Utility of Individual Neurocognitive Domains of the Rowland Universal Dementia Assessment Scale to Detect Cognitive Impairment in an Urban Illiterate Population.

Introduction: Brief cognitive tests like the RUDAS are useful for early detection of neurodegenerative diseases, especially in low-literacy populations in low- and middle-income countries. This study assesses the diagnostic performance of the RUDAS by subdomains to detect MCI and dementia in illiterate individuals in Lima, Peru.

Methods: We performed a secondary analysis of a cohort of randomly selected illiterate individuals, recruited for validation of RUDAS in Lima, Peru.

Variable and interactive effects of Sex, APOE ε4 and TREM2 on the deposition of tau in entorhinal and neocortical regions.

The canonical Alzheimer's Disease (AD) pathological cascade posits that the accumulation of amyloid beta (Aβ) is the initiating event, accelerating the accumulation of tau in the entorhinal cortex (EC), which subsequently spreads into the neocortex. Here in a multi-cohort study (ADNI, A4, HABS-HD) of 1354 participants with multimodal imaging and genetic information we queried how genetic variation affects these stages of the AD cascade. We observed that females and APOE-ε4 homozygotes are more susceptible to the effects of Aβ on the primary accumulation of tau, with greater EC tau for a given level of Aβ.

Back to the Future: Predicting Individual Tau Progression in Alzheimer's Disease.

Alzheimer's Disease (AD) is characterized by the spread of tau neurofibrillary tangles along the brain's structural network. The marked variability in pathology spread patterns across individuals necessitates a precision medicine approach. Here we introduce Stage-based Network Diffusion (StaND), a novel algorithm that combines statistical staging with biophysical modeling to predict patient-specific tau progression.

Practice effects persist over two decades of cognitive testing: Implications for longitudinal research.

Background: Repeated cognitive testing can boost scores due to practice effects (PEs), yet it remains unclear whether PEs persist across multiple follow-ups and long durations. We examined PEs across multiple assessments from midlife to old age in a nonclinical sample.

Method: Men (N=1,608) in the Vietnam Era Twin Study of Aging (VETSA) underwent neuropsychological assessment comprising 30 measures across 4 waves (~6-year testing intervals) spanning up to 20 years.

Changes of a Cerebral Cavernous Malformation Associated With Lecanemab Therapy in a Patient With Alzheimer Disease.

Background And Objectives: Antiamyloid immunotherapies are associated with increased risk of intracerebral hemorrhage, particularly in the setting of -ε4 carriership, anticoagulation, thrombolytics, and other lesions at risk of hemorrhagic conversion. It is not known whether patients with cavernous malformations are at increased risk of complication because patients with these lesions were excluded from clinical trials.

Methods: We describe a case of a patient with Alzheimer disease (AD) with an incidental cavernous malformation treated with lecanemab.

Radical Imagination: An Afrofuturism and Creative Aging Program for Black Women's Brain Health and Wellness.

Intersectional oppression and invisibility are primary drivers of cognitive and mental health disparities that affect Black women's wellness. Older Black women additionally experience compounding effects of ageism, which may place them at increased risk for a decline in cognitive functioning and mental wellness. To date, limited strengths-based, culturally relevant programming has focused on aging Black women.

The Use of Age-Friendly Technology in the Care of Older Adults: Two Implementation Case Studies.

Telemedicine has become standard in health care, and telehealth access is increasingly important. Some populations such as older adults may not have the tools nor the understanding to successfully use telehealth. We describe two cases where GrandPad, a tablet designed for older adults, was implemented at the University of California, San Francisco in (1) a home-based primary care practice and (2) a dementia specialty clinic.

Val66Met polymorphism moderates associations between physical activity and neurocognitive outcomes in older adults.

Introduction: Increased brain-derived neurotrophic factor (BDNF) release through physical activity (PA) is thought to underlie protective effects of PA on brain aging. The Val66Met single-nucleotide polymorphism (rs6265) reduces activity-dependent BDNF release and has been linked to early Alzheimer's disease (AD) pathology and cognition. We examined whether genotype influences the association of PA with plasma markers of AD, axonal degeneration, and neuroinflammation, along with consequences for cognition, in older adults without dementia.

Exploring the relationship between mean performance and within-person variability on smartphone-based cognitive testing in adults across the lifespan.

