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This research aims to answer the question if e-commerce favoured in a special way the growth of low-cost carriers within the civil aviation market. After defining low-cost and traditional carriers’ business models, data on transported passengers were collected for three countries (Italy, Germany and Spain) and confronted with the number of e-consumers. Despite a significant correlation in all the three markets, only in Italy our hypothesis has been supported by Granger causality, and the regression analysis allows to forecast a future characterized by a growing dominance of LCCs. Although the definition of an econometric model will require further studies, the distinctive features of the Italian market might represent a starting point for future research on the complex relationship between e-commerce and air transport.

Abstract Our study aimed to investigate the clinical characteristics of PD patients stratified by OH status before and after levodopa challenge to explore the hypothesis that OH might serve as a clinical marker for the body-first subtype of PD. Supine and standing blood pressure were measured in a large cross-sectional cohort of PD patients at the OFF status before and after levodopa challenge test (LCT). Based on OH status, patients were divided into three groups: spontaneous OH (SOH), only levodopa-induced OH (LOH) and non-OH (NOH). Clinical characteristics and associated factors were compared among the groups. A total of 928 patients with a mean age of 62.4 years and average disease duration of 7.9 years were included. There were 224 (24.1%) patients with SOH, 321 (34.6%) with LOH, and 383 (41.3%) with NOH. Compared to NOH, both SOH and LOH were associated with older age, motor fluctuations, and probable rapid eye movement sleep behavior disorder (pRBD). In addition, OH was more associated with cardiovascular and digestive dysfunction, disease severity and worse quality of life. Results of the current study suggest that PD patients developed OH which is more likely to comorbid with RBD, severe autonomic dysfunction and motor fluctuations, consistent with the body-first subtype of PD.

Abstract Background Data quality is a major challenge for most health institutions and organizations across the globe. The Ghana Health Service, supported by other non-governmental organizations, has instituted various strategies to address and improve data quality issues in regional and district health facilities in Ghana. This study sought to assess routine data quality of Expanded Programme on Immunization, specifically for Penta 1 and Penta 3 vaccines. Methods A descriptive cross-sectional study design was used for the study. A simple random sampling method was used to select thirty-four health facilities across seven sub-municipalities. Records from the Expanded Programme on Immunization (EPI) Tally Books and Monthly Vaccination Summary Report were reviewed and compared with data entered into the District Health Information Management System 2 (DHIMS2) software for the period of January to December 2020. The World Health Organization Data quality self-assessment (DQS) tool was used to compare data recorded in the EPI tally books with monthly data from summary reports and DHIMS2. Data accuracy ratio was determined by the data quality assessment tools and STATA version 14.2 was used to run additional analysis. A data discrepancy is when two corresponding data sets don’t match. Results The results showed discrepancies between recounted tallies in EPI tally books and summary reports submitted as well as DHIMS2. Verification factor of 97.4% and 99.3% and a discrepancy rate of 2.6 and 0.7 for Penta 1 and Penta 3 respectively were recorded for tallied data and summary reports. A verification factor of 100.5% and 99.9% and a discrepancy of -0.5 and 0.1 respectively for the same antigens were obtained for the summary reports and DHIMS2. Data timeliness was 90.7% and completeness was 100% for both antigens. Conclusion The accuracy of Penta 1 and Penta 3 data on EPI in the Upper East Region of Ghana was high. The data availability, timeliness and completeness were also high.

The development of a detailed strategy to mitigate the negative consequences of any natural calamities depends on accurately identifying sensitive zones where natural hazards frequently happen. In the present investigations, three widely utilized probabilistic approaches viz., frequency ratio (FR), statistical index (SI), and weighting factor (WF) have been utilized for prediction of flsh flood susceptibility zones in the Coochbehar urban and peri-urban area (CUPUA) (area = 26.22 km2). Ten flash flood conditioning factors have been used in this assessment based on previous literatures and experts' opinions. In the FR model, 29.40 % area is observed in the high and very high flood zones, whereas 36.27 % and 31.16 % area is identified in SI and WF model, respectively. The FR model demonstrates that five conditioning factors, viz., topographic position index (TPI), land use and land cover (LULC), normalized difference vegetation index (NDVI), distance to drainage (DtD) and rainfall were highly impacted in flash flood prediction (FFP) analysis; in SI model, LULC is the major influencing parameter, and in WF model LULC, rainfall, NDVI, and distance to road (DtR) are the effective parameters. The success rate curve of the FR, SI and WF models manifest SI model has highest training (AUC=0.903) and prediction (AUC=0.925) accuracy, and FR and WF also have very good accuracy as their AUC values are 0.899 and 0.877 (in success rate curve) and 0.900 and 0.881 (in prediction rate curve). Therefore, the application of probabilistic approaches in this active flash flood-prone region is excellently performed, and the results of this study will help hydrologists, engineers, and water management administrators to control the areas that are extremely susceptible to flash floods and reduce possible damages.

