Digit Symbol Substitution Test Performance Research Articles

The circulating proteome and brain health: Mendelian randomisation and cross-sectional analyses

Decline in cognitive function is the most feared aspect of ageing. Poorer midlife cognitive function is associated with increased dementia and stroke risk. The mechanisms underlying variation in cognitive function are uncertain. Here, we assessed associations between 1160 proteins’ plasma levels and two measures of cognitive function, the digit symbol substitution test (DSST) and the Montreal Cognitive Assessment in 1198 PURE-MIND participants. We identified five DSST performance-associated proteins (NCAN, BCAN, CA14, MOG, CDCP1), with NCAN and CDCP1 showing replicated association in an independent cohort, GS (N = 1053). MRI-assessed structural brain phenotypes partially mediated (8–19%) associations between NCAN, BCAN, and MOG, and DSST performance. Mendelian randomisation analyses suggested higher CA14 levels might cause larger hippocampal volume and increased stroke risk, whilst higher CDCP1 levels might increase intracranial aneurysm risk. Our findings highlight candidates for further study and the potential for drug repurposing to reduce the risk of stroke and cognitive decline.

A comparison of two obesity-related hypoventilation disorders: Impact on sleep, quality of life and neurocognitive outcomes and the effects of positive airway pressuretherapy.

Symptom impact and neurocognitive function have not been previously compared between patients with obesity-associated hypoventilation disorders (obesity hypoventilation syndrome [OHS]) and hypoventilation in the setting of obesity and obstructive airways disease (OHAD). The aim of this study is to compare baseline sleep-related symptoms, health-related quality of life, and neurocognitive function between OHS and OHAD and the impact of PAP therapy on these outcomes. Epworth Sleepiness Scale (ESS), Pittsburgh Sleepiness Quality Index (PSQI), SF36, and various neurocognitive tests, in addition to anthropometric, polysomnography, lung function, and blood gas data from participants with OHS and participants with OHAD, were included in the analysis. These data were originally collected in their respective randomized clinical trials, comparing the efficacy of different PAP modes (bilevel PAP vs. CPAP) in resolving hypercapnia. Between groups (OHS vs OHAD), pre- and post-treatment (with 3 months of positive airway pressure) comparisons were made using linear mixed modeling. 45 OHS participants (mean age 51 years old, 33% female, BMI 52kg/m2, FER 0.81, PaCO2 54 mmHg, AHI 87/h) and 32 OHAD participants (mean age 61years old, 31% female, BMI 43kg/m2, FER 0.60, PaCO2 54 mmHg, AHI 59/h) were included in the analysis. Both OHS and OHAD had similar baseline ESS (14(5.6) vs. 12(5.4)), Global PSQI (10(3.2) vs. 11(4.8)), SF36 and neurocognitive test performances (other than OHAD had lower digit symbol substitution test performance). Treatment with PAP therapy resulted in similar ESS, Global PSQI, and SF36 improvements in both groups. Neurocognitive performance did not significantly improve after PAP therapy in either group. The symptom impact between two separate hypoventilation disorders (OHS and OHAD), in terms of sleepiness, sleep quality, quality of life, and cognitive function, were similar. OHS and OHAD had similar treatment responses in these parameters after 3 months of PAP therapy.Nocturnal ventilatory support in OHS.

Relationship between Walking and Driving, and Cognitive Functioning Common to Both Modes of Mobility, in Healthy Older Adults

Introduction: Driving and walking, the two main modes of mobility, require numerous common skills in the motor, sensory, and cognitive domains that deteriorate with age. The objective of this study was to investigate the relationship between walking and driving in healthy older drivers and to determine whether certain cognitive processes are involved in both modes of mobility. Method: Seventy-six older drivers from the Safe Move cohort were assessed in the following three domains: (1) cognition, using parts A and B of the Trail Making Test (TMT), the digit symbol substitution test (DSST), the Stroop test, and the Digit span; (2) gait, using a dual-task (DT) paradigm with a counting task; and (3) driving, assessed via a 40–50 min on-road test. Analyses were also performed on 2 subgroups: young-old (70–74 years old; n = 43) and old-old (≥75 years; n = 33). Results: Four significant correlations were found across the whole sample between gait performance under DT conditions and driving scores. One correlation was also found in old-old adults. None were found in young-old adults. Furthermore, several cognitive measures were significantly correlated to both modes of mobility: TMT-A and B completion time in the whole sample, and DSST performance in the whole sample and old-old adults. Discussion/Conclusion: Walking in complex conditions and on-road driving performance are closely related in healthy older drivers. Visuospatial attention, processing speed, and executive function are crucial and common cognitive processes to both modes of mobility in this population. Impairment in these cognitive functions should thus alert health professionals as it can quickly lead to mobility disorders, loss of autonomy and social isolation. Developing specific preventive programs and mobility support systems for healthy older adults is also crucial.

