Dementia & Alzheimer’s

BACKGROUND: People with dementia in nursing homes often experience pain, but often do not receive adequate pain therapy. The experience of pain has a significant impact on quality of life in people with dementia, and is associated with negative health outcomes. Untreated pain is also considered to be one of the causes of challenging behaviour, such as agitation or aggression, in this population. One approach to reducing pain in people with dementia in nursing homes is an algorithm-based pain management strategy, i...

BACKGROUND: Remote cognitive assessments are increasingly needed to assist in the detection of cognitive disorders, but the diagnostic accuracy of telephone- and video-based cognitive screening remains unclear. OBJECTIVES: To assess the test accuracy of any multidomain cognitive test delivered remotely for the diagnosis of any form of dementia. To assess for potential differences in cognitive test scoring when using a remote platform, and where a remote screener was compared to the equivalent face-to-face test...

BACKGROUND: Experiencing anxiety and depression is very common in people living with dementia and mild cognitive impairment (MCI). There is uncertainty about the best treatment approach. Drug treatments may be ineffective and associated with adverse effects. Guidelines recommend psychological treatments. In this updated systematic review, we investigated the effectiveness of different psychological treatment approaches. OBJECTIVES: Primary objective To assess the clinical effectiveness of psychological interventions in reducing depression and anxiety in people with dementia or MCI...

BACKGROUND: In primary care, general practitioners (GPs) unavoidably reach a clinical judgement about a patient as part of their encounter with patients, and so clinical judgement can be an important part of the diagnostic evaluation. Typically clinical decision making about what to do next for a patient incorporates clinical judgement about the diagnosis with severity of symptoms and patient factors, such as their ideas and expectations for treatment. When evaluating patients for dementia, many GPs report using their own judgement to evaluate cognition, using information that is immediately available at the point of care, to decide whether someone has or does not have dementia, rather than more formal tests...

BACKGROUND: Alzheimer's disease is a progressive, irreversible, and fatal disease for which accumulation of amyloid beta is thought to play a key role in pathogenesis. Aducanumab is a human monoclonal antibody directed against aggregated soluble and insoluble forms of amyloid beta. OBJECTIVES: We evaluated the efficacy and safety of aducanumab in early Alzheimer's disease. DESIGN: EMERGE and ENGAGE were two randomized, double-blind, placebo-controlled, global, phase 3 studies of aducanumab in patients with early Alzheimer's disease...

Amyloid-related imaging abnormalities (ARIA) are adverse events reported in Alzheimer's disease trials of anti-amyloid beta (Aβ) therapies. This review summarizes the existing literature on ARIA, including bapineuzumab, gantenerumab, donanemab, lecanemab, and aducanumab studies, with regard to potential risk factors, detection, and management. The pathophysiology of ARIA is unclear, but it may be related to binding of antibodies to accumulated Aβ in both the cerebral parenchyma and vasculature, resulting in loss of vessel wall integrity and increased leakage into surrounding tissues...

In this article we address how the recent, and anticipated upcoming, FDA approvals of novel anti-amyloid medications to treat individuals with mild Alzheimer's disease (AD) dementia could impact disclosure of biomarker results among asymptomatic research participants. Currently, research is typically the context where an asymptomatic individual may have the option to learn their amyloid biomarker status. Asymptomatic research participants who learn their amyloid status may have questions regarding the meaning of this result and the implications for accessing a potential intervention...

Neuropsychological assessment using the Boston Process Approach (BPA) suggests that an analysis of the strategy or the process by which tasks and neuropsychological tests are completed, and the errors made during test completion convey much information regarding underlying brain and cognition and are as important as overall summary scores. Research over the last several decades employing an analysis of process and errors has been able to dissociate between dementia patients diagnosed with Alzheimer's disease, vascular dementia associated with MRI-determined white matter alterations, and Parkinson's disease; and between mild cognitive impairment subtypes...

A new paradigm of cell therapy-based approaches as a solution to several diseases caused by damage or loss of cells/tissues leading to organ failure heralded the birth of a new branch in medicine called regenerative medicine (RM), which was further fueled by in vitro cell expansion and tissue engineering (TE) technologies, including the ability to grow embryonic stem cells, induce pluripotent stem cells, and so on. RM addresses organ failure by repair, regeneration, or restoration, rejuvenation using cells, stem cells, or progenitor cells as tools having added cell-derived products also as a tool, and extracellular matrix component-based support, either direct or indirect (e...

Alzheimer's disease (AD) is the most common cause of dementia globally. There is increasing evidence showing AD has no single pathogenic mechanism, and thus treatment approaches focusing only on one mechanism are unlikely to be meaningfully effective. With only one potentially disease modifying treatment approved, targeting amyloid-β (Aβ), AD is underserved regarding effective drug treatments. Combining multiple drugs or designing treatments that target multiple pathways could be an effective therapeutic approach...