The Zika virus, a member of the Flaviviridae family, is a mosquito-borne disease-causing virus that gained worldwide attention after a severe outbreak in Brazil in 2015. During this outbreak, some alarming evidence suggests that fetal microcephaly and other neuro-developmental disorders were associated with Zika infection. The virus also causes multi-organ failure and thrombocytopenia and also affects the eyes, leading to a potentially inflammatory disease called uveitis in adult individuals. It could be transmitted through sexual intercourse or the transplacental route, which is not commonly observed in other flaviviruses. In this review, we are interested in discovering the specific role of microglia in the pathogenesis of Zika virus-induced neuroinflammation. The virus comes into contact with microglial cells through the blood and causes activation and neuroinflammatory consequences, leading to the death of developing neurons and ultimately resulting in altered neuron-glia interaction. Despite its severity, there is still no specific medicine or vaccine available to combat the Zika infection. An essential aspect of this review is to identify cost-effective treatment strategies and accurate diagnostic methods for broader populations. In conclusion, an understanding of the cellular basis of Zika pathogenesis can help ensure potential treatment strategies to combat the global outbreak of the Zika virus.

Abstract While numerous single nucleotide variants and small indels have been identified in Parkinson’s disease (PD), the contribution of structural variants (SVs), copy number variants (CNVs), and short tandem repeats (STRs) remains poorly understood. Here we investigated the association using the high-depth whole-genome sequencing data from 466 Chinese PD patients and 513 controls. Totally, we identified 29,561 SVs, 32,153 CNVs, and 174,905 STRs, and found that CNV deletions were significantly enriched in the end-proportion of autosomal chromosomes in PD. After genome-wide association analysis and replication in an external cohort of 352 cases and 547 controls, we validated that the 1.6 kb-deletion neighboring MUC19, 12.4kb-deletion near RXFP1 and GGGAAA repeats in SLC2A13 were significantly associated with PD. Moreover, the MUC19 deletion and the SLC2A13 5-copy repeat reduced the penetrance of the LRRK2 G2385R variant. Moreover, genes with these variants were dosage-sensitive. These data provided novel insights into the genetic architecture of PD.

Abstract Asymptomatic Leucine-Rich Repeat Kinase 2 Gene (LRRK2) carriers are at risk for developing Parkinson's disease (PD). We studied presymptomatic substantia nigra pars compacta (SNc) regional neurodegeneration in asymptomatic LRRK2 carriers compared to idiopathic PD patients using neuromelanin-sensitive MRI technique (NM-MRI). Fifteen asymptomatic LRRK2 carriers, 22 idiopathic PD patients, and 30 healthy controls (HCs) were scanned using NM-MRI. We computed volume and contrast-to-noise ratio (CNR) derived from the whole SNc and the sensorimotor, associative, and limbic SNc regions. An analysis of covariance was performed to explore the differences of whole and regional NM-MRI values among the groups while controlling the effect of age and sex. In whole SNc, LRRK2 had significantly lower CNR than HCs but non-significantly higher volume and CNR than PD patients, and PD patients significantly lower volume and CNR compared to HCs. Inside SNc regions, there were significant group effects for CNR in all regions and for volumes in the associative region, with a trend in the sensorimotor region but no significant changes in the limbic region. PD had reduced volume and CNR in all regions compared to HCs. Asymptomatic LRRK2 carriers showed globally decreased SNc volume and CNR suggesting early nigral neurodegeneration in these subjects at risk of developing PD.

