Mitofusin-2 Regulates Platelet Mitochondria and Function.

BACKGROUND: Single-nucleotide polymorphisms linked with the rs1474868 T allele (MFN2 [mitofusin-2] T/T) in the human mitochondrial fusion protein MFN2 gene are associated with reduced platelet MFN2 RNA expression and platelet counts. This study investigates the impact of MFN2 on megakaryocyte and platelet biology. METHODS: Mice with megakaryocyte/platelet deletion of Mfn2 (Mfn2-/- [Mfn2 conditional knockout]) were generated using Pf4-Cre crossed with floxed Mfn2 mice. Human megakaryocytes were generated from cord blood and platelets isolated from healthy subjects genotyped for rs1474868. Ex vivo approaches assessed mitochondrial morphology, function, and platelet activation responses. In vivo measurements included endogenous/transfused platelet life span, tail bleed time, transient middle cerebral artery occlusion, and pulmonary vascular permeability/hemorrhage following lipopolysaccharide-induced acute lung injury. RESULTS: Mitochondria was more fragmented in megakaryocytes derived from Mfn2-/- mice and from human cord blood with MFN2 T/T genotype compared with control megakaryocytes. Human resting platelets of MFN2 T/T genotype had reduced MFN2 protein, diminished mitochondrial membrane potential, and an increased rate of phosphatidylserine exposure during ex vivo culture. Platelet counts and platelet life span were reduced in Mfn2-/- mice accompanied by an increased rate of phosphatidylserine exposure in resting platelets, especially aged platelets, during ex vivo culture. Mfn2-/- also decreased platelet mitochondrial membrane potential (basal) and activated mitochondrial oxygen consumption rate, reactive oxygen species generation, calcium flux, platelet-neutrophil aggregate formation, and phosphatidylserine exposure following dual agonist activation. Ultimately, Mfn2-/- mice showed prolonged tail bleed times, decreased ischemic stroke infarct size after cerebral ischemia-reperfusion, and exacerbated pulmonary inflammatory hemorrhage following lipopolysaccharide-induced acute lung injury. Analysis of MFN2 SNPs in the iSPAAR study (Identification of SNPs Predisposing to Altered ALI Risk) identified a significant association between MFN2 and 28-day mortality in patients with acute respiratory distress syndrome. CONCLUSIONS: Mfn2 preserves mitochondrial phenotypes in megakaryocytes and platelets and influences platelet life span, function, and outcomes of stroke and lung injury.

Periprosthetic joint infections in patients with rheumatoid arthritis are associated with higher complication and mortality rates.

INTRODUCTION: Periprosthetic joint infection (PJI) remains the most devasting complication after total joint arthroplasty (TJA). There has been a significant focus on this topic in recently-published medical literature. However, relatively little has been published about PJI in patients with rheumatoid arthritis (RA), which are often physiologically frail and immunocompromised. A better understanding of PJI in this patient population is therefore crucial. The main aims of this paper are to (1) report complication and mortality rates in a cohort of PJI-RA patients; and (2) clinically characterize them. METHODS: Medical and surgical records of all RA PJI patients treated surgically from 2003 to 2020 were retrospectively reviewed. Medical history, physical examination, reactive protein (CRP) level, procalcitonin, white blood cell (WBC) count, joint aspiration results, and cultures were used to determine PJI. RESULTS: 54PJIs, 49 of them chronic, were treated in 53RA patients. Mean patient age was 65 yrs. (range = 32-88); 33females and 20 males (one bilateral hip). The overall mortality rate was 18.9%(n = 10), with five deaths directly attributed to PJI. Staphylococci accounted for 34 infections (63%), while 11(20.4%) had multiorganism infections and six culture-negative PJI. At the end of treatment 79.6%(n = 43) still had an implanted TJR, 7.4% (n = 4) had spacers, 5.6%(n = 3) had undergone resection arthroplasty, 3.7%(n = 2) arthrodesis, and one each amputation and exarticulation. CONCLUSIONS: Mortality and specially complication rates were (are) high in this RA patients group presenting PJI. Delays to diagnosis and treatment may explain some of these poor outcomes. LEVEL OF EVIDENCE: A cohort level III retrospective study.