Can we use machine learning to predict cognitive performance from actigraphy data? Preliminary results from the UK Biobank Study

AbstractBackgroundCircadian rhythms (i.e., the ∼24‐hour biological clock) are critical to the maintenance of the sleep‐wake cycle, and sleep‐wake disturbances are common in people at risk for cognitive decline and dementia. Several studies have identified circadian factors associated with cognitive decline using actigraphy (a common field measure for indexing the sleep‐wake cycle). However, there are currently untapped opportunities to use the power of artificial intelligence, specifically machine learning (ML), to improve our ability to identify signs of cognitive decline from actigraphy data. As a first step towards this goal, we examined the utility of two supervised ML models for predicting cognitive performance using data from the UK Biobank study.MethodA cross‐sectional analysis of participants in the UK Biobank study (40‐69 years at entry) with valid actigraphy data and complete cognitive data (N = 49,469). Participants completed computerized versions of Trail Making Test B‐A (TMT) and Digit Symbol Substitution Test (DSST). Actigraphy data were collected over 7 days, with average hourly movement being indexed. Along with 24‐hour actigraphy data, we included the following features in each model: age, biological sex, household income, educational attainment, smoking and alcohol intake, ethnicity, body mass index, and Townsend Deprivation Index. Seventy percent of participants were randomized to the training set, with the remaining 30% held out as a test set. We developed two separate ML models to predict cognitive performance: 1) a linear regression approach; and 2) a 3‐hidden layer (40 hidden units per layer) neural network. Model accuracy was compared using the coefficient of determination (R2).ResultMean age was 55 years (SD = 8 years) and 56% of participants were female. Average TMT time was 27.22 seconds (SD = 20.10 seconds), and mean DSST score was 20.06 (SD = 5.04). Our supervised linear regression had modest predictive ability of TMT (R2 = 8%) and DSST performance (R2 = 21%); the 3‐hidden layer neural network had similar predictive capability for both TMT (R2 = 8%) and DSST (R2 = 21%).ConclusionML approaches for predicting cognitive performance using actigraphy data show modest capability. Further work is needed to identify how ML can be used to predict cognitive function from biometric data.

Trajectories in Depressive Symptoms and Midlife Brain Health

AbstractBackgroundEvidence in older adults suggests that depressive symptoms may be part of prodromal mood changes in dementia, rather than a risk factor. However, it is unclear whether variations in depressive symptoms in adulthood exhibit distinct characteristics in brain structure and cognitive function in midlife.MethodsFrom the Coronary Artery Risk Development in Young Adults study, we identified 662 Black and White participants (age 23‐36 at baseline) who completed the Center for Epidemiological Studies Depression scale (CES‐D) at six time points over 20 years. 20 years after baseline, the participants underwent magnetic resonance imaging to characterize gray matter (GM) structures (total GM, temporal cortex, hippocampus, and entorhinal cortex) and white matter hyperintensities (WMHs). Participants also completed neuropsychological tests including the Digit Symbol Substitution Test (DSST), Rey‐Auditory Verbal Learning Test (RAVLT), Stroop Test, Montreal Cognitive Assessment (MoCA), and category and letter fluency tests, analyzed as z‐scores.ResultsUsing growth mixture modeling, we identified four trajectories of depressive symptoms (Figure 1): consistently low scorers (“steady low”; n = 509, 76.9%), a class with an early peak and decline in symptoms (“declining”; n = 63, 9.5%), a class with late increases in symptoms (“increasing”; n = 49, 7.4%), and consistently high scorers (“steady high”; n = 41, 6.2%). Compared to the steady low class, the steady high class had lower entorhinal cortex volume (β: ‐180.80, 95% CI: ‐336.69 to ‐24.91). The increasing class, had more WMHs (β: 0.55, 95% CI: 0.22 to 0.89) and less total brain volume (β: ‐9269.25, 95% CI: ‐17104.67 to ‐1444.82). Both the steady high and the increasing classes had poorer performance on the Stroop task (β: ‐0.40, 95% CI: ‐0.70 to ‐0.10; β: ‐0.39, 95% CI: ‐0.64 to ‐0.14, respectively), however the steady high also had poorer DSST performance (β: ‐0.40, 95% CI: ‐0.67 to ‐0.13), while the increasing class had poorer performance on the MoCA (β: ‐1.20, 95% CI: ‐2.04 to ‐0.37). The declining group was not significantly different from the steady low group on any brain or cognitive measures.ConclusionsOur findings suggest that trajectories in depressive symptoms in young to mid‐adulthood show different cognitive and brain phenotypes in midlife.

