Four odorants for olfactory training are enough: a pilot study.

BACKGROUND:  Olfactory training (OT) is commonly used for the treatment of olfactory disorders. Nevertheless, there is an ongoing debate about the most effective OT regimen. We aimed to compare the effects of OT with 7 items (rose, lemon, eucalyptus, cloves, stewed apple, balm, mint) to 4-item-OT (rose, lemon, eucalyptus, cloves) over 3 months. Methods: Participants were 40 patients with olfactory dysfunction receiving 4-item-OT or 7-item-OT and 60 gender- and age-matched individuals with normal sense of smell receiving no OT, 4-item-OT, or 7-item-OT. Before and after the OT we assessed n-butanol odor thresholds, discrimination, and identification (TDI score), additionalthresholds for (R)-(-)-carvone, ß-damascenone, salicyclic acid benzylester, the degree of phantosmia and parosmia, cognitive function, and ratings of olfactory function. Results: In both patient groups, the TDI score increased with the use of OT, regardless of the number of odors used (p < 0.001; 3.48 ± 4.21 and lower than control groups). The clinically significant increase of 5.5 points in TDI score correlated with change of ratings of parosmia (r 0.62; p < 0.01) and with ratings of olfactory dysfunction (r = 0.51; p < 0.05). CONCLUSION:  Concluding, OT over a 3-months period with 4 or 7 odors appears to produce similar results, although the sample size has to be considered.

Validation and convergent validity of the Boston cognitive assessment (BOCA) in an Italian population: a comparative study with the Montreal cognitive assessment (MoCA) in Alzheimer's disease spectrum.

BACKGROUND: The Boston Cognitive Assessment (BOCA) is a self-administered online test developed for cognitive screening and longitudinal monitoring of brain health in an aging population. The study aimed to validate BOCA in an Italian population and to investigate the convergent validity with the Montreal Cognitive Assessment (MOCA) in healthy ageing population and patients within the Alzheimer Disease spectrum. METHODS: BOCA was administered to 150 participants, including cognitively healthy controls (HC, n = 50), patients with mild cognitive impairment (MCI, n = 50), and dementia (DEM, n = 50). The BOCA reliability was assessed using (i) Spearman's correlation analysis between subscales; (ii) Cronbach's alpha calculation, and (iii) Principal Component Analysis. Repeated-measures ANOVA was employed to assess the impact of the sequence of test administrations between the groups. BOCA performance between HS, MCI and DEM and within different severity subgroups were compared using Kruskall Wallis test. Furthermore, a comparison was conducted between MCI patients who tested positive for amyloid and those who tested negative, utilizing Mann Whitney's U-test. RESULTS: Test scores were significantly different between patients and controls (p < 0.001) suggesting good discriminative ability. The Cronbach's alpha was 0.82 indicating a good internal consistency of the BOCA subscales and strong-to-moderate Spearman's correlation coefficients between them. BOCA total and subscores differ across different MoCA severity subgroups and demonstrated strong correlation with MoCA scores (rho = 0.790, p < 0.001). CONCLUSIONS: The Italian version of the BOCA test exhibited validity, feasibility, and accurate discrimination closely performing as MoCA.

Dynamics of Cognitive Impairment in MCI Patients over a Three-Year Period: The Informative Role of Blood Biomarkers, Neuroimaging, and Genetic Factors.

Given the high growth rates of cognitive decline among the elderly population and the lack of effective etiological treatments, early diagnosis of cognitive impairment progression is an imperative task for modern science and medicine. It is of particular interest to identify predictors of an unfavorable subsequent course of cognitive disorders, specifically, rapid progression. Our study assessed the informative role of various risk factors on the dynamics of cognitive impairment among mild cognitive impairment (MCI) patients. The study included patients with MCI (N = 338) who underwent neuropsychological assessment, magnetic resonance imaging (MRI) examination, blood sampling for general and biochemical analysis, APOE genotyping, and polygenic risk score (PRS) evaluation. The APOE ε4/ε4 genotype was found to be associated with a diminished overall cognitive scores initial assessment and negative cognitive dynamics. No associations were found between cognitive changes and the PRS. The progression of cognitive impairment was associated with the width of the third ventricle and hematological parameters, specifically, hematocrit and erythrocyte levels. The absence of significant associations between the dynamics of cognitive decline and PRS over three years can be attributed to the provided suitable medical care for the prevention of cognitive impairment. Adding other risk factors and their inclusion in panels assessing the risk of progression of cognitive impairment should be considered.