Safety and efficacy of lithium in patients with amyotrophic lateral sclerosis: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVES: This study provides a systematic review and meta-analysis of randomized controlled trials (RCTs) investigating the safety and efficacy of lithium in amyotrophic lateral sclerosis (ALS) patients. METHODS: PubMed, Web of Science, Cochrane CENTRAL, Scopus, and Your Journals@Ovid were searched up to 9 December 2022. RCTs investigating lithium, either alone or with any supplement, in ALS patients were included. Meta-analysis was performed using RevMan and results are presented in forest plot. RESULTS: Four RCTs with 469 patients met the inclusion criteria and were included in our study. Lithium doses varied among the included studies and one study used a combined therapy of lithium with valproate. Meta-analysis showed no difference between lithium and placebo regarding severe adverse events (odds ratio = 1.13, 95% confidence interval: 0.73 to 1.75, P = 0.58). No significant differences were observed with regard to survival rate between the two groups (hazard ratio = 0.95, 95% confidence interval: 0.65 to 1.37, P = 0.77). There were also no significant differences between the two groups with regard to average changes of revised amyotrophic lateral sclerosis functional rating scale (P = 0.35) and forced vital capacity percentage predicted (P = 0.73). Subgroup analysis showed no significant differences regarding all investigated outcomes either for lithium alone or lithium with valproate. CONCLUSION: Current evidence suggests a safety profile with no benefit of lithium for ALS. However, given the limited number of RCTs and the safety findings, we recommend further well-designed RCTs to investigate lithium and valproate in ALS patients.

Design, Synthesis, and Evaluation of Homochiral Peptides Containing Arginine and Histidine as Molecular Transporters.

Linear (HR)n and cyclic [HR]n peptides (n = 4,5) containing alternate arginine and histidine residues were synthesized. The peptides showed 0⁻15% cytotoxicity at 5⁻100 µM in human ovarian adenocarcinoma (SK-OV-3) cells while they exhibited 0⁻12% toxicity in human leukemia cancer cell line (CCRF-CEM). Among all peptides, cyclic [HR]4 peptide was able to improve the delivery of a cell impermeable fluorescence-labeled phosphopeptide by two-fold. Fatty acids of different alkyl chain length were attached at the N-terminal of the linear peptide (HR)4 to improve the molecular transporter property. Addition of fatty acyl chains was expected to help with the permeation of the peptides through the cell membrane. Thus, we synthesized seven fatty acyl derivatives of the linear (HR)4 peptide. The peptides were synthesized using Fmoc/tBu solid phase peptide chemistry, purified by reverse-phase high-performance liquid chromatography (RP-HPLC) and characterized by matrix-assisted laser desorption/ionization (MALDI) spectrometry. The fatty acyl peptides containing C8, C12, C14, and C18 alkyl chain did not show cytotoxicity on SK-OV-3 or CCRF-CEM cell lines up to 50 µM concentration; however, at higher concentration (100 µM), they showed mild cytotoxicity. For example, C16-(HR)4 was also found to reduce the proliferation of SK-OV-3 cells by 11% at 50 µM and C20-(HR)4 showed mild toxicity at 10 µM, reducing the proliferation of SK-OV-3 cells by 21%. Increase in the length of alkyl chain showed cytotoxicity to the cell lines. C20-(HR)4 peptide showed better efficiency in translocation of F'-GpYEEI to SK-OV-3 than the phosphopeptide alone. Further investigation of C20-(HR)4 peptide efficacy showed that the peptide could deliver doxorubicin and epirubicin into SK-OV-3 and also improved the drug antiproliferative ability. These studies provided insights into understanding the structural requirements for optimal cellular delivery of the fatty acyl-(HR)4 peptide conjugates.

Design, Synthesis, and Evaluation of the Kinase Inhibition Potential of Pyridylpyrimidinylaminophenyl Derivatives.

In view of potent kinase inhibitors for the treatment of myriad human disorders, we synthesized some structurally variant amide/cyclic amide derivatives based on pyridylpyrimidinylaminophenyl amine, the key pharmacophore of the kinase inhibitor drug molecule, imatinib, and evaluated their kinase inhibition potency. Among the various synthesized amides, compound 20, a cyclic amide/pyridin-2(1H)-one derivative, exhibited an IC50 value comparable to that of the drug imatinib against c-Src kinase, and another compound (14) containing a 2-((4-methyl-2-oxo-2H-chromen-6-yl)oxy)acetamide demonstrated an IC50 value of 8.39 µM. Furthermore, the constitution of the cyclic amide derivative was confirmed by the single-crystal X-ray diffraction technique. These results may serve as a gateway for developing novel next-generation kinase inhibitors.

Synthesis and evaluation of c-Src kinase inhibitory activity of pyridin-2(1H)-one derivatives.

