Cognitive Battery Research Articles

FEASIBILITY OF A COMMUNITY-LEVEL PHYSICAL ACTIVITY STRATEGY FOR OLDER ADULTS WITH MOTORIC COGNITIVE RISK SYNDROME

Abstract The motoric cognitive risk syndrome (MCR) is a pre-dementia syndrome characterized by slow walking speeds and subjective memory complaints. To date, the feasibility of a community-based physical activity (PA) program for improving outcomes in MCR has not been examined. To address this knowledge gap, we conducted a translational randomized controlled trial (RCT) of 24-weeks of PA or a healthy aging education (HE) control intervention delivered within the existing infrastructure of an urban senior center in Greater Boston. A senior center employee was trained to administer the multimodal group-based PA program that included moderate-intensity aerobic walking, strength, flexibility and balance training. A total of 79 older adults attended the senior center for a screening visit of whom 25 met the MCR criteria and were randomized to PA or HE (mean age: 74.4 ± 7 yrs; BMI: 32.4 ± 7 kg/m2; 85% female; 3MSE score: 92.4 ± 7; gait speed: 0.52 ± 0.1 m/sec; SPPB score 4.8 ± 1.9). Due to COVID-19 the study was terminated early, however participants successfully completed baseline and follow-up study assessments that included objective tests of physical function and an iPad-based cognitive testing battery. Participants could appropriately adhere to the study interventions (overall attendance rate: PA: 69.3% vs. HE:70.1% at study termination). No study-related adverse events occurred. Trends for improved executive cognitive performance were exhibited in PA compared to HE. Our study provides important preliminary information to aid the design of larger-scale RCTs to preserve the independence of vulnerable older adults with MCR in community-based settings.

RACIAL/ETHNIC DIFFERENCES IN NEUROCOGNITIVE PROFILES OF OLDER ADULTS WITH 6-YEAR INCIDENT DEMENTIA

Abstract Hispanic and non-Hispanic Black (NHB) older adults have higher dementia rates than non-Hispanic Whites (NHWs). Estimates of dementia prevalence and incidence in community-based cohorts are mostly based on threshold value performance on cognitive assessment batteries. We used longitudinal data from the HRS Harmonized Cognitive Assessment Protocol (HCAP) to (1) generate and compare, across race/ethnicity, neurocognitive profiles for older adults (>65 years) not meeting research criteria for dementia in 2010 and developing dementia by 2016 (using Langa-Weir’s dementia classification), (2) assess racial/ethnic differences in these profiles, and (3) test socio-demographic effects on dementia-specific differences in neurocognitive performance. Performance on all HCAP measures was highly sensitive to 6-year incident dementia classification. However, we found notable domain-specific differences in test sensitivity, whereby performance on general screeners (e.g., MMSE) and memory-based tests (e.g., CERAD word list recognition) were significantly lower (≤2 SDs from normed population means). Hispanics and NHBs generally performed lower than NHWs, with more pronounced group differences in general screeners and executive function tests. Sociodemographic characteristics significantly attenuated Hispanic differences, but less so for NHBs, relative to NHWs. Despite these group differences, NHWs with incident dementia had worse neurocognitive profiles than their NHB and Hispanic counterparts. Dementia classification algorithms (e.g., Langa-Weir) sensitively detect cognitive impairment. However, these algorithms more accurately identify higher severity cognitive impairment in NHWs compared to NHBs and Hispanics. Such methods can yield dementia estimates biased by sociocultural factors. Further research is needed to identify culturally appropriate neurocognitive tests that enhance precise dementia diagnosis, using population-level epidemiological data.

CHILDHOOD FAMILY ENVIRONMENT, GENETIC RISK FOR ALZHEIMER’S DISEASE, AND LATE-LIFE COGNITIVE DECLINE

Abstract How genetic risks for Alzheimer’s disease (AD) interact with environmental factors to shape individuals’ cognitive trajectories across the lifespan is a burgeoning area of research. However, relatively little is known about the role childhood family environment plays in the relationship between genetic risk factors for AD and cognitive decline in later life. This study examined whether and how early-life family environments may modify cognitive decline associated with genetic AD risks. Using longitudinal data from the Health and Retirement Study (HRS; 1998-2018), we followed over 9,000 individuals aged 51 and older during the observation period spanning nearly two decades. Cognitive functioning was assessed with the full cognitive battery from the HRS. Childhood family environment was evaluated separately with the relationship quality with one’s mother and the number of household adults before the age of 16. We estimated a series of multilevel models to assess the association between polygenic risk score for AD (PGS-AD) and changes in cognitive functioning, and whether the association was moderated by the two measures of childhood social capital. Findings indicated that childhood maternal relationship quality, but not the number of household adults, protected against cognitive decline accelerated by PGS-AD. That is, the associations between higher PGS-AD and accelerated cognitive decline were attenuated for individuals who reported a better childhood maternal relationship. Findings are in line with the biopsychosocial model of health and suggest that a better quality of maternal relationships in childhood may have a protective effect on cognitive functioning across the lifespan.