Cross-sectional association between high-sensitivity C-reactive protein and cognitive function in community-dwelling older adults: the SONIC study.

BACKGROUND: A decline in cognitive function is associated with inflammatory processes. However, the association between high-sensitivity C-reactive protein (hs-CRP) levels and cognitive decline in the Japanese population remains inconclusive. Thus, this study aimed to determine whether hs-CRP is associated with low cognitive function in 70- and 80-year-old community-dwelling Japanese individuals. METHODS: The participants in this cross-sectional study were 872 Japanese residents aged 70 and 80 years who voluntarily participated in the Septuagenarians, Octogenarians, Nonagenarians Investigation with Centenarians (SONIC) study between 2010 and 2011. Blood sample collection, cognitive assessment, and other measurements were performed at the venue. Low cognitive function was defined as a score of 25 points or lower on the Japanese version of the Montreal Cognitive Assessment. The odds ratio (OR) and 95% confidence interval (95% CI) for each hs-CRP quartile were calculated using logistic regression analysis. RESULTS: A total of 288 (69.9%) parsons in the 70-year-old group and 372 (80.9%) in the 80-year-old group exhibited low cognitive function. The association between hs-CRP levels and low cognitive function was significant among 70- and 80-year-old Japanese community-dwelling adults. In particular, the fourth quartile of hs-CRP (0.727-7.420 mg/L) in the 70-year-old group and the second and fourth quartiles (0.214-0.404 and 0.911-9.890 mg/L) in the 80-year-old group were associated with low cognitive function. Furthermore, the third quartile (0.409-0.892 mg/L) in the 80-year-old group was closely associated with low cognitive function. CONCLUSIONS: High hs-CRP levels were associated with lower cognitive function in 70- and 80-year-old Japanese community-dwelling individuals, suggesting that high hs-CRP levels may influence cognitive function.

Urinary bladder carcinogenic potential of 4,4'-methylenebis(2-chloroaniline) in humanized-liver mice.

Occupational exposure to 4,4'-methylenebis(2-chloroaniline) (MOCA) has been linked to an increased risk of bladder cancer among employees in Japanese plants, indicating its significance as a risk factor for urinary bladder cancer. To investigate the role of MOCA metabolism in bladder carcinogenesis, we administered MOCA to non-humanized (F1-TKm30 mice) and humanized-liver mice for 4 and 28 weeks. We compared MOCA-induced changes in metabolic enzyme expression, metabolite formation, and effects on the urinary bladder epithelium in the two models. At week 4, MOCA exposure induced simple hyperplasia, cell proliferation, and DNA damage in the urothelium of the humanized-liver mice, while in the non-humanized mice these effects were not observed. Notably, the concentration of 4-amino-4'-hydroxylamino-3,3'-dichlorodiphenylmethane (N-OH-MOCA) in the urine of humanized-liver mice was more than 10 times higher than that in non-humanized mice at the 4-week mark. Additionally, we observed distinct differences in the expression of cytochrome P450 isoforms between the two models. Although no bladder tumors were detected after 28 weeks of treatment in either group, these findings suggest that N-OH-MOCA significantly contributes to the carcinogenic potential of MOCA in humans.

Comparing psychometric characteristics of a computerized cognitive test (BrainCheck Assess) against the Montreal cognitive assessment.