Left Frontoparietal Connectivity Counteracts Locus Coeruleus‐Related Attentional Decline in Preclinical Alzheimer’s Disease

AbstractBackgroundAutopsy work reported that neuronal density in the locus coeruleus (LC) provides neural reserve against cognitive decline in dementia. Recent neuroimaging and pharmacological studies have also ascribed a protective role of the LC against cognitive decline, possibly mediated by prefrontal functional connectivity (FC). Interestingly, higher left frontoparietal network (LFPN) FC provides resilience against cognitive decline in preclinical sporadic or autosomal Alzheimer’s disease (AD). Given that the FPN and the LC play an important role in attentional control, and attention deficits are affected early in the disease process, we aimed to examine whether LFPN‐FC can counteract the impact of poor LC structural health on attention in the context of AD pathology.Method143 participants from the Harvard Aging Brain study who underwent 3T resting‐state functional MRI, LC structural imaging, PiB(Aβ)‐PET, and up to 4 years of cognitive follow‐ups were included (90 F, mean age = 75±9.88, Table 1). The Digit Symbol Substitution Test (DSST) assessed attentional control. Robust linear regression associated LC integrity or LFPN connectivity to DSST performance at baseline. Robust mixed effect analyses examined the associations between DSST decline and (i) the two‐way interaction between LC integrity (or LFPN‐FC) and PiB (DVR‐PVC), or (ii) the three‐way interaction between LC integrity, LFPN‐FC, and PiB (DVR‐PVC). All analyses were adjusted for age, sex, and years of education.ResultAt baseline, lower LFPN‐FC (p = 0.001) was related to worse performance on the DSST, while no such association was found for LC integrity (p = 0.26). Longitudinally, both, lower LC integrity (p<0.001) and LFPN‐FC (p = 0.026) were associated with faster DSST decline, especially at higher PiB levels (Figure 1). The modulating effect of LFPN‐FC is most prominent under lower LC structural integrity values, where higher levels of LFPN‐FC were associated with less steep decline on the DSST, in particular in individuals with higher PiB (p = 0.036, Figure 2).ConclusionOur findings demonstrate that when LC structural health is poor, higher LFPN‐FC can maintain cognitive performance even at higher levels of Aβ deposition in preclinical AD. These results provide critical insights and targets to support specific brain mechanisms that delay symptom progression in the early stages of the disease.

P065 A Comparison of Two Obesity Related Hypoventilation Disorders – Impact on Sleep, Quality of Life and Neurocognitive Outcomes and the Effects of PAP Therapy

Abstract Introduction Symptom burden and neurocognitive function have not been previous compared between patients with obesity-associated hypoventilation disorders (obesity hypoventilation syndrome, OHS), and hypoventilation in the setting of obesity and obstructive airways disease (OHAD). The aim of this study is to compare baseline sleep-related symptoms, health-related quality of life and neurocognitive function between OHS and OHAD and the impact of PAP therapy on these outcomes. Methods ESS, PSQI, SF36, and various neurocognitive tests, in addition to anthropometric, polysomnography, lung function and blood gas data from 45 patients with OHS and 32 patients with OHAD, were included in the analysis. Between groups (OHS vs OHAD), pre- and post-treatment (with 3 months of positive airway pressure) comparisons were made using linear mixed modelling. Results Both OHS and OHAD had similar baseline ESS (14(5.6) vs. 12(5.4)), Global PSQI (10(3.2) vs 11(4.8)), SF36 and neurocognitive test performances (other than OHAD had lower digit symbol substitution test performance). Treatment with PAP therapy resulted in similar improvements in ESS, Global PSQI, and SF36 in both groups. Neurocognitive performance did not significantly improve after PAP therapy in either group. Discussion The symptom burden between two separate hypoventilation disorders (OHS and OHAD), in terms of sleepiness, sleep quality, quality of life and cognitive function, were similar. OHS and OHAD had similar treatment responses in these parameters after 3 months of PAP therapy.

