Vortioxetine for the treatment of post-COVID-19 condition: a randomized controlled trial.

Hitherto no therapeutic has received regulatory approval for the treatment of post-COVID-19 condition (PCC). Cognitive deficits, mood symptoms and significant reduction in health-related quality of life (HRQoL) are highly replicated and debilitating aspects of PCC. We sought to determine the impact of vortioxetine on the foregoing symptoms and HRQoL in persons living with PCC. An 8-week randomized, double-blind, placebo-controlled study of adults ≥ 18 years of age residing in Canada and who are experiencing symptoms of World Health Organization (WHO)-defined PCC, with a history of confirmed SARS-CoV-2 infection, was conducted. Recruitment began November 2021 and ended January 2023. Of the 200 participants enrolled (487 invited: 121 ineligible and 59 eligible but declined participation; 307 cleared pre-screening stage), a total of 149 participants were randomized (1:1) to receive either vortioxetine (5-20 mg, n = 75) or placebo (n = 74) daily for 8 weeks of double-blind treatment (i.e. end point). The primary outcome was the change from baseline-to-end point in the Digit Symbol Substitution Test. Secondary outcomes included the effect on depressive symptoms and HRQoL, as measured by changes from baseline-to-end point on the Quick Inventory of Depressive Symptomatology 16-item and WHO Wellbeing Scale 5-item, respectively. A total of 68 (90.7%) participants randomized to vortioxetine and 73 (98.6%) participants randomized to placebo completed all 8 weeks. Between-group analysis did not show a significant difference in the overall change in cognitive function [P = 0.361, 95% confidence interval (CI) (-0.179, 0.492)]. However, in the fully adjusted model, a significant treatment × time interaction was observed in favour of vortioxetine treatment with baseline c-reactive protein (CRP) as a moderator (P = 0.012). In addition, a significant improvement in Digit Symbol Substitution Test scores were observed in vortioxetine versus placebo treated participants in those whose baseline CRP was above the mean (P = 0.045). Moreover, significant improvement was obtained in measures of depressive symptoms [P < 0.001, 95% CI (-4.378, -2.323)] and HRQoL [P < 0.001, 95% CI (2.297, 4.647)] in vortioxetine-treated participants and between the treatment groups [depressive symptoms: P = 0.026, 95% CI (-2.847, -0.185); HRQoL: P = 0.004, 95% CI (0.774, 3.938)]. Although vortioxetine did not improve cognitive function in the unadjusted model, when adjusting for CRP, a significant pro-cognitive effect was observed; antidepressant effects and improvement in HRQoL in this debilitating disorder were also noted.

Development and first-stage validation of a digital version of the Digit Symbol Substitution test for use in assessing cognitive function in older people with diabetes.

AIMS: To describe the development and report the first-stage validation of a digital version of the digit symbol substitution test (DSST), for assessment of cognitive function in older people with diabetes. MATERIALS AND METHODS: A multidisciplinary team of experts was convened to conceptualize and build a digital version of the DSST and develop a machine-learning (ML) algorithm to analyse the inputs. One hundred individuals with type 2 diabetes (aged ≥ 60 years) were invited to participate in a one-time meeting in which both the digital and the pencil-and-paper (P&P) versions of the DSST were administered. Information pertaining to demographics, laboratory measurements, and diabetes indices was collected. The correlation between the digital and P&P versions of the test was determined. Additionally, as part of the validation process, the performance of the digital version in people with and without known risk factors for cognitive impairment was analysed. RESULTS: The ML model yielded an overall accuracy of 89.1%. A strong correlation was found between the P&P and digital versions (r = 0.76, p < 0.001) of the DSST, as well as between the ML model and the manual reading of the digital DSST (r = 0.99, p < 0.001). CONCLUSIONS: This study describes the development of and provides first-stage validation data for a newly developed digital cognitive assessment tool that may be used for screening and surveillance of cognitive function in older people with diabetes. More studies are needed to further validate this tool, especially when self-administered and in different clinical settings.

The association between waist-to-height ratio and cognitive function in older adults.

