Influence of birthplace and age at migration on cognitive aging among Hispanic/Latino populations in the U.S.: Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

Background And Objectives: While Hispanic/Latino populations in the U.S. are remarkably diverse in terms of birthplace and age at migration, we poorly understand how these factors are associated with cognitive aging.

Is the freezing index a valid outcome to assess freezing of gait during turning in Parkinson's disease?

Introduction: Freezing of gait (FOG) is a disabling symptom for people with Parkinson's disease (PwPD). Turning on the spot for one minute in alternating directions (360 turn) while performing a cognitive dual-task (DT) is a fast and sensitive way to provoke FOG. The FOG-index is a widely used wearable sensor-based algorithm to quantify FOG severity during turning.

Anti-Amyloid Therapies for Alzheimer's Disease and Amyloid-Related Imaging Abnormalities: Implications for the Emergency Medicine Clinician.

Alzheimer's disease is the neurodegenerative disorder responsible for approximately 60% to 70% of all cases of dementia and is expected to affect 152 million by 2050. Recently, anti-amyloid therapies have been developed and approved by the Food and Drug Administration as disease-modifying treatments given as infusions every 2 to 5 weeks for Alzheimer's disease. Although this is an important milestone in mitigating Alzheimer's disease progression, it is critical for emergency medicine clinicians to understand what anti-amyloid therapies are and how they work to recognize, treat, and mitigate their adverse effects.

Step Width Haptic Feedback for Gait Stability in Spinocerebellar Ataxia: Preliminary Results.

Background: Wider step width and lower step-to-step variability are linked to improved gait stability and reduced fall risk. It is unclear if patients with spinocerebellar ataxia (SCA) can learn to adjust these aspects of gait to reduce fall risk.

Objectives: The aims were to examine the possibility of using wearable step width haptic biofeedback to enhance gait stability and reduce fall risk in individuals with SCA.

Sex-specific Associations of Gene Expression with Alzheimer's Disease Neuropathology and Ante-mortem Cognitive Performance.

The biological mechanisms underlying women's increased Alzheimer's disease (AD) prevalence remain undefined. Previous case/control studies have identified sex-biased molecular pathways, but sex-specific relationships between gene expression and AD endophenotypes, particularly sex chromosomes, are underexplored. With bulk transcriptomic data across 3 brain regions from 767 decedents, we investigated sex-specific associations between gene expression and post-mortem β-amyloid and tau as well as antemortem longitudinal cognition.

Machine Learning and Statistical Analyses of Sensor Data Reveal Variability Between Repeated Trials in Parkinson's Disease Mobility Assessments.

Mobility tasks like the Timed Up and Go test (TUG), cognitive TUG (cogTUG), and walking with turns provide insights into the impact of Parkinson's disease (PD) on motor control, balance, and cognitive function. We assess the test-retest reliability of these tasks in 262 PD participants and 50 controls by evaluating machine learning models based on wearable-sensor-derived measures and statistical metrics. This evaluation examines total duration, subtask duration, and other quantitative measures across two trials.

Vascular endothelial growth factor receptor-1 (FLT1) interactions with amyloid-beta in Alzheimer's disease: A putative biomarker of amyloid-induced vascular damage.

We have identified FLT1 as a protein that changes during Alzheimer's disease (AD) whereby higher brain protein levels are associated with more amyloid, more tau, and faster longitudinal cognitive decline. Given FLT1's role in angiogenesis and immune activation, we hypothesized that FLT1 is upregulated in response to amyloid pathology, driving a vascular-immune cascade resulting in neurodegeneration and cognitive decline. We sought to determine (1) if in vivo FLT1 levels (CSF and plasma) associate with biomarkers of AD neuropathology or differ between diagnostic staging in an aged cohort enriched for early disease, and (2) whether FLT1 expression interacts with amyloid on downstream outcomes, such as phosphorylated tau levels and cognitive performance.

Adaptive measurement of cognitive function based on multidimensional item response theory.

Introduction: Up to 20% of older adults in the United States have mild cognitive impairment (MCI), and about one-third of people with MCI are predicted to transition to Alzheimer's disease (AD) within 5 years. Standard cognitive assessments are long and require a trained technician to administer. We developed the first computerized adaptive test (CAT) based on multidimensional item response theory (MIRT) to more precisely, rapidly, and repeatedly assesses cognitive abilities across the adult lifespan.

Growing empathy through art therapy, life story, and relationships: experiential learning in adult day services.

Introduction: Empathy is a fundamental element of high-quality healthcare, though it has been shown to be in decline among medical students and residents. Appeals have therefore been made for the development of evidence-based empathy-enhancing experiential learning and training models. Bringing Art to Life (BATL) is a service-learning program designed within experiential learning pedagogy for psychology and pre-healthcare students.

MRI free water mediates the association between diffusion tensor image analysis along the perivascular space and executive function in four independent middle to aged cohorts.

Introduction: Diffusion tensor image analysis along the perivascular space (DTI-ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI-ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID).

Methods: Four independent cohorts were examined.

Social Engagement and Neurocognition in Latino and Non-Latino White Older Persons with HIV.

The present study investigated differences in the quantity and quality of social engagement, and their associations with neurocognition among older Latino and non-Latino White persons with HIV (PWH). Participants were age 50 + community-dwelling PWH living in southern California (n = 116; 50% Latino [53% Spanish-speaking], 50% non-Latino White; Age: M = 58.03; Education: M = 13.

Life-Space Mobility Is Related to Loneliness Among Living-Alone Older Adults: Longitudinal Analysis With Motion Sensor Data.

Background: Life-space mobility can be a behavioral indicator of loneliness. This study examined the association between life-space mobility measured with motion sensors and weekly vs. annually reported loneliness.

