Measures Of Cognitive Function Research Articles

Risk Factors for Falls and Fall-Related Fractures in Community-Living Older People with Pain: A Prospective Cohort Study.

(1) Background: This prospective study aimed to identify predictors of falls and fall-related fractures in community-dwelling older people with pain; (2) Methods: Participants comprised 389 community-dwelling older people aged 70+ years who had musculoskeletal pain in the neck, back, hip, leg/knee and/or feet. Demographic, anthropometric, balance, mobility, cognitive function, psychological status and physical activity level measures were obtained at baseline. Falls were monitored with monthly falls calendars for 12 months. Logistic regression analyses were performed to identify predictors of falls and fall-related fractures during a 12-month follow-up; (3) Results: Of the 389 participants, 175 (45.0%) and 20 (5.1%) reported falls and fall-related fractures during the 12-month follow-up, respectively. Greater postural sway on foam, more depressive symptoms and lower physical activity levels at baseline were associated with falls during the 12-month follow-up. Slower walking speed at baseline was associated with fall-related fractures during the 12-month follow-up. These associations remained significant after adjusting for age, sex, body mass index, comorbidities and medication use; (4) Conclusions: This study suggests poor balance, low mood and a less active lifestyle are predictors of falls, and slower walking speed predicts fall-related fractures among community-dwelling older people with pain.

Remote Administration of ADHD-Sensitive Cognitive Tasks: A Pilot Study

Objective: We assessed the feasibility and validity of remote researcher-led administration and self-administration of modified versions of two cognitive tasks sensitive to ADHD, a four-choice reaction time task (Fast task) and a combined Continuous Performance Test/Go No-Go task (CPT/GNG), through a new remote measurement technology system. Method: We compared the cognitive performance measures (mean and variability of reaction times (MRT, RTV), omission errors (OE) and commission errors (CE)) at a remote baseline researcher-led administration and three remote self-administration sessions between participants with and without ADHD (n = 40). Results: The most consistent group differences were found for RTV, MRT and CE at the baseline researcher-led administration and the first self-administration, with 8 of the 10 comparisons statistically significant and all comparisons indicating medium to large effect sizes. Conclusion: Remote administration of cognitive tasks successfully captured the difficulties with response inhibition and regulation of attention, supporting the feasibility and validity of remote assessments.

Effect of resistance training on cognition in older women with differing levels of resistance training experience: Active Aging Longitudinal Study

BACKGROUND: We aimed to analyze the impact of previous resistance training (RT) experience on cognitive function in older women.METHODS: Sixty-one physically independent women (>60 years) were assigned to one of the three groups: novice (N.=21, untrained individuals with no RT experience or who had not trained for several months), intermediate (N.=22, active individuals with 24 weeks of standardized RT experience), and a non-exercise control group (N.=18, untrained individuals). Novice and intermediate groups underwent a 12-week RT program for the whole-body (eight exercises, three sets, 8-12 repetitions, three alternate days per week). Measurements of cognitive performance (Stroop Test, Trail making Test A and B, letter and category verbal fluency test, Montreal Cognitive Assessment Test) were performed before and after the experimental period. ANCOVA was used for the comparison between groups over time.RESULTS: Improvement in the scores of almost all tests was observed in both novice and intermediate groups after RT (P<0.05), while the control group presented worse MoCA and Stroop Test scores after intervention (P<0.05). Thus, both exercise groups showed significantly different scores from the control group (P<0.05). Interestingly, a larger effect size was found for the intermediate group (ES=0.25-0.66) than for the novice group (ES = 0.16-0.35).CONCLUSIONS: Our results suggest that cumulative effect seems to exist, with more experienced individuals presenting more significant improvements.

Digital Health Games for Older Adults: Development, Implementation, and Programmatic Implications of Health Game Use in Senior Centers

AbstractBy 2030, an estimated 21.6% of the U.S. population will exceed 65 years old. Within this demographic, ongoing broad efforts are needed to address modifiable factors related to common chronic conditions of aging. Digital, or “serious,” health games offer one innovative approach to reach and engage older adults, with documented positive impacts on physical, mental/cognitive, and social health. Informed by healthy aging theory and community‐engaged, user‐centered design methods, our multidisciplinary team has developed a prototype multicomponent educational exergame designed to educate about and promote healthy lifestyle behaviors (i.e., healthy eating, physical activity), stimulate cognitive functioning, engage movement, and promote social connection. Additionally, we included functional near infrared spectroscopy (fNIRS) in our pilot work to measure real time brain activation during gameplay. Our objectives are to: 1) describe the formative development and testing process of an example multi‐component educational exergame, including multidisciplinary team science collaboration, application of aging theory, and use of community‐engaged and user‐centered approaches; and 2) present a pilot study examining implementation and multiple aspects of an innovative educational exergame, including usability, acceptability, preliminary impact, and cognitive function measurement using brain imaging technology (fNIRS) to measure changes in cognitive load during gameplay. The results provide initial support for acceptability, usability, and positive perceived impact, as well as the preliminary encouraging pre to post improvements in behavioral intention, content knowledge, and relative neural efficiency. This paper also explores the potential of implementing serious health games in senior centers as part of their regular programming.

