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Alzheimer's & Dementia : the Journal of... Jul 2024Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the...
INTRODUCTION
Vascular contributions to cognitive impairment and dementia (VCID) represent a major factor in cognitive decline in older adults. The present study examined the relationship between cerebrovascular reactivity (CVR) measured by magnetic resonance imaging (MRI) and cognitive function in a multi-site study, using a predefined hypothesis.
METHODS
We conducted the study in a total of three analysis sites and 263 subjects. Each site performed an identical CVR MRI procedure using 5% carbon dioxide inhalation. A global cognitive measure of Montreal Cognitive Assessment (MoCA) and an executive function measure of item response theory (IRT) score were used as outcomes.
RESULTS
CVR and MoCA were positively associated, and this relationship was reproduced at all analysis sites. CVR was found to be positively associated with executive function.
DISCUSSION
The predefined hypothesis on the association between CVR and a global cognitive score was validated in three independent analysis sites, providing support for CVR as a biomarker in VCID.
HIGHLIGHTS
This study measured a novel functional index of small arteries referred to as cerebrovascular reactivity (CVR). CVR was positively associated with global cognition in older adults. This finding was observed in three independent cohorts at three sites. Our statistical analysis plan was predefined before beginning data collection.
PubMed: 38951718
DOI: 10.1002/alz.13888 -
Psychogeriatrics : the Official Journal... Jul 2024
PubMed: 38951714
DOI: 10.1111/psyg.13159 -
Nature Cell Biology Jul 2024α-Synuclein (αSYN), a pivotal synaptic protein implicated in synucleinopathies such as Parkinson's disease and Lewy body dementia, undergoes protein phase separation....
α-Synuclein (αSYN), a pivotal synaptic protein implicated in synucleinopathies such as Parkinson's disease and Lewy body dementia, undergoes protein phase separation. We reveal that vesicle-associated membrane protein 2 (VAMP2) orchestrates αSYN phase separation both in vitro and in cells. Electrostatic interactions, specifically mediated by VAMP2 via its juxtamembrane domain and the αSYN C-terminal region, drive phase separation. Condensate formation is specific for R-SNARE VAMP2 and dependent on αSYN lipid membrane binding. Our results delineate a regulatory mechanism for αSYN phase separation in cells. Furthermore, we show that αSYN condensates sequester vesicles and attract complexin-1 and -2, thus supporting a role in synaptic physiology and pathophysiology.
PubMed: 38951707
DOI: 10.1038/s41556-024-01451-6 -
Scientific Reports Jul 2024Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented...
Overly restrictive clinical trial eligibility criteria can reduce generalizability, slow enrollment, and disproportionately exclude historically underrepresented populations. The eligibility criteria for 196 Alzheimer's Disease and Related Dementias (AD/ADRD) trials funded by the National Institute on Aging were analyzed to identify common criteria and their potential to disproportionately exclude participants by race/ethnicity. The trials were categorized by type (48 Phase I/II pharmacological, 7 Phase III/IV pharmacological, 128 non-pharmacological, 7 diagnostic, and 6 neuropsychiatric) and target population (51 AD/ADRD, 58 Mild Cognitive Impairment, 25 at-risk, and 62 cognitively normal). Eligibility criteria were coded into the following categories: Medical, Neurologic, Psychiatric, and Procedural. A literature search was conducted to describe the prevalence of disparities for eligibility criteria for African Americans/Black (AA/B), Hispanic/Latino (H/L), American Indian/Alaska Native (AI/AN) and Native Hawaiian/Pacific Islander (NH/PI) populations. The trials had a median of 15 criteria. The most frequent criterion were age cutoffs (87% of trials), specified neurologic (65%), and psychiatric disorders (61%). Underrepresented groups could be disproportionately excluded by 16 eligibility categories; 42% of trials specified English-speakers only in their criteria. Most trials (82%) contain poorly operationalized criteria (i.e., criteria not well defined that can have multiple interpretations/means of implementation) and criteria that may reduce racial/ethnic enrollment diversity.
