Digit Symbol Substitution Test Research Articles

Association between Life's Essential 8 and cognitive function among older adults in the United States

The American Heart Association (AHA) recently redefined cardiovascular health (CVH) with the introduction of Life's Essential 8 (LE8), which encompasses eight areas (diet, physical activity, nicotine exposure, sleep duration body mass index, non-HDL cholesterol, blood glucose, and blood pressure). This study aimed to explore the relationships between both the aggregate and individual CVH metrics, as defined by Life's Essential 8, and cognitive function in older adults in the United States. This cross-sectional, population-based study analyzed data from the National Health and Nutrition Examination Survey conducted between 2011 and 2014, focusing on individuals aged 60 years and older. CVH was categorized as low (0–49), moderate (50–79), or high (80–100). Cognitive function was assessed through the CERAD tests, Animal Fluency test, and Digit Symbol Substitution test. Multivariable logistic models and restricted cubic spline models were employed to investigate these associations. This study included a total of 2279 older adults in the United States. Only 11% of adults achieved a high total CVH score, while 12% had a low score. After further adjustment for potential confounding factors, higher LE8 scores were significantly associated with higher scores on CERAD: delayed recall score (0.02[0.01, 0.03]; P < 0.001), CERAD: total score (3 recall trials) (0.04[0.02, 0.06]; P < 0.001), animal fluency: total score (0.09[0.05, 0.12]; P < 0.001), and digit symbol: score (0.29[0.18, 0.41]; P < 0.001), demonstrating a linear dose–response relationship. Similar patterns were also observed in the associations between health behavior and health factor scores with cognitive function tests. LE8 scores exhibited positive linear associations with cognitive function. Maintaining better levels of CVH may be associated with higher levels of cognitive function in older Americans, but further research is needed to confirm the causal and temporal relationships between LE8 and cognitive function.

Increased Odds of Cognitive Impairment in Adults with Depressive Symptoms and Antidepressant Use.

The relationship between antidepressant use and class with cognition in depression is unclear. This study aimed to evaluate the association of cognition with depressive symptoms and antidepressant use (class, duration, number). Data from the National Health and Nutrition Examination Survey were examined for cognitive function through various tests and memory issues through the Medical Conditions questionnaire. Depressive symptoms were assessed using the Patient Health Questionnaire-9. A total of 2867 participants were included. Participants with depressive symptoms had significantly higher odds of cognitive impairment (CI) on the animal fluency test (aOR=1.89, 95% CI=1.30, 2.73, P=0.002) and Digit Symbol Substitution test (aOR=2.58, 95% CI=1.34, 4.9, P=0.007), as well as subjective memory issues (aOR=7.25, 95% CI=4.26, 12.32, P<0.001) than those without depression. There were no statistically significant associations between any of the CI categories and depressive symptoms treated with an antidepressant and antidepressant use duration. Participants who were using more than one antidepressant had significantly higher odds of subjective memory issues than those who were using one antidepressant. Specifically, users of atypical antidepressants, selective serotonin reuptake inhibitors, or tricyclic antidepressants (TCAs) had significantly higher odds of subjective memory issues in comparison to no antidepressants, with TCAs showing the largest odds (aOR=4.21, 95% CI=1.19, 14.86, P=0.028). This study highlights the relationship between depressive symptoms, antidepressant use, and CI. Future studies should further evaluate the mechanism underlying this phenomenon.

Application of a new definition of sarcopenic obesity in middle-aged and older adults and association with cognitive function: Findings from the National Health and Nutrition Examination Survey 1999–2002

Background & aimsThe role of sarcopenic obesity (SO) in impaired cognitive function has been investigated in several observational studies, but results have been mixed. This study applied the proposed European Society for Clinical Nutrition and Metabolism (ESPEN)-European Association for the Study of Obesity (EASO) definition of SO to a representative population aged ≥50 years to identify the association between SO and cognitive function. MethodsData from the National Health and Nutrition Examination Survey 1999-2002 waves were used. At the screening phase, body mass index or waist circumference were used to evaluate obesity; sarcopenia was identified using the SARC-F questionnaire. At the diagnostic phase I and II, sarcopenia was assessed using knee extensor isometric strength and appendicular lean mass, and fat mass percent was used to assess obesity. Cognitive function in older participants (60-85 years) was assessed using the Digit Symbol Substitution Test. A self-reported memory question was used in middle-aged individuals (50-59 years). ResultsThe sample included 2,356 participants (men, 44.7%). The prevalence of SO was 32.3%, 21.2% and 15.0% at the screening, diagnosis phase I, and diagnosis phase II, respectively. Significant associations between SO and cognitive impairment were observed in individuals aged 60-85 at diagnosis phase I (OR: 2.3, 95%CI 1.4-3.8, P=0.007) and phase II (OR: 2.7, 95%CI 1.5-4.9, P=0.004). ConclusionThe new ESPEN-EASO definition of SO identified a high prevalence of SO cases. A significant association between SO and poor cognitive function in older individuals was observed.