Introduction: Previous validation studies demonstrated that BrainCheck Assess (BC-Assess), a computerized cognitive test battery, can reliably and sensitively distinguish individuals with different levels of cognitive impairment (i.e., normal cognition (NC), mild cognitive impairment (MCI), and dementia). Compared with other traditional paper-based cognitive screening instruments commonly used in clinical practice, the Montreal Cognitive Assessment (MoCA) is generally accepted to be among the most comprehensive and robust screening tools, with high sensitivity/specificity in distinguishing MCI from NC and dementia. In this study, we examined: (1) the linear relationship between BC-Assess and MoCA and their equivalent cut-off scores, and (2) the extent to which they agree on their impressions of an individual's cognitive status. Methods: A subset of participants (N = 55; age range 54-94, mean/SD = 80/9.5) from two previous studies who took both the MoCA and BC-Assess were included in this analysis. Linear regression was used to calculate equivalent cut-off scores for BC-Assess based on those originally recommended for the MoCA to differentiate MCI from NC (cut-off = 26), and dementia from MCI (cut-off = 19). Impression agreement between the two instruments were measured through overall agreement (OA), positive percent agreement (PPA), and negative percent agreement (NPA). Results: A high Pearson correlation coefficient of 0.77 (CI = 0.63-0.86) was observed between the two scores. According to this relationship, MoCA cutoffs of 26 and 19 correspond to BC-Assess scores of 89.6 and 68.5, respectively. These scores are highly consistent with the currently recommended BC-Assess cutoffs (i.e., 85 and 70). The two instruments also show a high degree of agreement in their impressions based on their recommended cut-offs: (i) OA = 70.9%, PPA = 70.4%, NPA = 71.4% for differentiating dementia from MCI/NC; (ii) OA = 83.6%, PPA = 84.1%, NPA = 81.8% for differentiating dementia/MCI from NC. Discussion: This study provides further validation of BC-Assess in a sample of older adults by showing its high correlation and agreement in impression with the widely used MoCA.

Large-scale evidence for the validity of remote MoCA administration among people with cerebellar ataxia.

Objective: For over half a century, studies of rare diseases using in-person cognitive tools have faced challenges, such as long study periods and small sample sizes (e.g. n = 10). The Montreal Cognitive Assessment (MoCA) was widely employed to assess mild cognitive impairment (MCI). We aimed to validate a modified online version of the MoCA in a large sample of a rare disease (population prevalence < .01%). Method: First, we analyzed 20 previous findings (n = 1,377), comparing the MoCA scores between large groups of neurotypically healthy (NH; n = 837) and cerebellar ataxia (CA; n = 540), where studies were conducted in-person. Second, we administered the MoCA in-person to a group of NH (n = 41) and a large group of CA (n = 103). Third, we administered a video conferencing version of the MoCA to NH (n = 38) and a large group of CA (n = 83). Results: We observed no performance differences between online and in-person MoCA administration in the NH and CA groups (p > .05, η2 = 0.001), supporting reliability. Additionally, our online CA group had lower MoCA scores than the NH group (p < .001, Hedges' g = 0.68). This result is consistent with previous studies, as demonstrated by our forest plot across 20 previous in-person findings, supporting construct validity. Conclusion: The results indicate that an online screening tool is valid in a large sample of individuals with CA. Online testing is not only time and cost-effective, but facilitates disease management and monitoring, ultimately enabling early detection of MCI.

Body mass index and cognitive functioning decline: Exploring the relationship.

BACKGROUND: Cognitive functions may play an important role in the management of obesity by promoting compliance towards lifestyle-related behaviours. This study aimed to identify cognitive deficits among adults and examine their association across different Body Mass Index (BMI) categories in an Indian setting. MATERIALS AND METHODS: The study is a cross-sectional survey of a sample attending a tertiary care hospital in northern India. The Montreal Cognitive Assessment (MoCA) scale was administered as part of an interview schedule to evaluate participants' cognitive performance across eight domains. The responses were analyzed to investigate the association between BMI and total MoCA scores, as well as domain-specific MoCA scores. RESULTS: Three hundred forty-nine participants, with a mean age of 36.9 ± 10.9 years and a BMI of 26.7 ± 4.6 kg/m2, were recruited. BMI was found to be significantly associated with the total MoCA score, indicating a negative relationship (P < 0.001). A significant negative association was found between six domain-specific scores, namely visuospatial, attention, language, abstraction, delayed recall (P < 0.001), orientation (P < 0.05), and BMI. CONCLUSION: An association between BMI and cognitive functioning (both overall and domain-specific) was observed, showing a dose-effect relationship. In these cases, visuospatial, attention, language, abstraction, delayed recall, and orientation were found to be affected.