Src kinase, a prototype member of the Src family of kinases (SFKs), is over-expressed in various human tumors, and has become a target for anticancer drug design. In this perspective, a series of eighteen 2-pyridone derivatives were synthesized and evaluated for their c-Src kinase inhibitory activity. Among them, eight compounds exhibited c-Src kinase inhibitory activity with IC50 value of less than 25µM. Compound 1-[2-(dimethylamino)ethyl]-5-(2-hydroxy-4-methoxybenzoyl)pyridin-2(1H)-one (36) exhibited the highest c-Src kinase inhibition with an IC50 value of 12.5µM. Furthermore, the kinase inhibitory activity of compound 36 was studied against EGFR, MAPK and PDK, however no significant activity was observed at the highest tested concentration (300µM). These results provide insights for further optimization of this scaffold for designing the next generation of 2-pyridone derivatives as candidate Src kinase inhibitors.

Adjuvant aromatase inhibitor therapy in patients with stage I breast cancer at a regional oncology center in Israel: implementation of a 'switching' policy in postmenopausal patients after initial tamoxifen.

OBJECTIVE: To analyze the implementation of a switching policy of adjuvant aromatase inhibitor (AI) therapy sequentially after tamoxifen in consecutively treated stage I (T1N0M0) hormone receptor (HR)-positive breast cancer (BC) patients. METHODS: The records of 279 consecutive HR-positive BC patients diagnosed between 2002 and 2006 and followed at the Soroka Medical Center were reviewed. RESULTS: Two-hundred-seventeen patients who initially received tamoxifen were suitable for switching and 28 received an AI as initial adjuvant treatment. The switch was accomplished in 82.5% of the 217 patients. Those who switched to an AI had a higher proportion of T1c stage than patients eligible who were not switched, but did not differ in age, histologic grade, or having received chemotherapy. Of the 179 patients who switched, 155 (86.6%) completed at least 4.5-5 years of adjuvant tamoxifen/AI therapy. Eighteen patients discontinued AI therapy prematurely because of toxicity. CONCLUSIONS: In this stage I BC population, despite the toxicities of AI therapy, >84% of eligible patients received an AI as adjuvant therapy. Measures to improve the management of AI toxicity, such as changing to a different AI, may reduce early stopping.

Synthesis of novel ciprofloxacin analogues and evaluation of their anti-proliferative effect on human cancer cell lines.

A series of twenty two novel 1-cyclopropyl-6-fluoro-4-oxo-7-(4-substituted piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid analogues have been synthesized, characterized ((1)H NMR, (13)C NMR and LCMS) and evaluated for their inhibitory activity on the proliferation of human caucasian acute lymphoblastic leukemia cells (CCRF-CEM), breast adenocarcinoma cells (MDA-MB-468) and human colon carcinoma cells (HCT-116). Among all the synthesized ciprofloxacin analogues 3t at 50 µM showed comparable potency to doxorubicin (10 µM) in all three cell lines and 3j inhibited proliferation of MDA-MB-468 up to 35% selectively over other two cell lines.

Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13, a gene coding for palmitoyl acyltransferase.

Protein palmitoylation has emerged as an important mechanism for regulating protein trafficking, stability, and protein-protein interactions; however, its relevance to disease processes is not clear. Using a genome-wide, phenotype driven N-ethyl-N-nitrosourea-mediated mutagenesis screen, we identified mice with failure to thrive, shortened life span, skin and hair abnormalities including alopecia, severe osteoporosis, and systemic amyloidosis (both AA and AL amyloids depositions). Whole-genome homozygosity mapping with 295 SNP markers and fine mapping with an additional 50 SNPs localized the disease gene to chromosome 7 between 53.9 and 56.3 Mb. A nonsense mutation (c.1273A>T) was located in exon 12 of the Zdhhc13 gene (Zinc finger, DHHC domain containing 13), a gene coding for palmitoyl transferase. The mutation predicted a truncated protein (R425X), and real-time PCR showed markedly reduced Zdhhc13 mRNA. A second gene trap allele of Zdhhc13 has the same phenotypes, suggesting that this is a loss of function allele. This is the first report that palmitoyl transferase deficiency causes a severe phenotype, and it establishes a direct link between protein palmitoylation and regulation of diverse physiologic functions where its absence can result in profound disease pathology. This mouse model can be used to investigate mechanisms where improper palmitoylation leads to disease processes and to understand molecular mechanisms underlying human alopecia, osteoporosis, and amyloidosis and many other neurodegenerative diseases caused by protein misfolding and amyloidosis.