Decreased/increased beta/alpha functional connectivity in pathological and healthy aging. A dual pattern of brain dynamics revealed by magnetoencephalography

AbstractBackgroundAlzheimer’s Disease (AD) is a progressive neurodegenerative disorder that develops unnoticed during several years prior to the onset of clinical symptomatology. The deterioration of delayed recall is one of the most significant predictive factors to define the progression of Mild Cognitive Impairment (MCI) to AD, and it has a strong relationship with medial temporal dysfunction. Identifying a reliable measurement of brain health and cognitive function is essential to mitigate the side effects of cognitive decline by promoting early intervention. The purpose of this study was to explore, in MCI patients and ‐healthy participants, how memory loss modifies the functional integrity of resting‐state brain activity, as measured with MEG.Method118 MCI (aged from 58 to 87) and 261 healthy (aged from 41 to 82) participants were recruited from the Hospital Universitario San Carlos (Madrid, Spain). They all underwent an extensive neuropsychological evaluation, MRI, and MEG recordings.Results Delayed recall (DR). The correlation analysis between functional connectivity (FC) and DR score showed a negative correlation, (rho = ‐0.208, p &lt;0.001), between beta‐band FC and LTM performance in the occipital region, so that participants with higher FC showed lower memory performance. Furthermore, the correlation between LTM and beta FC‐st remained significant when looking at the MCI (rho = ‐0.236, p &lt; 0.01) and healthy groups separately (rho = ‐0.207, p&lt; 0.001). Short Term Memory (STM). The STM was found to be associated, (rho = 0.175, p &lt; 0.001), with increased occipital alpha‐band FC, indicating that those participants with the higher FC, the higher the memory performance. Interestingly, a separate analysis of both groups revealed that this correlation was present only in the healthy group (rho = 0.141, p &lt;0.02).ConclusionA dual pattern of a respective decreased/increased beta/alpha FC in the occipital brain region appeared to be associated with memory performance in healthy and pathological aging.

ASSESSING CAUSALITY BETWEEN CAROTID-FEMORAL PULSE WAVE VELOCITY AND COGNITIVE FUNCTION: A MENDELIAN RANDOMIZATION STUDY

Objective: Arterial stiffness is usually significantly associated with cognitive function. We conducted a Mendelian randomization study to investigate the causal relationship between measures of arterial stiffness and cognitive function in a cross-sectional survey. Design and method: A total of 1516 adults aged more 30 years old in the CardioVascular Disease risk FACTors in two townships Study (CVDFACTS) with wave 6 and wave 7 during 2013-2020 were evaluated for artery stiffness with carotid-femoral pulse wave velocity (CFPWV) and cognitive function with Mine-Mental Short Evaluation (MMSE). A genome-wide association study was used to identify the genetic variants associated with CFPWV. Mendelian Randomization analysis was conducted using the R software. Results: A total of 87 SNP were identified (p-value&lt;10-6) in the KDM4B gene (Chromosome-19) and 3 SNPs [rs10085112, rs2613776 and rs147498368] of them were independently associated with CFPWV. We constructed a polygenetic risk score (PRS, 1-6) with the 3 significant SNPs. PRS was the genetic variant and instrumental variable in the Mendelian Randomization. PRS was significantly associated with CFPWV (beta = -0.37, p = 0.0003), the “exposure”, and MMSE (beta = 0.14, p = 0.031), the “outcome”. In contrast, PRS was not associated with age, sex, systolic/diastolic blood pressure, body mass index, fasting glucose, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, C-reactive protein, creatinine and uric acid, the “confounders”. Mendelian Randomization estimate (95% confidence intervals) of the causal effect of the exposure (CFPWV) on the outcome (MMSE) was -0.433 (-0.810, -0.056, p-value = 0.0244). Conclusions: Our study provides evidence that KDM4B gene may be instrumental in the causal relationship between artery stiffness measured by CFPWV and cognitive function measured by MMSE in a Han Chinese population.

Nationwide phase II randomized controlled trial of low-dose ibuprofen vs placebo for cancer-related cognitive impairment (CRCI).