OBJECTIVES: The waist-to-height ratio (WHtR) is a simple, practical, and effective tool used to assess central obesity. Despite its usefulness, few studies have investigated the association between WHtR and cognitive function among older adults in the United States. This study aims to investigate the associations between WHtR and cognitive function. METHODS: The study sample comprised adults who participated in the National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014. WHtR was calculated from measured waist circumference and height. Cognitive function was assessed using the digit symbol substitution test. A weighted multiple linear regression analysis was performed to evaluate the association between WHtR and cognitive function, with smooth curve fitting applied to detect non-linearities. RESULTS: Our analysis included 1709 participants over the age of 65. After adjusting for potential confounders, WHtR was found to have a negative association with cognitive function (ß = -36.91, 95% CI: -54.54 to -19.29, P < 0.001). Subgroup analyzes stratified by sex and race showed that the negative correlation of WHtR with cognitive function remained in both men and women, as well as in non-Hispanic white and other races. Among women, the association between WHtR and cognitive function followed an inverted U-shaped curve, with an inflection point of 0.68. CONCLUSION: This study provides evidence of a negative association between WHtR and cognitive function in older adults. These findings suggest that in advanced age, central obesity may have negative implications for cognitive function.

Effects of lunges inserted in walking (eccentric walking) on lower limb muscle strength, physical and cognitive function of regular walkers.

INTRODUCTION: Walking is a popular exercise but does not increase lower limb muscle strength and balance. We hypothesized that muscle strength, physical and cognitive function would be improved by inserting lunges in conventional walking. METHODS: Eleven regular walkers (54-88 years) who had more than 5000 steps in exercise walking a day at least 5 days a week participated in this study. They walked as usual for the first 4 weeks and included lunges and descending stairs or slope walking (i.e., eccentric walking) for the next 8 weeks. The steps of eccentric walking were gradually increased from 100 to 1000 steps per week over 8 weeks. RESULTS: The average steps per day were 10,535 ± 3516 in the first 4 weeks, and 10,118 ± 3199 in the eccentric walking period without a significant difference. No significant changes in maximal voluntary isometric contraction torque of the knee extensors (MVC), 30-s chair stand (CS), 2-min step, balance assessed by center of pressure movement area with eyes close, sit and reach, a digit symbol substitution test (DSST) for cognitive function were observed in the first 4 weeks. However, significant (P < 0.05) improvements were evident in MVC (18.6 ± 15.7%), CS (24.2 ± 17.3%), balance ( - 45.3 ± 34.5%), and DSST (20.8 ± 16.7%) from weeks 4 to 12. Serum complement component 1q concentration decreased (P < 0.05) from weeks 4 to 12, although no changes in serum glucose, triglyceride, and cholesterol concentrations were observed. CONCLUSION: These results supported the hypothesis, and suggest that eccentric walking provides effects that are not achieved by conventional walking.

Impacts of metabolic disruption, body mass index and inflammation on cognitive function in post-COVID-19 condition: a randomized controlled trial on vortioxetine.

BACKGROUND: Post-COVID-19 Condition (PCC), as defined by the World Health Organization (WHO), currently lacks any regulatory-approved treatments and is characterized by persistent and debilitating cognitive impairment and mood symptoms. Additionally, metabolic dysfunction, chronic inflammation and the associated risks of elevated body mass index (BMI) have been reported. In this study, we aim to investigate the efficacy of vortioxetine in improving cognitive deficits in individuals with PCC, accounting for the interaction of metabolic dysfunction, elevated inflammation and BMI. METHODS: This is a post-hoc analysis of an 8-week randomized, double-blind, placebo-controlled trial that was conducted among adults aged 18 years and older living in Canada who were experiencing WHO-defined PCC symptoms. The recruitment of participants began in November 2021 and concluded in January 2023. A total of 200 individuals were enrolled, where 147 were randomized in a 1:1 ratio to receive either vortioxetine (5-20 mg, n = 73) or placebo (n = 74) for daily treatment under double-blind conditions. The primary outcome measure was the change in the Digit Symbol Substitution Test (DSST) score from baseline to endpoint. RESULTS: Our findings showed significant effects for time (χ2 = 7.771, p = 0.005), treatment (χ2 = 7.583, p = 0.006) and the treatment x time x CRP x TG-HDL x BMI interaction (χ2 = 11.967, p = 0.018) on cognitive function. Moreover, the between-group analysis showed a significant improvement with vortioxetine at endpoint (mean difference = 0.621, SEM = 0.313, p = 0.047). CONCLUSION: Overall, vortioxetine demonstrated significant improvements in cognitive deficits among individuals with baseline markers of metabolic dysfunction, elevated inflammation and higher BMI at endpoint as compared to placebo. TRIAL REGISTRATION: NCT05047952 (ClinicalTrials.gov; Registration Date: September 17, 2021).