Differential neuropsychiatric associations of plasma biomarkers in older adults with major depression and subjective cognitive decline

Older adults with major depressive disorder (MDD) or early cognitive decline during the subjective cognitive decline (SCD) stage may exhibit neuropsychiatric symptoms such as anxiety, depression, and subtle cognitive impairment. The clinicopathological features and biological mechanisms of MDD differ from those of SCD among older adults; these conditions thus require different treatment strategies. This study enrolled 82 participants above 50 years old with normal cognitive levels from the communities to examine biomarker–behavior correlations between MDD (n = 23) and SCD (n = 23) relative to a normal control (NC) group (n = 36). Multidomain assessments were performed for all participants, including immunomagnetic reduction tests to detect plasma beta-amyloid (Aβ), total tau (Tau), phosphorylated tau-181 (p-Tau181), neurofilament light chain, and glial fibrillary acidic protein (GFAP). This study observed that depressive symptoms in MDD were associated with amyloid pathology (plasma Aβ40 vs. HADS-D: R = 0.45, p = 0.031; Aβ42/Aβ40 vs. HADS-D: R = −0.47, p = 0.024), which was not observed in the NC (group difference p < 0.05). Moreover, cognitive decline in MDD was distinguished by a mixed neurodegenerative process involving amyloid (plasma Aβ42 vs. facial memory test: R = 0.48, p = 0.025), tau (Tau/Aβ42 vs. digit symbol substitution test (DSST): R = −0.53, p = 0.01), and astrocytic injury (plasma GFAP vs. Montreal cognitive assessment score: R = −0.44, p = 0.038; plasma GFAP vs. DSST: R = −0.52, p = 0.014), findings that did not apply to the NC (group difference p < 0.05). Moreover, this study revealed different biomarker–behavior correlations between individuals with SCD and the NC. Compared with the NC, cognitive decline in the SCD group might be unrelated to amyloid pathology and instead might be early manifestations of tau pathology. This study underscores the difference in clinicopathological features between MDD and SCD among older adults, which differ from those of the NC. These findings enhance our understanding of the mechanisms underlying MDD and SCD in older individuals.

Healthy Dietary Pattern Improves Cognitive Function in Elderly Persons With Periodontitis: A Cross-Sectional Study of NHANES

AimCognitive decline is more prevalent in elderly persons with periodontitis. Greater adherence to Healthy Eating Index (HEI)-2015 has been reported to improve cognitive function in the elderly population. However, whether the benefits of HEI-2015 on cognitive function apply to elderly patients with periodontitis remains unknown. MethodsThis is a cross-sectional study based on the National Health and Nutrition Examination Survey (NHANES). The data were extracted from database 2011–2014. Cognitive function was measured through the Consortium to Establish a Registry for Alzheimer's Disease battery for immediate recall (CERAD-WL) and delayed recall (CERAD-DR), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The data of HEI-2015 were acquired from 24-hour dietary recalls. Weighted linear regression models were performed to investigate the association between HEI-2015 and cognitive function in elderly patients with periodontitis. The associations were further investigated in subgroups of sex, cardiovascular disease status, and depression status. ResultsA total of 1862 participants were included, and 1223 of them had periodontitis. Periodontitis was negatively associated with cognitive function (β = −0.45; 95% confidence interval [CI], −0.87 to −0.03). No statistically significant relationship was observed between HEI-2015 and cognitive function (β = 0.33; 95% CI, −0.02 to 0.69). Low HEI-2015 score was associated with high odds of cognitive decline in patients with periodontitis (β = −0.73; 95% CI, −1.25 to −0.21; P for trend = .01). Higher HEI-2015 was related to the lower incidence of cognitive function decline in patients with periodontitis who were female (β = −0.53; 95% CI, −1.03 to −0.03), had a socioeconomic status from 0 to 3 (β = −0.55; 95% CI, −1.00 to −0.09), did not have cardiovascular disease (β = −0.60; 95% CI, −1.14 to −0.05), and did not have depression (β = −0.57; 95% CI, −1.11 to −0.03). ConclusionsGreater HEI-2015 adherence may improve cognitive function amongst elderly patients with periodontitis. Further studies were needed to investigate this association in elderly persons with periodontitis.

