Search Results (379)

Background/Objectives: Multifactorial prevention of falls in persons with dementia has minimal or non-significant effects. Personalised prevention is recommended. We have previously shown that gait speed, basic activities of daily living (ADL), and depression (high Cornell scores) were independent predictors of falls in persons with mild and moderate cognitive impairment. This study explored person-specific risks of falls related to physical, mental, and cognitive functions and types of dementia: Alzheimer’s disease (AD), vascular dementia (VD), mixed Alzheimer’s disease/vascular dementia (MixADVD), frontotemporal dementia (FTD), and dementia with Lewy bodies (DLB). Methods: The study used data from “The Norwegian Registry of Persons Assessed for Cognitive Symptoms” (NorCog). Differences between the dementia groups and predictors of falls, gait speed, ADL, and Cornell scores were analysed. Results: Among study participants, 537/1321 (40.7%) reported a fall in the past year, with significant variations between dementia diagnoses. Fall incidence increased with age, comorbidity/polypharmacy, depression, and MAYO fluctuation score and with reduced physical activity, gait speed, and ADL. Persons with VD and MixADVD had high fall incidences and impaired gait speed and ADL. Training of physical fitness, endurance, muscular strength, coordination, and balance and optimising treatment of comorbidities and medication enhance gait speed. Improving ADL necessitates, in addition, relief of cognitive impairment and fluctuations. Relief of depression and fluctuations by psychological and pharmacological interventions is necessary to reduce the high fall risk in persons with DLB. Conclusions: The fall incidence and fall predictors varied significantly. Personalised interventions presuppose knowledge of each individual’s fall risk factors. Full article

Alzheimer’s disease (AD) is a progressive, complex, multifactorial, neurodegenerative disease and accounts for most cases of dementia. The currently approved therapy includes cholinesterase inhibitors, NMDA-receptor antagonists and monoclonal antibodies. However, these medications were gradually discovered to be ineffective in removing the root of AD pathogenesis, having only symptomatic effects. Thus, the priority remains prevention and clarifying AD etiology. A better understanding of the neuroprotective mechanisms undertaken by specific genes is crucial to guide the design of novel therapeutic agents via selective ligands and precision medicine. In this review, we present a perspective of the physiological phase of the AD spectrum, of risk factors in AD with a focus on therapeutic approaches in three categories: neurotransmitters/ion modulations, peptide deposit control and aspecific treatments, followed by a discussion of treatment limitations. An overview of innovative strategies and non-pharmaceutical ancillary support is given. Full article

Alzheimer’s disease (AD) is a leading cause of dementia, characterized by progressive cognitive and language impairments that significantly impact communication and quality of life. Neuromodulation techniques, including repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS), and deep brain stimulation (DBS), have emerged as promising interventions. This study employs bibliometric analysis to evaluate global research trends in neuromodulation treatments for AD-related language impairments. A total of 88 publications from the Web of Science Core Collection (2006–2024) were analyzed using bibliometric methods. Key indicators such as publication trends, citation patterns, collaboration networks, and research themes were examined to map the intellectual landscape of this field. The analysis identified 580 authors across 65 journals, with an average of 34.82 citations per article. Nearly half of the publications were produced after 2021, indicating rapid recent growth. The findings highlight a predominant focus on non-invasive neuromodulation methods, particularly rTMS and tDCS, within neurosciences and neurology. While research activity is increasing, significant challenges persist, including ethical concerns, operational constraints, and the translational gap between research and clinical applications. This study provides insights into the current research landscape and future directions for neuromodulation in AD-related language impairments. The results emphasize the need for novel neuromodulation techniques and interdisciplinary collaboration to enhance therapeutic efficacy and clinical integration. Full article

