Curr Alzheimer Res [JOURNAL]
Sun
200 papers
The Role of Digital Health Technologies in Early Detection and Management of Alzheimer's Disease.
Mehrabadi S
Curr Alzheimer Res · 2026 Jun · PMID 42381141 · Publisher ↗
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and functional impairment, posing significant challenges for early detection and management. In recent years, digita...
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline and functional impairment, posing significant challenges for early detection and management. In recent years, digital health technologies have emerged as promising tools to enhance the diagnosis, monitoring, and treatment of AD. This review paper explores the multifaceted role of digital health technologies in the early detection and management of Alzheimer's disease. We examine the use of wearable devices that monitor cognitive function and daily activities, as well as mobile health applications designed for cognitive training and symptom tracking. Additionally, we analyze the impact of telehealth services in providing remote care, particularly for underserved populations. The integration of artificial intelligence and machine learning for analyzing behavioral and cognitive data to support early diagnosis and risk assessment is also discussed. Furthermore, we explore the concept of digital biomarkers and their potential to complement traditional diagnostic methods. Ethical considerations surrounding privacy, data security, and informed consent are addressed to ensure responsible implementation of these technologies. Finally, we highlight gaps in current research and propose future directions for integrating digital health technologies into Alzheimer's care, emphasizing the potential for personalized interventions tailored to individual patient needs. This review underscores the transformative potential of digital health to reshape Alzheimer's disease management and improve patient outcomes.
Quantifying Short-Term Functional Changes After Lecanemab Treatment in Early Alzheimer's Disease: An Exploratory 3-Month Follow-Up Case Report Using Eye Movement and Gait Analysis.
Li Y, Xie K, Qian S … +3 more , Wang Z, Zhang H, Si L
Curr Alzheimer Res · 2026 Jun · PMID 42381140 · Publisher ↗
INTRODUCTION: Lecanemab is a monoclonal antibody targeting amyloid-β (Aβ) and is currently used in clinical practice for the treatment of early Alzheimer's disease (AD). However, noninvasive biomarkers reflecting its ear...
INTRODUCTION: Lecanemab is a monoclonal antibody targeting amyloid-β (Aβ) and is currently used in clinical practice for the treatment of early Alzheimer's disease (AD). However, noninvasive biomarkers reflecting its early efficacy are still unclear. This exploratory case report aims to investigate the combination of eye movement and gait analysis to quantitatively monitor shortterm functional changes during lecanemab treatment. CASE PRESENTATION: Two male patients, both diagnosed with mild Alzheimer's disease through amyloid- PET and both with the APOE ε3/ε3 genotype, received intravenous lecanemab (10 mg/kg, every two weeks) for three months. Cognitive assessments (Montreal Cognitive Assessment, Mini- Mental State Examination, Clinical Dementia Rating), eye movement tests (smooth pursuit, overlapping saccades, anti-saccades), and gait analysis under single-task and dual-task conditions were conducted at baseline and follow-up. Patient 1 (79 years old) showed stable cognitive function, significant improvement in multiple eye movement parameters, and partial improvement in gait under single-task conditions. Patient 2 (60 years old) did not follow up on cognitive function tests as scheduled and showed inconsistent changes in eye movement parameters, but improved selected gait measures under dual-task conditions, particularly a shorter turning time. Neither patient experienced Amyloid-Related Imaging Abnormalities or infusion-related adverse events during the infusion process. CONCLUSION: This exploratory case report suggests that eye movement and gait analysis may be sensitive to short-term functional changes following lecanemab treatment, which were not consistently captured by traditional cognitive scales. These findings are hypothesis-generating and warrant further investigation in larger studies. Multimodal functional assessment may hold promise as a tool for monitoring early treatment effects in Alzheimer's disease.
Corrigendum to: Advancing Alzheimer's Disease Diagnosis Using VGG19 and XGBoost: A Neuroimaging-Based Method.
Boudi A, He J, El Kader IA … +2 more , Liu X, Mouhafid M
Curr Alzheimer Res · 2026 · PMID 42374762 · Publisher ↗
The publisher identified that references 42 and 43 were duplicated in the published version of this article [1]. The error has now been corrected. The original article can be found online at: https://www.benthamscience.c...
The publisher identified that references 42 and 43 were duplicated in the published version of this article [1]. The error has now been corrected. The original article can be found online at: https://www.benthamscience.com/article/150567 Details of the error and the correction are provided below: Original: [42] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190, 110095. [43] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190: 110095. http://dx.doi.org/10.1016/j.compbiomed.2025.110095 PMID: 40158456 Corrected: [42] Muksimova S, Umirzakova S, Iskhakova N, Khaitov A, Cho YI. Advanced convolutional neural network with attention mechanism for Alzheimer's disease classification using MRI. Comput Biol Med 2025; 190, 110095. http://dx.doi.org/10.1016/j.compbiomed.2025.110095 PMID: 40158456 [43] Olaimat MA, Bozdag S, Saeed F. TA-RNN: An attention-based time-aware recurrent neural network architecture to predict progression of Alzheimer's disease. Alzheimer's Dement 2024; 20(S1).
Corrigendum to: Lithium Chloride Improves Electrophysiological and Memory Deficits in Rats with Streptozotocin-Induced Alzheimer's Disease.