ASSESSING MOTOR FUNCTION IN FRAIL OLDER ADULTS IN THEIR HOME SETTING: CHALLENGES AND OPPORTUNITIES

Abstract Motor function is essential for older adults to perform daily activities and remain in their home as they age. Mounting evidence suggests that physical activity (PA) helps maintain motor function in older adults. However, few evidence-based PA programs exist for home-bound older adults who have difficulties walking or standing. They are typically excluded from randomized controlled trials (RCT). Evidence is difficult to establish, because of the lack of instruments and protocols for assessing motor function safely and effectively in this population. The goal of this paper is to present challenges and opportunities that we encountered in assessing motor function in 119 participants of the Pro-Home study right before the COVID-19 pandemic. As expected, participants had significant physical limitations. One third of the participants did not feel safe doing balance tests or chair stand test included in the Short Physical Performance Battery. Of those who did the balance tests, two thirds had to use compensatory movement or hold on to an object to maintain balance. Interestingly, 30% of participants had cognitive impairment as defined by 1.5 Standard Deviation below the normative mean measured by NIH Toolbox Cognition Battery, although they passed a six-item cognition screener to be eligible for Pro-Home. The challenges of assessing frail older adults have led to opportunities to adapt assessment protocols. We made instructions clear and easy-to-follow and developed a new measure appropriate and safe for our target, frail older participants. Additional safety measures are needed to facilitate motor function assessments in frail older adults.

BLOOD PRESSURE MEASURES ARE NOT CORRELATED WITH NIH TOOLBOX COGNITIVE BATTERY PERFORMANCE IN BLACK OLDER ADULTS

Abstract Elevated blood pressure has been inconsistently associated with cognitive performance in older adults. Black adults experience higher rates of elevated blood pressure and cognitive impairment than White adults. This study investigated whether blood pressure measurements were associated with cognitive performance on the NIH Toolbox Cognition Battery (NIHTB-CB) in older Black adults. 77 older Black adults 65+ years of age (M=72.6, SD=4.9) with subjective cognitive decline were administered the NIHTB-CB, a battery of computer-based cognitive tests. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured before and after cognitive testing and a cognitive task-based EEG/ERP. Average SBP, DBP, and pulse pressure (PP) were calculated. Difference scores from pre- to post-EEG/ERP served as a reactivity index following cognitive task engagement. A ratio of the difference scores to the baseline measures controlled for resting blood pressure. Bayesian correlations examined the relations between blood pressure measurements and NIHTB-CB performance. Data analysis used fully corrected T scores from the NIHTB-CB subtests. Average SBP, SBP difference scores, and baseline SBP were not associated with NIHTB-CB performance on any measurement (all BF10 < 3.0). Similarly, DBP and PP were unrelated to NIHTB-CB performance. Systolic and diastolic blood pressure were not associated with any NIHTB-CB measure. Additionally, blood pressure reactivity was not related to cognitive performance. Future research may investigate the relationship between SBP reactivity and cognitive performance across multiple measurement periods. Antihypertensive medication and duration of hypertension among hypertensive individuals may also be an important consideration in future studies.