Error-related brain activity in pediatric major depressive disorder: An ERP and time-frequency investigation.

BACKGROUND: The error-related negativity (ERN) reflects individual differences in error monitoring. However, findings on the ERN in adult and adolescent depression have been inconsistent. Analyzing electroencephalographic (EEG) data in both the time- and time-frequency domain can be useful to better quantify neural response to errors. The present study aimed at examining electrocortical measures of error monitoring in early adolescents with and without depression. METHOD: EEG activity was collected during an arrowhead version of the flanker task in 29 (25 females) early adolescents with depression and 34 without MDD (29 females). RESULTS: The depression group showed reduced ERN amplitude, reduced error-related theta power and increased error-related beta power compared to the control group. When all variables that related to MDD diagnosis were considered simultaneously, both theta and beta power, but not the ERN, were independently related to an increased likelihood of being diagnosed with depression. CONCLUSIONS: By examining both time-domain and separate time-frequency measures, the present study provided novel evidence on error monitoring alterations in youth depression, suggesting that depression during adolescence may be characterized by reduced error monitoring (i.e., reduced ERN and error-related theta) and post-error inhibition (i.e., greater error-related beta power). These results support that time-frequency measures might be better suited for examining error-related neural activity in MDD relative to time-domain measures.

Meta-Analysis on the Safety and Efficacy of Sodium Glucose Cotransporters 2 Inhibitors in Patients With Heart Failure With and Without Diabetes.

Heart failure (HF) is the most common cardiovascular cause of hospitalization in patients over 60 years, affecting about 64.3 million patients worldwide. Few studies have investigated the role of sodium glucose cotransporter inhibitors (SGLT2Is) in patients with HF without and without diabetes. Thus, we conducted our meta-analysis to further investigate the role of SGLT2I role in patients with HF without and without diabetes. PubMed, Scopus, Web of Science, and Embase were searched. All clinical trials that compared the effect of SGLT2Is versus placebo on patients with HF were included. Dichotomous data were extracted, pooled as risk ratio (RR) with 95% confidence interval (CI), and analyzed using RevMan version 5.3 for windows using the Mantel-Haenszel method. A total of 13 randomized clinical trials were included for analysis, with a total number of 75,287 patients. SGLT2Is significantly lowered the risk of hospitalization for HF in patients with (RR = 0.68, 95% CI 0.63 to 0.74) and without diabetes (RR = 0.75, 95% CI 0.62 to 0.89). Furthermore, they lowered the mortality risk in both patients with diabetes with statistical significance (RR = 0.87, 95% CI 0.77 to 0.99), yet without statistical significance in patients without diabetes (RR = 0.93, 95% CI 0.70 to 1.23). Further analyses for serious adverse events were conducted, and SGLT2I showed a significant lower risk in patients with diabetes (RR = 0.94, 95% CI 0.90 to 0.98) and without diabetes (RR = 0.72, 95% CI 0.38 to 1.39). in patients with diabetes, SGLT2Is significantly reduced cardiovascular mortality, HHF, and serious adverse events. However, in patients without, despite showing a significant reduction in HHF, SGLT2I reduced cardiovascular mortality or serious adverse events but without statistical significance.

Atrial septal defect in a pediatric patient with Williams Syndrome: a rare presentation.

Characterized by congenital heart defects (CHD) and elfin-like facies, Williams-Beuren syndrome (WS) is a multisystemic disorder that occurs approximately in 1 in 10 000 newborns [1]. WS is caused by a contiguous gene microdeletion of the Williams Beuren syndrome critical region (WBSCR) on chromosome 7q11.23, resulting in an abnormal elastin gene (ELN). There is a wide range of CHD in patients with WS, with supravalvular aortic stenosis (SAS) being the most common, and atypically the atrial septal defect (ASD) [2]. Few reports and reviews have linked the appearance of ASD to WS. Thus, data on the management of ASD secondary to WS is not well-documented. The following case report consists of the diagnosis and management of an ASD in a pediatric patient with WS.

Maze Control Training on Kinesthetic Awareness in Patients with Stroke: A Randomized Controlled Trial.

