Frontiers in Aging Neuroscience

aStructured abstractO_ST_ABSBACKGROUNDC_ST_ABSOver the past couple of decades, the role of infections, as well as the involvement of the immune system, have been highlighted in the development of dementia. METHODData from the Wisconsin Registry for Alzheimers Prevention cohort were utilized for the analysis. A history of medical conditions was searched across the cohort, and known infections and autoimmune conditions were recorded for each participant. These conditions were then compared with t...

Neurodevelopmental disorders (NDDs) influence lifespan neurocognitive trajectories and can be conceptualized as falling on a continuum. However, transdiagnostic neurodevelopmental investigations in cognitive aging are rare. This preliminary, cross-sectional study aimed at exploring lifespan manifestations of neurodevelopmental vulnerabilities (DVs) in cognitive aging, while adopting a dimensional approach to NDDs. The objectives, covered from childhood to adulthood, were: 1) to describe NDDs-rel...

ImportanceTraumatic brain injury (TBI) is a risk factor for dementia and is known to impact levels of several Alzheimers disease (AD) blood biomarkers. Plasma pTau217/ A{beta}42 ratio has been reported to be 90% accurate for detection of brain amyloid in civilian cohorts. ObjectiveTo evaluate the accuracy of emerging AD blood biomarkers in Veterans with and without TBI history. DesignWe assessed the performance of the FDA-approved plasma pTau217/A{beta}42 ratio and plasma levels of pTau217 and...

Primary Progressive Aphasias (PPA) are a group of neurodegenerative disorders characterized by the gradual decline of language abilities. They are typically divided into three major clinical variants: the non-fluent (nfvPPA), the semantic (svPPA) and the logopenic (lvPPA) variant. Even with an extensive clinical examination, a correct differential diagnosis among variants can be difficult due to the overlapping of dysfunctional language features. In this context, the combination of Transcranial ...

BackgroundAlzheimers disease (AD) patients are characterized by an early decline of episodic memory due to hippocampal damage. Nonetheless, besides the classical negative symptoms related to episodic memory deficits, i.e. failure to retrieve information, it has been shown that AD patients can also suffer from positives symptoms, i.e. confabulations. Some theoretical accounts have been proposed to explain the cognitive mechanisms underlying confabulation. Yet, even if most of these models have le...

Freezing of gait (FoG) prediction is clinically meaningful only when warnings arrive sufficiently early for subsequent action. Therefore, we adopt a Freezing Prediction Horizon (FPH) evaluation that reports prediction performance as a function of the warning horizon before onset, making the lead-time versus reliability trade-off explicit. Within this protocol, we develop a Transformer-based predictor with a progressive self-paced learning strategy and evaluate it on a 55-patient clinical dataset...

BACKGROUNDEpisodic memory declines early with aging, reflecting reduced neural resources and diminished memory specificity. However, few studies have created a cognitive challenge with multiple levels of task demand to investigate this early subtle decline. Furthermore, it is unclear whether the genetic Alzheimers disease risk factor APOE4 and early Alzheimers pathology constrain the neural resources required to cope with increasing task demands. METHODSIn this preregistered behavioral study na...

Background and ObjectivesSleep has been associated with cognition and risk of dementia. However, sleep is a highly complex and multi-dimensional state, and there is uncertainty about which aspects of sleep are most relevant to cognitive performance and dementia risk. We applied a data-driven approach to identify clusters of sleep variables that reflect meaningful sleep composites and examined their association with cognitive performance and dementia risk. MethodsData from the Sleep and Dementia...

One of the objectives of digital neuropsychology is to apply computational methods to improve the accuracy of traditional assessments. We created and evaluated a computerized TMT (cTMT) that preserves its original structure and records high-resolution mouse trajectories. Seventy-four older adults (41 with mild cognitive impairment and 33 healthy controls) completed the cTMT and a standard diagnostic battery. We also developed NeuroTask, a Python library that extracts features from cursor time se...