DISPARITIES IN MOCA AND MMSE SCORES AMONG DIVERSE OLDER ADULTS: A CASE ANALYSIS OF CREOLE-SPEAKING PARTICIPANTS

Abstract Almost 11% of older adults in the US have Alzheimer’s or related dementia. Most studies suggest that those who are Black or Hispanic are at higher risk. A culturally diverse sample, including Haitian older adults, was recruited from South Florida communities to participate in a longitudinal study, “In-Vehicle Sensors to Detect Change in Cognition of Older Drivers.” An extensive cognitive battery was administered for comparison with driving behaviors. No validated translations in Creole were available, so three Haitian-born examiners translated and back-translated test items into Creole. Two additional bilingual examiners verified the results. An analysis of variance (ANCOVA) comparing Haitian participants (N=12) and European Americans (N=135) on the MoCA controlling for age and education indicated the European American group scored higher (M = 25.78, SD = 2.57) than the Haitian Group (M =24.17, SD = 3.01), a significant difference in test performance, F (1, 124) = 6.11, P= .015. Results on four subscales of the MoCA evidenced significantly higher scores for the European American group: Visual EX Total, F (1, 124) = 22.52, p < .001; Serial-7, F (1, 124) = 12.09, p <.001; Attention Total, F (1, 124) = 5.10, p <.001; Letter Score F (1, 124) = 13.09, p <.001. No differences in language, abstract, delayed recall, or orientation were found. These preliminary results suggest cultural influences may account for differences in test performance. Further investigation with a larger sample of Haitian older adults is needed to explain differences in performance on this widely used test.

A LEAP! FORWARD?: DOES PERSONALIZED EXERCISE HELP MAINTAIN COGNITIVE FUNCTION IN OLDER ADULTS?

Abstract Maintaining cognitive function is important to health in older adulthood. Physical activity can decrease the risk of cognitive decline in older individuals. We tested whether LEAP! Rx, a personalized exercise, and lifestyle education program would improve cognition in older adults. We randomized 220 participants (Mean age (SD) = 72 (4.83)), into the program or a control group. We used the NIH Toolbox Cognitive Battery to assess cognition. We analyzed change in cognitive performance from baseline to week 12 using repeated measures ANCOVA to compare the intervention and control groups, adjusting for age, gender, and education. Referral source (self- vs. physician-referred), treatment group (intervention vs. control), and measurement time (baseline vs. week 12) had a significant three-way interaction F(8, 212) = 4.57, p< 0.05. That is, clinician-referred participants in the intervention group improved more (vs. the clinician-referred control group), whereas self-referred control group participants improved more (vs. the self-referred intervention group). Older age, male gender, and lower education predicted poorer verbal learning F(1,218 = 18.79, p< 0.05; F(1, 218) = 28.67, p< 0.05; F(1, 219) = 4.13. Overall, cognitive scores improved more over 12 weeks in the intervention group compared to the control group. Thus, we conclude that personalized exercise programs may enhance or maintain cognitive function in older adults. The differences we observed in physician-referred versus self-referred participants has implications for implementation and scalability of health behavior change interventions, as well as implications for recruitment methods and representation in clinical trials research broadly.

Impulsivity, decision-making, and risk behavior in bipolar disorder and major depression from bipolar multiplex families.

Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision-making, and risk-taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision-making, and risk-taking behavior in BD and MDD patients from bipolar multiplex families. Eighty-two participants (BD type I, n=25; MDD, n=26; healthy relatives (HR), n=17; and healthy controls (HC), n=14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision-making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains. Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision-making was associated with both mood disorders (BD and MDD). In risk-taking behavior, no significant impairment was found in any group. As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power. Our findings show that alterations of cognitive domains-while present in both disorders-are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders.

Cognitive deficits profiles in the first-episode of schizophrenia, clinical high risk of psychosis, and genetically high-risk of psychosis.

Cognitive deficits are core characteristics of schizophrenia, presenting before the emergence of psychotic symptoms. Individuals with a clinical high-risk for psychosis (CHR) and those with genetically high-risk of psychosis (GHR) also exhibit cognitive impairments. Nonetheless, it remains uncertain in which domains of cognitive impairments in these two groups were more similar to those of schizophrenia patients. Moreover, it is unclear which domains of impairment are caused by quality factors and which are more related to the state of disease. This research initiative aimed to extensively examine the distinct cognitive impairment profiles among the CHR, GHR, and first-episode schizophrenia (FES) cohorts. We compared the cognitive functions of the three groups and a healthy control group (HCs) using the MATRICS Consensus Cognitive Battery (MCCB). The participants for this study were recruited from the Beijing Anding Hospital of Capital Medical University. Our sample consisted of 56 patients with FES, 42 with CHR, 26 with GHR, and 62 HCs. The participants across all groups were matched in terms of gender, age, and level of education. Individuals with FES, GHR, and CHR showed significant impairment across the majority of MCCB domains, with the exception of visual learning, in comparison to HCs. None of the MCCB domains demonstrated a discerning ability to accurately differentiate between individuals with CHR and those with GHR. In the speed of processing and attention/vigilance domains, individuals with GHR and CHR exhibited scores between those of FES and HCs, with all group differences reaching statistical significance. This pattern of results indicates an intermediate level of cognitive function in individuals with GHR and CHR. Conversely, the levels of impairment observed in working memory and verbal learning were relatively consistent across all three groups: FES, CHR, and GHR. Notably, individuals in the CHR group exhibited performance akin to that of the HCs in the reasoning/problem-solving domain, while showing significant differences from the FES group, with the CHR individuals demonstrating better performance. Additionally, individuals with GHR displayed performance in social cognition similar to that of the HCs, while also demonstrating significant distinctions from the FES group, with the GHR individuals demonstrating better performance. Significant cognitive deficits exist in individuals with CHR, GHR, and FES, and these deficits vary across domains. Processing speed and attention/vigilance could potentially serve as robust biomarkers for identifying individuals at a risk of psychosis. The impairment observed in reasoning/problem-solving abilities might signify a qualitative trait, whereas deficits in social recognition could indicate a state characteristic specific to schizophrenia.

