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Nature Aging May 2023The increasing number of people with dementia globally illustrates the urgent need to reduce dementia's scale and impact. Lifetime social participation may affect... (Review)
Review
The increasing number of people with dementia globally illustrates the urgent need to reduce dementia's scale and impact. Lifetime social participation may affect dementia risk by increasing cognitive reserve, and through brain maintenance by reducing stress and improving cerebrovascular health. It may therefore have important implications for individual behavior and public health policy aimed at reducing dementia burden. Observational study evidence indicates that greater social participation in midlife and late life is associated with 30-50% lower subsequent dementia risk, although some of this may not be causal. Social participation interventions have led to improved cognition but, partly due to short follow-up and small numbers of participants, no reduction in risk of dementia. We summarize the evidence linking social participation with dementia, discuss potential mechanisms by which social participation is likely to reduce and mitigate the impact of neuropathology in the brain, and consider the implications for future clinical and policy dementia prevention interventions.
Topics: Humans; Dementia; Social Participation; Brain; Cognition; Cognitive Reserve; Observational Studies as Topic
PubMed: 37202513
DOI: 10.1038/s43587-023-00387-0 -
Neuropharmacology May 2020Molecular genetics has been an invaluable tool to help understand the molecular basis of neurodegenerative dementias. In this review, we provide an overview of the... (Review)
Review
Molecular genetics has been an invaluable tool to help understand the molecular basis of neurodegenerative dementias. In this review, we provide an overview of the genetic architecture underlying some of the most prevalent causes of dementia, including Alzheimer's dementia, frontotemporal lobar degeneration, Lewy body dementia, and prion diseases. We also discuss the complexity of the human genome and how the novel technologies have revolutionized and accelerated the way we screen the variety of our DNA. Finally, we also provide some examples about how this genetic knowledge is being transferred into the clinic through personalized medicine. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
Topics: Alzheimer Disease; Animals; Dementia; Frontotemporal Lobar Degeneration; Genetic Testing; Humans; Lewy Body Disease; Neurodegenerative Diseases; Pharmacogenetics; Prion Diseases
PubMed: 32097768
DOI: 10.1016/j.neuropharm.2020.108014 -
Neurologic Clinics Feb 2020Neuroimaging provides a window on the biological events underlying dementia. Amyloid PET is positive in Alzheimer disease (AD) and some cases of diffuse Lewy body... (Review)
Review
Neuroimaging provides a window on the biological events underlying dementia. Amyloid PET is positive in Alzheimer disease (AD) and some cases of diffuse Lewy body disease, but negative in the frontotemporal dementias (FTDs). Tau PET using the current tracers shows the greatest signal in AD and a lesser signal in FTD. Quantifying volume loss with MRI and measuring metabolism with fluorodeoxyglucose PET helps separate different causes of dementia and follow their progression. Brain inflammation can be assessed with PET. Some of these techniques, still investigational, are likely to find their clinical niche in the near future.
Topics: Alzheimer Disease; Dementia; Disease Progression; Frontotemporal Dementia; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Neuroimaging; Positron-Emission Tomography; tau Proteins
PubMed: 31761062
DOI: 10.1016/j.ncl.2019.08.003 -
Neurological Sciences : Official... Apr 2019Over the past four decades, Alzheimer disease has become near synonymous with dementia and the amyloid/tau hypothesis as its dominant explanation. However, this monorail... (Review)
Review
Over the past four decades, Alzheimer disease has become near synonymous with dementia and the amyloid/tau hypothesis as its dominant explanation. However, this monorail approach to etiology has failed to yield a single disease-modifying drug. Part of the explanation stems from the fact that most dementias in the elderly result from interactive Alzheimer and cerebrovascular pathologies. Stroke and dementia share the same risk factors and their control is associated with a decrease in stroke and some dementias. Additionally, intensive control of risk factors and enhancement of protective factors improve cognition. Moreover, anticoagulation of atrial fibrillation patients decreases their chance of developing dementia by 48%. Preliminary data suggest that treating blood pressure to a target of 120 mmHg systolic compared to a target of 140 mmHg decreases the chances of mild cognitive impairment by 19%. The Berlin Manifesto establishes the scientific bases of "preventing dementia by preventing stroke." Enlarging our vista of dementia to include cerebrovascular disease offers the opportunity of preventing not only stroke, but some dementias, beginning now.
Topics: Cerebrovascular Disorders; Dementia; Humans
PubMed: 30666474
DOI: 10.1007/s10072-019-3714-1 -
Psychogeriatrics : the Official Journal... Mar 2015Sleep is a complex behavioural state, the ultimate functions of which remain poorly understood. It becomes more fragmented as we age, with more night-time awakenings and... (Review)
Review
Sleep is a complex behavioural state, the ultimate functions of which remain poorly understood. It becomes more fragmented as we age, with more night-time awakenings and greater tendency for daytime sleep. The magnitude of disordered sleep among individuals affected by dementia has been clearly demonstrated, and disturbed sleep is a major clinical problem in dementia. Comorbid insomnia and other sleep disturbances are common in patients with neurodegenerative disorders, such Alzheimer's disease and other dementing disorders. How and when sleep problems manifest themselves can depend on the type of dementia involved as well as the stage of the dementia. However, differences in sleep pattern presentation show more variation during the initial stages of dementias than they do during the later stages. Effective, pragmatic interventions are largely anecdotal and untested.