Waist-to-weight index and cognitive impairment: Understanding the link through depression mediation in the NHANES

BackgroundIn recent years, several studies have suggested that obesity may play an important role in cognitive impairment. Individuals with cognitive impairment often also exhibit depressive symptoms. This study aimed to explore the association between obesity and cognitive impairment and to elucidate the mediating role of depressive symptoms in this association. MethodsOlder participants in the U.S. were examined in this cross-sectional study (n = 2391). The WWI was computed as follows: WWI = waist circumference/square root of body weight. The Consortium for Alzheimer's Disease Word Learning (CERAD-WL), the Animal Fluency Test (AFT), and the Digit Symbol Substitution Test (DSST) were used to evaluate cognitive function. Depression symptoms were evaluated with the Patient Health Questionnaire 9 (PHQ-9). Subgroup analysis and multiple logistic regression analysis were utilized to investigate the relationships between the WWI and depressive symptoms and cognitive decline. Threshold effects were computed using a two-segment linear regression model. To ascertain whether depression mediates the relationship between the WWI and cognitive impairment, mediation analysis was also employed. ResultsA total of 2391 participants were included, 33.29 % of whom had cognitive impairment. There was a significant correlation between the WWI and depressive symptoms and cognitive function (P < 0.05). With increasing WWI quartiles, the prevalence of cognitive impairment increased (Q1: 27.09 %, Q2: 33.00 %, Q3: 31.44 %, Q4: 41.64 %). It was highly likely that the WWI and cognitive impairment were positively correlated (OR = 1.34, 95 % CI = 1.13, 1.59), and this link was steady across all subgroups (P for trend >0.05). A nonlinear curve with an inflection point of 10.71 connected the WWI and cognitive deterioration. A significant correlation was found between the WWI and cognitive impairment on the left side of the inflection point (OR = 3.58, 95 % CI = 1.57, 8.15). With a 5.4 % mediation rate, mediation analysis revealed that depressive symptoms mediated the relationship between cognitive impairment and the WWI. ConclusionsThere was a positive association between the WWI and the incidence of cognitive impairment in older Americans. Among other factors, depressive symptoms slightly mediated the association between the WWI and cognitive impairment. However, large-scale prospective studies are still needed to analyse the interactions between the three factors in depth.

Independent and joint associations between urinary polycyclic aromatic hydrocarbon metabolites and cognitive function in older adults in the United States.

Polycyclic aromatic hydrocarbons (PAHs), as organic pollutants widely present in daily environments, have been shown by existing epidemiological studies to be significantly associated with deficits in learning and memory functions in children and adults. However, the association between exposure to PAHs and cognitive function in older adults remains unclear. Additionally, existing related studies have only assessed the association between individual PAH exposures and cognitive assessments, overlooking the risks posed by mixed exposures. This study aims to use three statistical models to investigate the individual and overall effects of mixed PAH exposures on the cognition of older adults in the United States. The study cohort was obtained from the NHANES database, which included individuals aged 60 and older from 2011 to 2014. Weighted generalized linear models (GLM), weighted quantile sum (WQS) models, and Bayesian kernel machine regression (BKMR) models were utilized to evaluate the connections between urinary PAH metabolites and the standardized Z-scores of four cognitive tests: Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). Our analysis involved 899 individuals aged 60 and above. In the fully adjusted GLM, 2-hydroxynaphthalene (2-OHNa), 3-hydroxyfluorene (3-OHFlu), and 2-hydroxyfluorene (2-OHFlu) demonstrated negative associations with DSST Z-scores. In the WQS model, six urinary PAH metabolites were negatively linked to AFT Z-scores (β (95% confidence intervals [CI]): -0.120 (-0.208, -0.033), p = 0.007) and DSST Z-scores (β (95% CI): -0.182 (-0.262, -0.103), p < 0.001). In both assessments, 2-OHNa exerted the greatest influence among the urinary PAH metabolites. In the BKMR model, there was an overall negative correlation between urinary PAH metabolites and AFT and DSST Z-scores when the concentration was within the 25th to 75th percentile, where 2-OHNa dominated the main effect of the mixture. The WQS and BKMR models were adjusted for all covariates. Increased concentrations of urinary PAH metabolites are associated with cognitive decline in older adults, mainly on language ability, executive function, sustained attention, working memory, and information processing speed, with 2-OHNa playing a major effect.

