therefore not surprising that the European Union supports various funding programmes in the hope of enhancing diagnosis, provide better treatment and improve care pathways and support for individuals with dementia, their caregivers and relatives. ; peer-reviewed

Fengjin Zhang,1,2 Linlan Jiang11Department of Pharmacy, General Hospital of Guangzhou Military Command, Guangzhou City, People's Republic of China; 2School of Bioscience and Bioengineering, South China University of Technology, Guangzhou City, People's Republic of ChinaAbstract: Amyloid-β plaques and neurofibrillary tangles are the main neuropathological hallmarks in Alzheimer's disease (AD), the most common cause of dementia in the elderly. However, it has become increasingly apparent that neuroinflammation plays a significant role in the pathophysiology of AD. This review summarizes the current status of neuroinflammation research related to AD, focusing on the connections between neuroinflammation and some inflammation factors in AD. Among these connections, we discuss the dysfunctional blood–brain barrier and alterations in the functional responses of microglia and astrocytes in this process. In addition, we summarize and discuss the role of intracellular signaling pathways involved in inflammatory responses in astrocytes and microglia, including the mitogen-activated protein kinase pathways, nuclear factor-kappa B cascade, and peroxisome proliferator–activated receptor-gamma transcription factors. Finally, the dysregulation of the control and release of pro- and anti-inflammatory cytokines and classic AD pathology (amyloid plaques and neurofibrillary tangles) in AD is also reviewed.Keywords: inflammation, blood–brain barrier, glial cells, intracellular signaling pathways, inflammatory factors

25 páginas, 6 figuras, 2 tablas ; Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele. ; This work was funded by a grant (EADB) from the EU Joint Programme – Neurodegenerative Disease Research. INSERM UMR1167 is also funded by the INSERM, Institut Pasteur de Lille, Lille Métropole Communauté Urbaine and French government's LABEX DISTALZ program (development of innovative strategies for a transdisciplinary approach to AD). Full consortium acknowledgements and funding are in the Supplementary Not ; Peer reviewed

BACKGROUND: Alzheimer's disease is the commonest cause of dementia affecting older people. One of the therapeutic strategies aimed at ameliorating the clinical manifestations of Alzheimer's disease is to enhance cholinergic neurotransmission in the brain by the use of cholinesterase inhibitors to delay the breakdown of acetylcholine released into synaptic clefts. Tacrine, the first of the cholinesterase inhibitors to undergo extensive trials for this purpose, was associated with significant adverse effects including hepatotoxicity. Other cholinesterase inhibitors, including rivastigmine, with superior properties in terms of specificity of action and lower risk of adverse effects have since been introduced. Rivastigmine has received approval for use in 60 countries including all member states of the European Union and the USA. OBJECTIVES: To determine the clinical efficacy and safety of rivastigmine for patients with dementia of Alzheimer's type. SEARCH METHODS: We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 2 March 2015 using the terms: Rivastigmine OR exelon OR ENA OR "SDZ ENA 713". ALOIS contains records of clinical trials identified from monthly searches of a number of major healthcare databases (Cochrane Library, MEDLINE, EMBASE, PsycINFO, CINAHL, LILACS), numerous trial registries and grey literature sources. SELECTION CRITERIA: We included all unconfounded, double‐blind, randomised, controlled trials in which treatment with rivastigmine was administered to patients with dementia of the Alzheimer's type for 12 weeks or more and its effects compared with those of placebo in a parallel group of patients, or where two formulations of rivastigmine were compared. DATA COLLECTION AND ANALYSIS: One review author (JSB) applied the study selection criteria, assessed the quality of studies and extracted data. MAIN RESULTS: A total of 13 trials met the inclusion criteria of the review. The trials had a duration of between 12 and 52 weeks. The older trials tested a ...

As late-onset alcohol consumption is rare, it often indicates a different underlying disorder. We present a case where late-onset alcohol drinking occurred during the onset of Alzheimer's disease.

AbstractThis study investigated the relational turning points experienced by caregiving spouses across the trajectory of Alzheimer's disease and related dementias. Data were collected using a modified version of the retrospective interviewing technique which facilitated close analysis of relational turning points and the role of communication in shaping and managing these turning points. Caregiving spouses described nine relational turning points across the disease trajectory. The turning points coalesced under four broad changes in the marital relationship: my spouse has dementia, from spouse to caregiver, my spouse is gone, and transcending dementia through love. Participants used five communication strategies to manage their relationships: having open and intimate conversations, avoiding confrontation, avoiding bringing attention to symptoms, engaging in daily conversations and activities, and communicating love and affection. Findings reveal the specific turning points that mark relational change across the disease trajectory and caregiving spouses' strategies to maintain their relationship through this prolonged end‐of‐life transition.

AbstractThis chapter focuses on new methods for the early detection of Alzheimer's disease, including brain imaging techniques and identification of genetic susceptibilities.

Alzheimer's disease is an illness of the brain. It causes large numbers of nerve cells in the brain to die. This affects a person's ability to remember things and think clearly. People with AD become forgetful and easily confused. They may have a hard time concentrating and behave in odd ways. These problems get worse as the illness gets worse, making it more difficult for caregivers. Caring for a person with Alzheimer's disease is a challenge that calls upon the patience, creativity, knowledge, and skills of each caregiver. This book is for those who provide in-home care for people with Alzhe

Traumatic brain injury (TBI) and post-traumatic stress disorder (PTSD) are signature injuries of the wars in Iraq and Afghanistan and have been linked to an increased risk of Alzheimer's disease (AD) and other dementias. A meeting hosted by the Alzheimer's Association and the Veterans' Health Research Institute (NCIRE) in May 2012 brought together experts from the U.S. military and academic medical centers around the world to discuss current evidence and hypotheses regarding the pathophysiological mechanisms linking TBI, PTSD, and AD. Studies underway in civilian and military populations were highlighted, along with new research initiatives such as a study to extend the Alzheimer's Disease Neuroimaging Initiative (ADNI) to a population of veterans exposed to TBI and PTSD. Greater collaboration and data sharing among diverse research groups is needed to advance an understanding and appropriate interventions in this continuum of military injuries and neurodegenerative disease in the aging veteran.