Xing Z, Jiang X, Yang W … +3 more , Wang Y, Zhang X, Zhao C
Curr Alzheimer Res · 2026 · PMID 42374761 · Publisher ↗
In the published version of this article [1], the email address of the co-corresponding author, Zheng Xing, was missing from the corresponding address section. This has now been corrected. The original article can be fou...
In the published version of this article [1], the email address of the co-corresponding author, Zheng Xing, was missing from the corresponding address section. This has now been corrected. The original article can be found online at: https://www.eurekaselect.com/article/149786 Details of the error and the correction are provided below: Original: Address correspondence to this author at the Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213004, P.R. China; E-mail: zhaochen3339@njmu.edu.cn (C.Z.); Corrected: Address correspondence to these authors at the Department of Pharmacy, The Second People's Hospital of Changzhou, The Third Affiliated Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213004, P.R. China; E-mails: zhaochen3339@njmu.edu.cn (C.Z.); xingzheng@cczu.edu.cn (Z.X.).
Apolipoprotein E Mimetics in Targeted Drug Delivery: Advances and Therapeutic Potential for Neurodegenerative and Cardiovascular Diseases.
Rishika C
Curr Alzheimer Res · 2026 Jun · PMID 42333549 · Publisher ↗
The need to improve the delivery of therapeutic compounds that require effective intracranial delivery across the Blood-Brain Barrier (BBB) has generated significant interest in apolipoprotein E (ApoE) mimetic peptides....
The need to improve the delivery of therapeutic compounds that require effective intracranial delivery across the Blood-Brain Barrier (BBB) has generated significant interest in apolipoprotein E (ApoE) mimetic peptides. These synthetic equivalents of the lipid-binding receptorsinteracting domains of natural ApoE are frequently reproducible when incorporated into nanocarriers or nano platforms, including reconstituted low-high density lipoproteins, polymeric nanoparticles, and liposomal systems. The progress in formulation science has led to the development of ApoE- functionalized nanoparticles and multifunctional liposomes with improved BBB translocation, cellular internalization, and Amyloid-beta (Aβ) affinity compared to conventional delivery vehicles. This review provides a comprehensive discussion of the process by which ApoE mimetics can be used to deliver therapeutic drugs and evaluates the different nanocarrier designs adapted to deliver drugs into the nervous system. Emphasis is also placed on new multifunctional systems in which ApoE mimetics are conjugated to therapeutic or diagnostic molecules, enabling imaging of the targeted area, delivery to the disease site, and disease-specific activity. Although the right direction has been taken, several issues still need to be addressed before ApoE-based strategies can be implemented in clinical practice. The problems that continue to limit larger use include formulation stability, unintended off-target interactions, pharmacokinetics, and scalability of complex nanocarrier systems. This review identifies key concerns needed to move ApoE-mimetic technologies toward effective, clinically viable therapies for central nervous system diseases, identifies the issues that inhibit progress, and analyzes possible methods for their management.
Association of Polymorphisms in Genes Involved in Serotonergic Signaling with the Risk of Developing Alzheimer's Disease.
Saeb L, Abtahi S, Masoudi R … +1 more , Javadpour A
Curr Alzheimer Res · 2026 Jun · PMID 42316566 · Publisher ↗
INTRODUCTION/AIM: Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter involved in mood, learning, and memory regulation. Disruptions in serotonin signaling have been linked to neurodegenerative disorder...
INTRODUCTION/AIM: Serotonin (5-hydroxytryptamine, 5-HT) is a monoamine neurotransmitter involved in mood, learning, and memory regulation. Disruptions in serotonin signaling have been linked to neurodegenerative disorders such as Alzheimer's Disease (AD). This case-control study aimed to examine whether specific polymorphisms in serotonergic genes are associated with AD risk in an Iranian population. MATERIALS AND METHODS: This research employed a case-control observational design to investigate potential associations between serotonin-related gene polymorphisms and the risk of Alzheimer's disease. Blood samples were collected from 68 patients diagnosed with AD and 69 healthy controls from southwest Iran. DNA was extracted, and genotyping for the 5-HT6 receptor gene C267T polymorphism, the 5-HT1A receptor promoter C(-1019)G polymorphism, and the 5- HTTLPR polymorphism in the serotonin transporter gene was performed using PCR with specific primers. Statistical analyses assessed associations between genotypes and AD risk. RESULTS: Statistical analysis showed significant associations between allele and genotype frequencies of these polymorphisms and AD. The T allele of the 5-HT6, C267T polymorphism increased the risk of Alzheimer's disease by 2.3 times (OR = 2.382, p= 0.017). In addition, a positive association was observed between individuals carrying the T allele and an increased risk of developing AD (OR = 2.202, p = 0.049). C allele of C(-1019)G was also associated with increased risk of AD (OR =1.72, p = 0.029). Individuals with the CG genotype (OR = 2.402, p= 0.024) or those carrying the C allele (OR = 2.500, p= 0.015) were more in risk of developing AD. Lastly, while no significant statistical association was found between 5-HTTLPR polymorphism and AD, adjustment for literacy suggested the SL genotype as a potential risk factor (OR = 4.163, p= 0.035). DISCUSSION: Our findings indicate that variations in serotonin-related genes may contribute to Alzheimer's Disease (AD) susceptibility, although their effects appear population-dependent. The 5-HT6 T and 5-HT1A C alleles were associated with a higher risk of AD, while the HTTLPR short allele showed significance only after adjusting for literacy, suggesting that education may influence genetic vulnerability. CONCLUSION: These results reinforce the multifactorial nature of AD, emphasizing the interaction between genetic and environmental factors. Larger, population-based studies are needed to validate these associations and clarify the mechanisms linking serotonergic signaling to AD pathogenesis.