Oscillatory coupling between respiration, heart rate, and cortical function is fundamental to physiological regulation yet remains poorly characterized in humans. Diminished respiratory heart rate variability (RespHRV)--the rhythmic heart rate modulation accompanying respiration--has emerged as a transdiagnostic biomarker of mental and physical health, reduced in anxiety, depression, cardiovascular disease, and aging (Beauchaine & Thayer, 2015; Menuet & Gourine et al., 2025). However, the cortic...

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...

INTRODUCTIONBilingualism is among several lifestyle factors associated with protection against cognitive decline, yet the biological mechanisms through which it exerts these effects remain poorly understood. METHODSWe compared neuropsychological functioning and biofluid markers of brain health between active (n = 280) and passive (n = 287) Spanish-Catalan bilinguals with biomarker-confirmed Alzheimers disease (AD). RESULTSActive bilinguals outperformed passive bilinguals on tests assessing att...

As cognitive decline progresses, older adults may self-regulate their driving. Avoidance of left turns across traffic is observable in naturalistic driving data but rarely self-reported. We studied 106 older adults using baseline and one-year follow-up neuropsychological assessments. In-vehicle sensors passively recorded driving behavior over 12 weeks. We identified 295,112 turns from vehicle heading changes. We used mixed-effects logistic regression to model the odds of turning left, with cogni...

AbstractO_ST_ABSBackgroundC_ST_ABSAlzheimers disease is associated with impairments in decision making that undermine autonomy, health behaviors, and quality of life. Effort-based decision making, the process of weighing reward value against effort costs, is particularly disrupted in aging and Alzheimers disease. However, aging is also characterized by a shift toward socioemotional and prosocial goals, which may preserve motivation and effortful behavior. Understanding prosocial effort-based dec...

IntroductionThe association between age at menopause and long-term cognitive decline remains largely unknown. We examined the association between age at menopause and 14-year cognitive trajectories among UK population. MethodsThis community-based study enrolled 4,082 postmenopausal women (mean age, 64.2{+/-}10.7 years) with baseline cognition and at least one follow-up assessment from the English Longitudinal Study of Ageing (ELSA) Waves 3-10. Age at menopause was categorized as <40 (premature)...

Amyotrophic Lateral Sclerosis (ALS) is a degenerative disease of motor neurons that leads to muscle wasting, paralysis, and death, with an average life expectancy of 2-5 years. Approximately 10-15% of ALS cases are familial (fALS), typically linked to, but not always caused by identifiable inherited genetic mutations. The remaining 85-90% are considered sporadic ALS (sALS), which typically occurs without a clear family history. It is thought to result from a combination of genetic and non-geneti...

BackgroundStressful life events (SLEs) across the life course have been associated with cognitive decline, but evidence on their cumulative impact and potential modifiers remains limited. We aimed to examine the associations between SLE exposure in childhood, adulthood, or both life stages and cognitive trajectories, and to investigate whether these associations vary by sex and level of education. MethodsWe used data from the China Health and Retirement Longitudinal Study (CHARLS), a nationally...

INTRODUCTIONConnected speech analyses can help characterize linguistic impairments in primary progressive aphasia (PPA) and classify variants, however, manual transcription of speech samples is time-consuming and expensive. Automated speech recognition (ASR) may be efficacious for transcribing PPA speech. METHODSTranscripts of picture descriptions (109 PPA, 32 healthy controls (HC)) were generated using a manual, automated (Whisper) or semi-automated approach including a quality control (QC) st...

Aging is often accompanied by cognitive decline, but the extent, timing, and severity of this process is subject to large inter-individual variability. Predicting cognitive decline along a continuum, encompassing healthy age-related decline, mild cognitive impairment, and dementia, allows for more precise individual-level predictions. Previous work has demonstrated that machine learning (ML) models combining risk factors, clinical, neuropsychological, and structural magnetic resonance imaging (M...

BackgroundDistinguishing individuals with cognitive decline (CD), including early Alzheimers disease, from cognitively normal (CN) individuals is essential for improving diagnostic accuracy and enabling timely intervention. Positron emission tomography (PET) captures functional brain alterations associated with CD, but its broader application is often limited by cost and radiation exposure. To enhance the clinical utility of PET while addressing data limitations, we propose a multi-representatio...