Effect of oxygen supplementation on cognitive performance among HEMS providers after acute exposure to altitude: the HEMS II randomized clinical trial

ImportanceEmergency medical services (EMS) providers transiently ascend to high altitude for primary missions and secondary transports in mountainous areas in helicopters that are unpressurised and do not have facilities for oxygen supplementation. The decrease in cerebral oxygen saturation can lead to impairment in attention and reaction time as well as in quality of care during acute exposure to altitude.ObjectiveThe primary aim of the current study was to investigate the effect of oxygen supplementation on cognitive performance in Helicopter EMS (HEMS) providers during acute exposure to altitude.Design, setting, and participantsThis interventional, randomized, controlled, double-blind, cross-over clinical trial was conducted in October 2021. Each trial used a simulated altitude scenario equivalent to 4000 m, in which volunteers were exposed to hypobaric hypoxia with a constant rate of ascent of 4 m/s in an environmental chamber under controlled, replicable, and safe conditions. Trials could be voluntarily terminated at any time. Inclusion criteria were being members of emergency medical services and search and rescue services with an age between 18 and 60 years and an American Society of Anesthesiologists physical status class I.ExposuresEach participant conducted 2 trials, one in which they were exposed to altitude with oxygen supplementation (intervention trial) and the other in which they were exposed to altitude with ambient air supplementation (control trial).Main outcomes and measuresMeasurements included peripheral oxygen saturation (SpO2), cerebral oxygenation (ScO2), breathing and heart rates, Psychomotor Vigilance Test (PVT), Digit-Symbol Substitution Test (DSST), n-Back test (2-BACK), the Grooved Pegboard test, and questionnaires on subjective performance, stress, workload, and positive and negative affect. Paired t-tests were used to compare conditions (intervention vs. control). Data were further analyzed using generalized estimating equations (GEE).ResultsA total of 36 volunteers (30 men; mean [SD] age, 36 [9] years; mean [SD] education, 17 [4] years) were exposed to the intervention and control trials. The intervention trials, compared with the control trials, had higher values of SpO2 (mean [SD], 97.9 [1.6] % vs. 86 [2.3] %, t-test, p = 0.004) and ScO2 (mean [SD], 69.9 [5.8] % vs. 62.1 [5.2] %, paired t-test, p = 0.004). The intervention trials compared with the control trials had a shorter reaction time (RT) on the PVT after 5 min (mean [SD], 277.8 [16.7] ms vs. 282.5 [15.3] ms, paired t-test, p = 0.006) and after 30 min (mean [SD], 276.9 [17.7] ms vs. 280.7 [15.0] ms, paired t-test, p = 0.054) at altitude. While controlling for other variables, there was a RT increase of 0.37 ms for each % of SpO2 decrease. The intervention trials showed significantly higher values for DSST number of correct responses (with a difference of mean [SD], 1.2 [3.2], paired t-test, p = 0.035). Variables in the intervention trials were otherwise similar to those in the control trials for DSST number of incorrect responses, 2-BACK, and the Grooved Pegboard test.Conclusions and relevanceThis randomized clinical trial found that oxygen supplementation improves cognitive performance among HEMS providers during acute exposure to 4000 m altitude. The use of oxygen supplementation may allow to maintain attention and timely reaction in HEMS providers. The impact of repeated altitude ascents on the same day, sleep-deprivation, and additional stressors should be investigated.Trial registration NCT05073406, ClinicalTrials.gov trial registration.

Non-linear association of liver enzymes with cognitive performance in the elderly: A cross-sectional study.