Prognostic relevance of gait-related cognitive functions for dementia conversion in amnestic mild cognitive impairment.

BACKGROUND: Increasing research suggests that gait abnormalities can be a risk factor for Alzheimer's Disease (AD). Notably, there is growing evidence highlighting this risk factor in individuals with amnestic Mild Cognitive Impairment (aMCI), however further studies are needed. The aim of this study is to analyze cognitive tests results and brain-related measures over time in aMCI and examine how the presence of gait abnormalities (neurological or orthopedic) or normal gait affects these trends. Additionally, we sought to assess the significance of gait and gait-related measures as prognostic indicators for the progression from aMCI to AD dementia, comparing those who converted to AD with those who remained with a stable aMCI diagnosis during the follow-up. METHODS: Four hundred two individuals with aMCI from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database were included. Robust linear mixed-effects models were used to study the impact of gait abnormalities on a comprehensive neuropsychological battery over 36 months while controlling for relevant medical variables at baseline. The impact of gait on brain measures was also investigated. Lastly, the Cox proportional-hazards model was used to explore the prognostic relevance of abnormal gait and neuropsychological associated tests. RESULTS: While controlling for relevant covariates, we found that gait abnormalities led to a greater decline over time in attention (DSST) and global cognition (MMSE). Intriguingly, psychomotor speed (TMT-A) and divided attention (TMT-B) declined uniquely in the abnormal gait group. Conversely, specific AD global cognition tests (ADAS-13) and auditory-verbal memory (RAVLT immediate recall) declined over time independently of gait profile. All the other cognitive tests were not significantly affected by time or by gait profile. In addition, we found that ventricles size increased faster in the abnormal gait group compared to the normal gait group. In terms of prognosis, abnormal gait (HR = 1.7), MMSE (HR = 1.09), and DSST (HR = 1.03) covariates showed a higher impact on AD dementia conversion. CONCLUSIONS: The importance of the link between gait and related cognitive functions in terms of diagnosis, prognosis, and rehabilitation in aMCI is critical. We showed that in aMCI gait abnormalities lead to executive functions/attention deterioration and conversion to AD dementia.

Effect of Vortioxetine on Cognitive Impairment in Patients With Major Depressive Disorder: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Dementia and depression are increasingly common worldwide, and their effective control could ease the burden on economies, public health systems, and support networks. Vortioxetine is a new antidepressant with multipharmacologic actions that elevate the concentration of serotonin and modulate multiple neurotransmitter receptors in the brain. We conducted a meta-analysis to explore whether the cognitive function of patients with major depressive disorder (MDD) treated with vortioxetine would improve. METHODS: We systematically reviewed randomized controlled trials (RCTs) in the PubMed, Embase, and Cochrane databases to assess the treatment effects of vortioxetine on the cognitive function of patients with MDD. The outcome measures included the Digit Symbol Substitution Test (DSST), Perceived Deficits Questionnaire (PDQ), and Montgomery-Åsberg Depression Rating Scale (MADRS) scores. Pooled results were calculated using a fixed-effects or random-effects model according to the heterogeneity of the included trials. RESULTS: Six RCTs with a total of 1782 patients were included in the meta-analysis, which demonstrated that vortioxetine improved DSST, PDQ, and MADRS scores in patients with MDD. The results were consistent at the 10- and 20-mg doses. In the 20-mg group, the decrease in MADRS scores was more significant than that in the placebo group. CONCLUSIONS: Both the 10- and 20-mg doses of vortioxetine can significantly increase DSST scores and decrease PDQ and MADRS scores in patients with MDD and cognitive dysfunction, but further studies with longer follow-up periods to assess mental function are required.

