Automatically generated software, especially code produced by Large Language Models (LLMs), is increasingly adopted to accelerate development and reduce manual effort. However, little is known about the long-term reliability of such systems under sustained execution. In this paper, we experimentally investigate the phenomenon of software aging in applications generated by LLM-based tools. Using the Bolt platform and standardized prompts from Baxbench, we generated four service-oriented applications and subjected them to 50-hour load tests. Resource usage, response time, and throughput were continuously monitored to detect degradation patterns. The results reveal significant evidence of software aging, including progressive memory growth, increased response time, and performance instability across all applications. Statistical analyzes confirm these trends and highlight variability in the severity of aging according to the type of application. Our findings show the need to consider aging in automatically generated software and provide a foundation for future studies on mitigation strategies and long-term reliability evaluation.
Family members caring for individuals with Alzheimer's disease and related dementias (AD/ADRD) provide the foundation of long-term care worldwide. In 2023, more than 11 million U.S. family and friends contributed 18 billion hours of unpaid care, often at the cost of their own physical and mental health. These informal caregivers -- also referred as the "invisible second patients" -- experience elevated rates of mental health problems. Yet research commonly reduces their complex psychosocial experiences to a single construct of caregiver burden, obscuring which specific needs are unmet or effectively supported. At the same time, digital and AI-enabled technologies are rapidly expanding, from smartphone apps and videoconferencing to sensor platforms and AI chatbots. However, the absence of shared frameworks across medicine, psychology, and technology research limits cumulative progress. This study introduces a Caregiver Mental Health and Technology Taxonomy that systematically links AD/ADRD caregiver needs with corresponding classes of technology-based interventions. Drawing from an interdisciplinary literature review and two qualitative studies with caregivers, the taxonomy identifi
Aging is a multifactorial process and a key factor of morbidity and mortality. Alzheimer's disease (AD) is an age-related disorder and a main cause of worldwide disability. Both aging and AD can be characterized by metabolic dysfunction. Metabolomics can quantify the complete set of metabolites in a studied sample and is helpful for studying metabolic alterations in aging and AD. In this review, we summarize the metabolomic changes regarding aging and AD, discuss their biological functions, and highlight their potential application as diagnostic biomarkers or therapeutic targets. Recent advances in multi-omics approaches for understanding the metabolic mechanism of aging and AD are also reviewed.
Progressive cognitive decline spanning across decades is characteristic of Alzheimer's disease (AD). Various predictive models have been designed to realize its early onset and study the long-term trajectories of cognitive test scores across populations of interest. Research efforts have been geared towards superimposing patients' cognitive test scores with the long-term trajectory denoting gradual cognitive decline, while considering the heterogeneity of AD. Multiple trajectories representing cognitive assessment for the long-term have been developed based on various parameters, highlighting the importance of classifying several groups based on disease progression patterns. In this study, a novel method capable of self-organized prediction, classification, and the overlay of long-term cognitive trajectories based on short-term individual data was developed, based on statistical and differential equation modeling. We validated the predictive accuracy of the proposed method for the long-term trajectory of cognitive test score results on two cohorts: the Alzheimer's Disease Neuroimaging Initiative (ADNI) study and the Japanese ADNI study. We also presented two practical illustrations
Alzheimer's disease is not the outcome of a single cause but the convergence of many. This review reframes dementia as a systemic failure, where amyloid plaques and tau tangles are not root causes but late-stage byproducts of the underlying metabolic collapse. We begin by tracing the historical merger of early- and late-onset Alzheimer's into a single disease category, a conceptual error that may have misdirected decades of research. We then synthesize evidence pointing to metabolic dysfunction - especially mitochondrial damage - as a more likely initiating event. Through this lens, we examine diverse contributing factors including type 2 diabetes, hyperglycemia-induced oxidative stress, infections and neuroinflammation. Finally, we assess current treatment limitations and argue that prevention, grounded in early metabolic and vascular interventions, holds the most promise for altering the course of this complex disease.