Relevance of neurocognition in chronic pain syndrome: a systematic and methodical approach

ABSTRACT Introduction Subjective and objective deficits in neurocognitive domains are well-documented in patients with chronic pain. However, neurocognitive deficits have not been investigated consistently. The main objective of this study was to conduct a comprehensive assessment of self-rated and objectively assessed cognitive differences between patients with chronic pain (CP) and healthy controls (HC). Method The cognitive functioning of 40 CP and 41 HC was assessed using a standardized computer-based test battery, enabling a comparison of subjective and objective neurocognitive factors. To achieve this, the Vienna Test System (VTS) was utilized, incorporating standardized tests from the Cognitive Basic Assessment Battery (COGBAT) with the advantage of objectivity, reliability, validity, efficiency, utility, and standardization. This approach enables the evaluation of cognitive functioning across all pertinent domains. Results CP reported cognitive deficits in overall performance as well as specific functions, such as attention, memory, and executive functions. Across all neurocognitive domains, CP showed a poorer performance. Affected subdomains of attention were intensity and selectivity of attention. Lower performance was found also in concentration performance, obtaining and overview, visual orientation performance and reactive stress tolerance. Regarding memory, CP performed worse in figural episodic memory and recognition tasks. In addition, CP exhibited poorer performance in mental flexibility, working memory, planning ability, and inhibition as components of executive functioning, when compared to HC. Conclusions CP expressed subjective cognitive deficits and demonstrated impaired neurocognitive performance.

Elevated homocysteine levels may moderate and mediate the association between HIV and cognitive impairment among middle-aged and older adults in an underserved population in Baltimore, Maryland.

Background: In the antiretroviral therapy (ART) era, HIV-associated neurocognitive disorders (HAND) remain a considerable challenge for people with HIV, yet not all such disorders can be attributed to HIV alone. This study aimed to: (1) identify factors influencing neurocognitive impairment (NCI) utilizing the NIH Toolbox Cognition Battery (NIHTB-CB) as per the revised research criteria for HAND; (2) ascertain the moderating role of high homocysteine levels in the association between NCI and HIV; and (3) assess the mediating effect of elevated homocysteine levels on this association.Methods: We analyzed data from 788 adults (≥45years) participating in a study on HIV-related comorbidities in underserved Baltimore communities, using NIHTB-CB to gauge neurocognitive performance. Special attention was given to results from the Dimensional Change Card Sort (DCCS) test within the executive function domain during causal mediation analysis.Results: Overall, HIV was not associated with NCI presence. However, HIV was associated with NCI among individuals with homocysteine >14μmol/L. Furthermore, HIV was both directly and indirectly associated with NCI in DCCS test scores. Notably, the mediating role of elevated homocysteine in DCCS scores was only observable among individuals who had never used cocaine or had used it for ≤ 10years, suggesting that extended cocaine use may have a substantial influence on cognitive performance.Conclusions: The findings from this study suggest elevated homocysteine levels may moderate and mediate the association between HIV and neurocognitive impairment.

Sensitivity of Individual and Composite Test Scores from the Cogstate Brief Battery to Mild Cognitive Impairment and Dementia Due to Alzheimer's Disease.