Alzheimer's disease (AD) is a neurodegenerative disease of unknown pathological origin. The clinical diagnosis of AD is time-consuming and needs to a combination of clinical evaluation, psychological testing, and imaging assessments. Biomarkers may be good indicators for the clinical diagnosis of AD; hence, it is important to identify suitable biomarkers for the diagnosis and treatment of AD. Peripheral inflammatory biomarkers have been the focus of research in recent years. This review summarizes the role of inflammatory biomarkers in the disease course of AD...

COVID-19 emerged as a global pandemic starting from Wuhan in China and spread at a lightning speed to the rest of the world. One of the potential long-term outcomes that we speculate is the development of neurodegenerative diseases as a long-term consequence of SARS-CoV-2 especially in people that have developed severe neurological symptoms. Severe inflammatory reactions and aging are two very strong common links between neurodegenerative diseases and COVID-19. Thus, patients that have very high viral load may be at high risk of developing long-term adverse neurological consequences such as dementia...

Given the complex bidirectional communication system that exists between the gut microbiome and the brain, there is growing interest in the gut microbiome as a novel and potentially modifiable risk factor for Alzheimer's disease (AD). Gut dysbiosis has been implicated in the pathogenesis and progression of AD by initiating and prolonging neuroinflammatory processes. The metabolites of gut microbiota appear to be critical in the mechanism of the gut-brain axis. Gut microbiota metabolites, such as trimethylamine-n-oxide, lipopolysaccharide, and short chain fatty acids, are suggested to mediate systemic inflammation and intracerebral amyloidosis via endothelial dysfunction...

BACKGROUND: Research on music therapy for dementia has taken a variety of measures and has been slow to consolidate evidence. Examining the outcomes that are currently being investigated and the measures that have been used can be useful for future research on music therapy for dementia. OBJECTIVES: This study used cited original papers from a review in the Cochrane Database of Systematic Reviews to determine if there are items that should be measured or scales that should be used in conducting research on music therapy for dementia...

BACKGROUND: Neuropsychiatric symptoms (NPS) are common in individuals with Alzheimer's disease (AD) dementia, but substantial heterogeneity exists in the manifestation of NPS. Sex differences may explain this clinical variability. We aimed to investigate the sex differences in the prevalence and severity of NPS in AD dementia. METHODS: Literature searches were conducted in Embase, MEDLINE/PubMed, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, PsycINFO, and Google Scholar from inception to February 2021...

BACKGROUND: Tau positron emission tomography (PET) is increasing in popularity for biomarker characterization of Alzheimer's disease (AD), and recent frameworks rely on tau PET cut-points to stage individuals along the AD continuum. Given the lack of standardization in tau PET thresholding methods, this study sought to systematically canvass and characterize existing studies that have derived tau PET cut-points and then directly assess different methods of tau PET thresholding in terms of their concurrent validity...

BACKGROUND: The need for preventive therapies that interrupt the progression of Alzheimer's disease (AD) before the onset of symptoms or when symptoms are emerging is urgent and has spurred the ongoing development of disease-modifying therapies (DMTs) in preclinical and early AD (mild cognitive impairment [MCI] to mild dementia). Assessing the meaningfulness of what are likely small initial treatment effects in these earlier stages of the AD patho-clinical disease continuum is a major challenge and warrants further consideration...

BACKGROUND: Alzheimer's disease is the most prevalent cause of dementia in the elderly. Neuronal death and synaptic dysfunctions are considered the main hallmarks of this disease. The latter could be directly associated to an impaired metabolism. In particular, glucose metabolism impairment has demonstrated to be a key regulatory element in the onset and progression of AD, which is why nowadays AD is considered the type 3 diabetes. METHODS: We provide a thread regarding the influence of glucose metabolism in AD from three different perspectives: (i) as a regulator of the energy source, (ii) through several metabolic alterations, such as insulin resistance, that modify peripheral signaling pathways that influence activation of the immune system (e...

BACKGROUND: Drug development for neurodegenerative disorders (NDDs) is a long, complex, and expensive enterprise. Methods to optimize drug development for NDDs are needed. Basket trials have been widely used in oncology and have been promoted by the Food and Drug Administration as a means of enhancing the efficiency of drug development. DISCUSSION: We reviewed clinical trials for NDDs registered on clinicaltrials.gov in the past 10 years. We identified 59 basket trials assessing the impact of treatment on more than one NDD in the trial...

Introduction: Numerous studies have reported brain alterations in behavioral variant frontotemporal dementia (bvFTD). However, they pointed to inconsistent findings. Methods: We used a meta-analytic approach to identify the convergent structural and functional brain abnormalities in bvFTD. Following current best-practice neuroimaging meta-analysis guidelines, we searched PubMed and Embase databases and performed reference tracking. Then, the coordinates of group comparisons between bvFTD and controls from 73 studies were extracted and tested for convergence using activation likelihood estimation...