Topics: Humans; Alzheimer Disease; Clinical Trials as Topic; Cognitive Dysfunction; Dementia; Eligibility Determination; Ethnicity; National Institute on Aging (U.S.); Patient Selection; United States; Black or African American; Hispanic or Latino; American Indian or Alaska Native; Native Hawaiian or Other Pacific Islander
PubMed: 38951633
DOI: 10.1038/s41598-024-65767-x -
Experimental & Molecular Medicine Jul 2024The amyloid cascade hypothesis suggests that amyloid beta (Aβ) contributes to initiating subsequent tau pathology in Alzheimer's disease (AD). However, the underlying...
The amyloid cascade hypothesis suggests that amyloid beta (Aβ) contributes to initiating subsequent tau pathology in Alzheimer's disease (AD). However, the underlying mechanisms through which Aβ contributes to tau uptake and propagation remain poorly understood. Here, we show that preexisting amyloid pathology accelerates the uptake of extracellular tau into neurons. Using quantitative proteomic analysis of endocytic vesicles, we reveal that Aβ induces the internalization of fibroblast growth factor receptor 3 (FGFR3). Extracellular tau binds to the extracellular domain of FGFR3 and is internalized by the FGFR3 ligand, fibroblast growth factor 2 (FGF2). Aβ accelerates FGF2 secretion from neurons, thereby inducing the internalization of tau-attached FGFR3. Knockdown of FGFR3 in the hippocampus reduces tau aggregation by decreasing tau uptake and improving memory function in AD model mice. These data suggest FGFR3 in neurons as a novel tau receptor and a key mediator of Aβ-induced tau uptake in AD.
PubMed: 38951140
DOI: 10.1038/s12276-024-01274-3 -
ENeuro Jul 2024
Topics: Alzheimer Disease; Humans; Antibodies, Monoclonal, Humanized
PubMed: 38951040
DOI: 10.1523/ENEURO.0319-23.2024 -
BMJ Open Jul 2024This review identifies and examines theoretical approaches (components and objectives) to person-centred dementia care in order to obtain a better understanding of what... (Review)
Review
OBJECTIVES
This review identifies and examines theoretical approaches (components and objectives) to person-centred dementia care in order to obtain a better understanding of what is meant by the concept of person-centred dementia care.
DESIGN
Following the approach of Whittemore and Knafl, an integrative literature review was conducted to answer the following questions: (1) Which theoretical approaches to person-centred dementia care have been published? (2) What are the components of the theoretical approaches to person-centred dementia care thus identified, and which objectives can be identified?
DATA SOURCES
MEDLINE (via PubMed), CINAHL (via EBSCO) and PsycINFO (via EBSCO) were searched through to 26 April 2021.
ELIGIBILITY CRITERIA
We included any kind of published literature that describes theoretical approaches to person-centred dementia care and that was written in German or English.
DATA EXTRACTION AND SYNTHESIS
Two independent reviewers extracted data. Data were pooled using a data extraction form developed by the Joanna Briggs Institute. A qualitative content analysis was conducted.
RESULTS
The analysis revealed heterogeneous perspectives within the identified approaches to person-centred dementia care. Statements pertaining to the components and objectives could be assigned to three different subcategories (microlevel, macrolevel and application level). This analysis enabled an enhanced understanding of how person-centred dementia care is currently described and whether and how the theoretical approaches differ in terms of their orientations and their focus on the individual and/or on sociality, which allows conclusions regarding the underlying conceptual idea of personhood.
CONCLUSIONS
There is a clear challenge for future research to overcome the dominance of the focus on the individual and to consider aspects of sociality to be at least equally important. This is needed in order to understand dementia as a multifaceted phenomenon that demands a differentiated consideration of theoretical notions of how to understand personhood in this context.
Topics: Humans; Patient-Centered Care; Dementia
PubMed: 38951009
DOI: 10.1136/bmjopen-2024-085051 -
The Journal of Rheumatology Jul 2024Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. The study aimed to examine how different diagnostic dementia definitions perform in those...
OBJECTIVE
Rheumatoid arthritis (RA) has been associated with an elevated dementia risk. The study aimed to examine how different diagnostic dementia definitions perform in those with RA compared to individuals without RA.