The Cogstate Brief Battery (CBB) is a computerized cognitive test battery used commonly to identify cognitive deficits related to Alzheimer's disease (AD). However, AD and normative samples used to understand the sensitivity of the CBB to AD in the clinic have been limited, as have the outcome measures studied. This study investigated the sensitivity of CBB outcomes, including potential composite scores, to cognitive impairment in mild cognitive impairment (MCI) and dementia due to AD, in carefully selected samples. Samples consisted of 4,871 cognitively unimpaired adults and 184 adults who met clinical criteria for MCI (Clinical Dementia Rating (CDR) = 0.5) or dementia (CDR > 0.5) due to AD and CBB naive. Speed and accuracy measures from each test were examined, and theoretically- and statistically-derived composites were created. Sensitivity and specificity of classification of cognitive impairment were compared between outcomes. Individual CBB measures of learning and working memory showed high discriminability for AD-related cognitive impairment for CDR 0.5 (AUCs ∼ 0.79-0.88), and CDR > 0.5 (AUCs ∼ 0.89-0.96) groups. Discrimination ability for theoretically derived CBB composite measures was high, particularly for the Learning and Working Memory (LWM) composite (CDR 0.5 AUC = 0.90, CDR > 0.5 AUC = 0.97). As expected, statistically optimized linear composite measures showed strong discrimination abilities albeit similar to the LWM composite. In older adults, the CBB is effective for discriminating cognitive impairment due to MCI or AD-dementia from unimpaired cognition with the LWM composite providing the strongest sensitivity.

Analysis of telomere length and the relationship with neurocognitive functions in euthymic bipolar disorder: A cross-sectional pilot study

BackgroundTelomere shortening has been considered a potential biological marker related to disease susceptibility and aging in psychiatric disorders. However, the relationship between telomere length and bipolar disorder (BD-I and BD-II) is uncertain. Moreover, whether telomere shortening is an independent factor of cognitive impairment in BD patients is still inconclusive. MethodsWe explore telomere length and cognitive function in patients with bipolar disorder and the relationship between them. We enrolled three groups (35 patients with euthymic BD-I, 18 with euthymic BD-II, and 38 healthy controls). Telomere length was measured by fluorescent quantitative polymerase chain reaction (q-PCR), and cognitive function was evaluated by the MATRICS Consensus Cognitive Battery (MCCB). SPSS 24.0 was used for statistical analysis. ResultsThe telomere length of euthymic patients with BD-I and BD-II was shorter than that of healthy controls (F = 8.228, P = 0.001, η2 = 0.176). Telomere length was not significantly different between BD-I and BD-II. Compared to HCs, poor performance was detected in attention and vigilance in BD-I patients (F = 3.473, P = 0.036). Working memory was positively correlated with telomere length in BD-II patients (Beta = 0.5, P = 0.041, Adjusted R2 = 0.2). ConclusionsThe current study provided evidence of shortened telomere length in euthymic BD patients, indicating that telomere shortening might be a promising biomarker of susceptibility to bipolar disorder. The telomere length predicted the working memory in BD-II patients. Further studies are needed to clarify the role of accelerated aging on cognitive functioning in a young group of patients with BD.

The association between cardiovascular health and cognition in adults with Down syndrome

IntroductionEvidence in the general population suggests that predictors of cardiovascular health such as moderate to vigorous physical activity (MVPA), cardiorespiratory fitness, and systolic blood pressure are associated with cognitive function. Studies supporting these associations in adults with Down syndrome (DS) are limited. The purpose of this study was to examine the associations between systolic blood pressure, cardiorespiratory fitness, and MVPA on cognition in adults with DS.MethodsThis is a cross-sectional analysis using baseline data from a trial in adults with DS. Participants attended a laboratory visit where resting blood pressure, cardiorespiratory fitness (VO2 Peak), and cognitive function (CANTAB® DS Battery) were obtained. The cognitive battery included tests measuring multitasking, episodic memory, and reaction time. Physical activity (accelerometer) was collected over the week following the laboratory visit. Pearson correlations and linear regressions were used to measure the impact of systolic blood pressure, cardiorespiratory fitness, and MVPA on cognitive outcomes.ResultsComplete data was available for 72 adults with DS (26.8 ± 9.3 years of age, 57% female). At baseline, VO2 Peak (21.1 ± 4.2 ml/kg/min) and MVPA were low (14.4 ± 14.4 min/day), and systolic blood pressure was 118.3 ± 13.3 mmHg. VO2 Peak was correlated with simple movement time (rho = − 0.28, p = 0.03) but was not significant using a linear regression controlling for age and sex. Systolic blood pressure was significantly associated with episodic memory (first attempt memory score: β = − 0.11, p = 0.002; total errors: β = 0.58, p = 0.001) and reaction time (five-choice movement time: β = 4.11, p = 0.03; simple movement time: β = 6.14, p = 0.005) using age- and sex-adjusted linear regressions. No associations were observed between MVPA and multitasking, episodic memory, or reaction time.ConclusionPredictors of cardiovascular health, including cardiorespiratory fitness and systolic blood pressure, were associated with some aspects of cognition in adults with DS. While future research should examine the role of improved cardiovascular health on delaying decreases in cognitive function and dementia in adults with DS, we recommend that health care providers convey the importance of exercise and cardiovascular health to their patients with DS.Trial registrationNCT04048759, registered on August 7, 2019.