Background Over the past few decades, World Health Organization (WHO) has made massive efforts to promote the development of a vaccine against Lassa virus (LASV), one of the top ten priority pathogens for research and development under the WHO R&D Blueprint for Emerging Infections. To date, several vaccines are at different stages of development. In this scenario, a validated and standardised assay to measure LASV neutralising antibodies is urgently needed for vaccine development and comparison. Methods The neutralisation assay remains the gold standard for determining antibody efficacy. Here we have proposed a safe and validated pseudotyped neutralisation assay for LASV, taking advantage of the development of the first WHO International Standard and Reference Panel for Anti-Lassa Fever (NIBSC code 21/332). Results and Conclusions The proposed results demonstrate that the pseudotyped luciferase neutralisation assay is a specific serological test for the measurement of LASV neutralising antibodies without cross-reacting with standard sera specific for heterologous viral infections. In addition, the assay is accurate, precise, and linear according to criteria and statistical analyses defined and accepted by international guidelines.

Typhoid and Paratyphoid fever cause a global health burden, especially for the children of Southern Asia. The impact of the disease is further exacerbated by the dramatic increase of antimicrobial resistance. While vaccines against Salmonella Typhi have been developed and successfully introduced, an effective vaccine targeting S. Paratyphi A is still lacking. Several efforts are currently ongoing to develop vaccines targeting both S. Typhi and S. Paratyphi A. In order to analyze the immune response induced by vaccination and in sero-epidemiological studies, easy to perform and high throughput immunoassays are needed. Here we present the setup and characterization of a customized ELISA assay and of a luminescent-based serum bactericidal assay (L-SBA) to measure the quantity of S. Paratyphi O antigen specific antibodies and their functional activity against S. Paratyphi A. Robust quality control criteria have been put in place both for ELISA and SBA and assays have been fully characterized in terms of quantitation limit, limit of blanks, specificity, linearity and precision. Assays are being employed to analyze samples from clinical trials, enabling the assessment of immunogenicity during clinical vaccine development.

Effective vaccines against Salmonella Typhi, targeting the Vi capsular polysaccharide, have been developed and are being introduced into routine immunization in endemic countries. Vi conjugated vaccines are also being tested in new multi-component vaccine formulations. Simple, high-throughput and cost-effective assays to quantify Vi-specific IgG in clinical sera are needed. In this study we present the development and qualification of a new anti-Vi ELISA with continuous readout, which expresses results as ELISA Unit/mL (EU/mL). We have qualified the assay in terms of precision, linearity and specificity, demonstrating performance in line with a commercially available anti-Vi ELISA. We have also calibrated the assay against the 16/138 anti-Vi international standard and established conversion factor between EU/mL and international units/mL, to allow comparability of results across studies. In summary, this new assay met all the suitability criteria and is being used to evaluate anti-Vi responses in clinical studies.

Abstract Introduction Semantic fluency is the ability to name items from a given category within a limited time, which relies on semantic knowledge, working memory, and executive function. Similar to patients with Parkinson's disease (PD), patients with progressive supranuclear palsy (PSP) scored lower than healthy adults in the well‐established semantic fluency test. However, it is unclear how unique are the produced words. This study examined the relationship between semantic fluency and words’ uniqueness in patients with PSP. Methods Twenty‐seven patients with PSP Richardson's syndrome (PSP‐RS), 37 patients with PD, and 41 healthy controls (HC) performed a standard semantic fluency test (animals), and their verbal responses were audio‐recorded. We used the uniqueness to reflect the ability to produce both original and effective work, that is, creativity. Results The PSP‐RS group produced fewer correct words and fewer unique words than the PD and HC groups. Moreover, the correlation between fluency and uniqueness was positive in the HC and PD groups but negative in the PSP‐RS group. Importantly, the actual levodopa dose was positively correlated with the fluency but negatively correlated with the uniqueness in PSP‐RS. The PSP‐RS patients who took a greater dose of levodopa tended to produce more correct words but fewer unique words. Conclusions These results suggested that levodopa may modulate semantic fluency and uniqueness in the early stages of PSP‐RS.

In this article, I examine the portrayal of animals in Lewis Carroll’s _Alice’s Adventures in Wonderland_ and Dodie Smith’s _The One Hundred and One Dalmatians_. Specifically, I consider the issue of the alterity (or “otherness”) of animals as a category, and the extent to which this is reflected (or not) in these two texts. I then proceed to consider this question in relation to more recent children’s books and my own practice as a writer. This article reflects on and develops, in the context of the specific texts cited above and my personal practice as a writer, the discussion by Mimi Thebo of animal representation in children’s literature in her article ‘Talking Tigers: Concepts of Representational Ethics Applied to Non-Human Characters in Writing Children’s Fiction’.

