GeroScience

Structured AbstractO_ST_ABSBACKGROUNDC_ST_ABSPositron emission tomography (PET), cerebrospinal fluid (CSF), and plasma assessments are used to measure amyloid abnormality in Alzheimers disease (AD). However, it remains unclear if these three measures are similarly associated with brain structure and cognitive measures. METHODSLinear regressions examined the relationship between amyloid levels measured by PET, CSF, and plasma and brain volumes, white matter hyperintensities (WMHs), and cognitive...

BackgroundWhile blood-based biomarkers for Alzheimers Disease (AD) such as p-Tau and NfL characterize established pathology, the systemic biological cascade triggering these events remains incompletely mapped. We hypothesized that proteins exhibiting a rising trajectory in the prodromal phase might reveal novel mechanisms of disease progression. MethodsUsing data from the UK Biobank Pharma Proteomics Project (N = 4,519 incident AD cases), we performed a blind trajectory scan of [~]3,000 plasma ...

INTRODUCTIONDementia reflects vascular and neurodegenerative processes in late life, yet studies often examine risks and outcomes individually. This study tested whether the cumulative burden of risks relates to structural brain pathology and cognition, and whether brain markers mediate these associations. METHODSCross-sectional data were drawn from 38,414 older adults in the National Alzheimers Coordinating Center database. A composite score summed ten binary risk factors: hypertension, diabet...

Biomarkers of aging, particularly DNA methylation-based clocks, have shown promise as tools to assess whether interventions may impact the rate of biological aging. Among possible interventions physical exercise has shown protective effects against many age-associated diseases, while time-restricted feeding (TRF), has shown metabolic benefits in preclinical models. The combined effect of exercise and TRF on aging biomarkers remains largely unexplored. In this 52-week four-armed, randomized, cont...

Population aging heightens the burden of cognitive decline and brain disorders, yet trajectories of brain aging vary widely across individuals. Because the human brain is intrinsically lateralized, age-related shifts in hemispheric asymmetry may reveal latent aging subtypes that are masked by bilateral averages. Here, we derived reproducible and interpretable asymmetry-based brain-aging modes and validated their behavioral, genetic, and molecular signatures. Using UK Biobank MRI, we computed co...

BackgroundTransthyretin amyloidosis cardiomyopathy (ATTR-CM) and Alzheimers disease (AD) are age-related disorders characterized by pathological protein aggregation. Despite shared risk factors and mechanisms, the relationship between ATTR-CM and AD remains poorly understood. MethodsWe performed a population-based case-control study using the French National Health Data System from 2019 to 2023. Individuals aged 65 years or older diagnosed with ATTR-CM were matched with controls without ATTR-CM...

Background and ObjectivesPhysical activity and sleep are potential modifiable risk factors for the development of Alzheimers disease and related disorders (ADRD), but few studies have objectively measured both domains in participants across the cognitive continuum. Research Design and MethodsStandard clinical assessment, accelerometry, and at-home EEG sleep data were obtained from older controls (n=9) and adults who met consensus diagnostic criteria for mild cognitive impairment (MCI; n=7), Alz...

IntroductionThis clinical trial investigates the efficacy and safety of a personalized 15-day accelerated intermittent theta-burst stimulation (aiTBS) protocol, targeted at either the default mode network (DMN) or the fronto-parietal network (FPN), in individuals with mild Alzheimers disease (AD). Methods45 patients with mild AD were randomized 1:1:1 to receive 15 consecutive days of high-dose aiTBS (7200 pulses/day) targeting the DMN or FPN, or sham. The primary outcome was the change in ADAS-...

BackgroundIntrinsic capacity (IC) is a key marker of healthy ageing, which captures an individuals physical and mental capacities, measured across five domains: cognitive, locomotor, psychological, vitality, and sensory. Although genetic factors are known to influence both general IC and its individual domains, existing IC indices have been developed primarily using phenotypic data, without accounting for the underlying biological architecture across domains. In this study, we developed a multi-...

BackgroundBody composition strongly influences clinical outcomes in older adults, yet body mass index (BMI) lacks discriminatory power, and standard tools such as bioelectrical impedance analysis (BIA), dual-energy X-ray absorptiometry are not routinely accessible. Deep learning enables scalable, opportunistic assessment of body composition from chest radiographs (CXRs), one of the most widely available imaging modalities. Methods and FindingsUsing the Inception-V3 architecture, we developed a ...