Although liver metabolic dysfunction has been found to potentially elevate susceptibility to cognitive impairment and dementia, there is still insufficient evidence to explore the non-linear association of liver enzymes with cognitive performance. Therefore, we aimed to elucidate the non-linear relationship between liver enzymes and cognitive performance. In this cross-sectional study, 2764 individuals aged ≥ 60 who participated in the National Health and Nutrition Survey (NHANES) between 2011 and 2014 were included. The primary data comprised liver enzyme levels (alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), AST/ALT ratio, and gamma-glutamyl transferase (GGT)), and cognitive performance was the major measured outcome. The associations were analyzed using weighted multivariate logistic regression, subgroup analysis, a generalized additive model, smooth fitting curves, and threshold effects. The results of the fully adjusted model indicated that ALP was negatively associated with the animal fluency test (AFT) score (OR = 1.48, 95% CI: 1.11-1.98), whereas ALT demonstrated a positive association with the consortium to establish a registry for Alzheimer's disease (CERAD) test score (OR = 0.72, 95% CI: 0.53-0.97). Additionally, the AST/ALT ratio was negatively associated with the global cognitive test (OR = 2.39, 95% CI: 1.53-3.73), CERAD (OR = 2.61, 95% CI: 1.77-3.84), and digit symbol substitution test (DSST) scores (OR = 2.51, 95% CI: 1.57-4.02). GGT was also negatively associated with the AFT score (OR = 1.16, 95% CI: 1.01-1.33) in unadjusted model. A non-linear relationship was observed between liver enzymes and the risk of cognitive impairment as assessed by the global cognitive test. Specifically, when ALP > 60 U/L, 0.77 < AST/ALT < 1.76, and 25 < GGT < 94 U/L, higher liver enzyme levels were significantly associated with an elevated cognitive impairment risk, while a lower cognitive impairment risk when ALT level was > 17 U/L. There is a non-linear relationship between liver enzymes and cognitive performance, indicating that liver enzyme levels should be maintained within a certain level to mitigate the risk of cognitive impairment.

Exposome-wide association study of cognition among older adults in the National Health and Nutrition Examination Survey.

Cognitive impairment among older adults is a growing public health challenge and environmental chemicals may be modifiable risk factors. A wide array of chemicals has not yet been tested for association with cognition in an environment-wide association framework. In the US National Health and Nutrition Examination Survey (NHANES) 1999-2000 and 2011-2014 cross-sectional cycles, cognition was assessed using the Digit Symbol Substitution Test (DSST, scores 0-117) among participants aged 60 years and older. Concentrations of environmental chemicals measured in blood or urine were log2 transformed and standardized. Chemicals with at least 50% of measures above the lower limit of detection were included (nchemicals=147, nclasses=14). We tested for associations between chemical concentrations and cognition using parallel survey-weighted multivariable linear regression models adjusted for age, sex, race/ethnicity, education, smoking status, fish consumption, cycle year, urinary creatinine, and cotinine. Participants with at least one chemical measurement (n=4,982) were mean age 69.8 years, 55.0% female, 78.2% non-Hispanic White, and 77.0% at least high school educated. The mean DSST score was 50.4 (standard deviation (SD)=17.4). In adjusted analyses, 5 of 147 exposures were associated with DSST at p-value<0.01. Notably, a SD increase in log2-scaled cotinine concentration was associated with 2.71 points lower DSST score (95% CI -3.69, -1.73). A SD increase in log2-scaled urinary tungsten concentration was associated with 1.34 points lower DSST score (95% CI -2.11, -0.56). Exposure to environmental chemicals, particularly heavy metals and tobacco smoke, may be modifiable factors for cognition among older adults.

Racialized experience, biomarkers of lead exposure, and later-life cognition: a mediation analysis.

We evaluated the role of the neurotoxicant lead (Pb) in mediating racial disparities in later-life cognition in 1,085 non-Hispanic Black and 2,839 non-Hispanic white participants in NHANES (1999-2002, 2011-2014) 60+ years of age. We operationalized Black race as a marker for the experience of racialization and exposure to systemic racism. We estimated patella bone Pb via predictive models using blood Pb and demographics. Concurrent cognition (processing speed, sustained attention, working memory) was measured by the Digit Symbol Substitution Test (DSST) and a global measure combining four cognitive tests. To obtain the portion mediated, we used regression coefficients (race on Pb * Pb on cognitive score)/(race on cognitive score), adjusting for age, NHANES cycle, and sample weights. Other confounder adjustment (education, poverty income ratio, smoking) was limited to the mediator-outcome (i.e., Pb-cognition) pathway because these factors do not lie upstream of race and so cannot confound associations with race. Pb was estimated to mediate 0.6% of the association between race and global cognition, and 4% of the DSST. Our results suggest that later-life cognitive health disparities may be impacted by avoidable lead exposure driven by environmental injustice, noting that a large proportion of the pathway of systemic racism harming cognition remains.