Associations Between Parity and Cognition: Race/Ethnic Differences.

Race/ethnicity is associated with differences in reproductive history and cognition individually, yet it remains an understudied factor in the relationship between parity and later-life cognition. To evaluate if the association between parity and cognition differs between racial/ethnic groups. Participants included 778 older, postmenopausal women from the Health and Nutrition Examination Survey (Latina: n = 178, Non-Latino Black [NLB]: n = 169, Non-Latino White [NLW]: n = 431) who self-reported at least one birth. Cognitive outcomes included working memory, learning memory, and verbal fluency. Covariates included age, education, cardiovascular and other reproductive health factors, adult socioeconomic status (SES) and depressive symptoms. We fit a series of linear models to examine a) whether parity was associated with cognitive functioning, b) if this association varied by race/ethnicity through parity by race/ethnicity interactions, and c) individual parity with cognition associations stratified by race/ethnicity. In the full sample, parity was significantly negatively associated with Digit Symbol Substitution Test (DSST) performance (b = -0.70, p = 0.024) but not Animal Fluency or word-list learning and memory. Tests of race/ethnicity-by-parity interactions were not statistically significant (ps > 0.05). However, stratified analyses by race/ethnicity showed a differential effect of parity on DSST performance, such that parity was significantly negatively associated with DSST performance (b = -1.66, p = 0.007) among Latinas but not in NLWs (b = -0.16, p = 0.74) or NLBs (b = -0.81, p = 0.191). Among Latina, but not NLB or NLW women, greater parity was associated with worse processing speed/executive functioning later in life. Further research is needed to understand the mechanisms driving racial/ethnic differences.

Aerobic exercise improves executive functions in females, but not males, without the BDNF Val66Met polymorphism

BackgroundAerobic exercise promotes cognitive function in older adults; however, variability exists in the degree of benefit. The brain-derived neurotropic factor (BDNF) Val66Met polymorphism and biological sex are biological factors that have been proposed as important modifiers of exercise efficacy. Therefore, we assessed whether the effect of aerobic exercise on executive functions was dependent on the BDNFval66met genotype and biological sex.MethodsWe used data from a single-blind randomized controlled trial in older adults with subcortical ischemic vascular cognitive impairment (NCT01027858). Fifty-eight older adults were randomly assigned to either the 6 months, three times per week progressive aerobic training (AT) group or the usual care plus education control (CON) group. The secondary aim of the parent study included executive functions which were assessed with the Trail Making Test (B–A) and the Digit Symbol Substitution Test at baseline and trial completion at 6 months.ResultsAnalysis of covariance, controlling for baseline global cognition and baseline executive functions performance (Trail Making Test or Digit Symbol Substitution Test), tested the three-way interaction between experimental group (AT, CON), BDNFval66met genotype (Val/Val carrier, Met carrier), and biological sex (female, male). Significant three-way interactions were found for the Trail Making Test (F(1,48) = 4.412, p < 0.04) and Digit Symbol Substitution Test (F(1,47) = 10.833, p < 0.002). Posthoc analyses showed female Val/Val carriers benefited the most from 6 months of AT compared with CON for Trail Making Test and Digit Symbol Substitution Test performance. Compared with CON, AT did not improve Trail Making Test performance in male Val/Val carriers or Digit Symbol Substitution Test performance in female Met carriers.ConclusionsThese results suggest that future randomized controlled trials should take into consideration BDNF genotype and biological sex to better understand the beneficial effects of AT on cognitive function in vascular cognitive impairment to maximize the beneficial effects of exercise and help establish exercise as medicine for cognitive health.

Periodontitis and low cognitive performance: A population-based study.

To study the epidemiological association between periodontitis and low cognitive performance among older adults, within a representative sample of the U.S. Data from 2086 older adults (≥60 years old), representative of 77.1million people, were retrieved from the NHANES 2011-2014 database. Periodontitis cases were identified and classified according to the AAP/CDC criteria (mild, moderate, and severe). Cognitive function was assessed through the Consortium to Establish a Registry for Alzheimer's disease (CERAD), the animal fluency test (AFT), the digit symbol substitution test (DSST), and the global cognition score. The lowest non-survey weighted quartile for each cognitive test was defined as low cognitive performance. Simple and multiple regression analyses were performed. Moderate and severe periodontitis were significantly associated with a low DSST performance (OR=1.66 and OR=2.97, respectively). Each millimetre increase in mean CAL was associated with a lower AFT (OR=1.44), DSST (OR=1.86), and global cognition (OR=1.50) performance. The findings of the present study suggest the existence of an independent association between periodontitis and low cognitive performance among older adults (≥60 years old).