Cannabis use and neurocognitive performance at 13–14 Years-Old: Optimizing assessment with hair toxicology in the Adolescent brain cognitive development (ABCD) study

ObjectiveCannabis is widely used, including in early adolescence, with prevalence rates varying by measurement method (e.g., toxicology vs. self-report). Critical neurocognitive development occurs throughout adolescence. Given conflicting prior brain-behavior results in cannabis research, improved measurement of cannabis use in younger adolescents is needed. MethodsData from the Adolescent Brain Cognitive Development (ABCD) Study Year 4 follow-up (participant age: 13–14 years-old) included hair samples assessed by LC-MS/MS and GC–MS/MS, quantifying THCCOOH (THC metabolite), THC, and cannabidiol concentrations, and the NIH Toolbox Cognitive Battery. Youth whose hair was positive for cannabinoids or reported past-year cannabis use were included in a Cannabis Use (CU) group (n = 123) and matched with non-using Controls on sociodemographics (n = 123). Standard and nested ANCOVAs assessed group status predicting cognitive performance, controlling for family relationships. Follow-up correlations assessed cannabinoid hair concentration, self-reported cannabis use, and neurocognition. ResultsCU scored lower on Picture Memory (p = .03) than Controls. Within the CU group, THCCOOH negatively correlated with Picture Vocabulary (r = -0.20, p = .03) and Flanker Inhibitory Control and Attention (r = -0.19, p = .04), and past-year cannabis use was negatively associated with List Sorting Working Memory (r = -0.33, p = .0002) and Picture Sequence Memory (r = -0.19, p = .04) performances. ConclusionsYouth who had used cannabis showed lower scores on an episodic memory task, and more cannabis use was linked to poorer performances on verbal, inhibitory, working memory, and episodic memory tasks. Combining hair toxicology with self-report revealed more brain-behavior relationships than self-report data alone. These youth will be followed to determine long-term substance use and neurocognition trajectories.

Association of plasma biomarkers with cognitive function in persons with dementia and cognitively healthy in the Democratic Republic of Congo

AbstractBackgroundCross‐sectional and longitudinal measurements of plasma biomarkers of Alzheimer’s disease (AD) in Western countries are being applied in clinical practice, whereas their associations with culturally validated cognitive tests in other settings remain unknown. We aim to examine cross‐sectional association of plasma protein biomarker concentrations and APOE proteotype with cognitive function and explore the discriminative role of these AD biomarkers in such an association.MethodThis is a cross‐sectional retrospective study completed from 2018 to 2022 in the Democratic Republic of Congo (DRC). Subjects were recruited from clinics, hospitals, churches, and across DRC. The study started in January 2018 until December 2022. Data were analyzed from May 2022 to December 2022. The DRC Memory clinic team recruited 1430 individuals 65 years and over. Based on Community Screening Instruments for Dementia (CSID), and Alzheimer’s Questionnaire (AQ), and DSM‐5 diagnostic criteria, participants included 44 individuals classified as major neurocognitive disorder (dementia) and 41 as healthy controls (HC). Subjects underwent cognitive assessment with a validated, culturally‐tailored cognitive battery. AD plasma biomarkers (Aβ42, Aβ40, Aβ42/40, p‐tau 181), APS (derived from Aβ42/40, APOE status, and age), and APOE proteotype were utilized to assess for genetic risk.ResultIndividuals with dementia had significantly lower Aβ42/40 levels, higher APS, and higher APOE ε4 prevalence compared to HC. Linear regressions showed significantly associations between Aβ42/40 and APS with ANT, ALMT, and AVMT scores, while APOE ε4 presence was associated with ANT, ALMT, AVMT, and APT scores. APS showed the highest AUC value (AUC = 0.78, 95% CI: 0.68‐0.88) followed by Aβ42/40 (AUC = 0.75, 95% CI: 0.66‐0.86) and APOE ε4 (AUC = 0.69 (CI 0.57‐0.81) in discriminating dementia from HC.ConclusionSelect AD biomarkers were associated with cognition and differentiated dementia from HC, consistent with extant research. These findings may have implications for the assessment of AD biomarkers in DRC.

