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Journal of Neuroinflammation Jan 2024Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and...
BACKGROUND
Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear.
METHODS
Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia.
RESULTS
There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors.
CONCLUSIONS
Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.
Topics: Humans; Gastrointestinal Microbiome; Cytokines; Genome-Wide Association Study; Mendelian Randomization Analysis; Parkinson Disease; Alzheimer Disease; Frontotemporal Dementia
PubMed: 38178103
DOI: 10.1186/s12974-023-02999-0 -
JAMA Neurology Dec 2023Nomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised... (Review)
Review
IMPORTANCE
Nomenclature in the field of neurodegenerative diseases presents a challenging problem. Inconsistent use of terms such as Alzheimer disease and dementia has compromised progress in clinical care, research, and development of therapeutics. Dementia-associated stigma further contributes to inconsistent and imprecise language. The result is a lack of clarity that produces confusion with patients and the general public and presents communication challenges among researchers. Therefore, the Advisory Council on Research, Care, and Services of the National Plan to Address Alzheimer's Disease authorized a committee to make recommendations for improvement.
OBJECTIVE
To establish a systematic neurodegenerative disease framework for information collection and communication to standardize language usage for research, clinical, and public health purposes.
EVIDENCE REVIEW
The Dementia Nomenclature Initiative organized into 3 major stakeholder working groups: clinicians, researchers, and the public (including individuals living with dementia and family caregivers). To inform the work, the initiative completed a narrative literature review of dementia nomenclature evolution over the last century across the PubMed, CINAHL, PsycInfo, and Scopus databases (January 1, 2000, through July 31, 2020). Initiative working groups used the results as a foundation for understanding current challenges with dementia nomenclature and implications for research, clinical practice, and public understanding. The initiative obtained additional input via focus groups with individuals living with dementia and caregivers, with separate groups for race and ethnicity (American Indian or Alaska Native, Asian or Pacific Islander, Black or African American, Hispanic or Latino, and White) as an initial assessment of the meaning of dementia-related terms to these groups.
FINDINGS
From working group deliberations, the literature review, and focus group input, the initiative developed a framework clearly separating the clinical syndromic presentation experienced by affected individuals from possible underlying pathophysiologies. In the framework, domains of clinical impairment, such as cognitive, behavioral, motor, and other neurologic features, are graded by level of impairment between none and severe. Next, biomarker information describes underlying disease processes, explains the syndrome, and identifies possible disease labels: Alzheimer disease, frontotemporal degeneration, dementia with Lewy bodies, or vascular cognitive impairment dementia.
CONCLUSIONS AND RELEVANCE
The Dementia Nomenclature Initiative established a framework to guide communication about cognitive impairment among older adults. Wider testing and refinement of the framework will subsequently improve the information used in communicating about cognitive impairment and the way in which the information is used in clinical, research, and public settings.
Topics: Humans; Aged; Alzheimer Disease; Dementia; Neurodegenerative Diseases; Cognitive Dysfunction; Dementia, Vascular
PubMed: 37843871
DOI: 10.1001/jamaneurol.2023.3664 -
Nature Human Behaviour Jul 2023Previous hypothesis-driven research has identified many risk factors linked to dementia. However, the multiplicity and co-occurrence of risk factors have been...
Previous hypothesis-driven research has identified many risk factors linked to dementia. However, the multiplicity and co-occurrence of risk factors have been underestimated. Here we analysed data of 344,324 participants from the UK Biobank with 15 yr of follow-up data for 210 modifiable risk factors. We first conducted an exposure-wide association study and then combined factors associated with dementia to generate composite scores for different domains. We then evaluated their joint associations with dementia in a multivariate Cox model. We estimated the potential impact of eliminating the unfavourable profiles of risk domains on dementia using population attributable fraction. The associations varied by domain, with lifestyle (16.6%), medical history (14.0%) and socioeconomic status (13.5%) contributing to the majority of dementia cases. Overall, we estimated that up to 47.0%-72.6% of dementia cases could be prevented.
Topics: Humans; Dementia; Biological Specimen Banks; Risk Factors; Life Style; United Kingdom
PubMed: 37024724
DOI: 10.1038/s41562-023-01585-x -
Alzheimer's & Dementia : the Journal of... Jul 2023Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect...