Cerebral Hyperperfusion with Lecanemab in Alzheimer's Disease Assessed by Amyloid PET and Arterial Spin Labeling.
Imai N, Yano H, Ikegame Y … +6 more , Yasuda S, Morishima R, Okumura A, Kumagai M, Shinoda J, Izumo T
Curr Alzheimer Res · 2026 Apr · PMID 42299007 · Publisher ↗
INTRODUCTION/OBJECTIVE: Alzheimer's Disease (AD) is characterized by cognitive decline, amyloid-β deposition, and decreased Cerebral Blood Flow (CBF). Lecanemab, a monoclonal antibody targeting amyloid-β, slows cognitive...
INTRODUCTION/OBJECTIVE: Alzheimer's Disease (AD) is characterized by cognitive decline, amyloid-β deposition, and decreased Cerebral Blood Flow (CBF). Lecanemab, a monoclonal antibody targeting amyloid-β, slows cognitive decline in AD; however, its effects on CBF remain unclear. This study aimed to characterize CBF changes following lecanemab treatment and their association with baseline amyloid burden. METHODS: Thirty patients with AD treated with lecanemab were analyzed retrospectively. Baseline amyloid deposition was quantified using the Centiloid scale, and patients were stratified into low, middle, and high groups. CBF was analyzed at baseline and at 8, 12, and 26 weeks using arterial spin labeling (ASL). Monoclonal antibody-triggered cerebral hyperperfusion (MATCH) was defined as a >20% CBF increase at week 8. RESULTS: Seven patients were MATCH-positive (median CBF: 133.5% [125.5-167.8] of baseline). All MATCH-positive patients exhibited a decrease in CBF at week 12 compared to week 8. MATCH occurred in 6 of 10 patients in the middle Centiloid group. The low Centiloid group showed stable CBF, while the high Centiloid group showed a decreasing trend. The MATCHpositive group showed a significant deterioration in Instrumental Activities of Daily Living scores. DISCUSSION: A transient CBF increase was closely associated with the middle Centiloid group. These CBF responses, including MATCH, may reflect amyloid removal, hyperperfusion, amyloidrelated imaging abnormalities, or immune responses. CONCLUSIONS: CBF changes differed according to baseline amyloid burden. Understanding these therapy-related CBF changes is crucial for elucidating AD pathology, and ASL provides a practical, non-invasive method for longitudinal CBF monitoring in routine clinical practice.
Multitask Sparse Canonical Correlation Analysis and Regression with Parameter Decomposition based on Deep Subspace Reconstruction for Alzheimer's Disease.
Kong W, Su P, Xu Y … +5 more , Wang S, Wei K, Ke F, Wen G, Yu Y
Curr Alzheimer Res · 2026 Jun · PMID 42260779 · Publisher ↗
INTRODUCTION: Multimodal imaging genomics overcomes the limitations of singlemodality analyses, offering a more comprehensive understanding of brain pathophysiology. Traditional methods like sparse canonical correlation...
INTRODUCTION: Multimodal imaging genomics overcomes the limitations of singlemodality analyses, offering a more comprehensive understanding of brain pathophysiology. Traditional methods like sparse canonical correlation analysis (SCCA) and its improved versions have been widely used to identify key brain regions and single nucleotide polymorphisms (SNPs) associated with neurodegenerative diseases, such as Alzheimer's disease (AD). However, the fusion of complex and heterogeneous multimodal neuroimages, along with the linear formulation of these methods, limits their ability to capture complex, nonlinear relationships in imaging-genetics data. METHODS: To address this limitation, a novel framework, DSR-PDMTSCCAR, is introduced for multimodal AD data. This framework combines deep subspace reconstruction for nonlinear mapping and parameter decomposition to extract modality-consistent and modality-specific features across structural MRI (sMRI) and positron emission tomography (PET) data. Additionally, multitask sparse canonical correlation analysis (MTSCCA) is incorporated to capture correlations across multiple tasks, facilitating modeling of heterogeneous multimodal associations. RESULTS: Evaluations on simulated datasets and the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort show that DSR-PDMTSCCAR outperforms conventional methods, including SCCA, partial least squares (PLS), and deep canonical correlation analysis (DCCA). The method identifies biomarkers such as hippocampal and amygdalar alterations in sMRI/PET and APOErelated genetic variants, all consistent with AD pathology. DISCUSSION: The maximum canonical correlation coefficient (CCC) achieved was 0.1759, compared to 0.1525 for MTSCCA. The PET-SNP correlation (0.1896) was more than double that of MTSCCA (0.0864). CONCLUSION: The DSR-PDMTSCCAR framework offers robust performance in multimodal imaging- genetics analysis, providing enhanced insights into AD pathophysiology and advancing precision medicine.
Long-Term Consequences of Perinatal Asphyxia in the Development of Alzheimer's Disease.
Tarkowska A, Furmaga-Jabłońska W, Pluta R
Curr Alzheimer Res · 2026 Jun · PMID 42253201 · Publisher ↗
Despite remarkable progress in medicine, perinatal asphyxia (PA) remains a significant clinical problem, and concerns regarding its long-term complications are increasingly being raised. Emerging evidence indicates that...