Impact of Multivitamin‐Mineral and Cocoa Extract on Incidence of Mild Cognitive Impairment and Dementia: Results from the Cocoa Supplement and Multivitamin Outcomes Study for the Mind COSMOS‐Mind

AbstractBackgroundCOSMOS‐Mind, a large, randomized placebo‐controlled pragmatic trial in older adults, recently reported that daily supplementation with multivitamin‐mineral, but not cocoa extract, benefited global cognition. We assessed effects of these supplements on prespecified secondary outcomes of mild cognitive impairment (MCI) and all‐cause dementia (DM). We also assessed treatment‐related cognitive trajectories leading to conversion to MCI or dementia.MethodCOSMOS‐Mind (N = 2262) administered a telephone‐based cognitive battery at baseline and annually for 3 years. Proxies of participants meeting criteria for suspected cognitive impairment based on a cognitive screener (TICSm) were interviewed. An expert panel adjudicated cognitive status. Incidence rates of MCI, and separately DM, were compared among arms with proportional hazards regression. Changes in cognitive trajectories leading to MCI and DM were assessed with linear models.ResultAt baseline, adjudication for suspected cognitive impairment was triggered for 419 (20%) participants, yielding adjudications of 217 (10%) MCI and 4 (0.2%) DM cases. During follow‐up, triggers were less frequent in the MVM than placebo arms: hazard ratio = 0.73 (p = 0.04). Across 3 years, 110 incident MCI and 14 incident DM cases were adjudicated. Incidence rates of these outcomes did not vary by assignment to multivitamin‐mineral or cocoa extract (all p≥0.05), however statistical power was low. Incident MCI was associated with a marked decline in cognitive function from the previous year (p<0.001). When participants assigned to multivitamin‐mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p<0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function). Daily cocoa extract use did not attenuate cognitive decline leading up to MCI.ConclusionCOSMOS‐Mind does not provide evidence that cocoa extract or multivitamin‐mineral therapy lowers risk of incident MCI or DM. Multivitamin‐mineral therapy, but not cocoa extract, may provide cognitive resilience countering conversion to MCI.

The Look AHEAD Aging Study: design, cohort characteristics, and cognitive function

AbstractBackgroundData on cognitive trajectories and characteristics associated with cognitive resilience among older individuals with type 2 diabetes and overweight or obesity are scant. To date, the NIA‐funded Action for Health in Diabetes (Look AHEAD) Aging Study has enrolled 1245 individuals, ages 64 to 95 years, who have been richly characterized over 18 years of prior follow‐up with factors associated with cognitive aging.MethodVolunteers from the Look AHEAD clinical trial of a multidomain lifestyle intervention and its subsequent clinic‐based post‐trial observational phase were invited to join a 4‐year telephone‐based observational study that includes annual cognitive assessments to assess memory, attention/processing speed, executive function, and global cognitive function. A composite measure of cognitive function based on the average standardized cognitive function tests was used to capture global cognitive function. Mild cognitive impairment and probable dementia will be centrally adjudicated. Additional measures include depressive symptoms, physical function and abilities, medical events, medication use, and health related quality of life. Recruitment will be completed in early 2023.ResultThe enrolled cohort to date (N = 1590) includes 62% women, 32% individuals from traditionally under‐represented racial/ethnic minorities, 49% without college education, and 52% who had been randomly assigned to the lifestyle intervention. The mean (SD) age is 76.3 (5.6) and years of diabetes is 25.5 (5.5). When last measured, the mean BMI was 33.8 (6.3) kg/m2 and 4 m walk speed was 0.86 (0.22) m/sec. Of 1060 who were tested, 20.6% have one apoE‐e4 allele and 1.1% have two apoE‐e4 alleles. Modified Telephone Interview for Cognitive Status (TICSm) scores ranged from 12 to 48, with mean 34.7 (4.7), with no difference between intervention groups (p = 0.66). While TICSm scores tended to be lower for older participants, many still demonstrated relatively high levels of cognitive functioning, even into the 8th decade of life (attached figure).ConclusionThe Look AHEAD Aging study holds great promise to identify factors across two decades of follow‐up that are associated with cognitive resilience in a large cohort with type 2 diabetes and overweight or obesity. Our presentation will provide data on the full cohort and cognitive battery.