BackgroundVestibular complaints are common in older adults and are linked to imbalance and falls. Some older adults show impaired vestibular perception despite preserved peripheral-reflex ("vestibular agnosia"). Yet it remains unclear if vestibular agnosia is independently linked to imbalance and falls in otherwise healthy older adults. We therefore investigated the prevalence of vestibular agnosia in community-dwelling older adults, and examined its association to balance and prospective falls....

Adaptation to physiological stress is fundamental to health but varies widely among individuals. In humans, this heterogeneity is evident in markedly different gains in fitness in response to identical exercise training. The molecular determinants of this variable "trainability" remain poorly understood. Here we identify insulin-like growth factor binding protein-7 (IGFBP7), a senescence-associated secreted protein, as a circulating constraint on exercise adaptation. Plasma proteomics in older a...

Structured AbstractO_ST_ABSBACKGROUNDC_ST_ABSPatient reports are the standard when examining subjective cognitive decline (SCD). Recent research suggests that informant and clinician reports may also be associated with cognition. This study examined differences between patient, informant, and clinician definitions of SCD and their relationship to cognition. METHODSData from 4290 older adults (n=1690 normal controls, NC; n=840 mild cognitive impairment, MCI; n=1760 Alzheimers disease, AD) were e...

The aim of this study was to investigate the effects of cognitive dual-tasking on low-frequency oscillations during quiet standing in older adults. Thirty-two older adults (age 71{+/-}8 yrs) were categorized into high- and low-risk fall groups. Both groups performed three trials each of the following tasks: 1) quiet standing with eyes open - on a force plate; 2) quiet standing with eyes open and verbal memory encoding task - on a force plate; and 3) quiet sitting with eyes open and verbal memory...

INTRODUCTIONAgitation is a common and burdensome neuropsychiatric symptom in dementia that fluctuates from day to day, but objective tools for short-term risk stratification are limited. We examined whether nocturnal physiological signals from unobtrusive under-mattress sensors predict next-day daytime agitation and whether associations differ for agitation occurrence versus severity. METHODSWe extracted cardiorespiratory, movement, and sleep-proxy features from two long-term care cohorts (N=55...

The Montreal Cognitive Assessment (MoCA) is widely used to screen for cognitive impairment, yet commonly applied cutoff scores have been found to perform poorly among US Latinos. Prior studies relied on small samples, combining persons with mild cognitive impairment (MCI) and dementia into a single group, or failing to account for multiple intersecting demographic factors. We identified optimal MoCA cutoffs for MCI and dementia among US Latinos while addressing these limitations. We analyzed cro...

ObjectivesTo characterize contemporary pharmacologic treatment patterns for Alzheimers disease and related dementias (ADRD) among U.S. long-term care residents and to examine facility- and resident-level factors associated with treatment. DesignRetrospective, observational study. Setting and ParticipantsElectronic health record data from 1,675,873 long-term care residents in the PointClickCare Life Sciences database included 359,801 with a documented ADRD diagnosis in skilled nursing facilitie...

ObjectivesTo develop a simple risk prediction model for cognitive decline in a Chinese older adult cohort, and to evaluate its performance and transportability through temporal validation and external validation in a Japanese older adult cohort. MethodsThe prediction model was developed using a derivation cohort of 5,985 cognitively normal older adults from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2015). A comparison of seven machine learning algorithms was conducted, an...

BackgroundBlood-based biomarkers offer a scalable alternative to cerebrospinal fluid and PET imaging for Alzheimers disease (AD) detection, yet traditional venipuncture limits participation among rural and socioeconomically disadvantaged populations. Self-collection using the Tasso+ capillary device could reduce access barriers, but its feasibility and validity for AD plasma biomarkers remain uncertain, particularly with real-world delays prior to processing. MethodsAdults aged 45-90 years from...

Gait variability is a critical functional indicator of dynamic balance and neurocognitive decline in health. Its translation into clinical practice is, however, challenged by a lack of age-related normative trajectories and reference values under real-world ecological settings. Furthermore, the conventional metrics used to estimate gait variability (Coefficient of Variation, CV; Standard Deviation, SD) have a fundamental methodological flaw: the inherent sensitivity of conventional metrics to th...