12116 Background: CRCI is an important clinical problem encompassing difficulties in attention, memory, and executive function. Interventions for CRCI during chemotherapy have not been established. Inflammation is associated with CRCI and thus targeting inflammation may alleviate CRCI. In a nationwide study, we investigated a low-dose of ibuprofen for alleviating CRCI in patients self-reporting cognitive problems during chemotherapy or after recent completion of chemotherapy. Methods: Participants with cancer currently on or recently completed chemotherapy and who self-reported cognitive problems were recruited via the NCI Community Oncology Research Program (URCC NCORP) and 11 affiliates. Participants completed pre-intervention assessments and were stratified by disease type (breast cancer; gastrointestinal cancer; other) and randomized to one of 2 groups for 6 weeks: ibuprofen (200 mg BID) or blinded placebo equivalent. At pre-intervention and post-intervention, participants completed a perceived cognitive function measure (FACT-Cog Perceived Cognitive Impairment (PCI)) and cognitive assessments including Rapid Visual Processing (RVP) latency, Delayed Match to Sample (DMS) visual memory, and Verbal Recognition Memory (VRM) word recall. ANCOVA was used to assess between group differences pre- to post-intervention adjusting for baseline cognitive test score. Results: In total, 87 participants were randomized; 45 were randomized to ibuprofen and 42 randomized to placebo (mean age = 55; 85% female; 47% breast cancer, 29% colon/colorectal cancer; 24% other diagnoses). Most participants were fully compliant and completed post-intervention assessments (86% in Ibuprofen arm, 87% in placebo arm). There were no gastrointestinal bleeding events of any grade in the ibuprofen arm and serious adverse events were rare in both arms occurring in only 4% and 7% of patients in the ibuprofen and placebo arms, respectively. For PCI, both groups significantly reported less impairment from pre- to post-intervention; there were no difference between groups. Patients randomized to ibuprofen had a significant improvement on RVP latency time compared to placebo (110.63 milliseconds; p &lt; 0.005). On the DMS, patients receiving ibuprofen had a trend toward improved function compared to placebo (7.39%; p = 0.08). However, patients in placebo performed better in word recall compared to ibuprofen from pre- to post-intervention (1.64 words; p &lt; 0.05). Conclusions: Low-dose, short duration ibuprofen was safe with minimal adverse events in patients with cancer receiving chemotherapy or recently completed chemotherapy. Ibuprofen showed improvements in processing speed time and visual memory in patients with cancer as hypothesized, but not verbal memory. These novel Phase II findings need to be replicated in a Phase III RCT. Funding: R21CA187500, UG1CA189961. Clinical trial information: NCT03186638 .

Exercise and epigenetic ages in older adults with myeloid malignancies

BackgroundOlder adults with myeloid malignancies are susceptible to treatment-related toxicities. Accelerated DNAm age, or the difference between DNA methylation (DNAm) age and chronological age, may be used as a biomarker of biological age to predict individuals at risk. In addition, cancer treatment can also lead to accelerated DNAm age. Exercise is a promising intervention to reduce or prevent functional, psychological, and cognitive impairments in older patients with myeloid malignancies, yet there is little evidence of the effects of exercise on DNAm age. We explored (1) the associations of accelerated DNAm age with physical, psychological, and cognitive functions at baseline; (2) changes in DNAm age from baseline to post-intervention; and (3) the associations of changes in accelerated DNAm age with changes in functions from baseline to post-intervention.MethodsWe enrolled older patients with myeloid malignancies to a single-arm pilot study testing a mobile health (mHealth) exercise intervention that combines an exercise program (EXCAP©®) with a mobile application over 2 cycles of chemotherapy (8–12 weeks). Patients completed measures of physical, psychological, and cognitive functions and provided blood samples for analyses of DNAm age at baseline and post-intervention. Paired t-tests or Wilcoxon signed rank tests assessed changes in DNAm ages, and Spearman’s correlation assessed the relationships between accelerated ages and functions.ResultsWe included 20 patients (mean age: 72 years, range 62–80). Accelerated GrimAge, accelerated PhenoAge, and DunedinPACE were stable from baseline to post-intervention. At baseline, DunedinPACE was correlated with worse grip strength (r = -0.41, p = 0.08). From baseline to post-intervention, decreases in accelerated GrimAge (r = -0.50, p = 0.02), accelerated PhenoAge (r = − 0.39, p = 0.09), and DunedinPace (r = − 0.43, p = 0.06) were correlated with increases in distance walked on 6-min walk test. Decreases in accelerated GrimAge (r = − 0.49, p = 0.03), accelerated PhenoAge (r = − 0.40, p = 0.08), and DunedinPace (r = − 0.41, p = 0.07) were correlated with increases in in grip strength.ConclusionsAmong older adults with myeloid malignancies receiving chemotherapy, GrimAge and PhenoAge on average are stable after a mHealth exercise intervention. Decreases in accelerated GrimAge, accelerated PhenoAge, and DunedinPACE over 8–12 weeks of exercise were correlated with increased physical performance. Future trials assessing the effects of exercise on treatment-related toxicities should evaluate DNAm age.Trial registration Clinicaltrials.gov identifier: NCT04981821.