COVID19 and cognitive impairment ‐ A follow‐up study with cognitive and neuroimaging evaluation of the Clinical Hospital of São Paulo

AbstractBackgroundPost‐COVID19 syndrome is characterized by signs and symptoms that occur within 3 months of the onset of COVID19 and last for at least 2 months. Cognitive impairment has frequently been associated with COVID19 with descriptions of attentional, executive, memory, and language disorders. Moreover, some morphological and metabolic changes have been described in MRI and FDG PET‐CT, respectively. There is no formal treatment for this condition.MethodWe selected patients less than 65 years of age with COVID19 at least 3 or more months of symptoms and no more than 6 months, no relevant structural brain lesions, no record of neurodegenerative disease. A cross‐over design study was performed with neuropsychological rehabilitation. They were evaluated 3 times by a neurologist (0, 3, and 6 months) with specific cognitive battery tests and questionnaires and then by a neuropsychologist for evaluation and training. Finally, most patients underwent neuroimaging with cranial MRI and FDG PET CT or MRI.Result44 patients performed the first baseline evaluation, 34 matched inclusion criteria and were referred to neuropsychological rehabilitation. 20 underwent functional and structural neuroimaging. This sample had a mean age of 44 (SD8.9) years, 61% of females, 16.1 (SD5.1) years of education, 17.6% of hypertension, 2.9% diabetes, 11.8% dyslipidemia and 23.5% obesity. Cognitive evaluation depicted that 90.6% had memory complaints; MMSE of 27.7 (SD1.8); delayed recall of 8.68 (SD1.6) out 10 in the brief cognitive screening battery; semantic verbal fluency of 18.24 (SD5.1); lexical fluency of 31.7 (SD11.7); forward digit span 6.62 (SD0.7); backward digit span 4.82 (SD 1.3); clock drawing test of 9.12 (SD1.6) and Boston naming test‐15 of 14.06 (SD1.5). 46.9% reported more than 5 points on the depression scale and 41.2% somnolence on the Epworth scale. 60% had abnormal findings (hypometabolism) in brain FDG PET, 16% with frontotemporal involvement, 33% basal ganglia, 8% frontoparietal, 41% cerebellum, 8% parietal only, 8% frontalmedial, and 25% temporal. Some (33%) had mixed patterns.Conclusionpost‐COVID19 syndrome and cognitive impairment are relatively common and we need prospective studies in low and middle‐income countries to understand the cognitive profile, structural and metabolic patterns in neuroimage, and the role of neuropsychological rehabilitation.

Feasibility and acceptability of automated cognitive assessment over the telephone in the SpeAK study

AbstractBackgroundThere is growing interest in the development of speech markers as novel, non‐invasive biomarkers of early Alzheimer’s disease (AD). Before including such speech assessments in clinical trials, the technology must be tested to confirm feasibility of administration and acceptability with the target population to ensure future engagement. This study aimed to assess feasibility and acceptability in an at‐risk population receiving automated administration of cognitive tasks over the telephone during the Speech on the Phone Assessment (SPeAk) study [35]. A second goal of the study was to assess participant acceptability of receiving cognitive test results ‐ an important consideration for psychological safety.MethodParticipants (n = 68, mean age 70.43 years, 52.9% male) completed a baseline – administered by a trained researcher ‐ and three month follow up visit – administered by an automated phonebot. Tasks included a spontaneous speech assessment and cognitive battery (immediate and delayed recall, digit span and verbal fluency). Participants were randomized to receive their cognitive test results after the final or after each study visit. Participants completed acceptability questionnaires electronically after each study visit.ResultRetention was high (98.5%), with few technical issues (n = 6.7%), there was good inter rater reliability, and test scores were similar when administered by phonebot compared to human administrator in most subtests. A significant lower mean score in digit span was noted at follow up. These findings indicate general feasibility of the assessment. Participants preferred a human tester but rated the automated assessments as acceptable and would be happy to complete a phonebot assessment again, confirming the ease of use of the technology and comfort of completing cognitive tasks on the phone. Participants generally reported feeling happy to receive their cognitive tests results, and this disclosure did not cause participants to feel worried.ConclusionThe results from this usability and acceptability analysis suggests that completing this brief battery of cognitive tests via a telephone call is both acceptable and feasible in a midlife‐to‐older adult population in the UK, living at risk for AD.