Impaired or not impaired: The accuracy of the Montreal Cognitive Assessment in detecting cognitive impairment among patients with alcohol use disorder.

BACKGROUND: Cognitive impairments are common in alcohol use disorder (AUD), but only a few studies have investigated the accuracy of the Montreal Cognitive Assessment (MoCA) in this population. We examined the accuracy and precision of the MoCA in detecting cognitive impairment in a sample of patients with AUD. In addition, we investigated whether the MoCA predicts premature discontinuation from treatment. METHOD: A sample of 126 persons with AUD undergoing treatment in specialist health services were administered the MoCA and a battery of 12 neuropsychological tests. Five cognitive domains were derived from the reference tests. A composite total score from these tests was used as a reference criterion for determining correct and incorrect classifications for the MoCA. We analyzed the optimal cut-off score for the MoCA and the accuracy and agreement of classification between the MoCA and the reference tests. RESULTS: Receiver operating characteristic (ROC) curve analyzes yielded an area under the curve (AUC) of 0.77 (95% CI [0.67, 0.87]). Applying 25 as the cut-off, MoCA sensitivity was 0.77 and specificity 0.62. The PPV was 0.53. The NPV was 0.84. Using a cut-off score of 24 yielded a lower sensitivity 0.60, but specificity was significantly better i.e., 0.79. PPV was 0.68. The NPV was 0.82. Kappa agreement between MoCA and the reference tests was fair to moderate, 0.38 for the cut-off of 25, and 0.44 for the cut-off of 24. MoCA did not predict discontinuation from treatment. CONCLUSIONS: Our findings indicate limitations in the classification accuracy of the MoCA in predicting cognitive impairment in AUD. Achieving the right balance between accurately identifying impaired cases without including too many false positives can be challenging. Further, MoCA does not predict discontinuation from treatment. Overall, the results do not support MoCA as a time-efficient screening instrument.

Alzheimer's Disease-Related Analytes Amyloid-ß and Tau in Perilymph: Correlation With Patient Age and Cognitive Score.

OBJECTIVE: To describe the collection methods for perilymph fluid biopsy during cochlear implantation, detect levels of amyloid ß 42 and 40 (Aß42 and Aß40), and total tau (tTau) analytes with a high-precision assay, to compare these levels with patient age and Montreal Cognitive Assessment (MoCA) scores, and explore potential mechanisms and relationships with otic pathology. STUDY DESIGN: Prospective study. SETTING: Tertiary referral center. METHODS: Perilymph was collected from 25 patients using polyimide tubing to avoid amyloid adherence to glass, and analyzed with a single-molecule array advanced digital enzyme-linked immunosorbent assay platform for Aß40, Aß42, and tTau. Cognition was assessed by MoCA. RESULTS: Perilymph volumes ranged from ∼1 to 13 µL, with analyte concentrations spanning 2.67 to 1088.26 pg/mL. All samples had detectable levels of tTau, Aß40, and Aß42, with a significant positive correlation between Aß42 and Aß40 levels. Levels of Aß42, Aß40, and tTau were positively correlated with age, while MoCA scores were inversely correlated with age. tTau and Aß42/Aß40-ratios were significantly correlated with MoCA scores. CONCLUSION: Alzheimer's disease-associated peptides Aß42, Aß40, and tau analytes are detectable in human perilymph at levels approximately 10-fold lower than those found in cerebrospinal fluid (CSF). These species increase with age and correlate with cognitive impairment indicators, suggesting their potential utility as biomarkers for cognitive impairment in patients undergoing cochlear implantation. Future research should investigate the origin of these analytes in the perilymph and their potential links to inner ear pathologies and hearing loss, as well as their relationships to CSF and plasma levels in individuals.

The Impact of Frailty and Severe Cognitive Impairment on Survival Time and Time to Initiate Dialysis in Older Adults With Advanced Chronic Kidney Disease: A Prospective Observational Cohort Study.