The relationship between mushroom consumption and cognitive performance among middle-aged and older adults: a cross-sectional study.

Objectives: Bioactive compounds in mushrooms may protect the brain from neurodegeneration by inhibiting the production of amyloid-β and playing an antioxidant role. This study aimed at examining the associations of mushroom consumption with cognitive function and mild cognitive impairment (MCI) among middle-aged and older adults in China. Design: A cross-sectional study. Setting and participants: This study was conducted in seven cities in China and included 2203 middle-aged and older adults. Methods: Data on mushroom consumption were collected using a semi-quantitative food frequency questionnaire. Cognitive function was evaluated by the Auditory Verbal Learning Test (AVLT), Verbal Fluency Test (VFT), Digit Symbol Substitution Test (DSST), and Trail Making Test-B (TMT-B). The composite z score was used to reflect global cognition. MCI was determined according to the Petersen criteria. Multiple linear regression and logistic regression were used to examine the relationship between mushroom consumption and cognitive performance. Results: This study included 2203 participants aged 55 years and above (mean age = 63.43 years). After controlling demographic characteristics, lifestyle factors, other dietary factors, and history of chronic disease, higher mushroom consumption was associated with better global cognition. Compared to the lowest quartile (Q1, 0-4.00 g day-1), the βs (95% confidence intervals, 95% CIs) were 0.10 (0.03, 0.18) for Q2 (4.01-10.42 g day-1), 0.13 (0.06, 0.20) for Q3 (10.43-20.84 g day-1), and 0.13 (0.06, 0.20) for Q4 (>20.84 g day-1). The higher mushroom consumption was positively related to better performance in DSST and TMT-B (P-values < 0.05). A 10 g day-1 increment in mushroom consumption was related to 12% lower odds of MCI (odds ratio = 0.88, 95% CI: 0.80-0.97). Conclusions: Higher mushroom consumption was positively related to better cognitive function and associated with lower odds of MCI. Further studies are needed to replicate our findings in other populations and determine the underlying mechanisms.

Validation of a digit symbol substitution test for use in supervised and unsupervised assessment in mild Alzheimer’s disease

ABSTRACT Introduction The Digit-Symbol-Substitution Test (DSST) is used widely in neuropsychological investigations of Alzheimer’s Disease (AD). A computerized version of this paradigm, the DSST-Meds, utilizes medicine-date pairings and has been developed for administration in both supervised and unsupervised environments. This study determined the utility and validity of the DSST-Meds for measuring cognitive dysfunction in early AD. Method Performance on the DSST-Meds was compared to performance on the WAIS Coding test, and a computerized digit symbol coding test (DSST-Symbols). The first study compared supervised performance on the three DSSTs versions in cognitively unimpaired (CU) adults (n = 104). The second compared supervised DSST performance between CU (n = 60) and mild-symptomatic AD (mild-AD, n = 79) groups. The third study compared performance on the DSST-Meds between unsupervised (n= 621) and supervised settings. Results In Study 1, DSST-Meds accuracy showed high correlations with the DSST-Symbols accuracy (r = 0.81) and WAIS-Coding accuracy (r = 0.68). In Study 2, when compared to CU adults, the mild-AD group showed lower accuracy on all three DSSTs (Cohen’s d ranging between 1.39 and 2.56) and DSST-Meds accuracy was correlated moderately with Mini-Mental State Examination scores (r = 0.44, p < .001). Study 3 observed no difference in DSST-meds accuracy between supervised and unsupervised administrations. Conclusion The DSST-Meds showed good construct and criterion validity when used in both supervised and unsupervised contexts and provided a strong foundation to investigate the utility of the DSST in groups with low familiarity to neuropsychological assessment.

Relationships between urinary metals concentrations and cognitive performance among U.S. older people in NHANES 2011-2014.