Mild cognitive impairment represents a transitional phase between healthy ageing and dementia, including Alzheimer’s disease. Early detection is essential for timely clinical intervention. This study explores the viability of smooth pursuit eye movements (SPEM) as a non-invasive biomarker for cognitive impairment. A total of 115 participants—62 with cognitive impairment and 53 cognitively healthy controls—underwent comprehensive neuropsychological assessments followed by an eye-tracking task involving smooth pursuit of horizontally and vertically moving stimuli at three different speeds. Quantitative metrics such as tracking accuracy were extracted from the eye movement recordings. These features were used to train machine learning models to distinguish cognitively impaired individuals from controls. The best-performing model achieved an area under the ROC curve (AUC) of approximately 68 %, suggesting that SPEM-based assessment has potential as part of an ensemble of eye-tracking based screening methods for early cognitive decline. Of course, additional paradigms or task designs are required to enhance diagnostic performance. Full article

Alzheimer’s disease (AD) is one of the primary dementia causes worldwide. For this reason, there is a need for plasma-based diagnostic biomarkers to facilitate the timely diagnosis of AD. This work synthesizes the current evidence concerning the tau protein p-tau phosphorylated at threonine 217 (p-tau217) as an emerging biomarker, emphasizing its utility in preclinical phases and its potential application in Latin American populations. The findings indicate that p-tau217 has superior sensitivity and specificity compared to classical biomarkers such as p-tau181 and Aβ42. Likewise, its plasma concentration regulates neuropathological progression, as studies by Braak have shown, enabling it to identify alterations from the early stages. In Latin America, studies in Peru, Colombia, and Brazil have shown promising results, albeit with methodological limitations. Some of them have small sample sizes or lack neuroimaging confirmation. Additionally, clinical factors common in the region, such as hypertension, diabetes, or chronic kidney disease, may alter the clinical interpretation. In short, p-tau217 represents a potential non-invasive diagnostic resource. More diverse cohorts are needed to confirm its validity in daily clinical practice. Full article

Alzheimer’s disease (AD), the most prevalent form of neurodegenerative dementia, is characterized by progressive cognitive decline and neuronal loss. Despite advances in pharmacological treatments, current therapies remain limited in efficacy and often induce adverse effects. Increasing evidence highlights oxidative stress, mitochondrial dysfunction, and disrupted neurotrophic signaling as key contributors to AD pathogenesis. Pulsed electromagnetic fields (PEMFs) are emerging as a non-invasive, multifactorial approach with promising biological effects. In this study, we investigated the neuroprotective potential of PEMFs in NGF-differentiated PC12 cells exposed to hydrogen peroxide (H₂O₂) or amyloid-β peptide (Aβ), both of which model pathological features of AD. PEMF treatment significantly counteracted H₂O₂- and Aβ-induced cytotoxicity by restoring cell viability, reducing reactive oxygen species production, and improving catalase activity. Furthermore, PEMFs preserved the mitochondrial membrane potential and decreased caspase-3 activation and chromatin condensation. Mechanistically, PEMFs inhibited ERK phosphorylation and enhanced cAMP levels, CREB phosphorylation, and BDNF expression, pathways known to support neuronal survival and plasticity. In conclusion, these findings suggest that PEMFs modulate multiple stress response systems, promoting neuroprotection under oxidative and amyloidogenic conditions. Full article

