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The New England Journal of Medicine Sep 2015
Topics: Alzheimer Disease; Feeding Methods; Humans; Male; Palliative Care
PubMed: 26398085
DOI: 10.1056/NEJMc1509349 -
Biological Psychiatry Feb 2018Alzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder caused by fully penetrant single gene mutations in a minority of cases, while the... (Review)
Review
Alzheimer's disease (AD) is a genetically heterogeneous neurodegenerative disorder caused by fully penetrant single gene mutations in a minority of cases, while the majority of cases are sporadic or show modest familial clustering. These cases are of late onset and likely result from the interaction of many genes and the environment. More than 30 loci have been implicated in AD by a combination of linkage, genome-wide association, and whole genome/exome sequencing. We have learned from these studies that perturbations in endolysosomal, lipid metabolism, and immune response pathways substantially contribute to sporadic AD pathogenesis. We review here current knowledge about functions of AD susceptibility genes, highlighting cells of the myeloid lineage as drivers of at least part of the genetic component in late-onset AD. Although targeted resequencing utilized for the identification of causal variants has discovered coding mutations in some AD-associated genes, a lot of risk variants lie in noncoding regions. Here we discuss the use of functional genomics approaches that integrate transcriptomic, epigenetic, and endophenotype traits with systems biology to annotate genetic variants, and to facilitate discovery of AD risk genes. Further validation in cell culture and mouse models will be necessary to establish causality for these genes. This knowledge will allow mechanism-based design of novel therapeutic interventions in AD and promises coherent implementation of treatment in a personalized manner.
Topics: Alzheimer Disease; Animals; Genome-Wide Association Study; Humans
PubMed: 28666525
DOI: 10.1016/j.biopsych.2017.05.014 -
Annual Review of Pathology 2015Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) is the most common neuropathologic substrate of dementia. It is characterized by synapse loss... (Review)
Review
Alzheimer's disease/senile dementia of the Alzheimer type (AD/SDAT) is the most common neuropathologic substrate of dementia. It is characterized by synapse loss (predominantly within neocortex) as well as deposition of certain distinctive lesions (the result of protein misfolding) throughout the brain. The latter include senile plaques, composed mainly of an amyloid (Aβ) core and a neuritic component; neurofibrillary tangles, composed predominantly of hyperphosphorylated tau; and cerebral amyloid angiopathy, a microangiopathy affecting both cerebral cortical capillaries and arterioles and resulting from Aβ deposition within their walls or (in the case of capillaries) immediately adjacent brain parenchyma. In this article, I discuss the hypothesized role these lesions play in causing cerebral dysfunction, as well as CSF and neuroimaging biomarkers (for dementia) that are especially relevant as immunotherapeutic approaches are being developed to remove Aβ from the brain parenchyma. In addition, I address the role of neuropathology in characterizing the sequelae of new AD/SDAT therapies and helping to validate CSF and neuroimaging biomarkers of disease. Comorbidity of AD/SDAT and various types of cerebrovascular disease is a major theme in dementia research, especially as cognitive impairment develops in the oldest old, who are especially vulnerable to ischemic and hemorrhagic brain lesions.
Topics: Alzheimer Disease; Animals; Biomarkers; Brain; Dementia; Humans; Neurofibrillary Tangles; Plaque, Amyloid
PubMed: 25387055
DOI: 10.1146/annurev-pathol-020712-163927 -
Revue Medicale Suisse Oct 2023Dementia is an umbrella term used to describe a group of symptoms associated with a decline in cognitive abilities that are severe enough to interfere with daily...
Dementia is an umbrella term used to describe a group of symptoms associated with a decline in cognitive abilities that are severe enough to interfere with daily functioning and independence. While Alzheimer's disease (AD) is the most frequent cause, dementia in old aged persons represents rather a syndrome caused by various underlying conditions and diseases. Successful treatment allows for the individual clinical picture, and should be aimed at helping the patient regarding his cognitive deficits, behavioral and psychiatric complaints, sleep disorders, as well as management of daily life. Recently published promising study results on the use of monoclonal antibody therapies in AD give reason to believe that treatments will be available soon that can modulate disease progression at the neurobiological level.