Dietary inflammatory index and memory function: population-based national sample of elderly Americans.

The objective of this study was to examine the association between dietary inflammatory potential and memory and cognitive functioning among a representative sample of the US older adult population. Cross-sectional data from the 2011-2012 and 2013-2014 National Health and Nutrition Examination Survey were utilised to identify an aggregate sample of adults 60-85 years of age (n 1723). Dietary inflammatory index (DII®) scores were calculated using 24-h dietary recall interviews. Three memory-related assessments were employed, including the Consortium to Establish a Registry for Alzheimer's disease (CERAD) Word Learning subset, the Animal Fluency test and the Digit Symbol Substitution Test (DSST). Inverse associations were observed between DII scores and the different memory parameters. Episodic memory (CERAD) (b adjusted=-0·39; 95 % CI -0·79, 0·00), semantic-based memory (Animal Fluency Test) (b adjusted=-1·18; 95 % CI -2·17, -0·20) and executive function and working-memory (DSST) (b adjusted=-2·80; 95 % CI -5·58, -0·02) performances were lowest among those with the highest mean DII score. Though inverse relationships were observed between DII scores and memory and cognitive functioning, future work is needed to further explore the neurobiological mechanisms underlying the complex relationship between inflammation-related dietary behaviour and memory and cognition.

The effects of flavanone-rich citrus juice on cognitive function and cerebral blood flow: an acute, randomised, placebo-controlled cross-over trial in healthy, young adults.

A plausible mechanism underlying flavonoid-associated cognitive effects is increased cerebral blood flow (CBF). However, behavioural and CBF effects following flavanone-rich juice consumption have not been explored. The aim of this study was to investigate whether consumption of flavanone-rich juice is associated with acute cognitive benefits and increased regional CBF in healthy, young adults. An acute, single-blind, randomised, cross-over design was applied with two 500-ml drink conditions - high-flavanone (HF; 70·5 mg) drink and an energy-, and vitamin C- matched, zero-flavanone control. A total of twenty-four healthy young adults aged 18-30 years underwent cognitive testing at baseline and 2-h after drink consumption. A further sixteen, healthy, young adults were recruited for functional MRI assessment, whereby CBF was measured with arterial spin labelling during conscious resting state at baseline as well as 2 and 5 h after drink consumption. The HF drink was associated with significantly increased regional perfusion in the inferior and middle right frontal gyrus at 2 h relative to baseline and the control drink. In addition, the HF drink was associated with significantly improved performance on the Digit Symbol Substitution Test at 2 h relative to baseline and the control drink, but no effects were observed on any other behavioural cognitive tests. These results demonstrate that consumption of flavanone-rich citrus juice in quantities commonly consumed can acutely enhance blood flow to the brain in healthy, young adults. However, further studies are required to establish a direct causal link between increased CBF and enhanced behavioural outcomes following citrus juice ingestion.

Normative data for the Digit Symbol Substitution for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA).

INTRODUCTION: Executive functioning and processing speed are crucial elements of neuropsychological assessment. To meet the needs of the Hispanic/Latino population, we aimed to provide normative data for the Digit Symbol Substitution (DSS) test. METHODS: The target population for the Study of Latinos-Investigation of Neurocognitive Aging included six heritage backgrounds (n = 6177). Average age was 63.4 ± 8.3 years, 54.5% were female, and mean education was 11.0 ± 4.7 years. Participants were administered the DSS as part of a larger battery. Heritage-adjusted DSS scores, and percentile cut-points were created using survey-adjusted regression and quantile regression models. RESULTS: Age, education, sex, heritage, and language preference were associated with DSS scores. DISCUSSION: Significant correlates of DSS performance should be considered when evaluating cognitive performance. Representative DSS norms for Hispanics/Latinos will advance assessment and accuracy of neurocognitive disorder diagnosis in clinical practice. To facilitate interpretation, we provide norms to reduce test biases and developed an online dashboard. Highlights: Normative data for the Digit Symbol Substitution (DSS) for diverse Hispanic/Latino adults: Results from the Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) This study is the first to develop norms for the DSS test across four regions of the United States.Factors such as age, education, sex, and Hispanic/Latino heritage and language preference are associated with differences in executive functioning and information processing speed.We created norms and an online dashboard (https://solincalab.shinyapps.io/dsst_shiny/) providing an easily accessible tool to evaluate processing speed and executive functioning in Hispanic/Latino adults.