METHODS
This study population included 2050 individuals (1025 with RA) from a retrospective population-based cohort in southern Minnesota and compared the performance of three code-based dementia diagnostic algorithms with medical record review diagnosis of dementia. For the overall comparison, no time frames were used, and each patient's complete medical history was used. Sensitivity analyses were performed using 1, 2, and 5-year windows around the date that dementia was identified in the medical record (reference standard).
RESULTS
Algorithms performed very similarly in persons with and without RA. The algorithms generally had high specificity, negative predictive values, and accuracy, regardless of the time window studied (>88%). Sensitivity and positive predictive values varied depending on the algorithm and the time window studied. Sensitivity values ranged from 56.5% to 95.9%, and positive predictive values ranged from 55.2% to 83.1%. Performance measures declined with more restrictive time windows.
CONCLUSION
Routinely collected electronic health record (EHR) data was used to define code-based dementia diagnosis algorithms with good performance (vs. diagnosis by medical record review). These results can inform future studies that use retrospective databases (especially in the same or similar EHR infrastructure) to identify dementia in individuals with RA.
PubMed: 38950951
DOI: 10.3899/jrheum.2024-0299 -
Ageing Research Reviews Jun 2024The blood brain barrier (BBB) is an indispensable structure that maintains the central nervous system (CNS) microenvironment for a correct neuronal function. It is... (Review)
Review
The blood brain barrier (BBB) is an indispensable structure that maintains the central nervous system (CNS) microenvironment for a correct neuronal function. It is composed by high specialized microvessels, surrounded by astrocytes, pericytes, neurons and microglia cells, which tightly control the influx and efflux of substances to the brain parenchyma. During aging, the BBB becomes impaired, and it may contribute to the development of neurodegenerative and neurological disorders including Alzheimer's disease and other dementias. Restoring BBB can be a strategy to prevent disease onset and development, reducing the symptoms of these conditions. This work critically reviews the major mechanisms underlying BBB breakdown in healthy and unhealthy aging, as well as biomarkers and methodologies that accurately assess its impairment. Complementarily, potential therapeutic targets are discussed as new strategies to restore the normal function of the BBB in aging.
PubMed: 38950867
DOI: 10.1016/j.arr.2024.102395 -
Journal of the American Medical... Jun 2024Mild cognitive impairment, a pressing concern in the face of a rapidly growing global older adult population, necessitates effective management strategies focused on...
OBJECTIVES
Mild cognitive impairment, a pressing concern in the face of a rapidly growing global older adult population, necessitates effective management strategies focused on sustained symptom relief and preventing deterioration. Community Dementia Care Centers, in partnership with in-network hospitals, aim to provide support for preventing mild cognitive impairment and dementia. Medical counseling, influenced by in-network hospitals, is crucial for tailoring interventions to the cognitive abilities and specific needs of each older adult, protecting against dementia. Disparities in the number of in-network hospitals and healthcare infrastructure can contribute to uneven access to dementia care, thereby creating health inequities.
DESIGN
Cross-sectional study.
SETTING AND PARTICIPANTS
Using data from the Korea Community Health Survey (2018-2019), this study focused on South Korean individuals aged 60 and older in 17 metropolitan areas and provinces.
METHODS
A multiple regression analysis was used to examine the relationship between the average number of in-network hospitals and medical counseling experience, considering sociodemographic factors and related variables.
RESULTS
Areas with a higher average number of in-network hospitals exhibited increased medical counseling experiences. Significantly higher odds for medical counseling experience were observed in regions with "more than 5 hospitals" (1.36; 95% CI, 1.20-1.54; P = .000) than those with "3 or fewer hospitals."
CONCLUSIONS AND IMPLICATIONS
This study underscores the importance of infrastructure, particularly collaborative hospitals that support Community Dementia Care Centers, in influencing individual dementia management and prevention. These findings highlight the significance of dementia prevention and management infrastructures, emphasizing the need for practical assistance, particularly in regions crucial for achieving health equity.
PubMed: 38950590
DOI: 10.1016/j.jamda.2024.105115