Brain phosphoproteomic analysis identifies diabetes-related substrates in Alzheimer's disease pathology in older adults.

Introduction: Type 2 diabetes increases the risk of Alzheimer's disease (AD) dementia. Insulin signaling dysfunction exacerbates tau protein phosphorylation, a hallmark of AD pathology. However, the comprehensive impact of diabetes on patterns of AD-related phosphoprotein in the human brain remains underexplored.

Late-life social activity and subsequent risk of dementia and mild cognitive impairment.

Introduction: Social activity is associated with better cognitive health in old age. To better translate epidemiological research for public health communication, we estimated relations of levels of social activity to average age at dementia onset.

Methods: In the Rush Memory and Aging Project (MAP), we followed 1923 dementia-free older adults and conducted annual clinical evaluations of dementia/mild cognitive impairment (MCI).

An analysis of RNA quality metrics in human brain tissue.

Human brain tissue studies have used a range of metrics to assess RNA quality but there are few large-scale cross-comparisons of presequencing quality metrics with RNA-seq quality. We analyzed how postmortem interval (PMI) and RNA integrity number (RIN) before RNA-seq relate to RNA quality after sequencing (percent of counts in top 10 genes [PTT], 5' bias, and 3' bias), and with individual gene counts across the transcriptome. We analyzed 4 human cerebrocortical tissue sets (1 surgical, 3 autopsy), sequenced with varying protocols.

Single-Nucleus Atlas of Cell-Type Specific Genetic Regulation in the Human Brain.

Genetic risk variants for common diseases are predominantly located in non-coding regulatory regions and modulate gene expression. Although bulk tissue studies have elucidated shared mechanisms of regulatory and disease-associated genetics, the cellular specificity of these mechanisms remains largely unexplored. This study presents a comprehensive single-nucleus multi-ancestry atlas of genetic regulation of gene expression in the human prefrontal cortex, comprising 5.

Performance of study partner reports in a non-demented at-risk sample.

Introduction: The Clinical Dementia Rating (CDR) Scale is a gold standard for staging impairment in Alzheimer's disease and other dementias (ADRD). The Quick Dementia Rating System (QDRS) offers similar results in 3 to 5 minutes without a trained clinician. This study aimed to (1) investigate concordance between comparably derived QDRS and CDR global scores, (2) examine item-level QDRS/CDR agreement, and (3) compare sample characteristics and cognitive performance across QDRS/CDR global concordant/discordant groups.

Sex and APOE ε4 allele differences in longitudinal white matter microstructure in multiple cohorts of aging and Alzheimer's disease.

Introduction: The effects of sex and apolipoprotein E (APOE)-Alzheimer's disease (AD) risk factors-on white matter microstructure are not well characterized.

Methods: Diffusion magnetic resonance imaging data from nine well-established longitudinal cohorts of aging were free water (FW)-corrected and harmonized. This dataset included 4741 participants (age = 73.

Alzheimer's disease-associated CD83(+) microglia are linked with increased immunoglobulin G4 and human cytomegalovirus in the gut, vagal nerve, and brain.

Introduction: While there may be microbial contributions to Alzheimer's disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+) microglia subtype associated with increased immunoglobulin G4 (IgG4) in the transverse colon (TC).

Methods: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

Exploring potential causal genetic variants and genes for endometrial cancer: Open Targets Genetics, Mendelian randomization, and multi-tissue transcriptome-wide association analysis.

Background: Endometrial cancer (EC) is the most common gynecological malignancy in developed countries, with incidence rates continuing to rise globally. However, the precise mechanisms underlying EC pathogenesis remain largely unexplored. This study aims to prioritize genes associated with EC by leveraging multi-omics data through various bioinformatic methods.

Cell Type Differentiation Using Network Clustering Algorithms.

Single cell RNA-seq (scRNA-seq) technologies provide unprecedented resolution representing transcriptomics at the level of single cell. One of the biggest challenges in scRNA-seq data analysis is the cell type annotation, which is usually inferred by cell separation approaches. In-silico algorithms that accurately identify individual cell types in ongoing single-cell sequencing studies are crucial for unlocking cellular heterogeneity and understanding the biological basis of diseases.

Plasticity of Human Microglia and Brain Perivascular Macrophages in Aging and Alzheimer's Disease.

The complex roles of myeloid cells, including microglia and perivascular macrophages, are central to the neurobiology of Alzheimer's disease (AD), yet they remain incompletely understood. Here, we profiled 832,505 human myeloid cells from the prefrontal cortex of 1,607 unique donors covering the human lifespan and varying degrees of AD neuropathology. We delineated 13 transcriptionally distinct myeloid subtypes organized into 6 subclasses and identified AD-associated adaptive changes in myeloid cells over aging and disease progression.

Mapping the microRNA landscape in the older adult brain and its genetic contribution to neuropsychiatric conditions.

MicroRNAs (miRNAs) play a crucial role in regulating gene expression and influence many biological processes. Despite their importance, understanding of how genetic variation affects miRNA expression in the brain and how this relates to brain disorders remains limited. Here we investigated these questions by identifying microRNA expression quantitative trait loci (miR-QTLs), or genetic variants associated with brain miRNA levels, using genome-wide small RNA sequencing profiles from dorsolateral prefrontal cortex samples of 604 older adult donors of European ancestry.

Association of Tailpipe-Related and Nontailpipe-Related Air Pollution Exposure with Cognitive Decline in the Chicago Health and Aging Project.

Background: Evidence suggests that long-term exposure to air pollution may increase the risk of dementia and related cognitive outcomes. A major source of air pollution is automotive traffic, which is modifiable by technological and regulatory interventions.

Objectives: We examined associations of four traffic-related air pollutants with rates of cognitive decline in a cohort of older adults.