0459 Cardiovascular Endpoints for Obstructive Sleep Apnea with Twelfth Nerve Stimulation: Measures of Sleep-Related Function

Abstract Introduction Obstructive sleep apnea (OSA) is an increasingly prevalent sleep-related breathing disorder linked to cognitive dysfunction and daytime sleepiness. Positive airway pressure (PAP) therapy, the first-line treatment for OSA, may improve cognitive function and sleepiness, but responses vary. Hypoglossal nerve stimulation (HGNS) is a novel and effective PAP alternative, but its effect on mitigating cognitive decline secondary to OSA is unknown. In the first sham-controlled HGNS trial, we evaluated the effect of HGNS therapy on cognitive measures and patient-reported outcomes (PROs) in patients with moderate-severe OSA. Methods In a double-blind, sham-controlled, randomized crossover therapy trial, patients already stabilized on HGNS therapy underwent four weeks of active and four weeks of sham HGNS, each with a 1-week washout period. Sham therapy was defined as the lowest voltage at which HGNS was sensed by the patient or visualized by the clinician. Cognitive measures (Psychomotor Vigilance Test [PVT], Digit Symbol Substitution Task [DSST]) and sleep-related PROs (Epworth Sleepiness Scale [ESS], Snoring Visual Analog Scale [VAS], Insomnia Severity Index [ISI], Functional Outcomes of Sleep Questionnaire [FOSQ]) were assessed after each 4-week period and compared between active and sham therapy. Results Sixty randomized patients were included. On average, participants were elderly (67.3±9.9 years), overweight (BMI 28.7±4.6 kg/m2) and had severe OSA prior to HGNS therapy (AHI 33.1±14.9 events/hour). Patients’ AHI decreased to 23.0±15.6 events/hour with sham therapy (p=0.0001) and 18.1±14.8 events/hour with active therapy (p&amp;lt; 0.0001), with a 4.9 event/hour decrease between active and sham therapy (p=0.014). There were no significant differences in performance measures on PVT or DSST between active and sham HGNS. All sleep-related PROs were statistically significant with moderately large (effect sizes ~0.41-0.56) improvements following active HGNS. Conclusion The HGNS system permits a unique investigation of the therapy “on/off” effect on measures of cognitive function. In the first sham-controlled, randomized crossover trial of patients using HGNS, all sleep-related PROs, but not objective measures of cognition, were significantly different between sham and active (therapeutic) levels. These findings warrant additional investigation examining the relationship between subjective and objective measures of function in OSA. Support (if any) American Heart Association (17SDG33670349) American Sleep Medicine Foundation (176-JF-17) National Institutes of Health (P01-HL094307)

0331 Effects of Cognitive Behavioral Therapy for Insomnia (CBTI) on Daytime Cognitive Functioning: A Report from the AIR Trial

Abstract Introduction Prior studies have shown that CBTI improves patient reported outcomes including daytime fatigue, mood status and quality of life, yet there are limited data concerning the effects of therapy on objective measures of daytime function. The current study tested the effects of CBTI on measures derived from the psychomotor vigilance test (PVT) in a sample of patients with comorbid insomnia disorder and sleep apnea. Methods Patients with insomnia and comorbid OSA, who were prescribed PAP therapy (N =155; Mage= 56.8±12.5 yrs.; 58.1% women) were randomized to digital CBTI (dCBTI) or Sleep Hygiene (CTRL). They completed PVT at baseline and after 8 weeks of treatment. Patients in the dCBTI arm who reached remission were offered no additional insomnia treatment, whereas those who did not were randomly assigned to 8 weeks of continued access to dCBTI or to a therapist delivered CBTI. Patients again completed the PVT after this second 8-week treatment phase. PVT outcome measures included mean reaction time, attentional lapses and efficiency scores. Linear mixed models were used to compare the PVT measures of patients receiving either of the CBTI treatment sequences with those assigned to the CTRL. Results Analyses showed significant group x time interactions for PVT attentional lapses (F = 3.04; p &amp;lt; .05) and for efficiency scores (F= 4.06; p&amp;lt; .025). Those who received either of the CBTI treatment sequences showed a greater reduction in attentional lapses and greater improvement in their efficiency scores from baseline to the post-treatment assessments than did those assigned the CTRL. Conclusion Findings indicate that CBTI improves objective indices of daytime cognitive functioning among those with comorbid apnea and insomnia disorder. Further tests of CBTI’s effects on these and other measures of cognitive functioning are warranted in other samples of insomnia patients who do and do not have medical, psychiatric and sleep disorder comorbidities. Support (if any) Funding support from the National Heart, Lung and Blood Institute, Grant # 1R01HL130559-01A1.

