Current Alzheimer research最新文献

{"title":"The Role of Ectopic Fat in Alzheimer's Disease.","authors":"Ye Yang, Xueyan Huang, Hexu Liu, Changyin Yu","doi":"10.2174/0115672050461650260406064722","DOIUrl":"https://doi.org/10.2174/0115672050461650260406064722","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Multimodal Framework for Alzheimer's Prevention: Diet, Exercise, Fasting, Sleep, and Gut Microbiota.","authors":"Shubham Kurmi, Sanket Shirodkar, Siddhi Bagwe Parab, Gaurav Doshi","doi":"10.2174/0115672050467997260323164241","DOIUrl":"https://doi.org/10.2174/0115672050467997260323164241","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Shared Mechanisms in Atherosclerosis and Alzheimer's Disease.","authors":"Devesh B Chaudhari, Kalyani Barve","doi":"10.2174/0115672050447493260327074829","DOIUrl":"https://doi.org/10.2174/0115672050447493260327074829","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"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.","authors":"Yulian Li, Luo Li, Qiao Yang, JianZhong Xiong","doi":"10.2174/0115672050437623260417063631","DOIUrl":"https://doi.org/10.2174/0115672050437623260417063631","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methodology: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut Microbiota Dysbiosis in Alzheimer's Disease and Possible Therapeutic Options.","authors":"Rakesh Kumar Nayak, Soumya Ranjan Mohapatra, Satyam Kumar Sahoo, Susanta Kumar Sahu, Bimalendu Chowdhury, Zeenath Banu, Nihar Ranjan Das","doi":"10.2174/0115672050448298260303052535","DOIUrl":"https://doi.org/10.2174/0115672050448298260303052535","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848370","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An Inverse Association Between the Composite Dietary Antioxidant Index and Alzheimer's Disease: Evidence from an NHANES-Based Cross-Sectional Study.","authors":"Yuxin Zhang, Shu Tong, Yan Chen, Chen Li, Yinhui Yao, Shiying Tang, Yazhen Shang","doi":"10.2174/0115672050462427260407045906","DOIUrl":"https://doi.org/10.2174/0115672050462427260407045906","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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).</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sodium-to-Potassium Ratio and Alzheimer's Disease: A Mendelian Randomization Study.","authors":"Haruka Yoshida, Takuro Inoue, Shigenori Suzuki, Yasutake Tomata","doi":"10.2174/0115672050472115260421093303","DOIUrl":"https://doi.org/10.2174/0115672050472115260421093303","url":null,"abstract":"<p><strong>Introduction: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Discussion: </strong>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.</p><p><strong>Conclusion: </strong>This MR study did not provide clear evidence supporting a causal association between urinary Na/K ratio and AD risk.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147848344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Voice Biomarkers: Cognitive Impairment, including Alzheimer's Disease, Dementia, or Mild Cognitive Impairment: Introduction to Peripheral Neuropathy.","authors":"Fatma Özcan","doi":"10.2174/0115672050454281260307134058","DOIUrl":"https://doi.org/10.2174/0115672050454281260307134058","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Alzheimer's disease (AD) can cause certain nervous disorders, which in turn can lead to voice disorders and abnormal values for certain acoustic parameters. Mild cognitive impairment (MCI) is probably the early stage of the disease. Dementia is one of the causes of Alzheimer's disease. Whether or not there is a link between these three cognitive impairments, lesions affecting the vocal cords or articulators can be caused by neurological structures that influence phonation. The potential of biomarkers in the detection of cognitive impairment is remarkable. In our study, we will examine vocal biomarkers obtained from the extraction of acoustic features. The aim of this study is to combine vocal biomarkers with cognitive diseases.</p><p><strong>Methods: </strong>The standardised dataset used has recently been made publicly available. Cognitive impairment, including Alzheimer's disease, dementia, or MCI, is diagnosed from /a/ and diadochokinesis-pataka vocalisations using Mel-Frequency Cepstral Coefficients (MFCCs) transformed into 2D scalogram images. For processing, we will use the pre-trained OpenL3 network, and our less resource-intensive network called Op1Net to classify diseased and healthy groups.</p><p><strong>Results: </strong>A significant difference was observed compared to the control group. For the /a/ vocalisation, classification accuracy across all ages and genders was 82.1%, and the AUC value was 88.3%, while for diadochokinesis-pataka, accuracy was 69.8% and the AUC value was 75.4%. In the group of women over 55 years of age, the accuracy was 80.93%, and the AUC value was 87.12%.