Despite remarkable progress in medicine, perinatal asphyxia (PA) remains a significant clinical problem, and concerns regarding its long-term complications are increasingly being raised. Emerging evidence indicates that similar pathological pathways are activated following PA and during neurodegeneration in Alzheimer's disease (AD). These similarities involve various mechanisms, including alterations in AD-related proteins and their gene expression. Disturbances in neurotransmitter function can lead to excitotoxicity and cell death via necrosis and delayed apoptosis. Additionally, as observed in AD, dysregulation of autophagic processes has been reported. Pathological changes initiated by hypoxia in the newborn may trigger chronic neuroinflammation that persists long-term. Similarly, neuroinflammation plays a critical role in the pathogenesis of AD. Other common mechanisms include oxidative stress and mitochondrial dysfunction. Estrogens appear to have a protective effect in both PA and AD; however, ovaries exposed to PA may exhibit a reduced ovarian reserve, potentially diminishing neuroprotection later in life. Epigenetic modifications have also been proposed as a link between PA and AD. This review focuses on the changes that occur in the neonatal brain following PA, with particular emphasis on long-term consequences. We highlight common pathogenetic and causal pathways that may connect PA to the development of AD. Furthermore, we summarize key studies from the past 25 years addressing these topics and briefly discuss current research directions in the treatment of experimental and clinical PA.
Mitochondrial Dysfunction in Alzheimer's Disease: Beyond Energy Failure Toward a Pathogenic Nexus.
Sridhar SK, Goudanavar P, Naveen NR
Curr Alzheimer Res · 2026 May · PMID 42227471 · Publisher ↗
BACKGROUND: Mitochondrial dysfunction has gained recognition as a central and early event in the pathophysiology of Alzheimer's disease (AD), extending beyond classical energy failure to encompass complex and dynamic per...
BACKGROUND: Mitochondrial dysfunction has gained recognition as a central and early event in the pathophysiology of Alzheimer's disease (AD), extending beyond classical energy failure to encompass complex and dynamic perturbations in organelle homeostasis. Despite extensive focus on amyloid-beta (Aβ) and tau, accumulating evidence implicates mitochondria as both targets and amplifiers of neurodegenerative cascades. This review provides a comprehensive synthesis of the mechanistic roles and therapeutic implications of mitochondrial dysfunction in AD, highlighting recent advances and emerging paradigms that underscore mitochondria as integrative nodes in disease onset, progression, and biomarker discovery. MATERIALS AND METHODS: We critically evaluate literature from molecular, cellular, and systemslevel studies-including postmortem brain tissue, transgenic models, and patient-derived cellsfocusing on key domains such as bioenergetic collapse, redox imbalance, mitochondrial dynamics and quality control, Aβ and tau interactions, calcium dysregulation, and apoptosis. Novel mitochondrial mechanisms such as mitochondria-associated membranes (MAMs), mitochondrial unfolded protein response (UPRmt), and mitonuclear communication are discussed alongside recent translational efforts. RESULTS: Alzheimer's disease is characterized by widespread mitochondrial abnormalities, including impaired oxidative phosphorylation, increased reactive oxygen species (ROS), disrupted mitochondrial fission/fusion equilibrium, defective mitophagy, and abnormal calcium buffering. Moreover, direct mitochondrial accumulation of Aβ and tau disrupts protein import, respiratory chain integrity, and transport dynamics. DISCUSSION: These dysfunctions synergistically activate caspase-mediated apoptotic pathways, exacerbating synaptic loss and neuronal death. Promising therapeutic avenues involve antioxidants, NAD+ precursors, mitophagy modulators, and MAM-targeted strategies. Concurrently, mitochondrial biomarkers such as circulating mtDNA, cytochrome c, and neuroimaging via 31P-MRS or PET are emerging as tools for early diagnosis and disease monitoring. CONCLUSION: Mitochondria constitute a mechanistic nexus in AD, bridging upstream pathological triggers with downstream neurodegeneration. Advancing the field will require patient-specific models (e.g., iPSC-derived neurons, brain organoids), a deeper understanding of mitochondrial heterogeneity, and integration of mitochondrial targets into multi-modal therapeutic strategies. Precision mitochondrial medicine holds promise to transform AD management through mechanismbased diagnosis, stratification, and intervention.
Immunotherapeutic Advances in Alzheimer's Disease: The Convergence of Vaccinology and Nanoscience.
Chellammal HSJ, Janakiraman AK, Ramachandran D … +7 more , Chellappan RD, Sheikuduman MST, Janakiram MKS, Boyina HK, Abdul Kader MSM, Kannan SK, Sugavasi R
Curr Alzheimer Res · 2026 May · PMID 42227470 · Publisher ↗
Amyloid-beta plaques and neurofibrillary tangles promote neuronal dysfunction and cognitive loss, the hallmarks of Alzheimer's disease (AD), a serious global health concern. Current medications offer only symptomatic all...
