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Neuromolecular Medicine Dec 2023Obesity is a major global health concern, with prevalence rates rapidly rising due to increased availability of highly processed foods rich in fats and/or sugars and... (Review)
Review
Obesity is a major global health concern, with prevalence rates rapidly rising due to increased availability of highly processed foods rich in fats and/or sugars and technological advances promoting more sedentary behaviour. There is increasing evidence to suggest that obesity predisposes individuals to developing cognitive impairment and dementia. However, the relationship between the brain and the peripheral metabolic state is complex, and many of the underlying mechanisms of cognitive impairment in obesity are yet to be fully elucidated. To better understand the links between obesity and dementia, further work is required to determine pathological changes occurring in the brain during obesity. In this mini-review, we discuss the role of two pathological features of obesity (the gut-brain axis and systemic inflammation) and their potential contribution to dementia.
Topics: Humans; Obesity; Cognitive Dysfunction; Brain; Inflammation; Dementia
PubMed: 37086380
DOI: 10.1007/s12017-023-08746-1 -
Fortschritte Der Neurologie-Psychiatrie Mar 2024Dementia is common and will continue to grow in importance and numbers in the future. However, as causal treatment is not possible in most cases, prevention is...
Dementia is common and will continue to grow in importance and numbers in the future. However, as causal treatment is not possible in most cases, prevention is particularly important. This is not only aimed at cognitively healthy people, but is also a central element in all phases of the disease.
Topics: Humans; Dementia
PubMed: 38490216
DOI: 10.1055/a-2230-1845 -
Aging & Mental Health 2023The indirect experience of dementia mediated through the arts shapes our preconceptions, educating us to understand dementia, gaining a deeper appreciation of how it may...
The indirect experience of dementia mediated through the arts shapes our preconceptions, educating us to understand dementia, gaining a deeper appreciation of how it may affect an individual. By contrast dementia research has largely regarded the arts through an 'instrumental' lens. They are treated as complex psychosocial interventions. Evidence from research on the arts and dementia remains piecemeal because most studies are small and not all are well designed. For numerous reasons the arts warrant further evaluation and investigation in relation to their potential impact on people with dementia. That research needs to be better-designed and adequately funded if it is to advance knowledge in this field. This is fraught with difficulties: the arts are dynamic and interactive; the medium (intervention) can be affected unpredictably by those people who engage with it. Many creative activities are deliberately participatory; think of group singing or stand-up comedy. The influence of human variability in relation to arts interventions means that large studies are necessary to control for individual differences. Moreover, few studies of the arts in dementia have been designed adequately to account for the intra-group interaction that is characteristic of many arts activities. Then, there is a lack of clarity around the purpose of the arts in dementia. There is scope for the development and adoption of comprehensive theoretical frameworks to guide research into the arts and dementia. This editorial sets out to clarify some aspects of the arts in dementia in order to pave way for further work.
Topics: Humans; Art Therapy; Dementia; Singing
PubMed: 37132440
DOI: 10.1080/13607863.2023.2205827 -
Der Nervenarzt Mar 2024With increasing life expectancy, the prevalence of dementia is increasing worldwide. Dementia is among the greatest challenges for healthcare and social systems of the...
With increasing life expectancy, the prevalence of dementia is increasing worldwide. Dementia is among the greatest challenges for healthcare and social systems of the future. Approximately 40% of newly diagnosed cases of dementia are associated with risk factors that can potentially be influenced by preventive measures. Based on the evidence from longitudinal studies, systematic reviews and meta-analyses, the Lancet commission on dementia prevention, intervention and care has defined 12 risk factors that are associated with an increased risk for dementia: low level of education, hearing impairment, traumatic brain injury, arterial hypertension, diabetes mellitus, smoking, excessive alcohol consumption, depression, obesity, social isolation, and air pollution.