BackgroundWe have shown that genetic factors associating with motor progression of Parkinson’s disease (PD), but their roles in cognitive function is poorly understood. One reason is that while cognitive performance in PD can be evaluated by various cognitive scales, there is no definitive guide indicating which tool performs better.MethodsData were obtained from the Parkinson’s Progression Markers Initiative, where cognitive performance was assessed using five cognitive screening tools, including Symbol Digit Modalities Test (SDMT), Montreal Cognitive Assessment, Benton Judgment of Line Orientation, Modified Semantic Fluency Test, and Letter Number Sequencing Test, at baseline and subsequent annual follow-up visit for 5 years. Genetic data including ApoE and other PD risk genetic information were also obtained. We used SPSS-receiver operating characteristic and ANOVA repeated measures to evaluate which cognitive assessment is the best reflecting cognitive performance in PD at early stage and over time. Logistic regression analyses were used to determine the genetic associations with the rapidity of cognitive decline in PD.ResultsSDMT performed better in detecting mild cognitive impairment at baseline (AUC = 0.763), and SDMT was the only tool showing a steady cognitive decline during longitudinal observation. Multigenetic factors significantly associated with cognitive impairment at early stage of the disease (AUC = 0.950) with IP6K2 rs12497850 more evident, and a significantly faster decline (AUC = 0.831) within 5 years after motor onset, particularly in those carrying FGF20 rs591323.ConclusionSDMT is a preferable cognitive assessment tool for PD and genetic factors synergistically contribute to the cognitive dysfunction in PD.

Background: This study aimed to show a 3-year trajectory of physical performance among Chinese elderly in Beijing communities and explore the associations between new adverse events during the 3-year follow-up period and decreased physical performance. Methods: A longitudinal observational study included baseline data and transitional information of physical performance from 456 community elders (mean age 67.3 ± 4.9 years, female 43.2 %) at a 3-year follow-up. The Mini-Mental State Examination (MMSE) and the Short Physical Performance Battery (SPPB) were used to measure cognition and physical performance, respectively. The number of chronic diseases, cognitive impairment, malnutrition, depression, knee pain, falls, and frailty were the principal independent variables in multivariate logistic regression analysis. Results: The proportion of the elderly with poor physical performance (26.97 %) increased to 42.11 % and the proportion of those with good physical performance (44.96 %) dropped to 30.48 % after the three-year follow-up. As for physical performance transitions, 39.47 % of the elderly progressed to a worsening physical status. After adjustment for covariates, only new onset cognitive impairment (OR: 5.17; 95%CI: 2.01–14.54; P = 0.001) was associated with physical performance deterioration. Conclusion: Cognitive impairment is an independent risk factor for decreased physical performance in elderly people. Active interventions targeted at cognitive impairment could help promote healthy aging.

Abstract Purpose Sequential working memory is the ability to maintain and manipulate sequential information at a second time scale. Patients with progressive supranuclear palsy (PSP) or Parkinson's disease (PD) perform poorly in tests that require the flexible arrangement of thoughts or actions. This study investigated whether sequential working memory is differently impaired in patients with PSP versus PD. Method Twenty‐nine patients with PSP Richardson's syndrome (PSP‐RS), 36 patients with PD, and 36 healthy controls (HC) completed 3 well‐established neuropsychological tests, including digit span forward (DST‐F), digit span backward (DST‐B), and adaptive digit ordering tests (DOT‐A). The DST‐F required maintaining digit sequences, and the DST‐B and DOT‐A required maintaining and manipulating digit sequences. Finding The PSP‐RS group scored lower than the PD and HC groups in the DST‐B and DOT‐A but not in the DST‐F, indicating that the ability to manipulate sequences was impaired, but the maintenance ability was preserved in PSP‐RS patients. Moreover, in PSP‐RS, the DST‐B score negatively correlated with the severity of motor symptoms. The actual levodopa dose positively correlated with the DST‐B ordering cost (DST‐F score vs. DST‐B score). The PSP patients who took a greater dose of levodopa tended to have higher DST‐B ordering cost. There was no effect of levodopa on DST‐B or DOT‐A in PD. Conclusion These results suggested that the ability to manipulate sequence was already reduced in patients with PSP‐RS and was worse than in patients with PD.