Topics: Humans; Middle Aged; Aged; Alzheimer Disease; Cognition Disorders; Cognitive Dysfunction; Cognition; Disease Progression
PubMed: 37791694
DOI: 10.53738/REVMED.2023.19.844.1797 -
Nature Reviews. Neurology May 2022Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are... (Review)
Review
Alzheimer disease and related dementias present considerable challenges to health-care and medical systems worldwide. In the USA, older Black and Latino individuals are more likely than older white individuals to have Alzheimer disease and related dementias. In this Perspective, we leverage our experience and expertise with older US Latino groups to review and discuss the need to integrate cultural factors into dementia research and care. We examine the importance of considering the effects of cultural factors on clinical presentation and diagnosis, dementia risk, clinical research and recruitment, and caregiving practices, with a focus on minoritized groups in the USA. We highlight critical gaps in the literature to stimulate future research aimed at improving the prevention and early detection of Alzheimer disease and related dementias and developing novel treatments and interventions across ethnoracially diverse populations. In addition, we briefly discuss some of our own initiatives to promote research and clinical care among Latino populations living in the USA.
Topics: Alzheimer Disease; Hispanic or Latino; Humans
PubMed: 35260817
DOI: 10.1038/s41582-022-00630-z -
European Geriatric Medicine Feb 2024Dementia and Alzheimer's disease (AD) pose significant challenges to public health globally with no effective treatment strategies available. Therefore, the research... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Dementia and Alzheimer's disease (AD) pose significant challenges to public health globally with no effective treatment strategies available. Therefore, the research focuses on developing effective prophylaxis to prevent the onset of these diseases. Recent studies have suggested that low-dose aspirin may help reduce the risk of dementia. Nonetheless, evidence regarding the correlation between aspirin consumption and the onset of dementia and AD is limited. This review aims to provide an up-to-date summary of the existing evidence and evaluate the association between aspirin and the onset of dementia and Alzheimer's disease.
METHODS
A systematic search of PubMed, Embase, Web of Science, PsycINFO, and CINAHL databases was conducted to find eligible studies published until April 2023. A random-effects meta-analysis of the eligible studies was then performed to assess the link between aspirin use and the onset of dementia and Alzheimer's disease. Additionally, we conducted subgroup analyses to evaluate the overall effect of low-dose (75-100 mg) aspirin consumption on the onset of dementia and AD.
RESULTS
A total of 875 studies were identified, with only 22 meeting the inclusion criteria. There was no statistically significant impact of aspirin consumption on the onset of dementia (HR 1.13, 11 studies) or Alzheimer's disease (HR 0.91, 3 studies). Additionally, subgroup analysis showed that taking low doses of aspirin (75-100 mg) did not significantly affect the onset of either dementia (HR 0.96, 13 studies) or Alzheimer's disease (HR 0.85, 2 studies).
CONCLUSIONS
Aspirin use does not decrease the risk of dementia or AD, even when taken in low doses. However, the quality of the studies analyzed was inadequate, with only three randomized controlled trials included in the review. Future high-quality studies are needed to assess the effect of aspirin consumption on these diseases. These findings may assist clinicians in selecting appropriate prophylactic strategies for patients at risk of developing dementia and AD.
Topics: Humans; Alzheimer Disease; Aspirin
PubMed: 37870707
DOI: 10.1007/s41999-023-00877-9 -
Clinical Pharmacology and Therapeutics Jun 2015Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, health care systems, and economies,... (Review)
Review
Given the lack of effective treatments for late-onset Alzheimer's disease (LOAD) and the substantial burden on patients, families, health care systems, and economies, finding an effective therapy is one of the highest medical priorities. The past few years have seen a growing interest in the medicinal uses of cannabinoids, the bioactive components of the cannabis plant, including the treatment of LOAD and other physical conditions that are common in older people. Several in vitro and in vivo studies have demonstrated that cannabinoids can reduce oxidative stress, neuroinflammation, and the formation of amyloid plaques and neurofibrillary tangles, the key hallmarks of LOAD. In addition, in population-based studies, cannabinoids reduced dementia-related symptoms (e.g., behavioral disturbances). The current article provides an overview of the potential of cannabinoids in the treatment of LOAD and related neuropsychiatric symptoms in older people. We also discuss the efficacy, safety, and pharmacokinetics of cannabinoid-based drugs in older people with dementia.
