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The need for identifying neuropsychiatric symptoms and neural correlates among racially and ethnically minoritized older adults. Commentary on "Neuropsychiatric symptoms and white matter hyperintensities in older adults without dementia" by Liampas et al
No abstract
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Polygenic burden of short tandem repeat expansions promotes risk for Alzheimer's disease
Studies of the genetics of Alzheimer's disease (AD) have largely focused on single nucleotide variants and short insertions/deletions. However, most of the disease heritability has yet to be uncovered, suggesting that there is substantial genetic risk conferred by other forms of genetic variation. There are over one million short tandem repeats (STRs) in the genome, and their link to AD risk has not been assessed. As pathogenic expansions of STR cause over 30 neurologic diseases, it is important...
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Association of Alzheimer's and Lewy body disease pathology with basal forebrain volume and cognitive impairment
CONCLUSION: In a heterogeneous autopsy sample, AD and LB pathology both contribute to cholinergic basal forebrain degeneration whereas hippocampus atrophy is more specifically related to AD pathology. Cognitive deficits are primarily associated with tau pathology which is partly mediated by hippocampus, but not basal forebrain atrophy.
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Improving estimation efficiency for survival data analysis by integrating a coarsened time-to-event outcome from an external study
In the era of big data, increasing availability of data makes combining different data sources to obtain more accurate estimations a popular topic. However, the development of data integration is often hindered by the heterogeneity in data forms across studies. In this paper, we focus on a case in survival analysis where we have primary study data with a continuous time-to-event outcome and complete covariate measurements, while the data from an external study contain an outcome observed at...
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Evaluating the association of <em>APOE</em> genotype and cognitive resilience in SuperAgers
CONCLUSIONS AND RELEVANCE: In the largest study to date, we demonstrated strong evidence that the frequency of APOE-ε4 and -ε2 alleles differ between non-Hispanic White SuperAgers and AD dementia cases and cognitively normal controls. Differences in the role of APOE in SuperAging by race underlines distinctions in mechanisms conferring resilience across race groups given likely differences in genetic ancestry.
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Improving Glycemic Control via Heat Therapy in older adults at risk for Alzheimer's Disease (FIGHT-AD): a pilot study
Impaired glycemic control increases the risk for type 2 diabetes (T2D) and Alzheimer's Disease (AD). Heat therapy (HT), via hot water immersion (HWI), has shown promise in improving shared mechanisms implicated in both T2D and AD, like blood glucose regulation, insulin sensitivity, and inflammation. The potential for HT to improve brain health in individuals at risk for AD has not been examined. This pilot study aimed to assess the feasibility and adherence of utilizing HT in cognitively healthy...
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LD-informed deep learning for Alzheimer's gene loci detection using WGS data
INTRODUCTION: The exponential growth of genomic datasets necessitates advanced analytical tools to effectively identify genetic loci from large-scale high throughput sequencing data. This study presents Deep-Block, a multi-stage deep learning framework that incorporates biological knowledge into its AI architecture to identify genetic regions as significantly associated with Alzheimer's disease (AD). The framework employs a three-stage approach: (1) genome segmentation based on linkage...
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Stereo-seq of the prefrontal cortex in aging and Alzheimer's disease
Aging increases the risk for Alzheimer's disease (AD), driving pathological changes like amyloid-β (Aβ) buildup, inflammation, and oxidative stress, especially in the prefrontal cortex (PFC). We present the first subcellular-resolution spatial transcriptome atlas of the human prefrontal cortex (PFC), generated with Stereo-seq from six male AD cases at varying neuropathological stages and six age-matched male controls. Our analyses revealed distinct transcriptional alterations across PFC layers,...
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Late-Life Alcohol Exposure Does Not Exacerbate Age-Dependent Reductions in Mouse Spatial Memory and Brain TFEB Activity
Alcohol consumption is believed to affect Alzheimer's disease (AD) risk, but the contributing mechanisms are not well understood. A potential mediator of the proposed alcohol-AD connection is autophagy, a degradation pathway that maintains organelle and protein homeostasis. Autophagy is regulated through the activity of Transcription factor EB (TFEB), which promotes lysosome and autophagy-related gene expression. The purpose of this study is to explore whether chronic alcohol consumption worsens...
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Patients with dementia with Lewy bodies display a signature alteration of their cognitive connectome
Cognition plays a central role in the diagnosis and characterization of dementia with Lewy bodies (DLB). However, the complex associations among cognitive deficits in different domains in DLB are largely unknown. To characterize these associations, we investigated and compared the cognitive connectome of DLB patients, healthy controls (HC), and Alzheimer's disease patients (AD). We obtained data from the National Alzheimer's Coordinating Center. We built cognitive connectomes for DLB (n = 104),...
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Lactylation of tau in human Alzheimer's disease brains
INTRODUCTION: Aggregation of hyperphosphorylated tau (tauopathy) is associated with cognitive impairment in patients with Alzheimer's disease (AD). In AD, a metabolic shift due to the Warburg effect results in increased lactate production. Lactate can induce a post-translational modification (PTM) on proteins that conjugates lactyl groups to lysine (K) residues, which is known as lactylation.
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Robust, fully-automated assessment of cerebral perivascular spaces and white matter lesions: a multicentre MRI longitudinal study of their evolution and association with risk of dementia and accelerated brain atrophy
BACKGROUND: Perivascular spaces (PVS) on brain MRI are surrogates for small parenchymal blood vessels and their perivascular compartment, and may relate to brain health. However, it is unknown whether PVS can predict dementia risk and brain atrophy trajectories in participants without dementia, as longitudinal studies on PVS are scarce and current methods for PVS assessment lack robustness and inter-scanner reproducibility.
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Association of APOE alleles and polygenic profiles comprising APOE-TOMM40-APOC1 variants with Alzheimer's disease neuroimaging markers
INTRODUCTION: TOMM40 and APOC1 variants can modulate the APOE-ε4-related Alzheimer's disease (AD) risk by up to fourfold. We aim to investigate whether the genetic modulation of ε4-related AD risk is reflected in brain morphology.
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Understanding Healthcare Barriers for Latino/a/e/x Families with Alzheimer's Disease: Insights from Primary Care Provider interviews
CONCLUSION: Most Latino/a/e/x older adults with ADRD will be cared for by a PCP at some point during their disease, which means that they require additional support and resources at primary care appointments to address the barriers to accessing care services and enhance health equity in Latino/a/e/x communities.
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Lewy body co-pathology in Alzheimer's disease and primary age-related tauopathy contributes to differential neuropathological, cognitive, and brain atrophy patterns
INTRODUCTION: Alzheimer's disease (AD) co-pathology with Lewy bodies (LB) is frequent and influences clinical manifestations and outcomes. Its significance in primary age-related tauopathy (PART) is unknown. We investigated the influence of LB on cognition and brain atrophy in AD and PART.