Development and validation of the Michigan Chronic Disease Simulation Model (MICROSIM).

Strategies to prevent or delay Alzheimer's disease and related dementias (AD/ADRD) are urgently needed, and blood pressure (BP) management is a promising strategy. Yet the effects of different BP control strategies across the life course on AD/ADRD are unknown. Randomized trials may be infeasible due to prolonged follow-up and large sample sizes. Simulation analysis is a practical approach to estimating these effects using the best available existing data. However, existing simulation frameworks cannot estimate the effects of BP control on both dementia and cardiovascular disease. This manuscript describes the design principles, implementation details, and population-level validation of a novel population-health microsimulation framework, the MIchigan ChROnic Disease SIMulation (MICROSIM), for The Effect of Lower Blood Pressure over the Life Course on Late-life Cognition in Blacks, Hispanics, and Whites (BP-COG) study of the effect of BP levels over the life course on dementia and cardiovascular disease. MICROSIM is an agent-based Monte Carlo simulation designed using computer programming best practices. MICROSIM estimates annual vascular risk factor levels and transition probabilities in all-cause dementia, stroke, myocardial infarction, and mortality in a nationally representative sample of US adults 18+ using the National Health and Nutrition Examination Survey (NHANES). MICROSIM models changes in risk factors over time, cognition and dementia using changes from a pooled dataset of individual participant data from 6 US prospective cardiovascular cohort studies. Cardiovascular risks were estimated using a widely used risk model and BP treatment effects were derived from meta-analyses of randomized trials. MICROSIM is an extensible, open-source framework designed to estimate the population-level impact of different BP management strategies and reproduces US population-level estimates of BP and other vascular risk factors levels, their change over time, and incident all-cause dementia, stroke, myocardial infarction, and mortality.

Alzheimer's Disease and Related Dementias in Muslim Women: Recommendations for Culturally Sensitive Care.

Alzheimer's disease and related dementias (ADRD) present significant challenges including cognitive and functional loss, behavioral disruption, emotional distress, and significant financial burden. These stressors are amplified in minority groups, who experience higher rates of ADRD but less frequent and later diagnosis. There is therefore a critical need to identify tangible approaches to culturally informed dementia assessment and care for patients from diverse communities. Muslim patients and particularly Muslim women are among the populations most understudied in the ADRD space. Muslim patients may hold unique religious, spiritual, and cultural beliefs and practices that can impact care-seeking for dementia symptoms, diagnostic accuracy, and treatment uptake. This paper outlines culturally informed approaches to assessing and treating Muslim women and families at each stage of ADRD care, though many recommendations extend to the broader Muslim community and others of diverse racial-ethnic backgrounds. We provide concrete suggestions for building rapport within and leveraging common family structures, respecting principles of modesty and privacy for all women including those who observe hijab or niqab, and communicating dementia diagnosis and care in the context of spiritual and ethical beliefs. While not intended as a comprehensive and prescriptive guide, this review provides important points of consideration and discussion with patients of Muslim backgrounds.

Effect of Population-Level Blood Pressure Treatment Strategies on Cardiovascular and Cognitive Outcomes.

BACKGROUND: The large and increasing number of adults living with dementia is a pressing societal priority, which may be partially mitigated through improved population-level blood pressure (BP) control. We explored how tighter population-level BP control affects the incidence of atherosclerotic cardiovascular disease (ASCVD) events and dementia. METHODS: Using an open-source ASCVD and dementia simulation analysis platform, the Michigan Chronic Disease Simulation Model, we evaluated how optimal implementation of 2 BP treatments based on the Eighth Joint National Committee recommendations and SPRINT (Systolic Blood Pressure Intervention Trial) protocol would influence population-level ASCVD events, global cognitive performance, and all-cause dementia. We simulated 3 populations (usual care, Eighth Joint National Committee based, SPRINT based) using nationally representative data to annually update risk factors and assign ASCVD events, global cognitive performance scores, and dementia, applying different BP treatments in each population. We tabulated total ASCVD events, global cognitive performance, all-cause dementia, optimal brain health, and years lived in each state per population. RESULTS: Optimal implementation of SPRINT-based BP treatment strategy, compared with usual care, reduced ASCVD events in the United States by ≈77 000 per year and produced 0.4 more years of stroke- or myocardial infarction-free survival when averaged across all Americans. Population-level gains in years lived free of ASCVD events were greater for SPRINT-based than Eighth Joint National Committee-based treatment. Survival and years spent with optimal brain health improved with optimal SPRINT-based BP treatment implementation versus usual care: the average patient with hypertension lived 0.19 additional years and 0.3 additional years in optimal brain health. SPRINT-based BP treatment increased the number of years lived without dementia (by an average of 0.13 years/person with hypertension), but increased the total number of individuals with dementia, mainly through more adults surviving to advanced ages. CONCLUSIONS: Tighter BP control likely benefits most individuals but is unlikely to reduce dementia prevalence and might even increase the number of older adults living with dementia.

Predicting 5-year dementia conversion in veterans with mild cognitive impairment.