OBJECTIVE: To determine the influence of adding maze control training to the selected conventional physical therapy on kinesthetic awareness in patients with chronic stroke. METHODS: Thirty adult patients of both genders with chronic cerebral stroke were assigned to control and experimental groups randomly: the control group (A) received the selected conventional physical therapy rehabilitation program, while the experimental group (B) received the same program as group A in addition to the maze control training. Measurements for sway index, risk of fall, and knee proprioception before and after 8 weeks of treatment (24 sessions; three times per week). RESULTS: There were significant decreases of both sway index and risk of fall in both groups (p ≤ 0.001 in all measures), significant improvements of the knee proprioception in 30° and 75° in the experimental group (p value = 0.016 and ≤0.001, respectively). The in-between groups' comparison showed significant differences corresponding to both the sway index and risk of fall (p ≤ 0.001), and a significant difference in 75° (p ≤ 0.001). CONCLUSION: Adding maze control training to the selected conventional physical therapy improved the kinesthetic awareness in patients with chronic stroke.

Applying a Fast-Scan Cyclic Voltammetry to Explore Dopamine Dynamics in Animal Models of Neuropsychiatric Disorders.

Progress in the development of technologies for the real-time monitoring of neurotransmitter dynamics has provided researchers with effective tools for the exploration of etiology and molecular mechanisms of neuropsychiatric disorders. One of these powerful tools is fast-scan cyclic voltammetry (FSCV), a technique which has progressively been used in animal models of diverse pathological conditions associated with alterations in dopamine transmission. Indeed, for several decades FSCV studies have provided substantial insights into our understanding of the role of abnormal dopaminergic transmission in pathogenetic mechanisms of drug and alcohol addiction, Parkinson's disease, schizophrenia, etc. Here we review the applications of FSCV to research neuropsychiatric disorders with particular attention to recent technological advances.

Imaging Replicative Domains in Ultrastructurally Preserved Chromatin by Electron Tomography.

Principles of DNA folding in the cell nucleus and its dynamic transformations that occur during the fulfillment of basic genetic functions (transcription, replication, segregation, etc.) remain poorly understood, partially due to the lack of experimental approaches to high-resolution visualization of specific chromatin loci in structurally preserved nuclei. Here we present a protocol for the visualization of replicative domains in monolayer cell culture in situ, by combining EdU labeling of newly synthesized DNA with subsequent label detection with Ag-amplification of Nanogold particles and ChromEM staining of chromatin. This protocol allows for the high-contrast, high-efficiency pre-embedding labeling, compatible with traditional glutaraldehyde fixation that provides the best structural preservation of chromatin for room-temperature sample processing. Another advantage of pre-embedding labeling is the possibility to pre-select cells of interest for sectioning. This is especially important for the analysis of heterogeneous cell populations, as well as compatibility with electron tomography approaches to high-resolution 3D analysis of chromatin organization at sites of replication, and the analysis of post-replicative chromatin rearrangement and sister chromatid segregation in the interphase.

Quantification of the effect of compression garments on fatigue behavior in cycling.

Effectiveness of compression garments to enhance athletic performance is the subject of numerous qualitative studies. This study aims at quantification of the effect of compression garments using nonlinear dynamics approach. Kinematic data of fifteen healthy male athletes was obtained and the state space was reconstructed. The trajectory drifts caused by fatigue in the state space were quantified using local flow variation technique. The study illustrates that compression garments (CGs) decrease rate of fatigue development and the body exhibits a more restricted complexity (more predictable and smaller fluctuations) when CGs are worn.

The influence of low- intensity laser irradiation versus hyperbaric oxygen therapy on transcutaneous oxygen tension in chronic diabetic foot ulcers: a controlled randomized trial.

BACKGROUND AND OBJECTIVE: Evaluation of the stage and severity of the chronic diabetic foot ulcer (CDFU) is vital to increase the healing rate and to select the suitable treatment. We aim to assess the influence of low-intensity laser irradiation (LILI) and hyperbaric oxygenation therapy (HBOT) to accelerate the CDFU healing thru the transcutaneous oxygen tension (TcPO2) measurements. MATERIALS AND METHODS: Seventy-five diabetic patients (type 2) of both genders, their ages ranged from 40-65 years with CDFUs (duration of ulcer < 6 weeks). All patients were randomly assigned into LILI, HBOT, and the control group. Measurement of TcPO2 using transcutaneous oximetry was performed for all patients once in the baseline and consequently in the second, fourth, and sixth- weeks duration. LILI utilized by a 33-diode cluster contact applicator with output power 1440 mW, energy density (fluency) was adjusted for 4 J/Cm2 at 10 kHz, and for 8 min per session, three times per week for a total of consecutive 6 weeks. HBOT was pressurized up to 2.5 ATA and patients delivered 100% oxygen for 60 min per session for 30 sessions. The Control group received conventional wound care only, twice daily, with saline and apply a new bandage after cleaning. RESULTS: MANOVA revealed a statistically insignificant difference in the control group, while statistically significant improvement in both the LILI and HBOT groups. The intergroup comparisons showed an insignificant statistical difference in the pre-test, while highly statistically significant differences for the three post-measures in favor of HBOT and LILI groups. The percentage of improvement of the HBOT group was higher than LILI. Post-hoc test using the least significant difference (LSD) revealed statistically significant differences of HBOT in favor of the LILI group. CONCLUSION: Both LILI and HBOT may be used as adjunctive methods to improve TcPO2 that accelerate healing in CDFUs. HBOT may be favorable in the improvement of TcPO2 than LILI.