Alzheimer's disease and Frontotemporal dementia are common forms of neurodegenerative dementia. Behavioral alterations and cognitive impairments are found in the clinical courses of both diseases and their differential diagnosis is sometimes difficult for physicians. Therefore, an accurate tool dedicated to this diagnostic challenge can be valuable in clinical practice. However, current structural imaging methods mainly focus on the detection of each disease but rarely on their differential diagnosis. In this paper, we propose a deep learning based approach for both problems of disease detection and differential diagnosis. We suggest utilizing two types of biomarkers for this application: structure grading and structure atrophy. First, we propose to train a large ensemble of 3D U-Nets to locally determine the anatomical patterns of healthy people, patients with Alzheimer's disease and patients with Frontotemporal dementia using structural MRI as input. The output of the ensemble is a 2-channel disease's coordinate map able to be transformed into a 3D grading map which is easy to interpret for clinicians. This 2-channel map is coupled with a multi-layer perceptron classifier for dif
Multifractality is an effective formalism for quantifying the nonlinear, scale-free properties of complex data. In this study, we propose a novel and efficient methodology, termed Multifractal Space-filling Curve Analysis (MFSCA), for quantifying the correlation structure of multidimensional data. Within this framework, the original multidimensional data - while preserving both local and long-range organisational properties - are projected onto a one-dimensional representation using a fractal space-filling curve. The resulting one-dimensional signal is then analysed using multifractal algorithms. We demonstrate the utility of the method using both artificially generated multifractal structures and real data. In particular, we apply MFSCA to analyse magnetic resonance imaging (MRI) data from Alzheimer patients at different stages of dementia. Based on the results, we estimate the multifractal profiles of the brain for healthy subjects of different ages as well as for dementia patients. The analysis reveals that the spatial organization of brain structures, as measured by the degree of multifractality, progressively weakens with age and the development of dementia. A transition from
Early prognosis of Alzheimer's dementia is hard. Mild cognitive impairment (MCI) typically precedes Alzheimer's dementia, yet only a fraction of MCI individuals will progress to dementia, even when screened using biomarkers. We propose here to identify a subset of individuals who share a common brain signature highly predictive of oncoming dementia. This signature was composed of brain atrophy and functional dysconnectivity and discovered using a machine learning model in patients suffering from dementia. The model recognized the same brain signature in MCI individuals, 90% of which progressed to dementia within three years. This result is a marked improvement on the state-of-the-art in prognostic precision, while the brain signature still identified 47% of all MCI progressors. We thus discovered a sizable MCI subpopulation which represents an excellent recruitment target for clinical trials at the prodromal stage of Alzheimer's disease.
We propose a mesh-based technique to aid in the classification of Alzheimer's disease dementia (ADD) using mesh representations of the cortex and subcortical structures. Deep learning methods for classification tasks that utilize structural neuroimaging often require extensive learning parameters to optimize. Frequently, these approaches for automated medical diagnosis also lack visual interpretability for areas in the brain involved in making a diagnosis. This work: (a) analyzes brain shape using surface information of the cortex and subcortical structures, (b) proposes a residual learning framework for state-of-the-art graph convolutional networks which offer a significant reduction in learnable parameters, and (c) offers visual interpretability of the network via class-specific gradient information that localizes important regions of interest in our inputs. With our proposed method leveraging the use of cortical and subcortical surface information, we outperform other machine learning methods with a 96.35% testing accuracy for the ADD vs. healthy control problem. We confirm the validity of our model by observing its performance in a 25-trial Monte Carlo cross-validation. The gen
{Introduction: } Dementia is a neurological disorder associated with aging that can cause a loss of cognitive functions, impacting daily life. Alzheimer's disease (AD) is the most common cause of dementia, accounting for 50--70\% of cases, while frontotemporal dementia (FTD) affects social skills and personality. Electroencephalography (EEG) provides an effective tool to study the effects of AD on the brain. {Methods: } In this study, we propose to use shallow neural networks applied to two sets of features: spectral-temporal and functional connectivity using four methods. We compare three supervised machine learning techniques to the CNN models to classify EEG signals of AD / FTD and control cases. We also evaluate different measures of functional connectivity from common EEG frequency bands considering multiple thresholds. {Results and Discussion: } Results showed that the shallow CNN-based models achieved the highest accuracy of 94.54\% with AEC in test dataset when considering all connections, outperforming conventional methods and providing potentially an additional early dementia diagnosis tool. \url{https://doi.org/10.3389%2Ffneur.2023.1270405}
Alzheimer's disease is a degenerative brain disease. Being the primary cause of Dementia in adults and progressively destroys brain memory. Though Alzheimer's disease does not have a cure currently, diagnosing it at an earlier stage will help reduce the severity of the disease. Thus, early diagnosis of Alzheimer's could help to reduce or stop the disease from progressing. In this paper, we proposed a deep convolutional neural network-based model for learning model using to determine the stage of Dementia in adults based on the Magnetic Resonance Imaging (MRI) images to detect the early onset of Alzheimer's.
