In a recent Viewpoint article (JAMA Neurol. 2024;81:789‒90), Okubadejo et al. raised concerns regarding two recent proposals for biological definitions and staging systems for synucleinopathies (the Neuronal Synuclein Disease Integrated Staging System and SynNeurGe system). While acknowledging these concerns, we provide an alternative perspective—that such frameworks represent important steps forward

INTRODUCTIONThis study investigated the associations of brain age gap (BAG)—a biological marker of brain resilience—with life exposures, neuroimaging measures, biological processes, and cognitive function.METHODSWe derived BAG by subtracting predicted brain age from chronological age in 739 septuagenarians without dementia or neurological disorders. Robust linear regression models assessed BAG associations

Background Engaging in physical activity is critical for maintaining well-being in older adults, particularly those at heightened risk for mobility disability. We assessed the effects of a physical activity (PA) intervention on perceived stress, fatigue, and depressive symptoms compared to a health education (HE) program in older adults with mobility challenges and evaluated differential effects of

Extracellular vesicles (EVs) play crucial roles in aging. In this National Institutes on Aging-funded study, we sought to identify circulating extracellular vesicle (EV) biomarkers indicative of longevity. The plasma EV proteome of 48 older adults (mean age 77.2 ± 1.7 years [range 72–80]; 50% female, 50% Black, 50% < 2-year survival, 50% ≥ 10-year survival) was analyzed by high-resolution mass spectrometry

The geroscience hypothesis proposes that underlying biological processes, such as the accumulation of senescent cells, have deleterious effects on multiple tissues and increase the risk of many chronic conditions with aging. Senescent cells produce heterogenous biomarkers, also called senescence-associated secretory phenotype (SASP). Circulating concentrations of senescence biomarkers may reflect an

To understand the potential benefits of emerging Alzheimer's disease (AD) therapies within and beyond clinical trial settings, there is a need to advance current outcome measurements into meaningful information relevant to all stakeholders. The relationship between the impact on disease biology and clinically measurable outcomes in cognition, function, and behavior must be considered when defining

INTRODUCTIONCerebrovascular dysfunction occurs in Alzheimer's disease (AD), impairing hemodynamic regulation. Large conductance Ca2+‐activated K+ channels (BKCa) regulate cerebrovascular reactivity and are impaired in AD. BKCa activity depends on intracellular Ca2+ (Ca2+ sparks) and nitro‐oxidative post‐translational modifications. However, whether these mechanisms underlie BKCa impairment in AD remains

INTRODUCTIONWhile 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).METHODSWe used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.RESULTSCD83(+)

Background Phenotypic age acceleration (PhenoAgeAccel) is a potential aging biomarker. While weekend catch-up sleep (WCS) is commonly practiced to compensate for weekday sleep deficits, its relationship with PhenoAgeAccel remains unclear. Methods In this cross-sectional study, we analyzed data from 7,683 participants in the National Health and Nutrition Examination Survey (NHANES). WCS duration was

Cellular senescence is a pivotal contributor to aging and age-related diseases. The targeted elimination of senescent cells, known as senolysis, has emerged as a promising therapeutic strategy for mitigating these conditions. Glutaminase 1 (GLS1), a key enzyme in the glutaminolysis pathway, has been implicated in various cellular senescence processes. However, its specific role in senescent renal tubular

INTRODUCTIONWe investigated whether early life exposure to state‐level structural sexism influenced late‐life memory trajectories among United Staes (U.S.) ‐born women and men and determined whether associations differed between racialized groups.METHODSParticipants were from the Washington Heights‐Inwood Columbia Aging Project (WHICAP; N = 2314) and Health and Retirement Study (HRS; N = 18,631). State‐level

INTRODUCTIONPlacental growth factor (PlGF) may regulate cerebrovascular permeability. We hypothesized that white matter interstitial fluid accumulation, estimated via magnetic resonance imaging (MRI) free water (FW), would explain the associations between elevated PlGF, white matter hyperintensities (WMH), and cognitive impairment.METHODSMarkVCID consortium participants ≥55 years old with plasma PlGF

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell‐mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias

INTRODUCTIONStudies using cross‐sectional data or with a short follow‐up period fail to distinguish whether the associations between sleep duration and physical activity with cognitive function result from reverse causation.METHODSThe longitudinal study examined the individual and joint associations, with specific temporality, between sleep duration and physical activity with cognitive function, using

