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Clinical Neurophysiology : Official... Oct 2021Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability,... (Review)
Review
Transcranial magnetic stimulation (TMS) is a powerful tool to probe in vivo brain circuits, as it allows to assess several cortical properties such asexcitability, plasticity and connectivity in humans. In the last 20 years, TMS has been applied to patients with dementia, enabling the identification of potential markers of thepathophysiology and predictors of cognitive decline; moreover, applied repetitively, TMS holds promise as a potential therapeutic intervention. The objective of this paper is to present a comprehensive review of studies that have employed TMS in dementia and to discuss potential clinical applications, from the diagnosis to the treatment. To provide a technical and theoretical framework, we first present an overview of the basic physiological mechanisms of the application of TMS to assess cortical excitability, excitation and inhibition balance, mechanisms of plasticity and cortico-cortical connectivity in the human brain. We then review the insights gained by TMS techniques into the pathophysiology and predictors of progression and response to treatment in dementias, including Alzheimer's disease (AD)-related dementias and secondary dementias. We show that while a single TMS measure offers low specificity, the use of a panel of measures and/or neurophysiological index can support the clinical diagnosis and predict progression. In the last part of the article, we discuss the therapeutic uses of TMS. So far, only repetitive TMS (rTMS) over the left dorsolateral prefrontal cortex and multisite rTMS associated with cognitive training have been shown to be, respectively, possibly (Level C of evidence) and probably (Level B of evidence) effective to improve cognition, apathy, memory, and language in AD patients, especially at a mild/early stage of the disease. The clinical use of this type of treatment warrants the combination of brain imaging techniques and/or electrophysiological tools to elucidate neurobiological effects of neurostimulation and to optimally tailor rTMS treatment protocols in individual patients or specific patient subgroups with dementia or mild cognitive impairment.
Topics: Brain; Dementia; Electroencephalography; Humans; Neuronal Plasticity; Transcranial Magnetic Stimulation
PubMed: 34482205
DOI: 10.1016/j.clinph.2021.05.035 -
Current Opinion in Ophthalmology Nov 2021Dementia is a term for loss of memory, language, problem-solving, and other thinking abilities, which significantly interferes with daily life. Certain dementing... (Review)
Review
PURPOSE OF REVIEW
Dementia is a term for loss of memory, language, problem-solving, and other thinking abilities, which significantly interferes with daily life. Certain dementing conditions may also affect visual function. The eye is an accessible window to the brain that can provide valuable information for the early diagnosis of people who suffer from Alzheimer's disease, Parkinson's disease, dementia with Lewy bodies as well as from more rare causes of dementias, such as Creutzfeldt-Jacob and Huntington's diseases. Herein, we present the ocular manifestations of neurocognitive disorders focusing on the neuro-ophthalmic ones and further discuss potential ocular biomarkers that could help in early detection of these disorders.
RECENT FINDINGS
Ophthalmic examination along with the recent developments in in-vivo testing have provided a strong foundation of useful knowledge about brain disorder in neurodegenerative diseases without the need for invasive studies. Currently, a number of visual measures, such as visual acuity, contrast sensitivity, pupil response, and saccades in addition to various ophthalmic tests, such as electroretinogram, visual evoked potential, optical coherence tomography (OCT), and OCT-angiography have been widely used and evaluated as potential biomarkers for different stages of dementia.
SUMMARY
Ophthalmologic and neuro-ophthalmic evaluation is evolving as an important part of the early diagnosis and management of people with dementia. A particular focus on ocular biomarkers in dementing illnesses has arisen over the past few years and there are several promising measures and imaging tools that have been proposed as potential biomarkers for these diseases.
Topics: Alzheimer Disease; Brain; Evoked Potentials, Visual; Humans; Huntington Disease; Parkinson Disease
PubMed: 34494975
DOI: 10.1097/ICU.0000000000000807 -
Arquivos de Neuro-psiquiatria May 2022The field of neurodegenerative dementia genetics has advanced significantly over the past two decades, but there are still more to be discovered (such as the gene... (Review)
Review
BACKGROUND
The field of neurodegenerative dementia genetics has advanced significantly over the past two decades, but there are still more to be discovered (such as the gene mutation in some familial forms of dementia).
OBJECTIVE
to provide a brief review of the most recent discoveries regarding monogenic dementia, and covering the most frequent genetic diseases that can cause dementia (neurodegenerative or not).
METHODS
a review of the literature will be carried out.
RESULTS
neurodegenerative dementias, vascular dementias and leukoencephalopathies caused by single pathogenic variants are presented.