Topics: Humans; Dementia; Risk Factors; Longitudinal Studies; Educational Status
PubMed: 38416181
DOI: 10.1007/s00115-024-01641-5 -
Alzheimer's & Dementia : the Journal of... Dec 2023The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as "deep phenotyping"... (Review)
Review
INTRODUCTION
The use of applied modeling in dementia risk prediction, diagnosis, and prognostics will have substantial public health benefits, particularly as "deep phenotyping" cohorts with multi-omics health data become available.
METHODS
This narrative review synthesizes understanding of applied models and digital health technologies, in terms of dementia risk prediction, diagnostic discrimination, prognosis, and progression. Machine learning approaches show evidence of improved predictive power compared to standard clinical risk scores in predicting dementia, and the potential to decompose large numbers of variables into relatively few critical predictors.
RESULTS
This review focuses on key areas of emerging promise including: emphasis on easier, more transparent data sharing and cohort access; integration of high-throughput biomarker and electronic health record data into modeling; and progressing beyond the primary prediction of dementia to secondary outcomes, for example, treatment response and physical health.
DISCUSSION
Such approaches will benefit also from improvements in remote data measurement, whether cognitive (e.g., online), or naturalistic (e.g., watch-based accelerometry).
Topics: Humans; Artificial Intelligence; Digital Health; Machine Learning; Dementia
PubMed: 37496259
DOI: 10.1002/alz.13391 -
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 -
Journal of Internal Medicine Sep 2023Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across...
BACKGROUND
Several chronic diseases accelerate cognitive decline; however, it is still unknown how different patterns of multimorbidity influence individuals' trajectories across the cognitive continuum.
OBJECTIVES
We aimed to investigate the impact of multimorbidity and of specific multimorbidity patterns on the transitions across cognitive stages (normal cognition, cognitive impairment, no dementia [CIND], dementia) and death.
METHODS
We included 3122 dementia-free individuals from the Swedish National study on Aging and Care in Kungsholmen. Using fuzzy c-means cluster analysis, multimorbid participants were classified into mutually exclusive groups characterized by commonly coexisting chronic diseases. Participants were followed up to 18 years to detect incident CIND, dementia, or death. Transition hazard ratios (HRs), life expectancies, and time spent in different cognitive stages were estimated using multistate Markov models.
RESULTS
At baseline, five multimorbidity patterns were identified: neuropsychiatric, cardiovascular, sensory impairment/cancer, respiratory/metabolic/musculoskeletal, and unspecific. Compared to the unspecific pattern, the neuropsychiatric and sensory impairment/cancer ones showed reduced hazards of reverting from CIND to normal cognition (HR 0.53, 95% CI 0.33-0.85 and HR 0.60, 95% CI 0.39-0.91). Participants in the cardiovascular pattern exhibited an increased hazard of progression from CIND to dementia (HR 1.70, 95% CI 1.15-2.52) and for all transitions to death. Subjects with the neuropsychiatric and cardiovascular patterns showed reduced life expectancy at age 75, with an anticipation of CIND (up to 1.6 and 2.2 years, respectively) and dementia onset (up to 1.8 and 3.3 years, respectively).
CONCLUSIONS
Multimorbidity patterns differentially steer individual trajectories across the cognitive continuum of older adults and may be used as a risk stratification tool.