IntroductionAccurately and objectively quantifying the clinical features of Parkinson's disease (PD) is crucial for assisting in diagnosis and guiding the formulation of treatment plans. Therefore, based on the data on multi-site motor features, this study aimed to develop an interpretable machine learning (ML) model for classifying the “OFF” and “ON” status of patients with PD, as well as to explore the motor features that are most associated with changes in clinical symptoms.MethodsWe employed a support vector machine with a recursive feature elimination (SVM-RFE) algorithm to select promising motion features. Subsequently, 12 ML models were constructed based on these features, and we identified the model with the best classification performance. Then, we used the SHapley Additive exPlanations (SHAP) and the Local Interpretable Model agnostic Explanations (LIME) methods to explain the model and rank the importance of those motor features.ResultsA total of 96 patients were finally included in this study. The naive Bayes (NB) model had the highest classification performance (AUC = 0.956; sensitivity = 0.8947, 95% CI 0.6686–0.9870; accuracy = 0.8421, 95% CI 0.6875–0.9398). Based on the NB model, we analyzed the importance of eight motor features toward the classification results using the SHAP algorithm. The Gait: range of motion (RoM) Shank left (L) (degrees) [Mean] might be the most important motor feature for all classification horizons.ConclusionThe symptoms of PD could be objectively quantified. By utilizing suitable motor features to construct ML models, it became possible to intelligently identify whether patients with PD were in the “ON” or “OFF” status. The variations in these motor features were significantly correlated with improvement rates in patients' quality of life. In the future, they might act as objective digital biomarkers to elucidate the changes in symptoms observed in patients with PD and might be used to assist in the diagnosis and treatment of patients with PD.

Abstract REM sleep behavior disorder (RBD) symptoms in Parkinson’s disease (PD) suggest both a clinically and pathologically malignant subtype. However, whether RBD symptoms are associated with alterations in the organization of whole-brain intrinsic functional networks in PD, especially at early disease stages, remains unclear. Here we use resting-state functional MRI, coupled with graph-theoretical approaches and network-based statistics analyses, and validated with large-scale network analyses, to characterize functional brain networks and their relationship with clinical measures in early PD patients with probable RBD (PD+pRBD), early PD patients without probable RBD (PD-pRBD) and healthy controls. Thirty-six PD+pRBD, 57 PD-pRBD and 71 healthy controls were included in the final analyses. The PD+pRBD group demonstrated decreased global efficiency (t = -2.036, P = 0.0432) compared to PD-pRBD, and decreased network efficiency, as well as comprehensively disrupted nodal efficiency and whole-brain networks (all eight networks, but especially in the sensorimotor, default mode and visual networks) compared to healthy controls. The PD-pRBD group showed decreased nodal degree in right ventral frontal cortex and more affected edges in the frontoparietal and ventral attention networks compared to healthy controls. Furthermore, the assortativity coefficient was negatively correlated with Montreal cognitive assessment scores in the PD+pRBD group (r = -0.365, P = 0.026, d = 0.154). The observation of altered whole-brain functional networks and its correlation with cognitive function in PD+pRBD suggest reorganization of the intrinsic functional connectivity to maintain the brain function in the early stage of the disease. Future longitudinal studies following these alterations along disease progression are warranted.

Background & Aims: Hepatocellular carcinoma (HCC) is a male-dominant disease, but targeted sex hormone therapies have not been successful. Bile acids are a potential liver carcinogen and are biomolecules with hormone-like effects. A few studies highlight their potential sex dimorphism in physiology and disease. We hypothesized that bile acids could be a potential molecular signature that explains sex disparity in HCC. Methods & Results: We used the farnesoid X receptor knockout (FxrKO) mouse model to study bile acid-dependent HCC. Temporal tracking of circulating bile acids determined more than 80% of FxrKO females developed spontaneous cholemia (ie, serum total bile acids ≥40 μmol/L) as early as 8 weeks old. Opposingly, FxrKO males were highly resistant to cholemia, with ∼23% incidence even when 26 weeks old. However, FxrKO males demonstrated higher levels of deoxycholate than females. Compared with males, FxrKO females had more severe cholestatic liver injury and further aberrancies in bile acid metabolism. Yet, FxrKO females expressed more detoxification transcripts and had greater renal excretion of bile acids. Intervention with CYP7A1 (rate limiting enzyme for bile acid biosynthesis) deficiency or taurine supplementation either completely or partially normalized bile acid levels and liver injury in FxrKO females. Despite higher cholemia prevalence in FxrKO females, their tumor burden was less compared with FxrKO males. An exception to this sex-dimorphic pattern was found in a subset of male and female FxrKO mice born with congenital cholemia due to portosystemic shunt, where both sexes had comparable robust HCC. Conclusions: Our study highlights bile acids as sex-dimorphic metabolites in HCC except in the case of portosystemic shunt.