</p><p><strong>Discussion: </strong>Performance results clearly show that there is a correlation between the voice and the neurodegenerative disease AD, dementia, or MCI. We can see that the results of the data classification, including all ages and genders, for the sound /a/ are higher than those for the 'pataka' vocalisations. The prolonged vowel provides more information about the disease.</p><p><strong>Conclusion: </strong>This preliminary multidisciplinary study clearly demonstrates the existence of a link between neurological disease and the voice, and raises several questions concerning the nervous system, particularly the vagus nerve and associated neuropathy.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629740","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rapidly Progressive Dementia Secondary to Vitamin B12 Deficiency: A Case Report.","authors":"Rongzhen Xu, Hong Wang, Xiaozong Jiang, Liuqing Wang","doi":"10.2174/0115672050446215260303072158","DOIUrl":"https://doi.org/10.2174/0115672050446215260303072158","url":null,"abstract":"<p><strong>Introduction: </strong>While vitamin B12 deficiency is classically associated with hematological abnormalities and subacute combined degeneration, its presentation as rapidly progressive cognitive decline with episodic movement disorders remains an underrecognized clinical phenomenon. This case highlights the diagnostic challenges posed by such non-classical neurological manifestations and underscores the need for increased clinical suspicion in cases of unexplained cognitive-motor decline.</p><p><strong>Case presentation: </strong>A patient presented with rapidly progressive memory impairment and episodic limb tremors in the absence of overt hematological signs. Serum anti-parietal cell antibody (Anti- PCA) was positive (++; titer 1:32), and anti-intrinsic factor antibody (Anti-IFA) was positive (+) in the patient. Extensive diagnostic workup ruled out common neurodegenerative and structural causes, leading to the detection of severe vitamin B12 deficiency. Initiation of high-dose B12 replacement therapy resulted in marked improvement in both cognitive function and tremor control over subsequent weeks.</p><p><strong>Conclusion: </strong>This case illustrates that vitamin B12 deficiency can manifest as a rapidly progressive neurocognitive disorder mimicking neurodegenerative conditions. It emphasizes the importance of routinely assessing B12 status in patients with unexplained cognitive and movement abnormalities, as timely intervention can prevent irreversible neurological injury and yield significant clinical improvement.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147619149","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of DW2009 on BDNF Levels as a Secondary Analysis of a Randomized Controlled Trial Across Sociodemographic Subgroups.","authors":"Min Cheol Kim, Dae Yeon Won, Hyunju Kim, Jong-Woo Paik, Ah Rah Lee, Yun-Ha Hwang","doi":"10.2174/0115672050457704260126083119","DOIUrl":"https://doi.org/10.2174/0115672050457704260126083119","url":null,"abstract":"<p><strong>Introduction: </strong>The prevalence of neurodegenerative disorders continues to increase with population aging. Brain-derived neurotrophic factor is a biomarker of cognitive function and neuroprotection. Lactobacillus plantarum C29-fermented soybean (DW2009) has been suggested to enhance cognition by modulating brain-derived neurotrophic factor. This secondary analysis of a randomized, double-blind, placebo-controlled trial investigated the influence of sociodemographic and lifestyle factors on serum brain-derived neurotrophic factor responsiveness to DW2009 supplementation.</p><p><strong>Methods: </strong>One hundred adults (age: 55-85 years) with mild cognitive impairment were randomized 1:1 to receive DW2009 (800 mg/day) or placebo (800 mg/day) for 12 weeks. The participants were examined, and their cognitive clinical features and serum brain-derived neurotrophic factor (BDNF) levels were measured at baseline and after a 12-week period.</p><p><strong>Results: </strong>We found that DW2009 significantly increased serum BDNF levels, especially in older men (≥ 68 years) and in those with lower educational attainment (≤ 11 years). Subgroup analysis also indicated that the effect of DW2009 was enhanced in participants who performed frequent physical activity (≥ 5 times/week) and those within the normal body mass index range (18.5-22.9 kg/m²).</p><p><strong>Discussion: </strong>Our findings suggest that the increase in serum BDNF after DW2009 supplementation is dependent on baseline characteristics, although this interpretation requires confirmation.</p><p><strong>Conclusion: </strong>DW2009 intake was linked to increased serum BDNF levels in individuals with specific sociodemographic and lifestyle characteristics. These findings suggest that personalized supplementation strategies may optimize functional benefits for cognitive health.</p>","PeriodicalId":94309,"journal":{"name":"Current Alzheimer research","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147611283","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}