Alzheimer's disease (AD) exhibits substantial clinical and biological heterogeneity, complicating efforts in treatment and intervention development. While new computational methods offer insights into AD progression, the reproducibility of these subtypes across datasets remains understudied, particularly concerning the robustness of subtype definitions when validated on diverse databases. This study evaluates the consistency of AD progression subtypes identified by the Subtype and Stage Inference (SuStaIn) algorithm using T1-weighted MRI data across 5,444 subjects from ANMerge, OASIS, and ADNI datasets, forming four independent cohorts. Each cohort was analyzed under two conditions: one using the full cohort, including cognitively normal controls, and another excluding controls to test subtype robustness. Results confirm the three primary atrophy subtypes identified in earlier studies: Typical, Cortical, and Subcortical, as well as the emergence of rare and atypical AD variants such as posterior cortical atrophy (PCA). Notably, each subtype displayed varying robustness to the inclusion of controls, with certain subtypes, like Subcortical, more influenced by cohort composition. This
Alzheimer's dementia (AD) is of increasing concern as populations achieve longer lifespans. Many of the recent failed AD clinical trials recruiting cognitively intact individuals had a low number of AD events and were thus underpowered. Previous trials have attempted to address this issue by requiring signs of cognitive decline in brain imaging for trial enrollment. However, this method systematically excludes people of color and those without access to healthcare and results in a selected sample that is not representative of the target population. We therefore propose the use of a predictive model based on cognitive test scores to enroll cognitively normal yet high risk participants in a hypothetical clinical trial. Cognitive test scores are a widely accessible tool, so their use in enrollment would be less likely to exclude marginalized populations than biomarkers (such as imaging), which are overwhelmingly available to exclusively high-income patients. We developed a novel longitudinal factor model to predict AD conversion within a 3-year window based on data from the National Alzheimer's Coordinating Center. Through simulation, we demonstrate that our predictive model provides
We describe a new method to automatically discriminate between patients with Alzheimer's disease (AD) or mild cognitive impairment (MCI) and elderly controls, based on multidimensional classification of hippocampal shape features. This approach uses spherical harmonics (SPHARM) coefficients to model the shape of the hippocampi, which are segmented from magnetic resonance images (MRI) using a fully automatic method that we previously developed. SPHARM coefficients are used as features in a classification procedure based on support vector machines (SVM). The most relevant features for classification are selected using a bagging strategy. We evaluate the accuracy of our method in a group of 23 patients with AD (10 males, 13 females, age $\pm$ standard-deviation (SD) = 73 $\pm$ 6 years, mini-mental score (MMS) = 24.4 $\pm$ 2.8), 23 patients with amnestic MCI (10 males, 13 females, age $\pm$ SD = 74 $\pm$ 8 years, MMS = 27.3 $\pm$ 1.4) and 25 elderly healthy controls (13 males, 12 females, age $\pm$ SD = 64 $\pm$ 8 years), using leave-one-out cross-validation. For AD vs controls, we obtain a correct classification rate of 94%, a sensitivity of 96%, and a specificity of 92%. For MCI vs c
Background: The increasing availability of databases containing both magnetic resonance imaging (MRI) and genetic data allows researchers to utilize multimodal data to better understand the characteristics of dementia of Alzheimer's type (DAT). Objective: The goal of this study was to develop and analyze novel biomarkers that can help predict the development and progression of DAT. Methods: We used feature selection and ensemble learning classifier to develop an image/genotype-based DAT score that represents a subject's likelihood of developing DAT in the future. Three feature types were used: MRI only, genetic only, and combined multimodal data. We used a novel data stratification method to better represent different stages of DAT. Using a pre-defined 0.5 threshold on DAT scores, we predicted whether or not a subject would develop DAT in the future. Results: Our results on Alzheimer's Disease Neuroimaging Initiative (ADNI) database showed that dementia scores using genetic data could better predict future DAT progression for currently normal control subjects (Accuracy=0.857) compared to MRI (Accuracy=0.143), while MRI can better characterize subjects with stable mild cognitive imp