Background: Cognitive impairment is common in patients with Parkinson’s disease (PD) and occurs through multiple mechanisms, including Alzheimer’s disease (AD) pathology and the involvement of α-synucleinopathies. We aimed to investigate the pathological biomarkers of both PD and AD in plasma and neuronal extracellular vesicles (EVs) and their association with different types of cognitive impairment in PD patients. Methods: A total of 122 patients with PD and 30 healthy controls were included in this cross-sectional cohort study between March 2021 and July 2023. Non-dementia PD patients were divided into amnestic and non-amnestic groups according to the memory domain of a neuropsychological assessment. Plasma and neuronal EV biomarkers, including α-synuclein (α-syn), beta-amyloid (Aβ), total tau (T-tau), phosphorylated tau181 (p-tau181), and glial fibrillary acidic protein (GFAP), were measured using a single-molecule array and a chemiluminescence immunoassay, respectively. Results: Neuronal EV but not plasma α-syn levels, were significantly increased in PD as compared to healthy controls, and they were positively associated with UPDRS part III scores and the severity of cognitive impairment. A lower plasma Aβ42 level and higher neuronal EV T-tau level were found in the amnestic PD group compared to the non-amnestic PD group. Conclusions: The results of the current study demonstrate that neuronal EV α-syn levels can be a sensitive biomarker for assisting in the diagnosis and disease severity prediction of PD. Both AD and PD pathologies are important factors in cognitive impairment associated with PD, and AD pathologies are more involved in amnestic memory deficit in PD.

Abstract Response to immunotherapy widely varies among cancer patients and identification of parameters associating with favourable outcome is of great interest. Here we show longitudinal monitoring of peripheral blood samples of non-small cell lung cancer (NSCLC) patients undergoing anti-PD1 therapy by high-dimensional cytometry by time of flight (CyTOF) and Meso Scale Discovery (MSD) multi-cytokines measurements. We find that higher proportions of circulating CD8+ and of CD8+CD101hiTIM3+ (CCT T) subsets significantly correlate with poor clinical response to immune therapy. Consistently, CD8+ T cells and CCT T cell frequencies remain low in most responders during the entire multi-cycle treatment regimen; and higher killer cell lectin-like receptor subfamily G, member 1 (KLRG1) expression in CCT T cells at baseline associates with prolonged progression free survival. Upon in vitro stimulation, CCT T cells of responders produce significantly higher levels of cytokines, including IL-1β, IL-2, IL-8, IL-22 and MCP-1, than of non-responders. Overall, our results provide insights into the longitudinal immunological landscape underpinning favourable response to immune checkpoint blockade therapy in lung cancer patients.

ObjectiveTo determine whether the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is associated with cognitive impairment (CI) in community-dwelling Chinese older adults, and to investigate whether this relationship is modified by the Apolipoprotein E (APOE) ɛ4 allele.MethodsThe study is a secondary analysis of 703 participants aged ≥60 years randomly enrolled from the Beijing Longitudinal Study of Aging II prospective cohort. The education-adjusted Mini-Mental State Examination and the Clinical Dementia Rating Scale were used to measure the cognitive performance of the subjects. The main effects and interactions (additive and multiplicative) of the BDNF Met and the APOE ε4 alleles on CI were estimated by logistic regression models.ResultsIn total, 84 out of 703 older adults aged ≥60 years old had CI. No significant difference was observed in the risk of CI between participants with the BDNF Met allele and that of subjects without the BDNF Met allele (p = 0.213; p = 0.164). Individuals carrying both the BDNF Met and APOE ε4 alleles had an almost 1.5-fold increased odds of CI compared with carriers of the BDNF Met allele but without the APOE ε4 allele. The additive association indicated a positive interaction of both BDNF Met and APOE ε4 alleles with wide CIs (p = 0.021; p = 0.018).ConclusionThe results suggest that the APOE ε4 allele may be a potential modifier for the association of the BDNF Val66Met polymorphism with CI in community-dwelling older adults.