Blood Pressure, Incident Cognitive Impairment, and Severity of CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood pressure, cognitive impairment, and severity of decreased kidney function in adults with chronic kidney disease. Longitudinal cohort study. 3,768 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Baseline SBP and DBP were examined as exposure variables, using continuous (linear, per 10-mm Hg higher), categorical (SBP<120 [reference], 120 to 140,>140mm Hg; DBP<70 (reference), 70 to 80, > 80mm Hg) and nonlinear terms (splines). Incident cognitive impairment defined as a decline in Modified Mini-Mental State Examination (3MS) score to greater than 1 standard deviation below the cohort mean. Cox proportional hazard models adjusted for demographics as well as kidney disease and cardiovascular disease risk factors. The mean age of participants was 58±11 (SD) years, estimated glomerular filtration rate (eGFR) was 44mL/min/1.73m2 ± 15 (SD), and the median follow-up time was 11 (IQR, 7-13) years. In 3,048 participants without cognitive impairment at baseline and with at least 1 follow-up 3MS test, a higher baseline SBP was significantly associated with incident cognitive impairment only in the eGFR>45mL/min/1.73m2 subgroup (adjusted hazard ratio [AHR], 1.13 [95% CI, 1.05-1.22] per 10mm Hg higher SBP]. Spline analyses, aimed at exploring nonlinearity, showed that the relationship between baseline SBP and incident cognitive impairment was J-shaped and significant only in the eGFR>45mL/min/1.73m2 subgroup (P=0.02). Baseline DBP was not associated with incident cognitive impairment in any analyses. 3MS test as the primary measure of cognitive function. Among patients with chronic kidney disease, higher baseline SBP was associated with higher risk of incident cognitive impairment specifically in those individuals with eGFR>45mL/min/1.73m2. High blood pressure is a strong risk factor for dementia and cognitive impairment in studies of adults without kidney disease. High blood pressure and cognitive impairment are common in adults with chronic kidney disease (CKD). The impact of blood pressure on the development of future cognitive impairment in patients with CKD remains unclear. We identified the relationship between blood pressure and cognitive impairment in 3,076 adults with CKD. Baseline blood pressure was measured, after which serial cognitive testing was performed over 11 years. Fourteen percent of participants developed cognitive impairment. We found that a higher baseline systolic blood pressure was associated with an increased risk of cognitive impairment. We found that this association was stronger in adults with mild-to-moderate CKD compared with those with advanced CKD.

Motor and cognitive skills implicated in the Motor Observation Questionnaire for Teachers (MOQ-T): A multidisciplinary approach

This study was designed to determine the relationship between an observational measure of motor skills for teachers (i.e., MOQ-T), age, and some objectively assessed cognitive and motor indices. Two further goals were to examine which motor and cognitive factors predicted MOQ-T scores and to explore whether pupils with very low motor skills identified through MOQ-T also exhibited lower scores on objectively assessed motor and visuo-spatial tasks. A sample of 156 pupils aged 8.4 years–11.3 years and attending Italian primary school completed a battery of tests assessing writing speed, visuo-spatial abstract reasoning, fluency, and static balance abilities objectively assessed by measuring postural sway. Small to medium associations were found between MOQ-T scores and age, motor, and cognitive parameters, respectively. Moreover, approximately 26% of the variance in MOQ-T was predicted by sway area in the eyes-open condition, visuo-spatial fluency, and writing speed. Finally, pupils at risk of developmental coordination disorder exhibited poorer writing speed, and motor and higher-order visuo-spatial deficits. In conclusion, the synergistic use of objective measures of motor and cognitive functioning and observational screening questionnaires such as MOQ-T should be encouraged at school to identify pupils at risk of developmental coordination disorder.

Does inclusion of cognitive measures improve the predictive performance of SCORE2 for future cardiovascular events in older adults?