Background: Diabetes is rapidly increasing in developing and industrializing nations, primarily due to type 2 diabetes (T2DM). With the global prevalence of diabetes steadily increasing, estimates suggest that by 2045, nearly 548 million people will be living with the disease worldwide. Alzheimer’s disease (AD), recognized as the primary contributor to dementia in aging populations, exhibits an escalating prevalence that parallels the demographic shifts toward older age groups worldwide. This progressive neurodegenerative disorder has emerged as a critical public health challenge, with epidemiological patterns closely tracking the trajectory of population aging across industrialized and developing nations. This study investigates whether metformin may help reduce the risk of dementia. Previous studies from various countries have explored the association between metformin use and dementia risk; however, the findings have been inconsistent. Therefore, we conducted this study to examine whether the observed protective effect of metformin also applies to the Taiwanese (Han Chinese) population, potentially providing valuable insights into ethnic or regional differences in drug response. Methods: We conducted a retrospective cohort study using data from the Longitudinal Health Insurance Database 2000 (LHID2000), including 2 million individuals from 2000 to 2013. Patients with T2DM aged ≥40 years who initiated metformin between 2000 and 2005 formed the exposed group, while those starting other second-line antidiabetic medications formed the non-exposed group. Propensity score matching was used to control for age, sex, index date, and major comorbidities. Incident dementia (2007–2013) was identified using relevant ICD-9-CM codes. Adjusted hazard ratios were estimated using Cox regression with time-dependent covariates. Results: The metformin-exposed cohort demonstrated a risk reduction for dementia incidence relative to the comparator group (adjusted HR 0.472, 95% CI = 0.328–0.679). This protective association remained robust in sex-stratified analyses and age-stratified subgroups. Temporal analysis further revealed a duration-dependent risk attenuation, with extended therapeutic exposure correlating with progressive dementia risk decrement. Conclusions: Our findings suggest that metformin use may be associated with a lower risk of developing dementia in individuals with type 2 diabetes mellitus. Full article

At the 14th Panhellenic Conference on Alzheimer’s Disease and 6th Mediterranean Conference on neurodegenerative diseases, we experienced an exciting journey, following the patient through the stages of their neurodegenerative disease: onset, diagnosis, progression, and eventual outcome. Fighting alongside him are researchers, doctors, psychologists, biologists, chemists, pharmacists, nurses, trainers, physiotherapists, speech therapists, occupational therapists, electrical engineers, architects, and other scientists, even actors and musicians, who aim to prevent and cure the disease, limit its progression, and improve the quality of life of those affected by it. Among them, their caregivers stand out as the most dedicated companions. In a collection of abstracts that reflects the work of all of the above, we capture the results of our biennial scientific meeting, which, thanks to them, is constantly evolving in a promising way. Full article

Transcranial pulse stimulation (TPS) is a non-invasive neuromodulation method that uses, high-intensity acoustic shockwaves to deliver focused mechanical stimulation to neural tissue with minimal thermal effects. The mechanism of action includes but is not limited to promotion of blood flow and angiogenesis through mechanotransduction. Clinical data to date are limited and preliminary. In Alzheimer’s disease (AD), TPS has demonstrated cognitive and mood improvements in pilot studies and secondary endpoint analysis in first randomized trials. The enhancement of gamma-band oscillations and network connectivity has been reported. Clinical observations in Parkinson’s disease (PD) suggest TPS as a hypothesis-generating approach to address non-motor symptoms—such as depression, cognitive decline, and the freezing of gait—through theoretical modulation of basal ganglia–cortical circuits. TPS is CE-marked in Europe for AD and shows a favorable safety profile; however, ethical considerations arise from the limited evidence base, potential impairment of patient autonomy and judgment in dementia, and the risk of withholding established treatments. TPS should only be offered under structured scientific protocols or within patient registries to ensure rigorous oversight. Ensuring that consent processes account for cognitive capacity, and that TPS is applied as adjunct rather than replacement therapy, is paramount. Future research must include large-scale randomized controlled trials (RCTs), standardize stimulation protocols, deepen mechanistic insight, and embed robust ethical frameworks. Full article

Neurodegenerative diseases (NDDs) that are characterized by the accumulation of alpha-synuclein (α-syn) aggregates in both neurons and the non-neuronal cells of the brain are called synucleinopathies. The most common synucleinopathies includes Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB). Significant progress has been made in the development of positron emission tomography (PET) radiotracers for synucleinopathies, yielding several α-syn tracers that have entered clinical studies. However, selective α-syn imaging still faces inherent challenges. This review provides a comprehensive overview of the progress in α-syn PET radiotracers from three angles: Alzheimer’s disease (AD)-derived scaffolds, representative compound scaffolds and analogs, and the identification of α-syn tracers through high-throughput screening (HTS). We discuss the characteristics, advantages, and limitations of the tracers for preclinical and clinical application. Finally, future directions in the development of radioligands for proteinopathies are discussed. There is no clinical available PET radiotracer for imaging α-syn aggregates, but these advances have laid a key foundation for non-invasive α-syn imaging and early diagnosis of synucleinopathies. Full article

