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MtDNA-depleted neuronal cell transcriptomes reveal Alzheimer's disease-related changes
CONCLUSION: MtDNA depletion alters gene expression in ways that recapitulate or predictably promote AD molecular phenomena.
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Affective Neuropsychiatric Symptom Metrics in the National Alzheimer's Coordinating Center Dataset
CONCLUSIONS: Though NPIQ severity rating cut-off choice should depend on study design, using a severity score of >1 for presence and =0 for absence may best fit clinical gestalt for affective NPS. Lewy Body Disorders present with more affective NPS than other common dementia etiologies. Future consensus on criteria for depression and anxiety syndromes in dementia may improve their identification.
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Cross-Ancestry Polygenic Risk Scores Enhance Alzheimer's Disease Risk Prediction in Multiethnic Cohorts
INTRODUCTION: Genome-wide association studies (GWAS) have identified 80+ genetic loci associated with Alzheimer's disease (AD), enabling the development of polygenic risk scores (PRS). However, the predictive accuracy of PRS in diverse populations remains low. Here, we evaluated the predictive accuracy of single-, multi-, and cross-ancestry AD-PRS models across multi-ancestral populations.
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The role of genomic-informed risk assessments in predicting dementia outcomes
INTRODUCTION: By integrating genetic and clinical risk factors into genomic-informed dementia risk reports, healthcare providers can offer patients detailed risk profiles to facilitate understanding of individual risk and support the implementation of personalized strategies for promoting brain health.
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Bridging the gap: addressing NACC's evolving cognition batteries across UDS versions
INTRODUCTION: The Uniform Data Set (UDS) version 3 neuropsychological battery replaced old tests used in UDS 1&2. Here, we validate domain scores for memory, executive functioning, and language co-calibrated across UDS eras.
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APOE4 carriers resistant to cognitive decline show unique relationships between cerebrovascular response to exercise and dual-task cognitive-balance performance
CONCLUSIONS: Cognitively-normal APOE4 carriers with preserved cognitive-balance dual-task function represent exceptions that may model aging resilience mechanisms. The unique cerebrovascular-behavioral relationships suggest that maintaining cerebrovascular function provides preliminary support for neuromotor and neurocognitive resilience to dual-task challenges in genetically vulnerable populations.
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Lifespan Trajectories of Asymmetry in White Matter Tracts
Asymmetry in white matter is believed to give rise to the brain's capacity for specialized processing and is involved in the lateralization of various cognitive processes, such as language and visuo-spatial reasoning. Although studies of white matter asymmetry have been previously documented, they have often been constrained by limited age ranges, sample sizes, or the scope of the tracts and structural features examined. While normative lifespan charts for brain structures are emerging,...
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TAS2R38-Linked MGAM Expression in Alzheimer's Disease: A Novel Target for Precision Drug Repurposing
OBJECTIVE: TAS2R38 is a taste receptor implicated in innate immunity. Identifying its genetic connection with Alzheimer's disease (AD) could aid in developing new drugs or repurposing existing ones for treatment.
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A lightweight machine learning tool for Alzheimer's disease prediction
INTRODUCTION: Alzheimer's disease (AD) is a progressive neurodegenerative disorder that needs better predictive tools. Using the National Alzheimer's Coordinating Center Uniform Data Set, this study developed machine learning (ML) models and a practical clinical tool for AD prediction.
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Integrative multi-omics approaches identify molecular pathways and improve Alzheimer's disease risk prediction
INTRODUCTION: Alzheimer's disease (AD) is a complex neurodegenerative disorder with heterogeneous genetic and molecular underpinnings. Polygenic scores (PGS) capture little of this complexity.
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The Neighborhoods Study: Examining the social exposome in Alzheimer's disease and related dementias
INTRODUCTION: The Neighborhoods Study (TNS) is a novel investigation of adverse social exposome and brain health leveraging 22 Alzheimer's Disease Research Centers (ADRCs). TNS aims to understand if the adverse social exposures increase Alzheimer's disease and related dementias (ADRD) risk.
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Generalizable MRI normative modelling to detect age-inappropriate neurodegeneration
CONCLUSIONS: Regional centile scores derived from an extensive normative dataset represent a generalizable method for objectively identifying atrophy in neurodegenerative diseases and can be applied to determine neurodegenerative atrophy at the individual level.
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Genome-wide association studies of TDP-43 proteinopathy and hippocampal sclerosis reveal shared genetic associations with APOE and TMEM106B
INTRODUCTION: Transactive response DNA binding protein 43 kDa (TDP-43) proteinopathy has been linked to cognitive decline and often co-occurs with hippocampal sclerosis (HS). To identify genetic markers of TDP-43 proteinopathy and HS, we performed genome-wide association studies (GWASs) of HS and TDP-43 inclusions.
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Neuropsychiatric symptoms and emerging dementia in people with Down syndrome and older adults
INTRODUCTION: Neuropsychiatric symptoms (NPS) are common as Alzheimer's disease (AD) dementia emerges, both in older adults (OA) and in individuals with Down syndrome (DS).
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Subtypes of multiple-etiology dementias and the heterogeneous impact of APOE variants
INTRODUCTION: Multiple-etiology dementias (MEDs) are frequently identified at autopsy but often missed in clinical diagnosis, limiting the efficiency of dementia research and treatment. This study aimed to characterize subtypes of MEDs, evaluate clinical underdiagnosis, and assess the heterogeneous impact of apolipoprotein E (APOE) variants on mortality across MED subtypes.