INTRODUCTION
Dementia is a leading cause of death and disability globally. Estimating total societal costs demonstrates the wide impact of dementia and its main direct and indirect economic components.
METHODS
We constructed a global cost model for dementia, presenting costs as cumulated global and regional costs.
RESULTS
In 2019, the annual global societal costs of dementia were estimated at US $1313.4 billion for 55.2 million people with dementia, corresponding to US $23,796 per person with dementia. Of the total, US $213.2 billion (16%) were direct medical costs, US $448.7 billion (34%) direct social sector costs (including long-term care), and US $651.4 billion (50%) costs of informal care.
DISCUSSION
The huge costs of dementia worldwide place enormous strains on care systems and families alike. Although most people with dementia live in low- and middle-income countries, highest total and per-person costs are seen in high-income countries.
HIGHLIGHTS
Global economic costs of dementia were estimated to reach US $1313.4 in 2019. Sixty-one percent of people with dementia live in low-and middle-income countries, whereas 74% of the costs occur in high-income countries. The impact of informal care accounts for about 50% of the global costs. The development of a long-term care infrastructure is a great challenge for low-and middle-income countries. There is a great need for more cost studies, particularly in low- and middle-income countries. Discussions of a framework for global cost comparisons are needed.
Topics: Humans; Dementia; Cost of Illness; Health Care Costs
PubMed: 36617519
DOI: 10.1002/alz.12901 -
International Journal of Molecular... Jul 2023Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social,... (Review)
Review
Frontotemporal dementia (FTD) is a neurodegenerative disease of growing interest, since it accounts for up to 10% of middle-age-onset dementias and entails a social, economic, and emotional burden for the patients and caregivers. It is characterised by a (at least initially) selective degeneration of the frontal and/or temporal lobe, generally leading to behavioural alterations, speech disorders, and psychiatric symptoms. Despite the recent advances, given its extreme heterogeneity, an overview that can bring together all the data currently available is still lacking. Here, we aim to provide a state of the art on the pathogenesis of this disease, starting with established findings and integrating them with more recent ones. In particular, advances in the genetics field will be examined, assessing them in relation to both the clinical manifestations and histopathological findings, as well as considering the link with other diseases, such as amyotrophic lateral sclerosis (ALS). Furthermore, the current diagnostic criteria will be explored, including neuroimaging methods, nuclear medicine investigations, and biomarkers on biological fluids. Of note, the promising information provided by neurophysiological investigations, i.e., electroencephalography and non-invasive brain stimulation techniques, concerning the alterations in brain networks and neurotransmitter systems will be reviewed. Finally, current and experimental therapies will be considered.
Topics: Middle Aged; Humans; Frontotemporal Dementia; Neurodegenerative Diseases; Pick Disease of the Brain; Amyotrophic Lateral Sclerosis; Temporal Lobe
PubMed: 37511491
DOI: 10.3390/ijms241411732 -
The Lancet. Healthy Longevity Dec 2023Modifiable risk factor estimates are sparse for early-onset dementia incidence. This study aimed to estimate and compare the risk factor profiles of early-onset dementia...
BACKGROUND
Modifiable risk factor estimates are sparse for early-onset dementia incidence. This study aimed to estimate and compare the risk factor profiles of early-onset dementia and late-onset dementia, and to explore the complex relationships between socioeconomic status, lifestyles, and early-onset dementia risk.
METHODS
In this prospective cohort study, we used data from the UK Biobank for analysis of early-onset dementia and late-onset dementia. For early-onset dementia analyses, data were collected on those aged younger than 60 years without prevalent dementia at baseline. For late-onset dementia analyses, data were collected on those aged 65 years or older at the end of follow-up. Participants with missing information on socioeconomic factors were excluded. Two models were used to test associations between early-onset dementia incidence and socioeconomic status. The first model tested associations between socioeconomic status and early-onset and late-onset dementia incidence, adjusting for covariates. Participant socioeconomic status was defined using education level, income, and employment status via latent class analysis. The second model additionally included a healthy lifestyle score, which was constructed using data on smoking, alcohol consumption, physical activity, and the Healthy Diet Index. Incident early-onset dementia was defined as a dementia case diagnosed before 65 years of age. Multivariable-adjusted Cox proportional hazard regression models were used to estimate the hazard ratio (HR) for risk of dementia. We used multivariable-adjusted Cox proportional-hazard regression models to estimate the HR for risk of both early-onset dementia and late-onset dementia.