Alzheimer’s Disease (AD) is a global issue, with increasing incidence and prevalence as the world’s population ages and life expectancy increases. Projections indicate that by 2050, over 150 million individuals worldwide will be personally living with AD, an impending crisis made worse by the absence of cure therapies. Moreover, the risk factor relationship of dementia with rising global temperatures and air pollution further necessitates the urgency of a coordinated international response. With an extensive economic and emotional burden, AD is no longer just a disease; it is a worldwide societal crisis. This review presents five calls to action to address the AD global health emergency. First, AD research must be approached as an internationally performed activity, involving standardized data sharing, collaborative innovation, and improved access to pharmaceutical studies in low- and middle-income countries (LMICs), alongside increased diversity, inclusion, and equity in research. Second, there must be a commitment to develop universally accessible, affordable, and non-invasive diagnostic tools for AD. Third, advancements in AD therapeutics should prioritize the development of affordable agents, allowing for widespread geographic distribution. Fourth, we identify focus areas for global dementia risk reduction: sleep, head injury prevention, exercise, learning, and diet (SHIELD risk reduction strategy). Fifth, improving care for individuals with AD requires eliminating stigma through educational programs for both the public and caregivers. The escalating AD crisis demands an unprecedented global coalition in research, diagnostics, therapeutics, prevention, and education to avoid a future where the disease becomes the defining crisis of our era. Full article

Biomarkers currently used to diagnose dementia, including Alzheimer’s disease (AD), primarily detect molecular and structural brain changes associated with the condition’s pathology. Although these markers are pivotal in detecting disease-specific neuropathological hallmarks, their association with the clinical manifestations of dementia frequently remains poorly defined and exhibits considerable variability. These biomarkers may show abnormalities in cognitively healthy individuals and frequently fail to accurately represent the severity of cognitive and functional impairments in individuals with dementia. Research indicates that synaptic degeneration and functional impairment occur early in the progression of AD and exhibit the strongest correlation with clinical symptoms. This identifies brain functional impairment measurements as promising early indicators for AD detection. Electroencephalography (EEG), a non-invasive and cost-effective method with high temporal resolution, is used as a biomarker for the early detection and diagnosis of AD through frequency-domain analysis of quantitative EEG (qEEG). Many researchers demonstrate that qEEG measures effectively identify disruptions in neuronal activity, including alterations in activity patterns, topographical distribution, and synchronization. Specific findings along the stages of AD include impaired neuronal synchronization, generalized EEG slowing, and an increase in lower-frequency bands accompanied by a decrease in higher-frequency bands of resting state EEG. Moreover, qEEG helps clinicians effectively correlate indicators of AD neuropathology and distinguish between various forms of dementia, positioning it as a promising, low-cost, non-invasive biomarker for dementia. However, additional clinical investigation is required to clarify the diagnostic and prognostic significance of qEEG measurements as early functional markers for AD. This narrative review examines time-frequency domain qEEG analysis as a potential biomarker across various types of dementia. Through a structured search of PubMed and Scopus, we identified studies assessing spectral and connectivity-based qEEG features. Consistent findings include EEG slowing, reduced functional connectivity, and network desynchronization. The review outlines key methodological challenges, such as lack of standardization and limited longitudinal validation, and recommends integrative, multimodal approaches to enhance diagnostic precision and clinical applicability. Full article