Cognitive performance is classically measured through measures of central tendency. However, intraindividual cognitive variability (IIV) also holds important information about cognitive functioning. Smartphone-based ecological momentary cognitive testing (EMCT) can capture IIV across days.

A community-led initiative to de-risk and advance Parkinson's disease therapeutic targets.

Identifying effective therapeutic targets for Parkinson's disease (PD) is challenging, with no current disease-modifying therapies available. To address this, The Michael J. Fox Foundation for Parkinson's Research launched the Targets to Therapies (T2T) initiative, uniting experts to prioritize and validate promising targets.

Decoding the Clinical Features that Associate with Progression, Causes, and Outcomes in Patients with Suspected Rapidly Progressive Dementia.

Objective: To determine the clinical features that identify patients with suspected rapidly progressive dementia (RPD) who will develop RPD.

Methods: Patients with suspected RPD were enrolled and followed at Mayo Clinic (Jacksonville, FL; January 2020 to October 2023) and Washington University (Saint Louis, MO; June 2016 to December 2019). Two dementia specialists independently reviewed clinical data and assigned diagnoses.

Transferability of European-derived Alzheimer's disease polygenic risk scores across multiancestry populations.

A polygenic score (PGS) for Alzheimer's disease (AD) was derived recently from data on genome-wide significant loci in European ancestry populations. We applied this PGS to populations in 17 European countries and observed a consistent association with the AD risk, age at onset and cerebrospinal fluid levels of AD biomarkers, independently of apolipoprotein E locus (APOE). This PGS was also associated with the AD risk in many other populations of diverse ancestries.

Translation and cultural adaptation of tools to assess diverse Asian American and Asian Canadian subgroups: The Asian Cohort for Alzheimer's Disease (ACAD) Study.

Introduction: The availability of sociocultural and language-appropriate study materials and instruments is critical for the assessment of cognitive function in people from diverse backgrounds. This report describes the translations and cultural adaptations of study materials for the Asian Cohort for Alzheimer's Disease (ACAD) study.

Methods: We performed translations and cultural adaptations in accordance with the World Health Organization (WHO) translation guidelines to ensure reliable, complete, and culturally appropriate translations from English to the specified Asian languages.

Interrogating the plasma proteome of repetitive head impact exposure and chronic traumatic encephalopathy.

Background: Exposure to repetitive head impacts (RHI) is associated with increased risk for chronic traumatic encephalopathy (CTE), a neurodegenerative tauopathy, and other neuropathological changes. Biological drivers of RHI-related neurodegeneration are not well understood. We interrogated the plasma proteome in aging adults with prior RHI compared to healthy controls (CTL) and individuals with Alzheimer's disease (AD), including a subset characterized neuropathologically at autopsy.

Frequency and Clinical Outcomes Associated With Tau Positron Emission Tomography Positivity.

Importance: Tau positron emission tomography (PET) allows in vivo detection of neurofibrillary tangles, a core neuropathologic feature of Alzheimer disease (AD).

Objective: To provide estimates of the frequency of tau PET positivity and its associated risk of clinical outcomes.

Design, Setting, And Participants: Longitudinal study using data pooled from 21 cohorts, comprising a convenience sample of 6514 participants from 13 countries, collected between January 2013 and June 2024.

Selective Vulnerability of Hippocampi for Nitric Oxide Synthases in Alzheimer's Disease Pathology and Cognitive Abilities.

Alzheimer's disease (AD) neuropathological changes (ADNC) are characterized by amyloid plaques and neurofibrillary tangles. The role of nitric oxide synthase (NOS) in disease progression remains unclear. This study investigates the expression of neural, inducible, and endothelial NOS (nNOS, iNOS, eNOS) and 3-nitrotyrosine (3-NT) in the hippocampal subregions of individuals with ADNC and their association with cognitive abilities.

Single-nucleus epigenomic dysregulation unmasks genetic risk-associated neurodegenerative glia states.

The accumulation of abnormal tau protein selectively affects distinct brain regions and specific populations of neurons and glial cells in tau-related dementias, such as Alzheimer's disease (AD), Pick's disease (PiD), and progressive supranuclear palsy (PSP). Although the three disorders share the feature of tau protein pathology, the regulatory circuitry of non-coding genetic variants underlying risk-associated cell states remains to be elucidated. Using paired single-nucleus profiling of chromatin accessibility and gene expression across AD, PiD, and PSP, we define cell-type-specific cis-regulatory elements (CREs) across six cell types and fifty subclasses.