Fiber-Like Organization as a Basic Principle for Euchromatin Higher-Order Structure.

A detailed understanding of the principles of the structural organization of genetic material is of great importance for elucidating the mechanisms of differential regulation of genes in development. Modern ideas about the spatial organization of the genome are based on a microscopic analysis of chromatin structure and molecular data on DNA-DNA contact analysis using Chromatin conformation capture (3C) technology, ranging from the "polymer melt" model to a hierarchical folding concept. Heterogeneity of chromatin structure depending on its functional state and cell cycle progression brings another layer of complexity to the interpretation of structural data and requires selective labeling of various transcriptional states under nondestructive conditions. Here, we use a modified approach for replication timing-based metabolic labeling of transcriptionally active chromatin for ultrastructural analysis. The method allows pre-embedding labeling of optimally structurally preserved chromatin, thus making it compatible with various 3D-TEM techniques including electron tomography. By using variable pulse duration, we demonstrate that euchromatic genomic regions adopt a fiber-like higher-order structure of about 200 nm in diameter (chromonema), thus providing support for a hierarchical folding model of chromatin organization as well as the idea of transcription and replication occurring on a highly structured chromatin template.

Production of cattle lacking prion protein.

Prion diseases are caused by propagation of misfolded forms of the normal cellular prion protein PrP(C), such as PrP(BSE) in bovine spongiform encephalopathy (BSE) in cattle and PrP(CJD) in Creutzfeldt-Jakob disease (CJD) in humans. Disruption of PrP(C) expression in mice, a species that does not naturally contract prion diseases, results in no apparent developmental abnormalities. However, the impact of ablating PrP(C) function in natural host species of prion diseases is unknown. Here we report the generation and characterization of PrP(C)-deficient cattle produced by a sequential gene-targeting system. At over 20 months of age, the cattle are clinically, physiologically, histopathologically, immunologically and reproductively normal. Brain tissue homogenates are resistant to prion propagation in vitro as assessed by protein misfolding cyclic amplification. PrP(C)-deficient cattle may be a useful model for prion research and could provide industrial bovine products free of prion proteins.

Vision impairment and cognitive function among urban-dwelling malaysians aged 55 years and over from the Malaysian Elders Longitudinal Research (MELoR) study.

INTRODUCTION: Published literature on vision impairment and cognitive function amongst older Malaysians remains scarce. This study investigates the association between vision impairment and cognitive function in an older Malaysian population. METHODS: Subjects aged 55 years and above from the Malaysian Elders Longitudinal Research (MELoR) study with available information on vision and Montreal Cognitive Assessment (MoCA) scores were included. Data were obtained through a home-based interview and hospital-based health check by trained researchers. Visual acuity (VA) was assessed with logMAR score with vision impairment defined as VA 6/18 or worse in the better-seeing eye. Cognition was evaluated using the MoCA-Blind scoring procedure. Those with a MoCA-Blind score of <19/22 were considered to have cognitive impairment. RESULTS: Data was available for 1144 participants, mean (SD) age = 68.57 (±7.23) years. Vision impairment was present in 143 (12.5 %) and 758 (66.3 %) had MoCA-Blind score of <19. Subjects with vision impairment were less likely to have a MoCA-Blind score of ≥19 (16.8 % vs 36.2 %, p < 0.001). Vision impairment was associated with poorer MoCA-Blind scores after adjustments for age, gender, and ethnicity (ß = 2.064; 95 % CI, -1.282 to 3.320; P = 0.003). In those who had > 6 years of education attainment, vision impairment was associated with a significant reduction of cognitive function and remained so after adjustment for age and gender (ß = 1.863; 95 % CI, 1.081-3.209; P = 0.025). CONCLUSION: Our results suggest that vision impairment correlates with cognitive decline. Therefore, maintaining good vision is an important interventional strategy for preventing cognitive decline in older adults.