The Drug Burden Index Is Associated With Measures of Cognitive Function Among Older Adults in the Health, Aging, and Body Composition Study.

BACKGROUND: Anticholinergic and sedative medications affect cognition among older adults. The Drug Burden Index (DBI) is a validated measure of exposure to these medications, with higher DBI scores indicating higher drug burden. This ancillary analysis investigated the association between DBI and cognition assessed by the Modified Mini-Mental State Examination (3MS) and the Digit Symbol Substitution Test (DSST). METHODS: The Health, Aging, and Body Composition Study was a prospective study of community-dwelling adults aged 70-79 years at enrollment. Using data from years 1, 5, and 10, DBI was calculated using medication data per participant. Linear mixed modeling was used to assess cross-sectional and longitudinal effects of DBI on 3MS and DSST. Adjusted models included biological sex, race, education level, APOE status, and death. Sensitivity analyses included testing the strength of the associations for each year and testing attrition due to death as a possible confounding factor via Cox-Proportional Hazard models. RESULTS: After adjustment, DBI was inversely associated with 3MS and DSST scores. These associations became stronger in each subsequent year. Neither DBI at year 1 nor within-person change in DBI were predictive of longitudinal declines in either cognitive measure. Sensitivity analyses indicated that DBI, 3MS, and DSST were associated with a greater risk of attrition due to death. CONCLUSIONS: Results suggest that in years when older adults had a higher DBI scores, they had significantly lower global cognition and slower processing speed. These findings further substantiate the DBI as a useful pharmacological tool for assessing the effect of medication exposure.

Rare genetic variants correlate with better processing speed.

We conducted a genome-wide association study of Digit Symbol Substitution Test scores administered in 4207 family members of the Long Life Family Study (LLFS). Genotype data were imputed to the HRC panel of 64,940 haplotypes resulting in ∼15M genetic variants with a quality score > 0.7. The results were replicated using genetic data imputed to the 1000 Genomes phase 3 reference panel from 2 Danish twin cohorts: the study of Middle Aged Danish Twins and the Longitudinal Study of Aging Danish Twins. The genome-wide association study in LLFS discovered 18 rare genetic variants (minor allele frequency (MAF) < 1.0%) that reached genome-wide significance (p-value < 5 × 10-8). Among these, 17 rare variants in chromosome 3 had large protective effects on the processing speed, including rs7623455, rs9821776, rs9821587, rs78704059, which were replicated in the combined Danish twin cohort. These SNPs are located in/near 2 genes, THRB and RARB, that belonged to the thyroid hormone receptors family that may influence the speed of metabolism and cognitive aging. The gene-level tests in LLFS confirmed that these 2 genes are associated with processing speed.

Association between serum globulin and cognitive impairment in older American adults.