Background and objectives Frailty and cognitive impairment significantly impact survival time and time to initiate dialysis in older adults with advanced chronic kidney disease (CKD). This study aims to evaluate the effects of frailty and cognitive impairment on these outcomes and determine the most effective assessment tool for predicting early dialysis initiation and short survival time. Materials and methods This prospective observational cohort study involved 240 patients aged ≥65 years with stage 4 or 5 CKD, recruited from a nephrology outpatient department (ambulatory care) between March 2020 and March 2021. Frailty was assessed using the Physical Frailty Phenotype (PFP), PRISMA-7, Clinical Frailty Scale (CFS), and FRAIL scale. Cognitive function was evaluated using the Montreal Cognitive Assessment (MoCA). The primary outcomes were time to initiate dialysis and survival time, with secondary outcomes including hospitalization rates, length of stay, and mortality after dialysis initiation. Results Frail patients only showed significantly shorter time to dialysis initiation when identified by the PFP and FRAIL scale (28.3 months for frail vs. 31.2 months for non-frail, p = 0.028; 26.9 months for frail vs. 30.9 months for non-frail, p = 0.038). The PFP, FRAIL, and CFS tools indicated significantly shorter survival times for frail patients compared to non-frail patients (26.8 months for frail vs. 30.6 months for non-frail, p = 0.003). Frailty is strongly correlated with severe cognitive impairment, as 45.5% of frail patients (according to the FRAIL scale) have dementia compared to 15.1% of non-frail patients (p<0.001). However, cognitive impairment did not significantly affect the time to dialysis initiation or survival time. Hospitalization rates and length of stay in the hospital were significantly higher only for frail patients identified by PRISMA-7, with a median hospital length of stay of 9.15 days for frail patients vs 6.37 days for non-frail patients (p = 0.044). Overall, 37.5% of the patients did not survive during the study follow-up, with frail patients having a higher mortality rate. Conclusion Frailty, mainly when assessed by PFP and FRAIL, is a significant predictor of early dialysis initiation and reduced survival time in older adults with advanced CKD. Cognitive impairment, while prevalent, did not independently predict these outcomes. Regular frailty screening should be incorporated into CKD management to tailor interventions and improve patient outcomes.

Montreal Cognitive Assessment's auditory items (MoCA-22): Normative data and reliable change indices.

Our objective was to establish normative data and reliable change indices (RCI) for the Montreal Cognitive Assessment's auditory items (MoCA-22). 4,935 cognitively unimpaired participants were administered the MoCA during an in-person visit to an Alzheimer's Disease Research Center (Mage = 67.9, Meducation = 16.2, 65.8% women, 75.9% non-Hispanic-White), with 2,319 unimpaired participants returning for follow-up. Normative values and cutoffs were developed using demographic predictions from ordinary and quantile regression. Test-retest reliability was calculated using Spearman and intraclass correlations. RCI values were calculated using Chelune and colleagues' (1993) formula. Education, age, and sex were all statistically related to MoCA-22 scores, with education having the strongest relationship. Notably, these relationships were not consistent across MoCA-22 quantiles, with education becoming more important and sex becoming less important for predicting low scores. These models were integrated into a calculator for deriving normative scores for an individual case. Furthermore, there was adequate-to-good test-retest reliability (ϱ = 0.56 95% CI [.54, .59]; ICC = 0.75, 95% CI [.73, .77]) and changes of at least 2-3 points are necessary to identify reliable change at 1-3-year follow-up. These findings add to the literature regarding utility of the MoCA-22 in the cognitive screening of older adults.

Association between TMSE/MoCA and MIS/NAF in ESKD patients undergoing hemodialysis: a cross-sectional study.