BackgroundEpidemiological evidence on Urine metals and cognitive impairment in older individuals is sparse and limited. The goal of this study was to analyze if there was a link between urinary metal levels and cognitive performance in U.S. people aged 60 and up.MethodsThe National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. Memory function was quantified using the following methods: Established Consortium for Word Learning in Alzheimer's Disease (CERAD-WL) (immediate learning and recall and delayed recall), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). An inductively coupled plasma mass spectrometry (ICP-MS) was used to estimate urine metal concentrations. The connection of Urine metals level with cognitive function was investigated employing binary logistic regression and restricted cubic spline models.ResultsA total of 840 participants aged 60 years and over were enrolled in this study. After controlling for confounders, the association between cadmium, barium, cobalt, cesium, manganese, and thallium and poor cognitive performance showed significance in multiple logistic regression compared to the lowest quartile of metals. In the DSST test, the weighted multivariate adjusted ORs (95% CI) for cadmium in the highest quartile, barium and cesium in the third quartile were 2.444 (1.310–4.560), 0.412 (0.180–0.942) and 0.440 (0.198–0.979), respectively. There were L-shaped associations between urine cesium, barium, or manganese and low cognitive performance in DSST. Urine lead, molybdenum and uranium did not show any significant relationships with cognitive impairment, respectively, compared to the respective lowest quartile concentrations.ConclusionThe levels of barium (Ba), cobalt (Co), cesium (Cs), manganese (Mn), and thallium (Tl) in urine were found to be negatively related to the prevalence of impaired cognitive performance in our cross-sectional investigation. Higher cadmium (Cd) levels were associated with cognitive impairment.

Relationship between urinary dichlorophenols and cognitive function among people over 60 years old from NHANES.

Studies have shown that exposure to dichlorophenols (DCPs) and their precursors might have potential neurotoxicity, which may be related to low cognitive function, but there are few large-scale, representative population data to explore the association between DCP exposure and cognitive function. We aimed to examine the relationship between urinary DCPs and cognitive function in the US older people. A total of 952 participants ≥ 60 years old from the National Health and Nutrition Examination Survey (NHANES) in two cycles (2011-2014) were enrolled. The Consortium to Establish a Registry for Alzheimer's disease Word Learning subtest (CERAD W-L), the Animal Fluency test (AFT), and the Digit Symbol Substitution test (DSST) were used to assess cognition. Multivariate logistic regression and restricted cubic spline (RCS) were used to evaluate the relationship between DCP exposure and cognitive function. A positive association between 2,5-DCP and the risk of bad performance of DSST was observed (P for trend = 0.024) after adjusting for the covariates. Compared to the lowest quartile, OR of DSST for the highest quartile of 2,5-DCP was 1.72 (95%CI:1.03-2.87, P = 0.039). There were no significant associations between DCPs and the other tests. The RCS plot showed an inverted J-shaped relationship between 2,5-DCP, 2,4-DCP, and the DSST score. The inflection points for the curves were found at 1.531 μg/L and 0.230 μg/L, respectively. On the right side of the inflection points, the DSST score dropped sharply. In subgroup analysis, those under 70 years old, smokers, and alcohol drinkers had a higher risk of bad performance in DSST when exposed to 2,5-DCP. The higher concentration of urinary DCPs is associated with a lower score of DSST in the US older people.

0125 Fluid Intelligence Does Not Mediate Cognitive Throughput Deficits during Total Sleep Deprivation

Abstract Introduction The Digit Symbol Substitution Test (DSST) has been used in sleep research to measure slowing of cognitive throughput. The task shows large aptitude differences in baseline performance and substantial inter-individual differences in vulnerability to performance deficits during total sleep deprivation (TSD). Fluid intelligence (Gf) is generally positively related to processing speed. However, DSST performance is typically found to be independent of Gf. The possible interaction of sleep loss with Gf on performance remains to be examined. Methods N=56 healthy adults (ages 22–37, 29 females) completed a 4-day/3-night in-laboratory study and were randomly assigned (2:1 ratio) to a TSD (n=37) or control (n=19) condition. Sleep opportunities were from 22:00–08:00 on the first (baseline) and last (recovery) night for the TSD group and on all three nights for the control group. Subjects completed a 4min, computerized DSST twice on day 2 (baseline) and twice on day 3 (TSD or control). At baseline, subjects also completed the Shipley Institute of Living Scale (SILS). The abstraction score was used to categorize fluid intelligence (Gf) as relatively high (≥34, n=36) or low (&amp;lt;34, n=20). Mean DSST throughput (number of correct responses in the 4min task) was analyzed using mixed-effects ANOVA with fixed effects for day (2, 3), condition (TSD, control), and their interaction, with and without Gf category (high, low) as a covariate. Results As expected, DSST throughput was significantly reduced by TSD (day by condition interaction: F[1,166]=27.99, p&amp;lt;0.001). Adding Gf had no effect on the day by condition interaction, and Gf category was not significant as a covariate (F[1,166]=1.67, p=0.20). Conclusion Our results indicate that the Gf measure from the SILS does not capture the aspects of cognition that are influenced by TSD and that lead to a decline in DSST throughput. This is consistent with findings that while the DSST has high sensitivity for cognitive dysfunction in clinical settings, it has low specificity in identifying components of cognition responsible for dysfunction. Support (If Any) ONR N00014-13-1-0302 and PRMRP W81XWH-20-1-0442.