Acute effects of a simulated quick return on subjective sleepiness, mood, and cognitive performance: A laboratory crossover controlled trial

ABSTRACT Sleep loss due to short time off between shifts has been proposed as a mechanism contributing to impaired functioning in occupational settings. This laboratory crossover trial (ClinicalTrials.gov identifier: NCT05162105, N = 66) compared subjective sleepiness, mood, and cognitive performance on a day shift after an evening shift with only 8 h off between shifts (quick return, QR) to a day shift after another day shift with 16 h off between shifts (control). Results indicated higher subjective sleepiness (Karolinska Sleepiness Scale) during the QR condition compared to the control condition (p < 0.001). No significant differences were found on mood (Positive and Negative Affect Schedule) and cognitive performance (Psychomotor Vigilance- and Digit Symbol Substitution Test) between the conditions. Findings of increased subjective sleepiness corroborate previous field studies. This trial is to our knowledge the first to compare mood and cognitive performance after a QR to a longer shift transition using an experimental design. Future research should explore the effects of accumulated sleep loss associated with QRs (e.g. having several QRs within a short time period) on behavioral outcomes.

Complex decongestive therapy improves finger tapping score in patients with breast cancer-related lymphedema.

Breast cancer-related lymphedema (BCRL) impairs upper limb function and cognitive performance. This study aimed to evaluate the effects of fifteen sessions of complex decongestive therapy (CDT) on fine motor performance and information processing speed in women with BCRL. Thirty-eight women with BCRL (54.97 ± 10.78years) were recruited in the study. Participants either received five times weekly CDT consisting of manual lymphatic drainage, skin care, compression bandaging, and remedial exercises (n = 19) or served as a wait-list control group (n = 19). We used the Finger Tapping Task to assess fine motor performance and the Digit Symbol Substitution Test to assess information processing speed. ANCOVA was performed to analyze the effect of CDT on the dependent variables, adjusting for covariates and baseline values. CDT significantly improved finger tapping score (p < 0.001) compared to the wait-list to the control group, whereas information processing speed did not significantly change (p = 0.673). The findings suggest that CDT is an effective conservative therapeutic approach to improve upper extremity fine motor function in women with BCRL. Future studies are needed to investigate the effect of CDT on different cognitive domains.

Very high high-density lipoprotein cholesterol may be associated with higher risk of cognitive impairment in older adults

BackgroundPrevious studies have shown that high-density lipoprotein cholesterol (HDL-C) levels are positively associated with cognitive function across a range of concentrations. However, recent studies have suggested that very high HDL-C levels may lead to poorer outcomes. Therefore, we aimed to investigate the relationship between different concentrations of HDL-C and cognitive impairment risk.MethodsWe collected data from 3632 participants aged over 60 years from the U.S. National Health and Nutrition Examination Survey (NHANES) between 2011 and 2014 to assess the relationship between HDL-C and cognitive function. Cognitive function was evaluated with the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) test, the animal fluency test (AFT), and the digit symbol substitution test (DSST). We used restricted cubic spline models and logistic regression to examine the association between HDL-C and cognitive function.ResultsA U-shaped was observed between HDL-C and cognitive outcomes, individuals with higher risk in those with both low and very high HDL-C levels compared with those with midrange values. Very high HDL-C levels (≥ 2.50 mmol/L) were associated with increased risk of cognitive impairment (OR = 2.19; 95% CI, 1.12–4.28) compared with those with HDL-C levels in the range of 1.50 to 1.99 mmol/L in older adults after adjustment for confounding factors. Interaction test demonstrated that relationship between very high HDL-C and the risk of cognitive impairment was not changed in different sex and race group (P for interaction > 0.05).ConclusionsVery high HDL-C levels were associated with an increased risk of cognitive impairment. HDL-C may not be a protective factor for maintaining brain health in older adults at very high levels.

Joint and Individual Mitochondrial DNA Variation and Cognitive Outcomes in Black and White Older Adults.