Determining whether disease-modifying treatments (DMTs) in early Alzheimer's disease (AD) provide clinically meaningful benefits to people living with AD is critical and has triggered much debate in the field.1-4 AD is a slowly progressive, ultimately fatal, neurodegenerative disease, characterized by progressive loss in cognitive ability and daily function.5 Current DMTs aim to slow disease progression

The Mexican Health and Aging Study (MHAS) is one of the largest ongoing longitudinal studies of aging in Latin America, with six waves over 20 years. MHAS includes sociodemographic, economic, and health data from a nationally representative sample of adults 50 years and older in urban and rural Mexico. MHAS is designed to study the impact of diseases on adults’ health, function, and mortality. As Mexico

Digital technology interventions (DTIs) are seen as promising interventions to prevent or delay cognitive decline in older adults, yet evidence from reviews is not conclusive. The aim of this study is to explore the effectiveness of DTIs in improving older adults’ cognitive function while taking study design and intervention characteristics as moderators. We searched the PubMed, Embase, CINAHL, PsycINFO

Objective Systematically review and critically appraise the evidence for the association between delirium and falls in community-dwelling adults aged ≥60 years. Methods We searched EMBASE, MEDLINE, PsycINFO, Cochrane Database of Systematic Reviews, CINAHL and Evidence-Based Medicine Reviews databases in April 2023. Standard methods were used to screen, extract data, assess risk of bias (using Newcastle–Ottawa

Background The impact of cardiometabolic multimorbidity (CMM) on functional dependency (FD) is well established, but the temporal effect of FD on CMM and its mechanisms remain underexplored. Design A multicohort study pooled data from three international cohorts. Setting Data were sourced from the Health and Retirement Study (USA), the China Health and Retirement Longitudinal Study (China) and the

The population of older adults is exponentially expanding. Alongside aging comes the onset of chronic disease, decline of functional capacity, and reduced quality of life. Thus, this population increase will stress the capacity and financial viability of health and long-term care systems. Developing pre-clinical models for age-related functional decline is imperative to advancing therapies that extend

Mosaic loss of Y chromosome (mLOY) is an acquired condition wherein a sizeable proportion of an organ’s cells have lost their Y. Large-scale cohort studies have shown that mLOY is age-dependent and a strong risk factor for all-cause mortality and adverse outcomes of age-related diseases. Emerging multi-omics approaches that combine gene expression, epigenetic and mutational profiling of human LOY cell

Ovarian aging is characterized by declines in follicular reserve and the emergence of mitochondrial dysfunction, reactive oxygen species production, inflammation, and fibrosis, which eventually results in menopause. Menopause is associated with increased systemic aging and the development of numerous comorbidities; therefore, the attenuation of ovarian aging could also delay systemic aging processes

Decline in the ability to perform activities of daily living (ADL) or ‘functional decline’ is a major health concern among aging populations. With intervention, ADL decline may be delayed, prevented or reversed. The capacity to anticipate the trajectory of future functional change can enhance care planning and improve outcome for residents. Methods This is a 36 months’ retrospective longitudinal analysis

Background Frailty, malnutrition and low socioeconomic status may mutually perpetuate each other in a self-reinforcing and interdependent manner. The intertwined nature of these factors may be overlooked when investigating impacts on perioperative outcomes. This study aimed to investigate the impact of frailty, malnutrition and socioeconomic status on perioperative outcomes. Methods A multicentre cohort

INTRODUCTIONProgressive supranuclear palsy (PSP) is a devastating 4R tauopathy affecting motor functions and is often misdiagnosed/underdiagnosed due to a lack of specific biomarkers. Synaptic loss is an eminent feature of tauopathies including PSP. Novel synaptic positron emission tomography tracer UCB‐J holds great potential for early diagnosis; however, there is a substantial knowledge gap in terms

Many aspects of inflammation increase with aging in mice and humans. Transcriptomic analysis revealed that many murine anti-aging interventions produce lower levels of pro-inflammatory proteins. Here, we explore the hypothesis that different longevity interventions diminish NF-κB levels, potentially mediating some of the anti-inflammatory benefits of lifespan-extending interventions. We found that

Background We assessed the association of adherence to the guidelines and subsequent changes over time in adherence with all-cause mortality. Methods We used data from 3518 and 3273 older adults, aged 60-96 years at baseline, from Seniors-ENRICA-1 and 2 cohorts, respectively. Adherence to 24-hour movement guidelines was defined as ≥150 minutes/week of moderate-to-vigorous physical activity (MVPA),

The SORL1 locus exhibits protective effects against Alzheimer's disease (AD) across ancestries, yet systematic studies in diverse populations are sparse.