Topics: Aged; Alzheimer Disease; Comorbidity; Dementia; Disease Progression; Humans; Psychopathology; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders
PubMed: 25515641
DOI: 10.1111/psyg.12069 -
Cold Spring Harbor Perspectives in... Apr 2017Neurodegenerative dementias are clinically heterogeneous, progressive diseases with frequently overlapping symptoms, such as cognitive impairments and behavior and... (Review)
Review
Neurodegenerative dementias are clinically heterogeneous, progressive diseases with frequently overlapping symptoms, such as cognitive impairments and behavior and movement deficits. Although a majority of cases appear to be sporadic, there is a large genetic component that has yet to be fully explained. Here, we review the recent genetic and genomic findings pertaining to Alzheimer's disease, frontotemporal dementia, Lewy body dementia, and prion dementia. In this review, we describe causal and susceptibility genes identified for these dementias and discuss recent research pertaining to the molecular function of these genes. Of particular interest, there is a large overlap in clinical phenotypes, genes, and/or aggregating protein products involved in these diseases, as well as frequent comorbid presentation, indicating that these dementias may represent a continuum of syndromes rather than individual diseases.
Topics: Dementia; Genetic Predisposition to Disease; Humans; Neurodegenerative Diseases
PubMed: 27940516
DOI: 10.1101/cshperspect.a023705 -
Current Neurology and Neuroscience... Apr 2015The molecular mechanism of neuronal loss and synaptic damage in Alzheimer's disease (AD), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD) and Lewy body... (Review)
Review
The molecular mechanism of neuronal loss and synaptic damage in Alzheimer's disease (AD), Parkinson's disease dementia (PDD), frontotemporal dementia (FTD) and Lewy body dementia (LBD) is poorly understood and could differ among different types of neurodegenerative processes. However, the presence of neuroinflammation is a common feature of dementia. In this setting, reactive microgliosis, oxidative damage and mitochondrial dysfunction are associated with the pathogenesis of all types of neurodegenerative dementia. Moreover, an increased body of evidence suggests that microglia may play a central role in AD progression. In this paper, we review the scientific literature on neuroinflammation related to the most common neurodegenerative dementias (AD, PDD, FTD and LBD) focussing on the possible molecular mechanisms and the available clinical evidence. Furthermore, we discuss the neuroimaging techniques that are currently used for the study of neuroinflammation in human brain.
Topics: Brain; Dementia; Encephalitis; Humans; Neuroimaging
PubMed: 25716012
DOI: 10.1007/s11910-015-0531-7 -
Handbook of Clinical Neurology 2017Alzheimer disease, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia are the most common central nervous system disorders that cause progressive... (Review)
Review
Alzheimer disease, vascular dementia, dementia with Lewy bodies, and frontotemporal dementia are the most common central nervous system disorders that cause progressive neurocognitive dysfunction and ultimately dementia. A number of biomarkers for pathologies reflecting each condition have been developed. Here, we review these and give an overview of the current state of practice and research regarding cerebrospinal fluid biomarkers for these disorders. The chapter discusses both established (most of which are tau- and amyloid β-related) and upcoming biomarkers and details, wherever appropriate, clinical use and differential diagnostics aspects.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Biomarkers; Dementia; Frontotemporal Dementia; Humans; Lewy Body Disease; Microglia; tau Proteins
PubMed: 29110781
DOI: 10.1016/B978-0-12-804279-3.00006-X -
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 -
International Psychogeriatrics Aug 2018In many countries around the world, owing to the lack of specialists and equipment, delay up to a few years in help-seeking and getting diagnostic examinations for...
In many countries around the world, owing to the lack of specialists and equipment, delay up to a few years in help-seeking and getting diagnostic examinations for dementia is not uncommon (Sayegh and Knight, 2013), and this situation is considerably more serious in "atypical dementias" due to the challenge they present for differential diagnosis. For instance, a survey in the USA showed that misdiagnosis was common in patients with Lewy body dementia who, on average, saw at least three physicians over a year's time or more before getting the proper diagnosis (Lewy Body Dementia Association, 2010). Furthermore, in multiethnic communities, cultural and language barriers between practitioners and patients may lead to substantial delay as well (Sayegh and Knight, 2013).
Topics: Communication Barriers; Dementia; Diagnosis, Differential; Diagnostic Errors; Humans; Lewy Body Disease; Truth Disclosure
PubMed: 29208076
DOI: 10.1017/S1041610217002757