BACKGROUND: Both cognitive impairment and malnutrition are common in hemodialysis (HD) patients and are associated with increased hospitalization rates, infection, poor clinical outcomes, and mortality. The study investigated the association between cognitive and nutrition status among end-stage kidney disease (ESKD) patients undergoing hemodialysis. METHODS: In this cross-sectional study, we enrolled 115 patients with ESKD who underwent regular hemodialysis (HD). Data collection included the use of screening tools for mild cognitive impairment (MCI), specifically Thai Mental State Examination (TMSE) and Montreal Cognitive Assessment (MoCA). In addition, we collected data using nutritional screening tools including Malnutrition Inflammation Score (MIS) and Nutrition Alert Form (NAF). Our primary outcome was to demonstrate whether there was a relationship between TMSE/MoCA and MIS/NAF scores in this population. Secondary outcomes were a prevalence of MCI and malnutrition status in ESKD patients, an association between TMSE and MoCA with other surrogate nutritional markers, and factors affecting MCI in such patients. RESULTS: A total of 109 patients undergoing HD completed our protocol. Their mean age was 63.42 (± 15.82) years, and 51.38% were male. Mean TMSE and MoCA were 23.98 (± 5.06) points and 18.3 (± 6.40) points, respectively. The prevalence of TMSE ≤ 23 and MoCA ≤ 24 were 39.45% and 83.49%, respectively. TMSE had a statistically significant negative correlation with MIS (R2 = 0.16, p < 0.001) and NAF. MoCA also negatively correlated with MIS and NAF. The age, total educational year, the status of whether having a caregiver, serum albumin, serum phosphorus level, handgrip strength, and lean mass tissue were correlated with TMSE. CONCLUSION: Nutritional parameters, including MIS score, NAF score, serum albumin, lean tissue mass, and lean tissue index, significantly correlate with TMSE and MoCA.

Adapted MoCA for Use among Arabic-Speaking Immigrants in the United States.

OBJECTIVE: Neuropsychological assessment among U.S. Arabic-speaking older adults is virtually non-existent due to lack of translated measures and normative data, as well as researchers' limited access to Middle Eastern/Arab Americans. The Montreal Cognitive Assessment (MoCA) is the only validated, widely-used dementia screen with Arabic language norms/cutoffs, yet, Arabic MoCA translations vary across countries and studies. We examined utility of a modified translation among Arabic-speaking immigrants in metro-Detroit. METHODS: The Arabic MoCA was modified to reflect consistency with the original English version while remaining meaningful in the Arabic language. The MoCA was then administered to 32 Arabic-speaking adults age 65 + living in metro-Detroit. Eight (25%) had an Alzheimer's disease or related dementia (ADRD) diagnosis. Each item was standardized and Cronbach's alpha assessed reliability. Ordinary least squares models examined whether an ADRD diagnosis predicts the total MoCA score and each item, adjusting for demographics. RESULTS: The mean age of the sample was 73 years old. The alpha was acceptably high at 0.87. Bivariate analyses show those with ADRD diagnosis scored lower overall on the MoCA. However, probability of diagnosis and age were confounded in the sample such that in multivariate analyses ADRD diagnosis did not explain additional variation beyond what is explained by age. Orientation, cube-copy test and serial 7s best distinguished those with ADRD. CONCLUSION: The modified Arabic language MoCA shows promise distinguishing those with an ADRD diagnosis. This translation provides a resource for neuropsychologists looking for translated tests when working with Arabic-speaking patients in the U.S.

The utility of the Montreal cognitive assessment (MoCA) in detecting cognitive impairment in surgical populations - A systematic review and meta-analysis.

STUDY OBJECTIVE: To determine the diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) in detecting cognitive impairment (CI) and assess the association of MoCA scores with adverse postoperative outcomes in surgical populations. DESIGN: Systematic review and meta-analysis. SETTING: Perioperative setting. PATIENTS: Adults undergoing elective or emergent surgery screened for CI preoperatively using the MoCA. MEASUREMENTS: The outcomes included the diagnostic accuracy of the MoCA in screening for CI and the pooled prevalence of CI in various surgical populations. CI and its association with adverse events including delirium, hospital length-of-stay (LOS), postoperative complications, discharge destination, and mortality was determined. MAIN RESULTS: Twenty-six studies (5059 patients, 18 non-cardiac studies, 8 cardiac studies) were included. With a MoCA cut-off score of <26, the prevalence of preoperative CI was 48% (95% CI: 41%-54%). The MoCA had 0.87 (95% CI: 0.79-0.93) sensitivity, 0.72 (95% CI: 0.62-0.80) specificity, PPV of 0.74 (95% CI: 0.65-0.81), and NPV of 0.86 (95% CI: 0.77-0.92) when validated against Petersen criteria, the Diagnostic and Statistical Manual of Mental Disorders, or the National Institute on Aging and the Alzheimer's Association criteria to identify CI. Using the MoCA as a screening tool, the LOS was 3.75 (95% CI: -0.03-7.53, P = 0.05, not significant) days longer in the CI group after non-cardiac surgeries and 3.33 (95% CI: 1.24-5.41, P < 0.002) days longer after cardiac surgeries than the non-cognitively impaired group. CONCLUSIONS: MoCA had been validated in the surgical population. MoCA with a cut-off score of <26 was shown to have 87% sensitivity and 72% specificity in identifying CI. A positive screen in MoCA was associated with a 3-day longer hospital LOS in cardiac surgery in the CI group than in the non-CI group.