FINDINGS
Between 2007 and 2010, 257 345 individuals were included in the analysis of early-onset dementia, and 294 133 older individuals were included in the analysis of late-onset dementia. During a mean follow-up of 11·9-12·5 years, 502 early-onset dementia cases and 5768 late-onset dementia cases were documented. Risk factor profiles were typically dissimilar between early-onset dementia and late-onset dementia. For instance, the age and sex adjusted HR for low socioeconomic status (vs high) was 4·40 (95% CI 3·43-5·65) for early-onset dementia and 1·90 (1·74-2·07) for late-onset dementia, yielding a ratio of HRs of 2·32 (1·78-3·02). After adjusting for various risk factors, participants with low socioeconomic status (vs high) had increased risk for early-onset dementia (3·38, 2·61-4·37), and overall lifestyle mediated 3·2% (1·8-5·7) of the association. Individuals with both low socioeconomic status and unhealthy lifestyles had a higher risk of early-onset dementia (5·40, 3·66-7·97). No significant interaction was observed between lifestyle and socioeconomic status. The association between socioeconomic status and early-onset dementia seemed to be more pronounced in individuals with type 2 diabetes (HR 11·21, 95% CI 2·70-46·57).
INTERPRETATION
Early-onset dementia and late-onset dementia might have different risk factor profiles; although risk factors were similar, the magnitude of associations between risk factors and dementia incidence was greater for early-onset dementia. Only a small proportion of the socioeconomic inequity in dementia risk was mediated by healthy lifestyles, which indicates that measures other than healthy lifestyle promotion to improve social determinants of health are warranted.
FUNDING
The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Hubei Province Science Fund for Distinguished Young Scholars, and the Fundamental Research Funds for the Central Universities.
Topics: Humans; Aged; Diabetes Mellitus, Type 2; Prospective Studies; Social Class; Healthy Lifestyle; Dementia
PubMed: 38042162
DOI: 10.1016/S2666-7568(23)00211-8 -
Alzheimer's & Dementia : the Journal of... Jul 2023The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry... (Review)
Review
INTRODUCTION
The projected growth of Alzheimer's disease (AD) and AD-related dementia (ADRD) cases by midcentury has expanded the research field and impelled new lines of inquiry into structural and social determinants of health (S/SDOH) as fundamental drivers of disparities in AD/ADRD.
METHODS
In this review, we employ Bronfenbrenner's ecological systems theory as a framework to posit how S/SDOH impact AD/ADRD risk and outcomes.
RESULTS
Bronfenbrenner defined the "macrosystem" as the realm of power (structural) systems that drive S/SDOH and that are the root cause of health disparities. These root causes have been discussed little to date in relation to AD/ADRD, and thus, macrosystem influences, such as racism, classism, sexism, and homophobia, are the emphasis in this paper.
DISCUSSION
Under Bronfenbrenner's macrosystem framework, we highlight key quantitative and qualitative studies linking S/SDOH with AD/ADRD, identify scientific gaps in the literature, and propose guidance for future research.
HIGHLIGHTS
Ecological systems theory links structural/social determinants to AD/ADRD. Structural/social determinants accrue and interact over the life course to impact AD/ADRD. Macrosystem is made up of societal norms, beliefs, values, and practices (e.g., laws). Most macro-level determinants have been understudied in the AD/ADRD literature.