Mitochondrial dysfunction manifests in neurodegenerative diseases and other age-associated disorders. In this study, we examined variation in inherited mitochondrial DNA (mtDNA) sequences in Black and White participants from 2 large aging studies to identify variants related to cognitive function. Participants included self-reported Black and White adults aged ≥70 years in the Lifestyle Interventions and Independence for Elders (LIFE; N = 1319) and Health Aging and Body Composition (Health ABC; N = 788) studies. Cognitive function was measured by the Digit-Symbol Substitution Test (DSST), and the Modified Mini-Mental State Examination (3MSE) at baseline and over follow-up in LIFE (3.6 years) and Health ABC (10 years). We examined the joint effects of multiple variants across 16 functional mitochondrial regions with cognitive function using a sequence kernel association test. Based on these results, we prioritized meta-analysis of common variants in Black and White participants using mixed effects models. A Bonferroni-adjusted p value of <.05 was considered statistically significant. Joint variation in subunits ND1, ND2, and ND5 of Complex I, 12S RNA, and hypervariable region (HVR) were significantly associated with DSST and 3MSE at baseline. In meta-analyses among Black participants, variant m.4216T>C, ND1 was associated with a faster decline in 3MSE, and variant m.462C>T in the HVR was associated with a slower decline in DSST. Variant m.5460G>C, ND2 was associated with slower and m.182C>T in the HVR was associated with faster decline in 3MSE in White participants. Among Black and White adults, oxidative phosphorylation Complex I variants were associated with cognitive function.

Persistent organic pollutants and cognitive decline among middle-aged or older adults in the Hispanic Community Health Study/Study of Latinos

Persistent organic pollutants may negatively impact cognition; however, associations between persistent organic pollutants and changes in cognition among United States Hispanic/Latino adults have not been investigated. Herein, we examined the associations between 33 persistent organic pollutants and cognitive changes among 1837 Hispanic/Latino adults. At baseline (2008–2011; Visit 1), participants provided biospecimens in which we measured levels of 5 persistent pesticides or pesticide metabolites, 4 polybrominated diphenyl ethers and 2,2’,4,4’,5,5’-hexabromobiphenyl, and 24 polychlorinated biphenyls. At Visit 1 and again at Visit 2 (2015–2018), a battery of neurocognitive tests was administered which included the Brief-Spanish English Verbal Learning Test, Word Fluency Test, and Digit Symbol Substitution Test. To estimate the adjusted associations between changes in cognition and each POP, we used linear regression for survey data. Each doubling in plasma levels of polychlorinated biphenyls 146, 178, 194, 199/206, and 209 was associated with steeper declines in global cognition (βs range:-0.053 to −0.061) with stronger associations for the Brief-Spanish English Verbal Learning Test. Persistent organic pollutants, in particular polychlorinated biphenyls, were associated with declines in cognition over 7 years and may be a concern for Hispanic/Latino adults.

Association between dietary riboflavin intake and cognitive decline in older adults: a cross-sectional analysis

ABSTRACT Background Research exploring the link between dietary riboflavin intake and cognitive decline in this demographic is limited. Our aim was to examine the association between riboflavin intake levels and cognitive decline. Methods The National Health and Nutrition Examination Survey (NHANES) data from 2011 to 2014 were utilized in this cross-sectional analysis. The Consortium to Establish a Registry for Alzheimer's Disease test Word Learning delayed recall trial (DR), Digit Symbol Substitution Test (DSST), Animal Fluency Test(AFT) and Z test were used to evaluate cognitive performance. Multivariate logistic regression, restricted cubic spline and subgroup analysis were performed to evaluate the associations between riboflavin intake and cognitive decline. Results The study included a total of 2255 patients, with 47.9% being male. The incidence of cognitive decline was 23.8%. After adjusting for all selected covariates, we found that high riboflavin intake was associated with a lower risk of cognitive impairment in adults in the United States. When riboflavin intake was used as a Categorical variable, compared to those with the lowest intake, the odds ratio (OR) of individuals with the highest riboflavin intake for DR test, AFT test, DSST test and Z test were 0.73 (95% CI: 0.53~1), 0.68(95% CI: 0.49–0.96),0.53(95% CI: 0.37–0.77) and 0.56(95% CI: 0.39–0.8). The study also found an L-shaped association between riboflavin intake and cognitive decline, with an inflection point at approximately 2.984 mg/d. Conclusions Our cross-sectional study in a nationwide sample of American old adults suggests that dietary riboflavin intake was negative associated with cognitive decline.

Renal function as an effect modifier of intensive glucose control in delaying cognitive function decline among individuals with type 2 diabetes: A revisit to the ACCORD MIND trial.