Amyloid-beta plaques and neurofibrillary tangles promote neuronal dysfunction and cognitive loss, the hallmarks of Alzheimer's disease (AD), a serious global health concern. Current medications offer only symptomatic alleviation, emphasizing the critical need for disease-- modifying therapy. This study was performed using MeSH term search by using keywords, like "Alzheimer's Disease", "AD", "Vaccines", "Nanoformulations", "Amyloid-Beta (Aβ) Vaccines", "lecanemab", "Tau protein Vaccines", "AADvac1", "Clinical trials". The development of vaccines and methods based on nanotechnology is the primary focal point of this review, which explores immunotherapeutic approaches. Active and passive immunization are used in the development of AD vaccines to target tau and amyloid-beta pathology. While passive immunization involves the direct delivery of pre-formed antibodies, active immunization aims to stimulate the patient's own immune system to produce antibodies in response to the antigen. The necessity for effective drug delivery across the blood-brain barrier (BBB), safety issues, and inconsistent efficacy are some of the difficulties facing vaccine delivery strategies. Nanotechnology can overcome the drawbacks of traditional treatments by providing novel approaches for gene therapy, RNA-based interventions, and targeted medication administration. Immunization approaches offer multiple benefits, including regulated and targeted antigen release, as well as stabilizing the vaccine antigens. Therapeutic drugs can be delivered across the BBB, and genes linked to AD can be modulated by nanoparticles and liposomes that resemble exosomes. Current developments, including the incorporation of short Aβ epitopes, liposomal formulations, conformational mimotopes, and virus-- like particles (VLPs), have markedly enhanced vaccine tolerability. Effective AD treatments depend on combination medications, individualized approaches, and ongoing research into crossing the BBB and improving the safety and effectiveness of vaccines.
Trends in Cerebrovascular Disease Mortality Among Alzheimer Patients in Older Adults Across the USA: A CDC Wonder Analysis.
Qasim R, Tariq Z, Ahmed S … +5 more , Raza M, Khan I, Zahra R, Noor A, Mehdi BJ
Curr Alzheimer Res · 2026 May · PMID 42163600 · Publisher ↗
INTRODUCTION: Alzheimer's Disease (AD) is the most common form of dementia, affecting more than 55 million individuals worldwide. Cerebrovascular Disease (CeVD) has been shown to co-exist with AD. This study aimed to she...
INTRODUCTION: Alzheimer's Disease (AD) is the most common form of dementia, affecting more than 55 million individuals worldwide. Cerebrovascular Disease (CeVD) has been shown to co-exist with AD. This study aimed to shed light on this mortality trend to make a positive difference in improving patient care. METHODS: Data were extracted from the Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database using CeVD as the underlying cause of death, and AD as a multiple cause of death, from 1999 to 2020 for older adults (≥ 65 years). The Age- Adjusted Mortality Rates (AAMRs) were calculated per 100,000 individuals, and trends were assessed using Joinpoint as the Average Annual Percentage Changes (AAPCs). RESULTS: In total, 64,749 deaths were reported. The overall AAMR declined from 10.21 (1999) to 5.28 (2020). Females had higher AAMRs than males (7.75 vs. 5.59). Non-Hispanic White individuals had the highest AAMR (7.26), while the West region (8.57) and non-metropolitan areas (9.14) showed elevated rates. Vermont (11.81) and Washington (11.56) exhibited the highest death rates, in contrast to Nevada (3.08) and New York (3.25). Most deaths occurred in nursing homes, followed by medical facilities. DISCUSSION: Mortality declined overall, attributed to advancements in healthcare and prevention, but significant disparities persist among women, non-Hispanic White populations, western, and rural regions. Limitations include potential death certificate misclassification. Future studies should further evaluate targeted interventions, such as community-tailored interventions, to enhance equity. CONCLUSION: These trends showed significant spatiotemporal and demographic variation. Targeted interventions are required to mitigate fatalities, particularly in high-risk populations.
Exploring the Mechanism of Saponins from Panax japonicus in Improving Alzheimer's Disease Based on Network Pharmacology and Molecular Docking.
Huang QQ, Zhang XL, He SJ … +3 more , Zhou YH, Wang T, Zhang CX
Curr Alzheimer Res · 2026 May · PMID 42152268 · Publisher ↗
INTRODUCTION: To study the mechanism of saponins from Panax japonicus (SPJ) in improving Alzheimer's disease based on network pharmacology and molecular docking technology. METHODS: The active components in the SPJ were...
INTRODUCTION: To study the mechanism of saponins from Panax japonicus (SPJ) in improving Alzheimer's disease based on network pharmacology and molecular docking technology. METHODS: The active components in the SPJ were obtained from the databases of CNKI, PubMed, and PubChem. The active component targets were retrieved from the databases of Swiss Target Prediction and Super-PRED. The disease targets were retrieved from the databases GeneCards, OMIM, and PharmGKB. Drug-disease intersection targets were obtained via Venny 2.1.0. The String database was utilized to establish the protein network. The drug- active ingredient- target network was constructed by Cytoscape 3.10.1 software. The Metascape database was employed to conduct the gene ontology function enrichment analysis and KEGG pathway enrichment analysis. AutoDock Tools 1.5.7 was used to perform the molecular docking analysis. RESULTS: A total of 57 active components were obtained from the SPJ, and 438 drug targets and 2294 disease targets were identified, including 169 identical targets. The key targets were SRC, STAT3, PIK3R1, AKT1, ESR1, EGFR, and JUN. Pseudoginsenoside F11, Vina-ginsenoside R2, and Chikusetsusaponin III might be the key active components of SPJ in improving Alzheimer's disease. The key active components showed good binding energy and better binding affinity within the active targets. DISCUSSION: Network pharmacology has screened out 57 potential active components of SPJ, including pseudo ginsenoside F11, ginsenoside R2, and III, which may exert therapeutic effects by acting on key targets such as SRC, STAT3, PIK3R1, AKT1, ESR1, EGFR, and JUN. These targets are closely related to core pathological processes of AD, such as Aβ production, Tau protein phosphorylation, neuroinflammation, neuronal survival, and synaptic plasticity. Functional analysis indicates that SPJ may act on multiple cellular sites, such as receptor complexes and synaptic membranes, by influencing biological processes such as cell migration, inflammatory response, and membrane potential regulation. Pathway enrichment suggests that its mechanism of action may be related to Alzheimer's disease pathways, the NF-κB signaling pathway, and the calcium signaling pathway. The continuous activation of NF-κB can exacerbate neuroinflammation and oxidative damage, while the disorder of the calcium signaling pathway will lead to intracellular calcium overload, mitochondrial dysfunction, and synaptic damage, all of which play key roles in the progression of AD. CONCLUSION: SPJ exerts a therapeutic effect and provides the basis for Alzheimer's disease through multiple components, targets, and pathways.