Identifying objective neuroimaging biomarkers to forecast Alzheimer's disease (AD) progression is crucial for timely intervention. However, this task remains challenging due to the complex dysfunctions in the spatio-temporal characteristics of underlying brain networks, which are often overlooked by existing methods. To address these limitations, we develop an interpretable spatio-temporal graph neural network framework to predict future AD progression, leveraging dual Stochastic Differential Equations (SDEs) to model the irregularly-sampled longitudinal functional magnetic resonance imaging (fMRI) data. We validate our approach on two independent cohorts, including the Open Access Series of Imaging Studies (OASIS-3) and the Alzheimer's Disease Neuroimaging Initiative (ADNI). Our framework effectively learns sparse regional and connective importance probabilities, enabling the identification of key brain circuit abnormalities associated with disease progression. Notably, we detect the parahippocampal cortex, prefrontal cortex, and parietal lobule as salient regions, with significant disruptions in the ventral attention, dorsal attention, and default mode networks. These abnormaliti
Alzheimer's disease and Frontotemporal dementia are two major types of dementia. Their accurate diagnosis and differentiation is crucial for determining specific intervention and treatment. However, differential diagnosis of these two types of dementia remains difficult at the early stage of disease due to similar patterns of clinical symptoms. Therefore, the automatic classification of multiple types of dementia has an important clinical value. So far, this challenge has not been actively explored. Recent development of deep learning in the field of medical image has demonstrated high performance for various classification tasks. In this paper, we propose to take advantage of two types of biomarkers: structure grading and structure atrophy. To this end, we propose first to train a large ensemble of 3D U-Nets to locally discriminate healthy versus dementia anatomical patterns. The result of these models is an interpretable 3D grading map capable of indicating abnormal brain regions. This map can also be exploited in various classification tasks using graph convolutional neural network. Finally, we propose to combine deep grading and atrophy-based classifications to improve dementia
Pre-symptomatic (or Preclinical) Alzheimer's Disease is defined by biomarker evidence of fibrillar amyloid beta pathology in the absence of clinical symptoms. Clinical trials in this early phase of disease are challenging due to the slow rate of disease progression as measured by periodic cognitive performance tests or by transition to a diagnosis of Mild Cognitive Impairment. In a multisite study, experts provide diagnoses by central chart review without the benefit of in-person assessment. We use a simulation study to demonstrate that models of repeated cognitive assessments detect treatment effects more efficiently compared to models of time-to-progression to an endpoint such as change in diagnosis. Multivariate continuous data are simulated from a Bayesian joint mixed effects model fit to data from the Alzheimer's Disease Neuroimaging Initiative. Simulated progression events are algorithmically derived from the continuous assessments using a random forest model fit to the same data. We find that power is approximately doubled with models of repeated continuous outcomes compared to the time-to-progression analysis. The simulations also demonstrate that a plausible informative mi
The systemic, metabolic, lifestyle factors have established associations with Alzheimer's Disease (AD) through epidemiologic and AD-specific biomarker studies. Whether colored fundus photography (CFP) contains retinal structural signatures corresponding to these AD-related risk domains remains unclear. To determine whether deep learning (DL) models can predict 12 AD-related risk factors from CFP and to characterize the retinal structures underlying these predictions, thereby assessing whether CFP reflects pathways to AD vulnerability. Using 62,876 CFPs from 44,501 unique participants from the UK Biobank, DL models were trained to predict 12 factors linked to AD incidence: 6 categorical (sex, smoking, sleeplessness, economic status, alcohol use, depression) and 6 continuous (age, age at completing education, BMI, systolic, diastolic blood pressure, HbA1c). Model performance, model saliency, and saliency-derived scores (CAM-Score) were evaluated and compared to retinal morphometry. The scores were also compared between incident-AD cases (average 8.55 years before onset) and matched controls. Performance of DL ranged from AUROC= 0.5654-0.9480 for categorical and R2=-0.0291-0.7620 for
We present a practical health-theme machine learning (ML) application concerning `AI for social good' domain for `Producing Good Outcomes' track. In particular, the solution is concerning the problem of a potential elderly adult dementia onset prediction in aging societies. The paper discusses our attempt and encouraging preliminary study results of behavioral responses analysis in a working memory-based emotional evaluation experiment. We focus on the development of digital biomarkers for dementia progress detection and monitoring. We present a behavioral data collection concept for a subsequent AI-based application together with a range of regression encouraging results of Montreal Cognitive Assessment (MoCA) scores in the leave-one-subject-out cross-validation setup. The regressor input variables include experimental subject's emotional valence and arousal recognition responses, as well as reaction times, together with self-reported education levels and ages, obtained from a group of twenty older adults taking part in the reported data collection project. The presented results showcase the potential social benefits of artificial intelligence application for elderly and establish