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – EU funding. Main funding source(s): National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) - Funded by the European Union – Next Generation EU. Introduction The cardiovascular disease (CVD) risk prediction model SCORE2 uses several biomedical and behavioural factors. It is likely that other factors also contribute to CVD risk prediction. Cognitive impairment and CVD are associated and share several risk factors. While the causality of this relationship remains unclear, adding cognitive measures to risk prediction may improve the prediction of future CVD events. Objective We tested the hypothesis that including simple measures of cognitive functions improve the prediction of SCORE2 for future CVD events among middle aged and older subjects. Methods We used data on 13,391 Polish, Lithuanian and Czech adults without CVD at baseline (45–69 years) from the Health, Alcohol and Psychosocial factors In Eastern Europe cohort. Incident cases of myocardial infarction (MI), stroke, CVD mortality and composite (fatal and non-fatal) CVD events were identified over a 10-year follow-up. Baseline cognitive measures included immediate and delayed word recall (verbal memory and learning), animal naming (verbal fluency) and letter cancellation (attention, mental speed and concentration). Using competing-risks regression, relationships between cognitive functions and CVD outcomes were examined. Improvement in Area Under Curve Receiver Operator Characteristic (AUC-ROC) was used to compare predictive performance for CVD events of models including SCORE2 variables combined with cognitive tests vs SCORE2 alone. Results The incidence rates of MI, stroke, CVD mortality and composite CVD events were 5%, 4%, 4% and 11%, respectively. In multivariable analyses, all four cognitive measures were inversely associated with CVD outcomes; e.g. one standard deviation increase in immediate word recall score was associated with a 28% and 17% reduction in risk of CVD mortality and composite CVD events, respectively (all p-values &amp;lt;0.001). Adding cognitive measures to SCORE2 variables slightly improved the AUC-ROC for prediction of MI, CVD mortality and composite CVD events. For example, for the composite CVD measure, inclusion of all four cognitive measures increased the AUC-ROC from 0.6948 to 0.7030 (p&amp;lt;0.001) and similar improvement was seen for word recall. The results were consistent across countries. Conclusion Inclusion of a simple cognitive test in the assessment of cardiovascular health is feasible and it may improve prediction of future CVD risk, although in our data the improvement was not clinically important (despite being statistically significant). Further studies are needed to assess this proposition in larger prospective datasets.

An association of CSF apolipoprotein E glycosylation and amyloid-beta 42 in individuals who carry the APOE4 allele

Carrying the apolipoprotein E (ApoE) Ɛ4 allele is associated with an increased risk of cerebral amyloidosis and late-onset Alzheimer’s disease, but the degree to which apoE glycosylation affects its development is not clear. In a previous pilot study, we identified distinct total and secondary isoform-specific cerebral spinal fluid (CSF) apoE glycosylation profiles, with the E4 isoform having the lowest glycosylation percentage (E2 > E3 > E4). In this work, we extend the analysis to a larger cohort of individuals (n = 106), utilizing matched plasma and CSF samples with clinical measures of AD biomarkers. The results confirm the isoform-specific glycosylation of apoE in CSF, resulting from secondary CSF apoE glycosylation patterns. CSF apoE glycosylation percentages positively correlated with CSF Aβ42 levels (r = 0.53, p < 0.0001). These correlations were not observed for plasma apoE glycosylation. CSF total and secondary apoE glycosylation percentages also correlated with the concentration of CSF small high-density lipoprotein particles (s-HDL-P), which we have previously shown to be correlated with CSF Aβ42 levels and measures of cognitive function. Desialylation of apoE purified from CSF showed reduced Aβ42 degradation in microglia with E4 > E3 and increased binding affinity to heparin. These results indicate that apoE glycosylation has a new and important role in influencing brain Aβ metabolism and can be a potential target of treatment.

Sex comparisons in the association of prediabetes and type 2 diabetes with cognitive function, depression, and quality of life: The Maastricht study.

There are sex differences in the excess risk of diabetes-associated cardiovascular disease. However, it is not clear whether these sex differences exist with regard to other complications like mental health aspects. Therefore, we investigated sex differences in the association of prediabetes and type 2 diabetes (T2D) with cognitive function, depression, and quality of life (QoL). In a population-based cross-sectional cohort study (n = 7639; age 40-75 years, 50% women, 25% T2D), we estimated sex-specific associations, and differences therein, of prediabetes and T2D (reference: normal glucose metabolism) with measures of cognitive function, depression, and physical and mental QoL. Sex differences were analysed using multiple regression models with interaction terms. In general, T2D, but not prediabetes, was associated with higher odds of cognitive impairment, major depressive disorder, and poorer QoL. The odds ratio (OR) of cognitive impairment associated with T2D was 1.29 (95% CI: 0.96-1.72) for women and 1.39 (1.10-1.75) for men. The OR of major depressive disorder associated with T2D was 1.19 (0.69-2.04) for women and 1.68 (1.02-2.75) for men. The mean difference of the physical QoL score (ranging from 0 to 100, with 100 indicating the best possible QoL) associated with T2D was -2.09 (-2.92 to -1.25) for women and -1.81 (-2.48 to -1.13) for men. The mean difference of the mental QoL score associated with T2D was -0.90 (-1.79 to -0.02) for women and -0.52 (-1.23 to 0.20) for men. There was no clear pattern of sex differences in the associations of either prediabetes or T2D with measures of cognitive function, depression, or QoL. In general, T2D was associated with worse cognitive function, depression, and poorer QoL. The strength of these associations was similar among women and men.