Topics: Humans; Alzheimer Disease; Dementia; Social Determinants of Health
PubMed: 37074203
DOI: 10.1002/alz.13027 -
Molecular Psychiatry Oct 2023Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as... (Review)
Review
Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as Alzheimer's disease (AD), Vascular dementia, Lewy Body Dementia (LBD) and Frontotemporal dementia (FTD). Early and accurate diagnosis of dementia subtype is critical to improving clinical care and developing better treatments. Structural and molecular imaging has contributed to a better understanding of the pathophysiology of neurodegenerative dementias and is increasingly being adopted into clinical practice for early and accurate diagnosis. In this review we summarise the contribution imaging has made with particular focus on multimodal magnetic resonance imaging (MRI) and positron emission tomography imaging (PET). Structural MRI is widely used in clinical practice and can help exclude reversible causes of memory problems but has relatively low sensitivity for the early and differential diagnosis of dementia subtypes. F-fluorodeoxyglucose PET has high sensitivity and specificity for AD and FTD, while PET with ligands for amyloid and tau can improve the differential diagnosis of AD and non-AD dementias, including recognition at prodromal stages. Dopaminergic imaging can assist with the diagnosis of LBD. The lack of a validated tracer for α-synuclein or TAR DNA-binding protein 43 (TDP-43) imaging remain notable gaps, though work is ongoing. Emerging PET tracers such as C-UCB-J for synaptic imaging may be sensitive early markers but overall larger longitudinal multi-centre cross diagnostic imaging studies are needed.
Topics: Humans; Frontotemporal Dementia; Diagnosis, Differential; Alzheimer Disease; Lewy Body Disease; Neuroimaging; Positron-Emission Tomography
PubMed: 37608222
DOI: 10.1038/s41380-023-02215-8 -
FP Essentials Nov 2023Dementia, also called major neurocognitive disorder, is characterized by a chronic progressive loss of cognitive function in the absence of fluctuating consciousness. It...
Dementia, also called major neurocognitive disorder, is characterized by a chronic progressive loss of cognitive function in the absence of fluctuating consciousness. It represents a primarily geriatric syndrome that may be caused by one of several underlying conditions. There is insufficient evidence to support universal screening for cognitive impairment in older adults; however, clinicians should be alert to patient and caregiver concerns about cognitive changes and investigate such concerns with validated cognitive assessment tools. Alzheimer disease is the leading cause and prototypical form of dementia, presenting insidiously and causing progressive cognitive impairment with increasing severity over a period of years. Vascular dementia is the second most common form of dementia and often co-occurs with other progressive cognitive disorders. Lewy body dementias encompass Parkinson disease dementia and dementia with Lewy bodies, which have similar features and are differentiated primarily by the order of motor and cognitive symptom onset. Frontotemporal dementias occur earlier than other forms of dementia, progress rapidly, and often have a genetic component. An understanding of the conditions that cause dementia will assist clinicians in making an accurate diagnosis and providing appropriate treatment recommendations and counseling regarding the diagnosis and prognosis.
Topics: Humans; Aged; Dementia; Parkinson Disease; Lewy Body Disease; Alzheimer Disease
PubMed: 37976169
DOI: No ID Found -
Psychiatry Research Nov 2023Dementia is a major cause of disability and dependency. Pharmacological interventions are commonly provided to patients with dementia to delay the deterioration of... (Meta-Analysis)
Meta-Analysis Review
Effects of music therapy on cognition, quality of life, and neuropsychiatric symptoms of patients with dementia: A systematic review and meta-analysis of randomized controlled trials.
Dementia is a major cause of disability and dependency. Pharmacological interventions are commonly provided to patients with dementia to delay the deterioration of cognitive functions but cannot alter the course of disease. Nonpharmacological interventions are now attracting increasing scholarly interest. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement, we aim to assess the effectiveness of music-based therapies on the cognition, quality of life (QoL), and neuropsychiatric symptoms of patients with dementia through a systematic review and meta-analysis of randomized controlled trials (RCTs). The PubMed, Embase, and Cochrane databases were searched for reports of RCTs examining the effectiveness of music-based therapies for dementia published as of April 2023. A total of 674 articles were screened, and 22 trials from 21 studies (1780 patients) met the eligibility criteria. In 15 trials, music-based therapies significantly improved the cognition of patients with dementia compared with non-music therapies. In 11 trials, music-based therapies also significantly improved the QoL of patients with dementia compared with non-music therapies. In six trials, music-based therapies significantly improved patients' neuropsychiatric symptoms compared with non-music therapies. In conclusion, music-based therapy is recognized as a safe and effective alternative approach for patients with dementia.
Topics: Humans; Music Therapy; Dementia; Randomized Controlled Trials as Topic; Cognition; Quality of Life
PubMed: 37783097
DOI: 10.1016/j.psychres.2023.115498