Boswellia serrata extract shows cognitive benefits in a double-blind, randomized, placebo-controlled pilot clinical trial in individuals who suffered traumatic brain injury

ABSTRACT Background: Traumatic brain injury (TBI) is a major cause of death and disability. TBI can result in neuropsychiatric and cognitive problems as well as neurodegenerative pathologies that can appear right after or develop and persist years after injury. Method: We conducted a double-blind, randomized, placebo-controlled clinical trial on patients who suffered from TBI three months to three years ago. The patients were randomized to placebo (n = 34) or K-Vie™ group (n = 46) for a treatment period of 3 months. The main primary outcomes include cognitive assessment in the Rey Auditory Verbal Learning Test-Recognition Test (RAVLT), Wechsler adult intelligence Digit Symbol Substitution Test (DSST) and trail-making test part B (TMT-B). Assessments were performed at baseline and at the month 3 follow-up visit. Linear mixed models were carried out to evaluate cognitive changes from baseline across all cognitive assessment tests. Result: The current study showed significant (p < 0.05) improvement in cognitive function of patients who were given K-Vie™ compared with placebo across the RAVLT, DSST and TMT-B performance assessments. A larger cohort would be beneficial to further confirm the clinical utility of K-Vie™ and assess its effects in acute phases of TBI.

Oxidative Stress Mediates the Association Between Dietary Fat Intake and Cognition in US Older Adults

OBJECTIVEDietary fat intake was considered as a modifiable factor influencing cognitive performance. The objective was to 1) examine the associations between different types of dietary fat intakes and cognitive outcomes among elder adults (≥60 years old); 2) assess whether peripheral oxidative stress and antioxidant biomarkers are potential mediators of dietary fat intake and cognitive impairment relationship. METHODSUsing data from National Health and Nutrition Examination Survey 2011-2014, total fat, saturated fatty acid (SFAT), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), cholesterol, ω-3 and ω-6 fatty acids were used to evaluate dietary fat intakes. Cognitive outcomes were assessed by word learning and recall modules from the consortium to establish a registry for Alzheimer's Disease (CERAD), animal fluency test, and digit symbol substitution test (DSST). Antioxidant biomarkers were assessed by gamma glutamyl transpeptidase (GGT), bilirubin, uric acid, and vitamin D levels. Linear regression models and causal mediation analysis were applied to quantify the associations. RESULTSA total of 2,253 elder adults were included in the data analyses. Dietary intake of PUFA and ω-6 fatty acid were positively associated with DSST [β (95% CI): 0.06 (0.01,0.10), t statistic = 2.39, df= 2238, p = 0.02; β (95% CI): 0.06 (0.01,0.11), t statistic = 2.54, df= 2238, p = 0.01, respectively]. GGT was negatively associated with DSST [β (95% CI): -0.04 (-0.07, -0.01), t statistic = -2.73, df= 2239, p = 0.01], whereas uric acid was positively associated with CERAD total score [β (95% CI): 0.04 (0.00,0.08), t statistic = 2.03, df= 2233, p = 0.04]. The association between dietary intake of PUFA/ω -3/ω -6 and DSST performance was partially mediated by GGT level. CONCLUSIONOur findings support that PUFAs in dietary sources were associated with lower risks for cognitive impairment partially via lowering oxidative stress. Dietary PUFA supplementation may potentially reduce risk of cognitive impairment via antioxidative mechanism.

Individual and Combined Associations of Glucose Metabolic ComponentsWith Cognitive Function Modified by Obesity.