The Mode Effect of Web-Based Surveying on the 2018 U.S. Health and Retirement Study Measure of Cognitive Functioning.

Measuring cognition in an aging populabtion is a public health priority. A move towards survey measurement via the web (as opposed to phone or in-person) is cost-effective but challenging as it may induce bias in cognitive measures. We examine this possibility using an experiment embedded in the 2018 wave of data collection for the U.S. Health and Retirement Study (HRS). We utilize techniques from multiple group item response theory to assess the effect of survey mode on performance on the HRS cognitive measure. We also study the problem of attrition by attempting to predict dropout and via approaches meant to minimize bias in subsequent inferences due to attrition. We find evidence of an increase in scores for HRS respondents who are randomly assigned to the web-based mode of data collection in 2018. Web-based respondents score higher in 2018 than experimentally matched phone-based respondents, and they show much larger gains relative to 2016 performance and subsequently larger declines in 2020. The differential in favor of web-based responding is observed across all items, but is most pronounced for the Serial 7 task and numeracy items. Due to the relative ease of the web-based mode, we suggest a cutscore of 12 being used to indicate CIND (cognitively impaired but not demented) status when using the web-based version rather than 11. The difference in mode may be nonignorable for many uses of the HRS cognitive measure. In particular, it may require reconsideration of some cutscore-based approaches to identify impairment.

Physical function across the lifespan in adults with multiple sclerosis: An application of the Short Physical Performance Battery.

Multiple sclerosis (MS) typically has its onset in early and middle adulthood, but the population is steadily becoming more dominated by older adults. One of the primary consequences of both MS and aging involves declines of lower extremity physical function and mobility. This cross-sectional study compared physical function status based on Short Physical Performance Battery (SPPB) summary and component scores between persons with MS and healthy controls across 6 age groups. We further examined associations between SPPB summary scores and component scores as well as associations between summary scores and measures of physical and cognitive function for identifying the strongest correlates of SPPB summary scores. The study involved secondary analysis of cross-sectional data from multiple studies. Ambulatory adults with MS who were relapse-free for the last 30 days were recruited, and controls were recruited based on similar criteria to adults with MS except without the diagnosis of MS or relapses. The sample of 345 persons with MS and 174 controls completed questionnaires regarding demographic and clinical information and underwent assessments of physical and cognitive function including the SPPB, 6-Minute Walk, Timed 25-Foot Walk, Symbol Digit Modalities Test, California Verbal Learning Test-Second Edition, and Brief Visuospatial Memory Test-Revised. The two-way ANOVA indicated a main effect of MS status (F(5,500)=34.74, p<.01, η2=0.065), a main effect of age (F(1,500)=3.88, p<.01, η2=0.037), and no MS status by age interaction (F(5,500)=1.20, p=.31, η2=0.012) on SPPB scores. The bivariate correlation analysis indicated that summary SPPB scores were associated with component SPPB scores in the overall samples of persons with MS (rs=0.71 to 0.83) and controls (rs=0.42 to 0.91) as well as within most age groups of MS (rs=0.63 to 0.91) and controls (rs=0.34 to 1.00). The associations between SPPB scores and physical function outcomes were larger in the sample of persons with MS (rs=-0.72 to 0.76) than controls (rs=-0.47 to 0.48). SPPB scores were further significantly associated with scores on cognitive outcomes in persons with MS (rs=0.31 to 0.43), whereas these associations were weaker in controls (rs=0.09 to 0.32). Overall, the associations between SPPB scores and physical function outcomes were stronger than the associations between SPPB scores and cognitive function outcomes. Overall, MS status and aging have additive effects on physical function, and the summary SPPB score may be driven by a specific component within each age group. SPPB scores may be driven more by mobility rather than cognition, and are consistent with cognitive-motor coupling in MS. The novelty of this study provides evidence of worsening physical function based on the application of the SPPB and its scores across the lifespan in persons with MS and controls, and this has important implications particularly given the increasing prevalence of older adults with MS.

Association Between the Attention Network Test, Neuropsychological Measures, and Disability in Post-Acute Traumatic Brain Injury.

