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Inflammation Associated With Obesity, Aging, and Amyloid Burden in Adults With Down Syndrome
CONCLUSIONS: Obesity, aging, and amyloid burden relate to systemic inflammation in adults with DS. Obesity showed the strongest and most consistent associations, emphasizing the value of regular monitoring and weight management strategies to help reduce inflammation. Aging and early amyloid accumulation showed more limited links with systemic inflammation; future work should examine whether these processes are more closely related to biomarkers of neuroinflammation as AD progresses.
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Higher Heart Rates During Locomotor High-Intensity Interval Training Are Associated With Gait Asymmetry and Fatigue After Stroke
CONCLUSION: Few baseline walking characteristics were associated with cardiovascular intensity during the initiation of locomotor HIIT, potentially because of large variability in the heart rate response. As individuals progressed over time and were able to reach higher cardiovascular intensity, the associations were abrogated.
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Feasibility, acceptability, and pre- post-program outcome changes of the real-world implementation of an informal caregiver support program via text message
BackgroundFew dementia caregiver support programs have been tested in real-world settings.ObjectiveWe tested the feasibility and pre- post-program outcome changes (e.g., preparedness for caregiving) of the first short message service texting program to support informal caregivers of people with dementia.MethodsWe analyzed observational data from 147 caregivers of people with dementia participating in a service program. This program was a remote, asynchronous, and bidirectional texting program...
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Neocortical tau burden determines the degree of cognitive impairment in individuals with Braak stage V neurofibrillary degeneration
Alzheimer disease neuropathologic change (ADNC) is considered to be the most common cause of cognitive decline and dementia worldwide. ADNC level is determined using the density of neuritic plaques in combination with the topographical distribution of β-amyloid (Aβ) plaques and hyperphosphorylated tau (p-tau)-positive neurofibrillary tangles (NFTs). While cognitive decline correlates with the level of ADNC, there remains a great deal of variation in cognitive outcomes between individuals that is...
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Evaluating the causal effect of mitochondrial dysfunction on Alzheimer's disease and Parkinson's disease using polygenic risk scores and Mendelian randomization
INTRODUCTION: Mitochondrial DNA copy number (mtDNAcn), a measure of mitochondrial genomes per nucleated cell, has an unclear causal relationship with Alzheimer's disease (AD) and Parkinson's disease (PD). We integrated genetic correlation, polygenic risk scores (PRSs), and Mendelian randomization (MR) to assess whether mtDNAcn influences the risk of AD and PD, and evaluate how study-specific factors in mtDNAcn genome-wide association studies (GWASs) distort these causal estimates.
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Frequency of mixed neuropathologies in individuals with down syndrome with and without Alzheimer's dementia
Individuals with Down syndrome (DS) develop Alzheimer's disease neuropathological change (ADNC) by the age of 40 years, and most develop dementia by their early 50s. The frequency of co-pathologies in clinically and neuropathologically characterized adults with DS has not been systematically characterized. We characterized the frequency of ADNC and common co-pathologies, including cerebral amyloid angiopathy (CAA), Lewy pathology (LP), limbic predominant age-related TDP-43 encephalopathy...
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Pilot evaluation of a dance-based physical activity program for adults with Down syndrome
CONCLUSION: Intervention retention, attendance, and satisfaction were all high and energy expenditure met the threshold for moderate intensity. Remotely-delivered dance may represent a feasible and effective exercise modality for adults with DS to increase overall exercise participation and should be tested in a larger intervention.
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Brain health care accelerator: A primary care-centered model for scaling dementia diagnosis and care
Plasma biomarkers and disease-modifying therapies for early Alzheimer's disease have created an urgent need for scalable care models. In this Perspectives, we describe how a health system is adapting dementia care delivery through a primary care provider (PCP)-centered initiative designed to improve diagnostic readiness and care capacity. The program integrates (1) blood-based biomarker testing into clinical workflows, (2) a Cognitive Assessment Visit (CAV) supported by Electronic Health...
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Downward bias in the association between APOE and Alzheimer's disease using prevalent and by-proxy disease sampling in the All of Us research program
CONCLUSIONS: Our study highlights how genetic associations with ADRD can be sensitive to how cases are defined in biobanks like All of Us, with effect sizes downwardly biased when using prevalent or by-proxy cases compared to incident cases.
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Neuropathological measures of increased tau phosphorylation across the Down syndrome lifespan
Individuals with Down syndrome (DS) have an increased risk of developing Alzheimer disease (AD), with nearly all individuals exhibiting AD neuropathology, including amyloid beta (Aβ) plaques and neurofibrillary tangles (NFT), by age 40 years. Fluid AD biomarker studies highlight an increase in several phosphorylated tau (p-tau) epitopes in DS. However, neuropathological measures of p-tau epitopes in DS have not been examined. Therefore, our main objective was to characterize p-tau epitope...
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Genetic and Hormonal Contributions to Psychosis Symptoms in Alzheimer's Disease: A Sex-Stratified Analysis
CONCLUSIONS: These findings underscore sex-specific genetic and biological contributors to psychosis in AD and support sex-stratified approaches to understanding and addressing psychosis symptoms in clinical settings.
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Effectiveness of a Remote Physical Activity Intervention in Individuals with Alzheimer's Disease and their Caregivers: Results from a Randomized Trial
CONCLUSIONS: Although MVPA did not increase in the RGV arm, both individuals with ADRD and caregivers demonstrated clinically meaningful gains in functional fitness, supporting the feasibility and benefit of remote dyadic PA programs.
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Structural signature of plasma proteins classifies the status of Alzheimer's disease
Alzheimer's disease (AD) involves proteostasis dysregulation causing protein misfolding, but whether these structural changes manifest as plasma conformational biomarkers remains unclear. We profiled plasma protein structures from 520 participants including individuals with AD, individuals with mild cognitive impairment (MCI) and healthy controls. Using mass spectrometry and machine learning, we systematically characterized the structural proteome changes associated with ApoE variations and...
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Increased Blood Plasma Levels of Methionine-Oxidized Clusterin Correlate with a Shift from Normal to Mild Cognitive Impairment and Alzheimer's Disease Stages
Clusterin is a chaperon protein that is involved in many physiological processes, including binding to beta-amyloid (Aβ). Recently, we showed that in Alzheimer's disease (AD) model mice and human postmortem brains, there are elevated levels of methionine-oxidized clusterin in the disease state versus controls. These observations prompted us to investigate the possibility that elevated methionine-oxidized levels of clusterin in human blood plasma correlate with clinical diagnosis of both mild...
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Waking up to the truth: Associations between sleep disorders and multidomain functional outcomes in Alzheimer's disease
INTRODUCTION: Sleep disorders are common in older adults and have been increasingly linked to cognitive dysfunction in Alzheimer's disease (AD); however, their associations with functional outcomes and underlying pathways remain insufficiently characterized.