Primary Open-Angle Glaucoma Is Associated with Short-Term Memory Decline and Dementia in Individuals of African Ancestry.

Background: Over the last decade, studies have suggested that primary open-angle glaucoma (POAG) may be associated with cognitive impairment and dementia, as both pathologies are age-related neurodegenerative processes. It remains unclear to what extent neurodegeneration in POAG extends to other neurological functions beyond vision, such as cognition. This follow-up study examined the potential association between POAG and cognitive decline in an African ancestry population. Methods: The Telephone-Montreal Cognitive Assessment (T-MoCA) was administered to POAG cases and controls previously enrolled in the Primary Open-Angle African American Glaucoma Genetics (POAAGG) study. Cases were assessed for retinal nerve fiber layer (RNFL) thickness and for the presence of dementia via chart review. Comparisons between POAG cases and controls were performed using two-sample t-tests for the T-MoCA total score and five subsection scores, and using chi-squared tests for incidence of dementia. Current scores were compared to scores from this same cohort from 7 years prior. Results: The T-MoCA was administered to 13 cases and 20 controls. The mean ± standard deviation (SD) T-MoCA total score was 15.5 ± 4.0 in cases and 16.7 ± 3.5 in controls (p = 0.36). However, there was a borderline significant difference in the delayed recall sub-score (2.3 ± 1.6 for cases vs. 3.4 ± 1.5 for controls, p = 0.052) and a significant difference in its sub-domain, the memory index score (MIS, 9.1 ± 4.3 for cases vs. 12.1 ± 3.0 for controls, p = 0.02). There were no significant differences between cases and controls for the remaining subsections. During 7 years of follow-up, a higher incidence of dementia was noted in POAG cases (7.1% for cases vs. 0% for controls, p = 0.058). Over 7 years, there was no significant deterioration in the cognitive performance of cases versus controls, and no association was seen between RNFL thinning and cognitive impairment. Conclusions: In this small-sample follow-up study of African ancestry individuals, POAG cases demonstrated worse short-term memory and higher incidence of dementia compared to controls. Future larger studies are needed to further investigate the presence and impact of neurodegeneration in POAG.

Molecular insight into the potential functional role of pseudoenzyme GFOD1 via interaction with NKIRAS2.

The glucose-fructose oxidoreductase/inositol dehydrogenase/rhizopine catabolism protein (Gfo/Idh/MocA) family includes a variety of oxidoreductases with a wide range of substrates that utilize NAD or NADP as redox cofactor. Human contains two members of this family, namely glucose-fructose oxidoreductase domain-containing protein 1 and 2 (GFOD1 and GFOD2). While GFOD1 exhibits low tissue specificity, it is notably expressed in the brain, potentially linked to psychiatric disorders and severe diseases. Nevertheless, the specific function, cofactor preference, and enzymatic activity of GFOD1 remain largely unknown. In this work, we find that GFOD1 does not bind to either NAD or NADP. Crystal structure analysis unveils that GFOD1 exists as a typical homodimer resembling other family members, but lacks essential residues required for cofactor binding, suggesting that it may function as a pseudoenzyme. Exploration of GFOD1-interacting partners in proteomic database identifies NK-κB inhibitor-interacting Ras-like 2 (NKIRAS2) as one potential candidate. Co-immunoprecipitation (co-IP) analysis indicates that GFOD1 interacts with both GTP- and GDP-bound forms of NKIRAS2. The predicted structural model of the GFOD1-NKIRAS2 complex is validated in cells using point mutants and shows that GFOD1 selectively recognizes the interswitch region of NKIRAS2. These findings reveal the distinct structural properties of GFOD1 and shed light on its potential functional role in cellular processes.