CONCLUSION
The spectrum of clinical presentations for most of the genes discussed is wide, and hence genetic testing in clinic should try to cover as many genes as possible.
Topics: Dementia; Humans; Mutation
PubMed: 35976293
DOI: 10.1590/0004-282X-ANP-2022-S103 -
La Revue Du Praticien Jan 2021
Topics: Alzheimer Disease; Dementia; Humans; Tomography, X-Ray Computed
PubMed: 34160961
DOI: No ID Found -
Environmental Research Nov 2023The ageing population has been steadily increasing worldwide, leading to a higher risk of cognitive decline and dementia. Environmental toxicants, particularly metals,... (Review)
Review
The ageing population has been steadily increasing worldwide, leading to a higher risk of cognitive decline and dementia. Environmental toxicants, particularly metals, have been identified as modifiable risk factors for cognitive impairment. Continuous exposure to metals occurs mainly through dietary sources, with older adults being particularly vulnerable. However, imbalances in the gut microbiota, known as dysbiosis, have also been associated with dementia. A literature review was conducted to explore the potential role of metals in the development of cognitive decline and the most prevalent primary neurodegenerative dementias, as well as their interaction with the gut microbiota. High levels of iron (Fe) and copper (Cu) are associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD), while low selenium (Se) levels are linked to poor cognitive status. Parkinson's disease dementia (PDD) is associated with elevated levels of iron (Fe), manganese (Mn), and zinc (Zn), but the role of copper (Cu) remains unclear. The relationship between metals and Lewy body dementia (LBD) requires further investigation. High aluminium (Al) exposure is associated with frontotemporal dementia (FTD), and elevated selenium (Se) levels may be linked to its onset. Challenges in comparing studies arise from the heterogeneity of metal analysis matrices and analytical techniques, as well as the limitations of small study cohorts. More research is needed to understand the influence of metals on cognition through the gut microbiota (GMB) and its potential relevance in the development of these diseases.
Topics: Humans; Aged; Dementia; Copper; Selenium; Parkinson Disease; Metals; Alzheimer Disease; Cognitive Dysfunction; Iron
PubMed: 37487923
DOI: 10.1016/j.envres.2023.116722 -
Seminars in Nuclear Medicine May 2021Imaging has made an immense contribution toward supporting the diagnosis of dementias, detecting preclinical and prodromal pathology, and allowing disease progression to... (Review)
Review
Imaging has made an immense contribution toward supporting the diagnosis of dementias, detecting preclinical and prodromal pathology, and allowing disease progression to be objectively tracked. This has led to consensus guidelines for the use of imaging in dementias to be published and a future task will be to validate these guidelines. Additionally, there needs to be standardised approaches over the use of binary thresholds when assigning an abnormality status. Other medical unmet needs include the need for specific imaging markers of (1) linear tau tangles, TDP-43 and alpha synuclein aggregates; (2) microglial phenotypes that throw light on the activity of these inflammatory cells; (3) activity of intracellular processes which normally act to clear misfolded proteins; (4) epigenetic activity which regulates gene expression. Future imaging studies are predicted to be active in all these areas. Finally, as safer and more effective immunotherapy and other protective strategies against the pathologies of dementias are developed and trialed, imaging will play a major future role in determining the efficacy of neuroprotective treatments and their mechanism of action to be examined.
Topics: Biomarkers; Dementia; Diagnostic Imaging; Disease Progression; Humans; tau Proteins
PubMed: 33353722
DOI: 10.1053/j.semnuclmed.2020.12.001 -
Innere Medizin (Heidelberg, Germany) Feb 2023The prevalence of dementia increases with age. In rare cases, people younger than 65 years old are also affected, with substantial consequences for the professional... (Review)
Review
The prevalence of dementia increases with age. In rare cases, people younger than 65 years old are also affected, with substantial consequences for the professional life. The symptoms depend on the form of dementia and can vary individually. Impairment of short-term memory is not always in the foreground and other neurocognitive domains, such as the disturbance of executive functions can have a significant impact on the ability to cope with everyday life. Pathophysiologically, neurodegenerative dementias with the major forms of Alzheimer's dementia, Lewy body dementia, and frontotemporal dementia are distinguished from vascular dementias. Mixed forms are common. There is no curative treatment, but progression can be slowed by nonpharmacological measures and, especially in Alzheimer's dementia, by pharmacological treatment. Appropriate measures can promote independence and autonomy for as long as possible; however, in the course of the disease restrictions in the extended activities of independent living will initially occur, such as banking transactions, use of means of transport and, in the further course, also in the basic activities of daily living. Legal capacity and the ability to consent to health interventions are restricted sooner or later; however, this must always be evaluated for the specific situation and is not generally the case with the diagnosis of dementia. Instruments such as living wills, identification of a health care proxy, and advanced care planning should be used at an early stage. To decrease family caregiver burden with the increased risk of developing depression, supportive, accompanying measures and education are of great importance.