The present study explored for the first time the blood-based proteomic signature that could potentially distinguish older adults with and without cognitive frailty (CF). The participants were recruited under the Malaysian Elders Longitudinal Research (MELoR) study. Cognition and physical frailty were determined using the Montreal Cognitive Assessment (MoCA) and Fried’s criteria, respectively. The

Fibroblast growth factor 21 (FGF21) is a key regulator of metabolism and cardiovascular health. However, its upregulation in aging and age-related disorders suggests the presence of FGF21 resistance. This study aimed to elucidate the mechanisms underlying senescence-associated FGF21 resistance in human umbilical vein endothelial cells (HUVECs) and to explore potential therapeutic interventions. Transcriptomic

Cognitive aging is described as the age-related decline in areas such as memory, executive function, reasoning, and processing speed. Super-Agers, adults over 80 years old, have cognitive function performance comparable to middle-aged adults. To improve cognitive reserve and potentially decrease Alzheimer’s disease (AD) risk, it is essential to contrast changes in regional brain volumes between “Positive-Agers”

Age-associated loss of muscle mass and function and subsequent mobility decline define poor health outcomes, reduced quality of life, and mortality risk. The rate and extent of aging-related muscle loss varies across older adults. It is challenging to understand the molecular pathogenesis of mobility decline, as anthropometric and imaging techniques, primarily used in muscle function assessment, do

INTRODUCTIONThis study investigated the impact of trisomy 21 mosaicism (mT21) on Alzheimer's disease (AD) neuropathology in a well‐characterized clinical case described by Ringman et al.METHODSWe describe AD neuropathology in mT21 including amyloid beta, phosphorylated tau, astrogliosis, microgliosis, α‐synuclein, and TAR DNA‐binding protein 43 (TDP‐43) in cerebral cortex, hippocampal subregions, and

INTRODUCTIONRecommendations for advance care planning (ACP) in persons with cognitive impairment are based on expert input without insight from actual ACP conversations.METHODSWe used thematic analysis to analyze transcripts of ACP conversations for 88 older adults with normal cognition (n = 15), mild cognitive impairment (n = 13), and scores consistent with dementia (n = 60).RESULTSPatients with dementia

Background The association between ultra-processed food (UPF) intake and markers of biological ageing has been scarcely investigated, despite the evident adverse health effects associated with UPF. This study aimed to test the association between UPF intake and biological ageing, and evaluate how much of this association is accounted for by overall diet quality. Methods This cross-sectional study assessed

Background Extreme temperatures are associated with negative health outcomes, in particular for older adults with pre-existing conditions. While climate change is expected to increase exposure to temperature levels that are detrimental for health, little is known about how dementia shapes vulnerability to extreme temperatures. Methods We leveraged repeated quarterly individual-level health claims from

Background Alzheimer’s disease (AD) affects over 6 million people and is the seventh-leading cause of death in the US. This study compares wrist-worn accelerometry-derived PA measures against traditional risk factors for incident AD in the UK Biobank. Methods Of 42,157 UK Biobank participants 65 years and older who had accelerometry data and no prior AD diagnosis, 157 developed AD by April 1, 2021

Background Climate change is expected to disrupt weather patterns across the world, exposing older adults to more intense and frequent periods of hot weather. Meanwhile, lab-based studies have established a causal relationship between ambient temperature and cognitive abilities, suggesting the expected rise in temperature may influence older adults’ cognitive functioning. Nevertheless, it is not clear

We investigated the hypothesis that tau burden in the locus coeruleus (LC) correlates with tau accumulation in cortical regions according to the Braak stages and examined whether the relationships differed according to cortical amyloid beta (Aβ) deposition.

The U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (U.S. POINTER) is evaluating lifestyle interventions in older adults at risk for cognitive decline and dementia. Here we characterize the baseline data set of the POINTER Imaging ancillary study.

Global average life expectancy has steadily increased over the last several decades and is projected to reach ~ 77 years by 2050. As it stands, the number of people > 60 years currently outnumbers children younger than 5 years, and by 2050, it is anticipated that the global population of people aged > 60 years will double, surpassing 2.1 billion. This demographic shift in our population is expected

Recent research highlights the critical role of inflammation in accelerating amyloid beta and phosphorylated tubulin‐associated protein tau cascade and Alzheimer's disease (AD) progression. Emerging evidence suggests that exercise influences AD by modulating inflammatory responses. We conducted a comprehensive search across multiple online databases. Our approach focused on previous and recent studies