Targeting Shared Mechanisms in Atherosclerosis and Alzheimer's Disease.
Chaudhari DB, Barve K
Curr Alzheimer Res · 2026 May · PMID 42099166 · Publisher ↗
Atherosclerosis and Alzheimer's Disease are two significant health concerns characterised by overlapping pathophysiological mechanisms, including chronic inflammation, oxidative stress, and lipid metabolism dysregulation...
Atherosclerosis and Alzheimer's Disease are two significant health concerns characterised by overlapping pathophysiological mechanisms, including chronic inflammation, oxidative stress, and lipid metabolism dysregulation. Impaired vascular integrity in atherosclerosis enhances the accumulation of Aβ plaque in the brain by reducing cerebral perfusion and compromising the clearance of Aβ. This review examines the shared pathways linking these conditions, emphasizing the role of the NLRP3 inflammasome, Receptor for Advanced Glycation End Products, and the apolipoprotein E4 allele in exacerbating vascular dysfunction that promotes neurodegeneration. The interplay between these factors underscores the potential of targeting these common pathways as a therapeutic strategy for both diseases. In preclinical studies, emerging treatments, NLRP3 inflammasome inhibitors like MCC950 and CY-09, show promise in mitigating both arterial plaque formation and neuronal amyloid deposition, while innovative microRNA-based therapies targeting miR-146a and miR-155 offer novel approaches to reduce inflammatory responses. Additionally, modulation of lipid metabolism through liver X receptor agonists like T0901317 and cholesteryl ester transfer protein inhibitors, including Anacetrapib, offers potential dual benefits for cardiovascular and neurological health. However, challenges such as restricted BBB permeability, genetic and sex variability, and limited long-term clinical evidence continue to constrain the effectiveness of dual-targeted therapeutic approaches. Future perspectives suggest integrating multi-- modal therapies that combine anti-inflammatory, lipid-regulatory, and antioxidant strategies to effectively address these interrelated diseases. Advancements in molecular biology and imaging techniques may facilitate the development of personalised medicine approaches, ultimately improving outcomes for patients suffering from both atherosclerosis and Alzheimer's Disease.
The Role of Ectopic Fat in Alzheimer's Disease.
Yang Y, Huang X, Liu H … +1 more , Yu C
Curr Alzheimer Res · 2026 May · PMID 42099165 · Publisher ↗
Alzheimer's Disease (AD) is a neurodegenerative disorder increasingly recognized to be associated with metabolic dysfunction. Accumulating evidence suggests that ectopic fat (abnormal fat deposition in non-adipose tissue...
Alzheimer's Disease (AD) is a neurodegenerative disorder increasingly recognized to be associated with metabolic dysfunction. Accumulating evidence suggests that ectopic fat (abnormal fat deposition in non-adipose tissue) is a key factor. This review summarizes the crucial role that ectopic fat plays in the onset and progression of AD, as well as the interrelated pathways through which ectopic fat deposition promotes the pathological process of AD. Adipocytes have been reported to produce and secrete amyloid-β (Aβ), a hallmark pathological feature of AD. Accordingly, ectopic fat may aggravate cerebral Aβ accumulation by impairing peripheral Aβ clearance. In addition, ectopic fat can also cause Insulin Resistance (IR), adipokine dysregulation, inflammatory responses, and oxidative stress. Therefore, ectopic fat is closely associated with the progression of AD and may play a contributory role in its pathogenesis. The effects of ectopic fat on the occurrence and development of Alzheimer's Disease (AD) pathology were reviewed through mechanisms such as metabolic disorders, inflammatory pathways, and Aβ deposition, and potential intervention strategies for this harmful cycle were highlighted. As current therapies for AD remain limited, new opportunities for its prevention and treatment may be provided through a better understanding of these associations.
Gut Microbiota Dysbiosis in Alzheimer's Disease and Possible Therapeutic Options.
Nayak RK, Mohapatra SR, Sahoo SK … +4 more , Sahu SK, Chowdhury B, Banu Z, Das NR
Curr Alzheimer Res · 2026 May · PMID 42099164 · Publisher ↗
Human microbiota consists of trillions of microbial cells dominated by bacteria, which live in the human body, while the term microbiome refers to the collective genetic material of microorganisms. Among them, the gut mi...