Topics: Humans; Aged; Alzheimer Disease; Activities of Daily Living; Lewy Body Disease; Caregivers; Frontotemporal Dementia
PubMed: 36692517
DOI: 10.1007/s00108-022-01462-1 -
Journal of Alzheimer's Disease : JAD 2023Lewy body dementia is the third most common and costliest type of dementia. It is an umbrella term for dementia with Lewy bodies and Parkinson's disease dementia, both... (Review)
Review
Lewy body dementia is the third most common and costliest type of dementia. It is an umbrella term for dementia with Lewy bodies and Parkinson's disease dementia, both of which place a substantial burden on the person and society. Recent findings outline ethnoracial differences in dementia risk. Delayed and misdiagnosis across ethnoracial groups contribute to higher levels of burden. In this context, we aimed to summarize current knowledge, gaps, and unmet needs relating to race and ethnicity in Lewy body dementia. In this narrative review, we provide an overview of studies on Lewy body dementia focusing on differences across ethnoracial groups and outline several recommendations for future studies. The majority of the findings comparing different ethnoracial groups were from North American sites. There were no differences in clinical prevalence and progression across ethnoracial groups. Compared to people identifying as non-Hispanic White, co-pathologies were more common and clinical diagnostic accuracy was lower for people identifying as Black. Co-morbidities (e.g., diabetes, hypertension) were more common and medication use rates (e.g., antidepressants, antiparkinsonian agents) were lower for people identifying as Black or Hispanic compared to people identifying as White. More than 90% of clinical trial participants identified as non-Hispanic White. Despite increasing efforts to overcome disparities in Alzheimer's disease and related dementias, inclusion of individuals from minoritized communities in Lewy body dementia studies continues to be limited and the findings are inconclusive. Representation of diverse populations is crucial to improve the diagnostic and therapeutic efforts in Lewy body dementia.
Topics: Humans; Lewy Body Disease; Dementia; Ethnicity; Parkinson Disease; Alzheimer Disease
PubMed: 37355902
DOI: 10.3233/JAD-230207 -
Advances in Experimental Medicine and... 2020Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation or mutations of the neuronal... (Review)
Review
Tauopathies are a heterogeneous group of neurodegenerative dementias involving perturbations in the levels, phosphorylation or mutations of the neuronal microtubule-binding protein Tau. Tauopathies are characterized by accumulation of hyperphosphorylated Tau leading to formation of a range of aggregates including macromolecular ensembles such as Paired Helical filaments and Neurofibrilary Tangles whose morphology characterizes and differentiates these disease states. Why nonphysiological Tau proteins elude the surveillance normal proteostatic mechanisms and eventually form these macromolecular assemblies is a central mostly unresolved question of cardinal importance for diagnoses and potential therapeutic interventions. We discuss the response of the Ubiquitin-Proteasome system, autophagy and the Endoplasmic Reticulum-Unfolded Protein response in Tauopathy models and patients, revealing interactions of components of these systems with Tau, but also of the effects of pathological Tau on these systems which eventually lead to Tau aggregation and accumulation. These interactions point to potential disease biomarkers and future potential therapeutic targets.
Topics: Dementia; Humans; Neurofibrillary Tangles; Phosphorylation; Proteasome Endopeptidase Complex; Proteostasis; Tauopathies; Ubiquitin; tau Proteins
PubMed: 32274757
DOI: 10.1007/978-3-030-38266-7_7 -
Current Neuropharmacology 2021Dementia is a collection of symptoms affecting a person's cognition. Dementia is debilitating, and therefore, finding an effective treatment is of utmost importance.... (Review)
Review
Dementia is a collection of symptoms affecting a person's cognition. Dementia is debilitating, and therefore, finding an effective treatment is of utmost importance. Resveratrol, which exhibits neuroprotective effects, has low bioavailability. However, its glucoside polydatin is more bioavailable. Here, the evidence that supports the protective role of polydatin against dementia- related diseases such as Alzheimer's disease, vascular dementia, alcohol-related dementia, and Lewy body dementias is presented. The beneficial effects of polydatin from a mechanistic perspective are specifically emphasized in this review. Future directions in this area of research are also discussed.
Topics: Alzheimer Disease; Dementia; Glucosides; Humans; Lewy Body Disease; Stilbenes
PubMed: 32525774
DOI: 10.2174/1570159X18666200611144825