Topics: Humans; Aged; Dementia; Multimorbidity; Cognitive Dysfunction; Cognition; Chronic Disease; Neoplasms
PubMed: 37306092
DOI: 10.1111/joim.13683 -
Nature Reviews. Neurology Sep 2023TAR DNA-binding protein 43 (TDP43) is a focus of research in late-onset dementias. TDP43 pathology in the brain was initially identified in amyotrophic lateral sclerosis... (Review)
Review
TAR DNA-binding protein 43 (TDP43) is a focus of research in late-onset dementias. TDP43 pathology in the brain was initially identified in amyotrophic lateral sclerosis and frontotemporal lobar degeneration, and later in Alzheimer disease (AD), other neurodegenerative diseases and ageing. Limbic-predominant age-related TDP43 encephalopathy (LATE), recognized as a clinical entity in 2019, is characterized by amnestic dementia resembling AD dementia and occurring most commonly in adults over 80 years of age. Neuropathological findings in LATE, referred to as LATE neuropathological change (LATE-NC), consist of neuronal and glial cytoplasmic TDP43 localized predominantly in limbic areas with or without coexisting hippocampal sclerosis and/or AD neuropathological change and without frontotemporal lobar degeneration or amyotrophic lateral sclerosis pathology. LATE-NC is frequently associated with one or more coexisting pathologies, mainly AD neuropathological change. The focus of this Review is the pathology, genetic risk factors and nature of the cognitive impairments and dementia in pure LATE-NC and in LATE-NC associated with coexisting pathologies. As the clinical and cognitive profile of LATE is currently not easily distinguishable from AD dementia, it is important to develop biomarkers to aid in the diagnosis of this condition in the clinic. The pathogenesis of LATE-NC should be a focus of future research to form the basis for the development of preventive and therapeutic strategies.
Topics: Adult; Humans; Aged, 80 and over; Neurodegenerative Diseases; Amyotrophic Lateral Sclerosis; Frontotemporal Lobar Degeneration; Alzheimer Disease; Frontotemporal Dementia; DNA-Binding Proteins
PubMed: 37563264
DOI: 10.1038/s41582-023-00846-7 -
Journal of Neurology, Neurosurgery, and... Mar 2024Understanding the causes of Alzheimer's disease and related dementias remains a challenge. Observational studies investigating dementia risk factors are limited by the...
Understanding the causes of Alzheimer's disease and related dementias remains a challenge. Observational studies investigating dementia risk factors are limited by the pervasive issues of confounding, reverse causation and selection biases. Conducting randomised controlled trials for dementia prevention is often impractical due to the long prodromal phase and the inability to randomise many potential risk factors. In this essay, we introduce Mendelian randomisation as an alternative approach to examine factors that may prevent or delay Alzheimer's disease. Mendelian randomisation is a causal inference method that has successfully identified risk factors and treatments in various other fields. However, applying this method to dementia risk factors has yielded unexpected findings. Here, we consider five potential explanations and provide recommendations to enhance causal inference from Mendelian randomisation studies on dementia. By employing these strategies, we can better understand factors affecting dementia risk.
Topics: Humans; Alzheimer Disease; Mendelian Randomization Analysis; Risk Factors; Causality
PubMed: 37967935
DOI: 10.1136/jnnp-2023-332293 -
Molecular & Cellular Proteomics : MCP Oct 2023Neurodegenerative dementias are progressive diseases that cause neuronal network breakdown in different brain regions often because of accumulation of misfolded proteins...
Neurodegenerative dementias are progressive diseases that cause neuronal network breakdown in different brain regions often because of accumulation of misfolded proteins in the brain extracellular matrix, such as amyloids or inside neurons or other cell types of the brain. Several diagnostic protein biomarkers in body fluids are being used and implemented, such as for Alzheimer's disease. However, there is still a lack of biomarkers for co-pathologies and other causes of dementia. Such biofluid-based biomarkers enable precision medicine approaches for diagnosis and treatment, allow to learn more about underlying disease processes, and facilitate the development of patient inclusion and evaluation tools in clinical trials. When designing studies to discover novel biofluid-based biomarkers, choice of technology is an important starting point. But there are so many technologies to choose among. To address this, we here review the technologies that are currently available in research settings and, in some cases, in clinical laboratory practice. This presents a form of lexicon on each technology addressing its use in research and clinics, its strengths and limitations, and a future perspective.
Topics: Humans; Alzheimer Disease; Brain; Biomarkers; Neurons; Precision Medicine; Amyloid beta-Peptides
PubMed: 37557955
DOI: 10.1016/j.mcpro.2023.100629