Human microbiota consists of trillions of microbial cells dominated by bacteria, which live in the human body, while the term microbiome refers to the collective genetic material of microorganisms. Among them, the gut microbiota has emerged as pivotal, producing its own metabolites, neurotransmitter precursors, and immune mediators that affect brain development and function. These signals function via the complex, bidirectional Gut-Brain Axis (GBA). This is a communication network that connects the gastrointestinal tract to the central nervous system. This axis plays an important role in the regulation of gastrointestinal homeostasis, neurodevelopment, emotional regulation, and cognitive processes. Increasing evidence suggests that microbial dysbiosis within the gastrointestinal tract is involved in the pathogenesis and progression of several neurological and neurodegenerative disorders, including mood disorders, schizophrenia, autism spectrum disorder, Alzheimer's Disease (AD), Parkinson's Disease (PD), and Huntington's Disease. These insights have opened new therapeutic possibilities, and multiple microbiota-targeted interventions, such as dietary modification, prebiotics, probiotics, postbiotics, psychobiotics, antibiotics, and Fecal Microbiota Transplantation (FMT), are now being explored for their therapeutic value, especially in Alzheimer's disease.
Comparative Efficacy and Safety of Cholinesterase Inhibitors and NMDA Receptor Antagonists in Alzheimer's Disease: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.
Li Y, Li L, Yang Q … +1 more , Xiong J
Curr Alzheimer Res · 2026 May · PMID 42099163 · Publisher ↗
INTRODUCTION: The study aims to evaluate and rank cholinesterase inhibitors, the NMDA antagonist memantine, anti-amyloid monoclonal antibodies, and non-drug modalities with respect to cognitive outcomes, functional statu...
INTRODUCTION: The study aims to evaluate and rank cholinesterase inhibitors, the NMDA antagonist memantine, anti-amyloid monoclonal antibodies, and non-drug modalities with respect to cognitive outcomes, functional status, neuropsychiatric symptoms, and tolerability. METHODOLOGY: We registered a protocol in PROSPERO and searched PubMed/MEDLINE, Embase, CENTRAL, Web of Science, trial registries, and gray literature through June 2025. Eligible randomized phase II/III trials in adults with clinically diagnosed AD were screened in duplicate. Data on interventions, comparators, outcomes (e.g., MMSE, ADAS-Cog, CDR-SB), and adverse events were extracted. Risk of bias was assessed using Cochrane RoB 2. A Bayesian random-effects NMA synthesized 125 trials (n > 30,000), estimating standardized Mean Differences (SMDs) with 95% Credible Intervals (CrIs). Heterogeneity (I²) and inconsistency (design-by-treatment, node-splitting) were evaluated. RESULTS: The network was well connected, with low-to-moderate heterogeneity (global I² = 38.5%) and no significant inconsistency (p = 0.48). Cognitive training (SMD = 0.45; 95% CrI 0.30-0.60; SUCRA 92%), aerobic exercise (SMD = 0.55; 95% CrI 0.35-0.75; SUCRA 87%), and galantamine (SMD = 0.40; 95% CrI 0.22-0.58; SUCRA 84%) ranked highest versus placebo. Donepezil (SMD = 0.21; 95% CrI 0.11-0.30; SUCRA 78%) and memantine (SMD = 0.24; 95% CrI 0.13-0.35; SUCRA 72%) showed modest benefits. DISCUSSION: Risk-of-bias ratings were low in 37% of trials, some concerns in 48%, and high in 15%. Subgroup analyses confirmed greater cholinesterase inhibitor efficacy in mild AD and superior memantine effects in moderate-to-severe disease. CONCLUSION: Non-pharmacological interventions demonstrated short-term cognitive benefits primarily in mild Alzheimer's disease populations and should be interpreted as adjunctive symptomatic strategies rather than direct substitutes for pharmacological therapy.
A Multimodal Framework for Alzheimer's Prevention: Diet, Exercise, Fasting, Sleep, and Gut Microbiota.
Kurmi S, Shirodkar S, Parab SB … +1 more , Doshi G
Curr Alzheimer Res · 2026 May · PMID 42099162 · Publisher ↗
Alzheimer's Disease (AD) and related dementias arise from a multifactorial interplay of genetic susceptibility, metabolic dysfunction, neuroinflammation, and lifestyle determinants. With limited disease-modifying pharmac...