AimWe aimed to detect the individual and combined effect of glucose metabolic components on cognitive function in particular domains among older adults.MethodsData of 2,925 adults aged over 60 years from the 2011 to 2014 National Health and Nutrition Examination Survey were analyzed. Individuals’ cognitive function was evaluated using the Digit Symbol Substitution Test (DSST), the Animal Fluency Test (AF), the Consortium to Establish a Registry for Alzheimer’s Disease Immediate Recall (CERAD-IR), and CERAD Delayed Recall (CERAD-DR). Participants’ glucose metabolic health status was determined based on fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and 2-h postload glucose. Linear regression models were used to delineate the associations of cognitive function with individual glucose metabolic component and with metformin use. Logistic regression models were performed to evaluate the associations of cognition with the number of glucose metabolic risk components.ResultsCERAD-IR was significantly associated with HOMA-IR and insulin. HbA1c was related to all the cognitive tests except AF. Among participants without obesity, HOMA-IR and insulin were both negatively associated with CERAD-IR and CERAD-DR. Odds of scoring low in DSST increased with the number of glucose metabolic risk components (odds ratio 1.94, 95% confidence interval [CI] 1.26 to 2.98). Metformin use was associated with better performance in DSST among diabetes patients (β = 4.184, 95% CI 1.655 to 6.713).ConclusionsOur findings support the associations of insulin resistance and glycemic level with cognitive function in key domains, especially among adults without obesity. There is a positive association between metformin use and cognition.

Cognitive throughput and working memory raw scores consistently differentiate resilient and vulnerable groups to sleep loss.

Substantial individual differences exist in cognitive deficits due to sleep restriction (SR) and total sleep deprivation (TSD), with various methods used to define such neurobehavioral differences. We comprehensively compared numerous methods for defining cognitive throughput and working memory resiliency and vulnerability. Forty-one adults participated in a 13-day experiment: 2 baseline, 5 SR, 4 recovery, and one 36 h TSD night. The Digit Symbol Substitution Test (DSST) and Digit Span Test (DS) were administered every 2 h. Three approaches (Raw Score [average SR performance], Change from Baseline [average SR minus average baseline performance], and Variance [intraindividual variance of SR performance]), and six thresholds (±1 standard deviation, and the best/worst performing 12.5%, 20%, 25%, 33%, 50%) classified Resilient/Vulnerable groups. Kendall's tau-b correlations compared the group categorizations' concordance within and between DSST number correct and DS total number correct. Bias-corrected and accelerated bootstrapped t-tests compared group performance. . The approaches generally did not categorize the same participants into Resilient/Vulnerable groups within or between measures. The Resilient groups categorized by the Raw Score approach had significantly better DSST and DS performance across all thresholds on all study days, while the Resilient groups categorized by the Change from Baseline approach had significantly better DSST and DS performance for several thresholds on most study days. By contrast, the Variance approach showed no significant DSST and DS performance group differences. Various approaches to define cognitive throughput and working memory resilience/vulnerability to sleep loss are not synonymous. The Raw Score approach can be reliably used to differentiate resilient and vulnerable groups using DSST and DS performance during sleep loss.

Acute and residual mood and cognitive performance of young adults following smoked cannabis

ObjectivesTo examine acute and residual mood and cognitive performance in young adult regular cannabis users following smoked cannabis. MethodsNinety-one healthy young adults completed this double-blind, placebo-controlled, parallel-groups study. Participants were randomized to receive active (12.5% THC) or placebo cannabis with a 2:1 allocation ratio, and mood [Profile of Mood States (POMS)] and cognitive performance [Hopkins Verbal Learning Test – Revised (HVLT-R), Digit Symbol Substitution Test (DSST), Continuous Performance Test (CPT), grooved pegboard (GPB)] were assessed before and 1, 24, and 48 (h) after smoking cannabis ad libitum. High and Low THC groups were based on blood THC concentrations. ResultsOne hour after smoking cannabis, compared to Placebo, in both the High and Low THC groups, there were increases in POMS Arousal and Positive Mood, and in the High THC group only, increases in Confusion, Friendliness, and Elation, and a decrease in Fatigue. Increases in Friendliness and Elation in the High THC group remained significant for 24 h. The only significant acute effect of cannabis on cognition was a decrease in the percent of words retained in the HVLT-R in the High THC group compared to Placebo (mean difference = 15.8%, 95% CI = 3.6–28.0%, p = 0.006). Unexpectedly, compared to Placebo, both the High and Low THC groups improved in DSST performance at 48 h (p ≤ 0.016). ConclusionsUnder the present experimental conditions, in young regular cannabis users, smoking cannabis ad libitum had significant effects on mood, some of which persisted 24 h later, yet minimal effects on cognition, and no evidence of residual cognitive impairment.