Background/Objectives: Alzheimer’s disease (AD) is a progressively debilitating neurodegenerative disorder characterized by the accumulation of abnormal proteins, such as amyloid-beta plaques and tau tangles, leading to disruptions in memory storage and neuronal degeneration. Despite its portability, non-invasiveness, and cost-effectiveness, electroencephalography (EEG) as a diagnostic tool for AD faces challenges due to its susceptibility to noise and the complexity involved in the analysis. Methods: This study introduces a novel methodology employing three distinct stages for data-driven AD diagnosis: signal pre-processing, frame-level classification, and subject-level classification. At the frame level, convolutional neural networks (CNNs) are employed to extract features from spectrograms, scalograms, and Hilbert spectra. These features undergo fusion and are then fed into another CNN for feature selection and subsequent frame-level classification. After each frame for a subject is classified, a procedure is devised to determine if the subject has AD or not. Results: The proposed model demonstrates commendable performance, achieving over 80% accuracy, 82.5% sensitivity, and 81.3% specificity in distinguishing AD patients from healthy individuals at the subject level. Conclusions: This performance enables early and accurate diagnosis with significant clinical implications, offering substantial benefits over the existing methods through reduced misdiagnosis rates and improved patient outcomes, potentially revolutionizing AD screening and diagnostic practices. However, the model’s efficacy diminishes when presented with data from frontotemporal dementia (FTD) patients, emphasizing the need for further model refinement to address the intricate nuances associated with the simultaneous detection of various neurodegenerative disorders alongside AD. Full article

Alzheimer’s disease (AD) is a leading cause of dementia and a growing public health concern worldwide. Despite decades of research, effective disease-modifying treatments remain elusive, partly due to limitations in current experimental models. The purpose of this review is to critically assess and compare existing murine and alternative models of AD to identify key strengths, limitations, and future directions for model development that can enhance translational relevance and therapeutic discovery. Traditional transgenic mouse models have advanced the understanding of amyloid-beta and tau pathologies, but often fail to capture the complexity of sporadic, late-onset AD. In response, alternative models—including zebrafish, Drosophila melanogaster, Caenorhabditis elegans, non-human primates, and human brain organoids—are gaining traction due to their complementary insights and diverse experimental advantages. This review also discusses innovations in genetic engineering, neuroimaging, computational modelling, and drug repurposing that are reshaping the landscape of AD research. By integrating these diverse approaches, the review advocates for a multi-model, multidisciplinary strategy to improve the predictive power, accelerate clinical translation, and inform personalised therapeutic interventions. Ethical considerations and equitable access to diagnostics and emerging treatments are also emphasised. Ultimately, this work aims to support the development of more accurate, effective, and human-relevant models to combat AD. Full article

Background/Objectives: Emerging evidence suggests that gut microbiota composition is influenced by both age and sex and may contribute to dementia-related brain pathologies. However, comprehensive microbiome-based biomarker discovery stratified by these factors remains limited. Methods: We performed a metagenomic analysis of the gut microbiota of participants stratified by sex (female vs. male) and age (<75 vs. ≥75 years). Alpha diversity (observed operational taxonomic unit, Chao1, Shannon, and Simpson) and linear discriminant analysis effect size analyses were conducted to identify dominant taxa associated with Alzheimer’s pathology, vascular pathology, and dementia-related structural brain changes. Results: Females and non-elderly participants (aged < 75 years) exhibited higher gut microbial diversity, characterized by an increased abundance of Bifidobacterium spp. and Blautia spp., whereas males and elderly participants (aged ≥ 75 years) exhibited increased levels of Bacteroides spp. and Bacteroidia, which have been associated with inflammation and dysbiosis. Several taxa, including Bifidobacterium spp. were consistently identified as potential protective biomarkers, while Bacteroides spp. was linked to a higher risk of dementia-related brain pathologies. Conclusions: Our findings demonstrate distinct age- and sex-specific differences in gut microbiota composition that may be closely associated with the pathophysiology of dementia-related brain pathologies. These results demonstrate that gut microbiota may serve as potential biomarkers for monitoring cerebrovascular conditions, potentially contributing to the development of personalized therapeutic strategies. Full article