Background and aims: Cognitive impairment is on the rise around the world, with profound economic and social consequences. Serum globulin, a marker of liver function, may also play a role in cognitive function. Unfortunately, no consistent conclusion exists regarding the association between serum globulin and cognitive function. Methods: Data from the 2011 to 2014 National Health and Nutrition Examination Survey were used to assess the association between serum globulin and cognitive impairment. Cognitive function was assessed by three tests: Consortium to Establish a Registry for Alzheimer's Disease (CERAD), Animal Fluency (AF), and Digit Symbol Substitution Test (DSST). Furthermore, the breakthrough point of cognitive impairment correlated with CERAD < 5, AF < 14, and DSST < 34. A weighted multiple logistics regression model was used to verify the association between serum globulin and cognitive impairment. Generalized additive models (GAMs) and a smooth curve fit (penalty spline method) were used to determine a non-linear relationship between serum globulin and cognitive impairment. Finally, subgroup analysis and interaction tests were conducted to further verify the association between serum globulin and cognitive impairment. Results: Data from 2,768 participants aged ≥60 (in accordance with the study design) were collected for the final analysis. Data suggested that serum globulin levels were associated with an elevated cognitive impairment based on the AF [full adjustment, OR = 1.05, 95% CI: 1.01-1.08] and DSST [full adjustment, OR = 1.06, 95% CI: 1.02-1.10] tests. Eventually, the GAM and smooth curve fit model was conducted to confirm that the association between serum globulin and cognitive impairment was non-linear. Moreover, the inflection point was 27 g/L serum globulin based on the CERAD test and 35 g/L serum globulin based on the AF test. Finally, the interaction term between serum globulin and cognitive impairment based on the AF test indicated no significant interactions among all variables (all p for interaction >0.05). Conclusion: The association between serum globulin levels and cognitive impairment is non-linear. A threshold effect exists between serum globulin and cognitive impairment. Large-scale prospective clinical trials are needed to validate our findings.

Sleep Loss, Daytime Sleepiness, and Neurobehavioral Performance among Adolescents: A Field Study.

The current study investigates the impact of sleep loss on neurobehavioral functioning and sleepiness in a natural setting among healthy adolescents. Fifty-nine adolescents (32 females) from grades 7 to 12 (mean age of 16.29 ± 1.86 years) participated in the study. All participants wore the actigraph for a continuous five to seven days, including school and nonschool days. Subjective sleepiness and neurobehavioral performance (using the psychomotor vigilance test and the digit symbol substitution test) were measured three times a day on two school days and one nonschool day. The results presented that sleep loss influenced subjective sleepiness reports, showing higher sleepiness scores following sleep loss than following sufficient night sleep. Neurobehavioral functioning across all measurements was also significantly worse following sleep loss. Furthermore, participants performed worse on weekday morning assessments than on assessments at other times of the day following sleep loss. These findings suggest that sleep loss in natural settings has a significant impact on neurobehavioral performance and subjective sleepiness. Our findings have essential implications for public policy on school schedules.

An App-Based Digit Symbol Substitution Test for Assessment of Cognitive Deficits in Adults With Major Depressive Disorder: Evaluation Study.

BACKGROUND: Cognitive dysfunction is an impairing core symptom of depression. Among adults with major depressive disorder (MDD) treated with antidepressants, residual cognitive symptoms interfere with patient-reported outcomes. The foregoing characterization of cognitive symptoms provides the rationale for screening and assessing the severity of cognitive symptoms at point of care. However, clinical neurocognitive assessments are time-consuming and difficult, and they require specialist expertise to interpret them. A smartphone-delivered neurocognitive test may offer an effective and accessible tool that can be readily implemented into a measurement-based care framework. OBJECTIVE: We aimed to evaluate the use of a smartphone-delivered app-based version of the established Cognition Kit Digit Symbol Substitution Test (DSST) neurocognitive assessment compared to a traditional paper-and-pencil version. METHODS: Convergent validity and test-retest reliability of the 2 versions were evaluated. Patient satisfaction with the app was also assessed. RESULTS: Assessments made using the app-based Cognition Kit DSST were highly correlated with the standard paper-and-pencil version of the test, both at the baseline visit (r=0.69, df=27; P<.001) and at the end-of-study visit (r=0.82, df=27; P<.001), and they were positively evaluated by 30 patients as being user-friendly, easy to navigate, and preferable over the paper-and-pencil version of the DSST. However, although the app-based Cognition Kit DSST was validated in patients with MDD, it still needs to be evaluated in healthy controls. CONCLUSIONS: App-based DSST may facilitate a more personalized, convenient, and cost-effective method of cognitive assessment, helping to guide measurement-based care and psychotherapeutic and pharmacologic treatment options for patients with MDD. TRIAL REGISTRATION: ClinicalTrials.gov NCT03999567; https://tinyurl.com/2p8pnyv7.