Topics: Aging; Alzheimer Disease; Cannabinoids; Endocannabinoids; Humans
PubMed: 25788394
DOI: 10.1002/cpt.117 -
Journal of Alzheimer's Disease : JAD 2019According to the World Health Organization (WHO), dementia is a disorder that occurs as result of a neurodegenerative process in brain, and usually is chronic or... (Review)
Review
According to the World Health Organization (WHO), dementia is a disorder that occurs as result of a neurodegenerative process in brain, and usually is chronic or progressive by nature. Most descriptions of senile dementia date back to Alois Alzheimer. In 1906, Alzheimer described the first patient, Auguste Deter, who suffered from the disorder that later became known as Alzheimer's disease. Although, the history of the disease before 1906 is quite rich, little has been said about the contributions of ancient and medieval physicians to the understanding of dementia. Over the centuries, the concept of senile dementia changed from an inevitable mental decline with aging, to different sets of clinical features with narrow limits of diagnosis of a disease in its own right. Documentation of the historical origins of prevention, diagnosis, and therapies of dementia would make an important contribution to a more complete understanding of this pathological degeneration of dementia. The present review focuses on the contributions of Avicenna (AD 980-1037) to the development of diagnosis and the discovery of etiology of different forms of dementia, with the goal of revealing the extent to which dementia was understood in the golden age of Islam in Persia.
Topics: Alzheimer Disease; History, Medieval; Humans; Persia
PubMed: 31524162
DOI: 10.3233/JAD-190345 -
Molecular Neurobiology Jun 2019Over the past three decades, there has been constant postulation regarding the infectious etiology of Alzheimer disease (AD), which in turn suggests the vital role of... (Review)
Review
Over the past three decades, there has been constant postulation regarding the infectious etiology of Alzheimer disease (AD), which in turn suggests the vital role of various infectious agents in AD-associated inflammatory pathways. Recent findings indicate anti-microbial properties of Aβ, and suggest that Aβ production and deposition in AD might be induced by infectious agents. Several types of spirochetes have been associated to dementia, cortical atrophy, and pathological and biological hallmarks of AD. A significant association between AD spirochetes and other pathogens like HSV-1 and Chlamydia pneumonia has now become well established. In neurons infected by HSV-1 showed Aβ and hyperphosphorylated Tau accumulation. The expression of pro-inflammatory molecules have been found to be enhanced by specific bacterial ligands, and viral and bacterial DNA and RNA, thus activating the immune system. Aβ has now been established as anti-microbial peptide capable of inducing pore formation, thus justifying their infection-mediated accumulation. Thus, a proper combination of anti-inflammatory, anti-viral, and antibiotic therapeutics might potentially prevent the progression of AD. Here, we discussed the potential role of bacterial, fungi, and viral infections in AD causation and progression, and the potential-associated therapies to counter the AD condition.
Topics: Alzheimer Disease; Animals; Humans; Inflammation; Models, Biological; Nervous System
PubMed: 30338482
DOI: 10.1007/s12035-018-1388-y -
Translational Neurodegeneration Jan 2024Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that... (Review)
Review
Ageing is a crucial risk factor for Alzheimer's disease (AD) and is characterised by systemic changes in both intracellular and extracellular microenvironments that affect the entire body instead of a single organ. Understanding the specific mechanisms underlying the role of ageing in disease development can facilitate the treatment of ageing-related diseases, such as AD. Signs of brain ageing have been observed in both AD patients and animal models. Alleviating the pathological changes caused by brain ageing can dramatically ameliorate the amyloid beta- and tau-induced neuropathological and memory impairments, indicating that ageing plays a crucial role in the pathophysiological process of AD. In this review, we summarize the impact of several age-related factors on AD and propose that preventing pathological changes caused by brain ageing is a promising strategy for improving cognitive health.
Topics: Animals; Humans; Alzheimer Disease; Amyloid beta-Peptides; Aging; Brain; Memory Disorders
PubMed: 38254235
DOI: 10.1186/s40035-024-00397-x