Alzheimer's Disease (AD) and related dementias arise from a multifactorial interplay of genetic susceptibility, metabolic dysfunction, neuroinflammation, and lifestyle determinants. With limited disease-modifying pharmacotherapies, lifestyle interventions have emerged as compelling, evidence-based avenues for prevention and early management. This review integrates mechanistic, translational, and clinical insights on major modifiable behaviours, physical activity, diet, intermittent fasting, sleep regulation, and gut-microbiome-based approaches that collectively shape cognitive ageing. Aerobic, anaerobic, and resistance exercises exert neuroprotective effects by activating BDNF-TrkB signalling, enhancing hippocampal neurogenesis, improving synaptic plasticity, and stimulating peripheral myokines (CTSB, IGF-1, GPLD1) that cross the blood-brain barrier to support neuronal resilience. Dietary interventions such as the Mediterranean, Mediterranean- DASH Intervention for Neurodegenerative Delay (MIND), and ketogenic diets mitigate AD pathology by reducing oxidative stress, inhibiting Aβ deposition, improving mitochondrial efficiency, and modulating APOE4-linked metabolic vulnerability. Intermittent fasting induces a metabolic shift toward ketone utilisation, activates autophagy pathways (AMPK, SIRT3, Nrf2), remodels the gut microbiome, and promotes angiogenesis through GDF11 signalling. The gut-brain axis contributes to cognitive health through microbial metabolites, such as Short-Chain Fatty Acids (SCFAs), tryptophan derivatives, modulation of neuroinflammation, and enhanced neuronal survival. Meanwhile, sleep quality, particularly slow-wave sleep, optimises glymphatic clearance and prevents the pathological accumulation of Aβ and tau. Collectively, the evidence suggests that multidomain lifestyle approaches offer synergistic benefits that exceed those of individual interventions, representing promising strategies for delaying cognitive decline. However, gaps remain regarding dose-response relationships, personalised protocols for APOE4 carriers, and long-term validation in diverse populations. Strengthening these research directions is crucial for integrating lifestyle medicine into preventive neurology and public health frameworks.
An Inverse Association Between the Composite Dietary Antioxidant Index and Alzheimer's Disease: Evidence from an NHANES-Based Cross-Sectional Study.
Zhang Y, Tong S, Chen Y … +4 more , Li C, Yao Y, Tang S, Shang Y
Curr Alzheimer Res · 2026 Apr · PMID 42083373 · Publisher ↗
INTRODUCTION: The relationship between the dietary Complex Antioxidant Index (CDAI) and Alzheimer's Disease (AD) is not clear. Our study is to investigate the relationship between CDAI and the risk of AD in general adult...
INTRODUCTION: The relationship between the dietary Complex Antioxidant Index (CDAI) and Alzheimer's Disease (AD) is not clear. Our study is to investigate the relationship between CDAI and the risk of AD in general adults. METHODS: This study included 116876 participants from the National Health and Nutrition Survey (NHANES). CDAI was calculated based on the intake of six dietary antioxidants. We used multivariate logistic regression to examine the relationship between CDAI and AD prevalence, and used restricted cubic splines to examine the nonlinear association. RESULTS: The study showed that in the multivariate logistic regression model with fully adjusted confounding variables, the odds ratio (OR) of CDAI and AD was 0.9983 (95% confidence interval: 0.9969,0.9998; P=0.024). In addition, restricted cubic spline analysis revealed a linear correlation (P for non-linearity = 0.097). DISCUSSION: This cross-sectional study reveals a linear negative association between the CDAI and AD prevalence in U.S. adults, with vitamin E, carotenoids, and selenium showing independent protective effects. These findings align with the hypothesis that dietary antioxidants may mitigate oxidative stress-related neurodegeneration. However, due to the cross-sectional design, causal inference is not possible, and reverse causation cannot be excluded. The modest effect size and reliance on self-reported dietary data necessitate cautious interpretation. These hypothesis-generating findings underscore the need for prospective cohort studies to confirm whether antioxidant-rich diets could serve as a primary prevention strategy for AD. CONCLUSION: This cross-sectional study found a negative linear association between CDAI and AD prevalence in US adults. These hypothesis-generating findings require confirmation in prospective cohort studies.
Sodium-to-Potassium Ratio and Alzheimer's Disease: A Mendelian Randomization Study.
Yoshida H, Inoue T, Suzuki S … +1 more , Tomata Y
Curr Alzheimer Res · 2026 Apr · PMID 42083372 · Publisher ↗
INTRODUCTION: A higher urinary sodium-to-potassium (Na/K) ratio has been associated with increased risk of hypertension and cardiovascular diseases, which are known risk factors for Alzheimer's Disease (AD). Mendelian Ra...
INTRODUCTION: A higher urinary sodium-to-potassium (Na/K) ratio has been associated with increased risk of hypertension and cardiovascular diseases, which are known risk factors for Alzheimer's Disease (AD). Mendelian Randomization (MR), which uses genetic variants as instrumental variables to infer causality while reducing confounding and reverse causation, was applied to investigate whether the urinary Na/K ratio is causally associated with AD risk. METHODS: A two-sample MR study was conducted using 31 single-nucleotide polymorphisms associated with urinary Na/K ratio as instrumental variables. The primary analysis employed Genome- Wide Association Study (GWAS) summary statistics for AD (n=85,934 individuals, including ADby- proxy). For sensitivity analysis, GWAS data specific to clinically diagnosed late-onset AD (n=21,982 individuals) were analyzed. RESULTS: Genetically predicted urinary Na/K ratio was not statistically significantly associated with AD risk in the primary analysis; odds ratio (OR per 1 mol/mol increase) = 1.02, 95% confidence interval (CI): 0.77-1.36. In the sensitivity analysis using clinically diagnosed late-onset AD, the point estimate was higher (OR = 1.49, 95% CI: 0.99-2.24), although the association was not statistically significant. DISCUSSION: Although no statistically significant causal association was observed, the study's findings may be consistent with previous observational studies linking higher sodium intake or a higher urine Na/K ratio to poorer cognitive performance. However, the sensitivity analysis suggested a possible association that warrants further investigation in larger MR studies using clinically confirmed AD datasets. As all data were derived from individuals of European ancestry, generalizability to other populations may be limited. CONCLUSION: This MR study did not provide clear evidence supporting a causal association between urinary Na/K ratio and AD risk.
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