Molecular signatures of regional vulnerability to tauopathy in excitatory cortical neurons.

Tauopathies are characterized by the aggregation and accumulation of hyperphosphorylated tau proteins that correlates with cognitive impairment in affected individuals. The presence of tauopathy follows a temporospatial spreading pattern in which certain neuronal cell types in specific brain regions are more vulnerable to tau accumulation and atrophy. However, the mechanisms underlying the selective vulnerability of these neurons and regions to pathological tau accumulation are not fully understood.

Tau phosphorylation at Alzheimer's disease biomarker sites impairs its cleavage by lysosomal proteases.

Introduction: Phospho-tau peptides from the proline-rich domain (PRD) of tau are sensitive biomarkers for Alzheimer's disease (AD). The PRD is known to be relatively resistant to lysosomal proteolytic cleavage, but the effects of phosphorylation on cleavage are unknown.

Methods: Using in silico modeling and in vitro protease assays, we quantified the effects of phosphorylation on lysosomal proteolysis of tau.

Association of [F]Flortaucipir-PET and plasma p-tau217 with tau neuropathology in AD and other neurodegenerative disorders.

Background And Objectives: Evaluating tau biomarkers in patients with available autopsy data is critical for validating their sensitivity and specificity to detect Alzheimer's disease neuropathologic changes (ADNC). We examined the association between tau-PET (using [F]Flortaucipir), plasma ptau-217, and measures of AD neuropathology in a group of clinically-impaired participants from a tertiary dementia center, including patients with AD and FTLD.

Methods: We analyzed Flortaucipir-PET (80-100 minutes post-injection acquisition, normalized to inferior cerebellar cortex) from 73 patients with a clinical diagnosis of various neurodegenerative diseases who underwent autopsy at the Neurodegenerative Disease Brain Bank (median [IQR] age: 67 [59, 73] years, 60% male, median [IQR] PET-to-autopsy duration: 3.

Interpersonal linkage in positive and negative emotional behaviors, emotional well-being, and physical functioning in dementia caregivers.

Caring for a person with dementia (PWD) can produce declines in caregivers' emotional well-being and physical functioning, which could result from disruptions in the emotional linkage between PWDs and caregivers. We examined the effects of interpersonal linkage in emotional behaviors on emotional well-being and physical functioning in caregivers and control partners. Forty-five PWD-caregiver dyads and 12 control dyads had a 10-minute unrehearsed conflict conversation in the laboratory.

DNA methylation age from peripheral blood predicts progression to Alzheimer's disease, white matter disease burden, and cortical atrophy.

Cross-sectional studies suggest a limited relationship between accelerated epigenetic aging derived from epigenetic clocks, and Alzheimer's disease (AD) pathophysiology or risk. However, most prior analyses have not utilized longitudinal analyses or whole-brain neuroimaging biomarkers of AD. Herein, we employed longitudinal modeling and structural neuroimaging analyses to test the hypothesis that accelerated epigenetic aging would predict AD progression.

Relationships between arts participation, social cohesion, and well-being: an integrative review of evidence.

Introduction: Arts and cultural strategies have increasingly been engaged by the public health sector to enhance social cohesion, health, and well-being, as well as to address the significant health risks posed by social isolation and loneliness. While numerous studies document relationships between arts participation and social cohesion or well-being, few studies have investigated the relationships between all three and, to date, no evidence synthesis has been conducted on this topic.

Methods: To address this gap, this integrative review aimed to identify, describe, and synthesize research on arts participation, social cohesion, and well-being in a community context by addressing the question: what is the evidence base regarding relationships between arts participation, social cohesion, and well-being? Literature searches were conducted using 10 databases, and analyses included descriptive statistics, thematic analysis and content-mechanism-outcomes analysis.

Sex differences in amyloid PET in a large, real-world sample from the Imaging Dementia-Evidence for Amyloid Scanning (IDEAS) Study.

Introduction: We examined sex effects on amyloid positron emission tomography (PET) in a large cohort of patients evaluated for cognitive complaints in a "real-world" specialty setting.

Methods: We analyzed 10,361 amyloid PET scans (51% females) from the Imaging Dementia-Evidence for Amyloid Scanning Study. Amyloid positivity was defined by either local visual read or central PET processing and quantification (≥ 24.