Cognitive impairment after traumatic brain injury (TBI) is persistent and disabling. Assessing cognitive function in a reliable and valid manner, using measures that are sensitive to the integrity of underlying neural substrates, is crucial in clinical research. The Attention Network Test (ANT) is one such assessment measure that has demonstrated associations with neural regions involved in attention; however, clinical utility of the ANT is limited because its relationship with neuropsychological measures of cognitive function (i.e., its construct validity) has not yet been established in TBI. We evaluated the association between the ANT and 1) a neuropsychological battery assessing executive function and memory and 2) global function assessed by the Glasgow Outcome Scale-Extended (GOSE). Forty-eight adults with complicated mild-severe TBI were evaluated ∼5 months post-injury. Using principal component analysis and multi-variate linear regression adjusted for age, gender, education, and cause of injury, we found that ANT reaction time and executive network scores predicted a principal component assessing processing speed and executive function. Conversely, the ANT did not predict a principal component assessing memory. The ANT was weakly associated with the GOSE. Among persons with TBI during the post-acute phase of recovery, the ANT has good construct validity as evidenced by its associations with neuropsychological measures of processing speed and executive function, but not memory. Given that ANT networks are known to relate to specific neuroanatomical regions, the ANT may be a useful outcome measure for evaluating novel therapeutics targeting attention and executive functions after TBI.

Associations of socioeconomic disparities with buccal DNA-methylation measures of biological aging

BackgroundIndividuals who are socioeconomically disadvantaged are at increased risk for aging-related diseases and perform less well on tests of cognitive function. The weathering hypothesis proposes that these disparities in physical and cognitive health arise from an acceleration of biological processes of aging. Theories of how life adversity is biologically embedded identify epigenetic alterations, including DNA methylation (DNAm), as a mechanistic interface between the environment and health. Consistent with the weathering hypothesis and theories of biological embedding, recently developed DNAm algorithms have revealed profiles reflective of more advanced aging and lower cognitive function among socioeconomically-at-risk groups. These DNAm algorithms were developed using blood-DNA, but social and behavioral science research commonly collect saliva or cheek-swab DNA. This discrepancy is a potential barrier to research to elucidate mechanisms through which socioeconomic disadvantage affects aging and cognition. We therefore tested if social gradients observed in blood DNAm measures could be reproduced using buccal-cell DNA obtained from cheek swabs.ResultsWe analyzed three DNAm measures of biological aging and one DNAm measure of cognitive performance, all of which showed socioeconomic gradients in previous studies: the PhenoAge and GrimAge DNAm clocks, DunedinPACE, and Epigenetic-g. We first computed blood-buccal cross-tissue correlations in n = 21 adults (GEO111165). Cross-tissue correlations were low-to-moderate (r = .25 to r = .48). We next conducted analyses of socioeconomic gradients using buccal DNAm data from SOEP-G (n = 1128, 57% female; age mean = 42 yrs, SD = 21.56, range 0–72). Associations of socioeconomic status with DNAm measures of aging were in the expected direction, but were smaller as compared to reports from blood DNAm datasets (r = − .08 to r = − .13).ConclusionsOur findings are consistent with the hypothesis that socioeconomic disadvantage is associated with DNAm indicators of worse physical health. However, relatively low cross-tissue correlations and attenuated effect sizes for socioeconomic gradients in buccal DNAm compared with reports from analysis of blood DNAm suggest that in order to take full advantage of buccal DNA samples, DNAm algorithms customized to buccal DNAm are needed.

Cannabis use in cancer patients: acute and sustained associations with pain, cognition, and quality of life

Aim: Given the myriad of negative sequalae associated with cancer and its treatment, the palliative use of cannabis by cancer patients is increasingly of special interest. This research sought to explore associations of acute and sustained use of legal market edible cannabis products on pain, cognition, and quality of life in a group of cancer patients. Methods: In this observational study, cancer patients completed a baseline appointment, a two-week ad libitum cannabis use period, and an acute administration appointment that included assessments before cannabis use, one-hour post-use, and two-hour post-use. Participants completed self-report questionnaires related to the primary outcomes and the Stroop task as a measure of objective cognitive function. Results: Twenty-five participants [mean (standard deviation, SD) age = 54.3 years (15.6); 13 females (52.0%)] completed all study appointments and were included in the analysis. Sustained cannabis use was associated with improvements in pain intensity, pain interference, sleep quality, subjective cognitive function, and reaction times in the Stroop task, but no change in general quality of life was observed. High levels of cannabidiol (CBD) use during the two-week ad libitum use period was associated with steeper improvements in pain intensity and sleep quality. Participants reported improvements in pain intensity and increased feelings of subjective high after acute use. High levels of ∆9-tetrahydrocannabinol (THC) use during the acute administration appointment was associated with steeper increases in feelings of subjective high. Improvements in pain were associated with improvements in subjective cognitive function. Conclusions: This observational study is among the first of its kind to examine associations between legal market, palliative cannabis use, and subjective and objective outcomes among cancer patients. These early findings concerning pain intensity, sleep quality, and cognitive function can help to inform future, fully powered studies of this important topic (ClinicalTrials.gov identifier: NCT03617692).