INTRODUCTIONBlood‐based biomarkers (BBMs) can enable early detection of brain amyloid beta (Aβ) pathology in cognitively unimpaired individuals. However, the extent to which common medical conditions affect biomarker performance remains unclear.METHODSParticipants (n = 348) included individuals without cognitive impairment. We studied how brain Aβ associated with BBMs (Aβ42/40, phosphorylated tau [p‐tau]

INTRODUCTIONUsing a single‐nucleus transcriptome derived from the dorsolateral prefrontal cortex of 424 Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP) participants, we investigated the cell type–specific effect of ten vascular endothelial growth factor (VEGF) genes on Alzheimer's disease (AD) endophenotypes.METHODSNegative binomial mixed models were used for differential gene

More than 2 million older Americans from underrepresented racial and ethnic minority groups (URGs) have early‐stage Alzheimer's disease and related dementias (ADRD). There are very few scalable recruitment strategies, particularly for Black older adults, to accelerate participation in ADRD research. The Indiana Alzheimer's Disease Research Center (IADRC) and its Community Advisory Board developed and

INTRODUCTIONChildhood adversity harms neurodevelopment. Literature on late‐life brain health is limited, and findings on late‐life cognition are mixed.METHODSPooling data from Kaiser Healthy Aging and Diverse Life Experiences (KHANDLE) and Study of Healthy Aging in African Americans (STAR) cohorts, we assessed the impact of childhood adversity (factor score from seven self‐reported items) on (a) executive

INTRODUCTIONHigh microglial heterogeneities hinder the development of microglia‐targeted treatment for Alzheimer's disease (AD).METHODSWe integrated 0.7 million single‐nuclei RNA‐sequencing transcriptomes from human brains using a variational autoencoder. We predicted AD‐relevant microglial subtype‐specific transition networks for disease‐associated microglia (DAM), tau microglia, and neuroinflammation‐like

INTRODUCTIONThis study presents a novel multi‐view learning approach for machine learning (ML)–based Alzheimer's disease (AD) diagnosis.METHODSA diffusion model is proposed to synthesize the fluorodeoxyglucose positron emission tomography (FDG PET) view from the magnetic resonance imaging T1 weighted imaging (MRI T1WI) view and incorporate two synthesis strategies: one‐way synthesis and two‐way synthesis

INTRODUCTIONWe evaluated whether higher Dietary Inflammatory Index (DII) scores were associated with increased incidence of all‐cause dementia and Alzheimer's disease (AD) dementia over 22.3 years of follow‐up in the community‐based Framingham Heart Study Offspring cohort.METHODSOne thousand four hundred eighty‐seven participants (mean ± standard deviation, age in years 69 ± 6) completed food frequency

BACKGROUNDThe diagnostic and prognostic performance of the novel fluid biomarkers brain‐derived tau (BD‐tau) and phospho‐tau217 (p‐tau217) in Creutzfeldt–Jakob disease (CJD) is not defined.METHODSWe measured cerebrospinal fluid (CSF) and plasma BD‐tau, p‐tau217, p‐tau181, total tau (t‐tau), neurofilament light (NfL), and 14‐3‐3 in 100 CJD patients, 100 with non‐prion rapidly progressive dementia (np‐RPD)

Frailty is characterized by loss of physical function and is preferably diagnosed at an early stage (e.g., during pre-frailty). Unfortunately, sensitive tools that can aid early detection are lacking. Blood-based biomarkers, reflecting pathophysiological adaptations before physical symptoms become apparent, could be such tools. We identified candidate biomarkers using a mechanism-based computational

Frailty is a complex condition characterized by a decline in multiple physiological systems, compromising an individual’s ability to maintain homeostasis. The onset and progression of frailty are linked to negative health outcomes such as disability, hospitalization, and mortality. To better understand frailty mechanisms, animal models have become valuable due to their accessibility to critical tissues

Cognitive frailty is considered a clinical entity associated with a high risk for adverse health outcomes. However, its clinical significance remains poorly understood. This study investigated the association between cognitive frailty and risk for functional disability among community-dwelling older adults. In total, 1,597 Japanese adults aged ≥ 65 years that were free of dementia and functional disability

The prevalence of hypertension increases with age and is the leading modifiable risk factor for cognitive impairment and dementia. At present, the neural mechanisms promoting hypertension across the lifespan are incompletely understood. Using the Sprague–Dawley (SD) rat as a model of normal aging, we hypothesized (1) blood brain barrier (BBB) disruption and neuroinflammation in the paraventricular

The influence of genetic variation on tau protein aggregation, a key factor in Alzheimer's disease (AD), remains not fully understood. We aimed to identify novel genes associated with brain tau deposition using pathway-based candidate gene association analysis in a Korean cohort.