Dysglycaemia accelerates cognitive decline. Intensive glucose control may help delay or prevent cognitive function decline (CFD). We aimed to determine how patient characteristics influence the effect of intensive glucose control [glycated haemoglobin (HbA1c) <6.0%] on delaying CFD in people with type 2 diabetes. In this post-hoc analysis of 2977 type 2 diabetes participants from the ACCORD MIND trial, we applied the causal forest and causal tree algorithms to identify the effect modifier of intensive glucose control in delaying CFD from 68 variables (demographics, disease history, medications, vitals and baseline biomarkers). The exposure was intensive versus standard glucose control (HbA1c <6.0% vs. 7.0%-7.9%). The main outcome was cognitive function changes from baseline to the 40th month follow-up, which were evaluated using the digit symbol substitution test, Rey auditory verbal learning test, mini-mental state examination and Stroop test. We used Cohen's d, a measure of standardized difference, to quantify the effect size of intensive glucose control on delaying CFD. Among all the baseline characteristics, renal function was the most significant effect modifier. Participants with urinary albumin levels <0.4 mg/dl [absolute function change (AFC): 0.51 in mini-mental state examination, 95% confidence interval (CI): 0.04, 0.98, Cohen's d: 0.25] had slower CFD with intensive glucose control. Patients with preserved renal function (estimated glomerular filtration rate between 60 and 90 ml/min/1.73 m2) were associated with small benefits (AFC: 1.28 in Stroop, 95% CI: 0.28, 2.27, Cohen's d: 0.12) when undergoing intensive glucose control. Conversely, participants with an estimated glomerular filtration rate <60 ml/min/1.73 m2 (AFC: -0.57 in the Rey auditory verbal learning test, 95% CI: -1.09, -0.05, Cohen's d: -0.30) exhibited faster CFD when undergoing intensive glucose control. Participants who were <60 years old showed a significant benefit from intensive glucose control in delaying CFD (AFC: 1.08 in the digit symbol substitution test, 95% CI: 0.06, 2.10, Cohen's d: 0.13). All p < .05. Our findings linked renal function with the benefits of intensive glucose control in delaying CFD, informing personalized HbA1c goals for those with diabetes and at risk of CFD.

Impact of food insecurity on cognitive health in older adults: insights from the NHANES 2011-2014 data.

To investigate the relationship between food insecurity and cognitive decline among elderly Americans. Utilizing NHANES 2011-2014 data, we examined cognitive function via the Immediate Recall Test (IRT), Delayed Recall Test (DRT), Animal Fluency Test (AFT), Digit Symbol Substitution Test (DSST) and assessed food security through the US Food Security Survey Module. Multiple regression models were used to adjust for demographic and health variables. Food insecurity demonstrated a significant association with lower cognitive function scores. The effects of food insecurity on cognitive function were moderated by factors such as smoking and alcohol use, indicating a direct influence of food insecurity on cognitive decline. This study underscores the importance of food security for cognitive health in the elderly and advocates for targeted interventions to address nutritional disparities and enhance cognitive functioning in aging populations.

Effectiveness of vortioxetine in elderly patients with major depressive disorder in real-world clinical practice: Results from the RELIEVE study.

Data demonstrating the real-world, long-term effectiveness of vortioxetine in elderly patients with major depressive disorder (MDD) are clinically useful to confirm findings from randomized trials. RELIEVE was a multinational, 24-week, observational, prospective study in outpatients with MDD initiating vortioxetine treatment in routine care settings (NCT03555136). Here, we report data from a subgroup of 130 patients aged ⩾ 65 years. The primary study outcome was changed from baseline in patient functioning assessed using the Sheehan Disability Scale (SDS). Other clinical outcomes included depression severity (Patient Health Questionnaire-9 [PHQ-9] and Clinical Global Impressions-Severity [CGI-S]), cognitive performance (Digit Symbol Substitution Test [DSST]) and symptoms (Perceived Deficits Questionnaire - Depression-5 item [PDQ-D-5]), and health-related quality of life (HRQoL) (EuroQoL 5 Dimensions 5 Levels [EQ-5D-5L]). Clinically meaningful and statistically significant improvements in patient functioning, depressive symptoms, cognitive function, and HRQoL were observed at week 24. Least squares mean SDS, PHQ-9, CGI-S, PDQ-D-5, DSST, and EQ-5D-5L scores improved from baseline by 6.5, 5.7, 1.2, 3.2, 4.4, and 0.11 points, respectively (p < 0.01 for all). Adverse events were observed in 23.1% of patients. Consistent with previous clinical studies of vortioxetine, this study supports the effectiveness and safety of vortioxetine in treating elderly patients with MDD in a real-world setting over a 6-month period. Patients showed clinically relevant and sustained improvements in psychosocial functioning, depressive symptoms, and cognitive function after receiving vortioxetine, which was generally well tolerated. Main study limitations include the open-label study design and lack of a placebo or comparator group.