Association between grip strength and cognitive impairment in older American adults.

Background and aims: Exponential population aging has led to an increased prevalence of cognitive impairment worldwide. Hand grip strength, which may be associated with physical activity, could be a useful predictor of cognitive impairment. However, few studies have reported the association, if any, between hand grip strength and cognitive function. Methods: We used data obtained from the National Health and Nutrition Examination Survey between 2011-2012 and 2013-2014 to investigate the association between hand grip strength and cognitive impairment. Cognitive impairment was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERAD), animal fluency (AF), and digit symbol substitution test (DSST) scores. Cutoff values of CERAD < 5, AF < 14, and DSST < 34 were used to define cognitive impairment. In this cross-sectional study, we used odds ratios to determine the potential usefulness of hand grip strength for the prediction of cognitive impairment. Results: This study included 2,623 participants aged ≥60 years. The DSST results showed that hand grip strength was associated with a low risk of cognitive impairment and that subgroup analysis showed that male sex, 60-69 years of age, and the Non-Hispanic (NH)-White, NH Black, and Asian were associated with a significantly low risk of cognitive impairment. The CERAD test results showed that 70-79 years of age and the NH White were significantly associated with a low risk of cognitive impairment. By following full adjustment, we did not observe statistically significant differences between hand grip strength and cognitive impairment based on the CERAD test. The AF test results showed that >80 years of age, female sex, and the NH White were associated with a significantly low risk of cognitive impairment. The most important finding is that a linear association lies between grip strength and cognitive impairment, as well as a sex-based linear association. Machine learning of the XGBoost model suggests that grip strength is one of the top two most important negative predictor variables. Conclusion: We observed an inverse relationship between hand grip strength and cognitive impairment, which might suggest a shared underlying mechanism that needs to be further investigated using a large-scale prospective clinical trial to validate our findings.

Estimated Phytate Intake Is Associated with Improved Cognitive Function in the Elderly, NHANES 2013-2014.

Phytate, an antioxidant, may improve cognition by inhibiting iron catalyzed hydroxyl radical formation. Particularly in the elderly, this provides a potential dietary approach for mitigating age-related brain neuronal dysfunction and loss. In this study, we investigated the relationship between phytate intake and cognitive function in the elderly. We used data from the 2013-2014 National Health and Nutrition Examination Survey (NHANES) and the corresponding Food Patterns Equivalents Database (FPED). Phytate content of food groups from published data were merged with the appropriate FPED data to estimate the total phytate intake for each subject. Principal component analysis was used to develop a composite score from four cognitive function scores in NHANES data, and regression analysis was used to determine the relationship between this score and phytate intake. Median phytate intake was 0.65 (0.61, 0.71) g/day. It was low among females, non-Hispanic blacks, and people with history of at least one chronic disease (p < 0.05). In regression analysis adjusted for confounders, phytate intake was positively associated with cognitive function (ß (95% CI) = 1.90 (0.73-3.07); p = 0.015). These results suggest that phytate may be associated with improved cognition, hence the need to consider including phytate-rich foods in the diet among the elderly.

Discriminant Validity of the WAIS-R Digit Symbol Substitution Test in Subjective Cognitive Decline, Mild Cognitive Impairment (Amnestic Subtype) and Alzheimer's Disease Dementia (ADD) in Greece.