Investigating cognitive impairment, biopsychosocial barriers, and predictors of return to daily life among older stroke survivors.

Purpose: The aim was to investigate the associations between cognitive impairment and biopsychosocial factors among older stroke survivors and predictors of poststroke return to daily life. Materials and methods: This cross-sectional study involved 117 stroke survivors (61% men) with an average age of 77 years (range 65-91). The participants completed two questionnaires (Riksstroke and Short Form 36 questionnaires). The Montreal Cognitive Assessment (MoCA) was used to assess cognitive abilities. The International Classification of Functioning, Disability, and Health (ICF) framework guided the selection of biopsychosocial variables. We used Spearman's correlation coefficient and multiple logistic regression in the analyses. Results: The average MoCA score was 21.7 points (range: 4-30, SD 5.6). The need for assistance from relatives and professionals, need for help with dressing and household chores, reliance on others for mobility, and reading and balance problems were correlated with more severe cognitive impairment (r = 0.20-0.33). Cognitive impairment, fatigue, and balance issues predicted an unfavorable return to daily life (odds ratio: 6.2-6.8). Conclusion: The study indicated that cognitive impairment is associated with difficulties in all ICF domains. Cognitive impairment, fatigue, and balance issues are associated with an unsuccessful return to daily life. Prioritizing these factors and screening for cognitive impairment with objective assessment tools may improve rehabilitation outcomes and enhance overall quality of life poststroke.

Glycoside-metabolizing oxidoreductase D3dgpA from human gut bacterium.

The Gfo/Idh/MocA family enzyme DgpA was known to catalyze the regiospecific oxidation of puerarin to 3"-oxo-puerarin in the presence of 3-oxo-glucose. Here, we discovered that D3dgpA, dgpA cloned from the human gut bacterium Dorea sp. MRG-IFC3, catalyzed the regiospecific oxidation of various C-/O-glycosides, including puerarin, in the presence of methyl ß-D-3-oxo-glucopyranoside. While C-glycosides were converted to 3"- and 2"-oxo-products by D3dgpA, O-glycosides resulted in the formation of aglycones and hexose enediolone from the 3"-oxo-products. From DFT calculations, it was found that isomerization of 3"-oxo-puerarin to 2"-oxo-puerarin required a small activation energy of 9.86 kcal/mol, and the O-glycosidic bond cleavage of 3"-oxo-products was also thermodynamically favored with a small activation energy of 3.49 kcal/mol. In addition, the reaction mechanism of D3dgpA was discussed in comparison to those of Gfo/Idh/MocA and GMC family enzymes. The robust reactivity of D3dgpA was proposed as a new general route for derivatization of glycosides.

Psychometric Reliability, Validity, and Generalizability of MoCA in American Indian Adults: The Strong Heart Study.

Standardized neuropsychological instruments are used to evaluate cognitive impairment, but few have been psychometrically evaluated in American Indians. We collected Montreal Cognitive Assessment (MoCA) in 403 American Indians 70 to 95 years, as well as age, sex, education, bilingual status, depression symptoms, and other neuropsychological instruments. We evaluated inferences of psychometric validity, including scoring inference using confirmatory factor analysis and structural equation modeling, generalizability inference using reliability coefficient, and extrapolation inference by examining performance across different contexts and substrata. The unidimensional (total score) model had good fit criteria. Internal consistency reliability was high. MoCA scores were positively associated with crystallized cognition (ρ = 0.48, p < .001) and inversely with depression symptoms (ρ = -0.27, p < .001). Significant differences were found by education (d = 0.79, p < .05) depression (d = 0.484, p < .05), and adjudicated cognitive status (p = .0001) strata; however, MoCA was not sensitive or specific in discriminating cognitive impairment from normal cognition (area under the curve <0.5). MoCA scores had psychometric validity in older American Indians, but education and depression are important contextual features for score interpretability. Future research should evaluate cultural or community-specific adaptations, to improve test discriminability in this underserved population.