OBJECTIVE: The aim of the current study was to estimate the discriminant potential and validity of the Digit Symbol Substitution Test (DSST) of the WAIS-R in the Greek elderly population meeting criteria for subjective cognitive decline (SCD), mild cognitive impairment (aMCI; amnestic subtype), or Alzheimer's disease dementia (ADD). METHOD: Four hundred eighty-eight community-dwelling older adults, visitors of the Day Center of Alzheimer Hellas, participated in the study. Two hundred forty-three of them met the criteria for ADD, one hundred eighty-two for aMCI and sixty-three for SCD. RESULTS: Path analysis indicated that the DSST score is affected by age group, educational level, and diagnostic category, but is not affected by gender. The ROC curve analysis showed that the DSST sum score could perfectly differentiate SCD from ADD patients, whereas test's discriminant potential between aMCI and dementia ADD's subtype was satisfactory. However, DSST was unable to separate the SCD from the aMCI group. CONCLUSION: It appears that the DSST is unable to separate the SCD from aMCI population. Therefore, the test in question may be insensitive to incipient cognitive decline. On the contrary, the discriminant potential of the DSST as regards SCD and ADD is excellent, while discrimination between aMCI and ADD is good.

Digital Technology Differentiates Graphomotor and Information Processing Speed Patterns of Behavior.

BACKGROUND: Coupling digital technology with traditional neuropsychological test performance allows collection of high-precision metrics that can clarify and/or define underlying constructs related to brain and cognition. OBJECTIVE: To identify graphomotor and information processing trajectories using a digitally administered version of the Digit Symbol Substitution Test (DSST). METHODS: A subset of Long Life Family Study participants (n = 1,594) completed the DSST. Total time to draw each symbol was divided into 'writing' and non-writing or 'thinking' time. Bayesian clustering grouped participants by change in median time over intervals of eight consecutively drawn symbols across the 90 s test. Clusters were characterized based on sociodemographic characteristics, health and physical function data, APOE genotype, and neuropsychological test scores. RESULTS: Clustering revealed four 'thinking' time trajectories, with two clusters showing significant changes within the test. Participants in these clusters obtained lower episodic memory scores but were similar in other health and functional characteristics. Clustering of 'writing' time also revealed four performance trajectories where one cluster of participants showed progressively slower writing time. These participants had weaker grip strength, slower gait speed, and greater perceived physical fatigability, but no differences in cognitive test scores. CONCLUSION: Digital data identified previously unrecognized patterns of 'writing' and 'thinking' time that cannot be detected without digital technology. These patterns of performance were differentially associated with measures of cognitive and physical function and may constitute specific neurocognitive biomarkers signaling the presence of subtle to mild dysfunction. Such information could inform the selection and timing of in-depth neuropsychological assessments and help target interventions.

A Multi-Institutional Study of Older Hearing Aids Beginners-A Prospective Single-Arm Observation on Executive Function and Social Interaction.

OBJECTIVES: To obtain new insights into research questions on how executive function and social interaction would be observed to change after the introduction of hearing aids (HAs) in older people with hearing impairment. DESIGN: Multi-institutional prospective single-arm observational study. SETTING AND PARTICIPANTS: Outpatients with complaints of hearing difficulty who visited HA clinics between October 18, 2017, and June 30, 2019, in 7 different university hospitals in Japan. METHODS: The inclusion criteria of the study named Hearing-Aid Introduction for Hearing-Impaired Seniors to Realize a Productive Aging Society-A Study Focusing on Executive Function and Social Activities Study (HA-ProA study) were age ≥60 years and no history of HA use. A series of multi-institution common evaluations including audiometric measurements, the digit symbol substitution test to assess executive functions, convoy model as an index of social relations, and hearing handicap inventory for the elderly (HHIE) were performed before (pre-HA) and after 6 months of the HA introduction (post-HA). RESULTS: Out of 127 enrollments, 94 participants completed a 6-month follow-up, with a mean age of 76.9 years. The digit symbol substitution test score improved significantly from 44.7 at baseline to 46.1 at 6 months (P = .0106). In the convoy model, the social network size indicated by the number of persons in each and whole circles were not significantly different between pre- and post-HA; however, the total count for kin was significantly increased (P = .0344). In the analyses of HHIE, the items regarding the family and relatives showed significant improvement. CONCLUSIONS AND IMPLICATIONS: HA use could benefit older individuals beginning to use HAs in executive function and social interaction, though the results should be interpreted cautiously given methodological limitations such as a single-arm short 6 months observation. Reduction in daily hearing impairment would have a favorable effect on relationships with the family.