INTRODUCTION: Identifying mild cognitive impairment (MCI) patients at risk for dementia could facilitate early interventions. Using electronic health records (EHRs), we developed a model to predict MCI to all-cause dementia (ACD) conversion at 5 years. METHODS: Cox proportional hazards model was used to identify predictors of ACD conversion from EHR data in veterans with MCI. Model performance (area under the receiver operating characteristic curve [AUC] and Brier score) was evaluated on a held-out data subset. RESULTS: Of 59,782 MCI patients, 15,420 (25.8%) converted to ACD. The model had good discriminative performance (AUC 0.73 [95% confidence interval (CI) 0.72-0.74]), and calibration (Brier score 0.18 [95% CI 0.17-0.18]). Age, stroke, cerebrovascular disease, myocardial infarction, hypertension, and diabetes were risk factors, while body mass index, alcohol abuse, and sleep apnea were protective factors. DISCUSSION: EHR-based prediction model had good performance in identifying 5-year MCI to ACD conversion and has potential to assist triaging of at-risk patients. Highlights: Of 59,782 veterans with mild cognitive impairment (MCI), 15,420 (25.8%) converted to all-cause dementia within 5 years.Electronic health record prediction models demonstrated good performance (area under the receiver operating characteristic curve 0.73; Brier 0.18).Age and vascular-related morbidities were predictors of dementia conversion.Synthetic data was comparable to real data in modeling MCI to dementia conversion. Key Points: An electronic health record-based model using demographic and co-morbidity data had good performance in identifying veterans who convert from mild cognitive impairment (MCI) to all-cause dementia (ACD) within 5 years.Increased age, stroke, cerebrovascular disease, myocardial infarction, hypertension, and diabetes were risk factors for 5-year conversion from MCI to ACD.High body mass index, alcohol abuse, and sleep apnea were protective factors for 5-year conversion from MCI to ACD.Models using synthetic data, analogs of real patient data that retain the distribution, density, and covariance between variables of real patient data but are not attributable to any specific patient, performed just as well as models using real patient data. This could have significant implications in facilitating widely distributed computing of health-care data with minimized patient privacy concern that could accelerate scientific discoveries.

Biomarkers of chronic inflammation and cognitive decline: A prospective observational study.

We sought to determine whether the biomarkers of chronic inflammation predict cognitive decline in a prospective observational study. We measured baseline serum soluble urokinase plasminogen activator receptor (suPAR) and high sensitivity C-reactive protein (hs-CRP) levels in 282 participants of the University of Michigan Memory and Aging Project. Cognitive function was measured using the Montreal Cognitive Assessment (MoCA) and the Clinical Dementia Rating (CDR) scale for up to five time points. SuPAR and hs-CRP levels were not significantly higher in participants with mild cognitive impairment (n = 97) or dementia (n = 59), compared to those with normal cognitive function (n = 126). Overall, 14% of participants experienced significant cognitive decline over the study period. The change in MoCA or CDR scores over time did not differ significantly according to baseline suPAR or hs-CRP levels. Chronic systemic inflammation, as measured by serum suPAR or hs-CRP levels, is unlikely to contribute significantly to cognitive decline.

Trajectory of Cognitive Function After Incident Heart Failure.

Background: The size/magnitude of cognitive changes after incident heart failure (HF) are unclear. We assessed whether incident HF is associated with changes in cognitive function after accounting for pre-HF cognitive trajectories and known determinants of cognition. Methods: This pooled cohort study included adults without HF, stroke, or dementia from six US population-based cohort studies from 1971-2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Linear mixed-effects models estimated changes in cognition at the time of HF (change in the intercept) and the rate of cognitive change over the years after HF (change in the slope), controlling for pre-HF cognitive trajectories and participant factors. Change in global cognition was the primary outcome. Change in executive function and memory were secondary outcomes. Cognitive outcomes were standardized to a t-score metric (mean [SD], 50 [10]); a 1-point difference represented a 0.1-SD difference in cognition. Results: The study included 29,614 adults (mean [SD] age was 61.1 [10.5] years, 55% female, 70.3% White, 22.2% Black 7.5% Hispanic). During a median follow-up of 6.6 (Q1-Q3: 5-19.8) years, 1,407 (4.7%) adults developed incident HF. Incident HF was associated with an acute decrease in global cognition (-1.08 points; 95% CI -1.36, -0.80) and executive function (-0.65 points; 95% CI -0.96, -0.34) but not memory (-0.51 points; 95% CI -1.37, 0.35) at the time of the event. Greater acute decreases in global cognition after HF were seen in those with older age, female sex and White race. Individuals with incident HF, compared to HF-free individuals, demonstrated faster declines in global cognition (-0.15 points per year; 95% CI, -0.21, -0.09) and executive function (-0.16 points per year; 95% CI -0.23, -0.09) but not memory ( -0.11 points per year; 95% CI -0.26, 0.04) compared with pre-HF slopes. Conclusions: In this pooled cohort study, incident HF was associated with an acute decrease in global cognition and executive function at the time of the event and faster declines in global cognition and executive function over the following years.

Psychological Distress among family caregivers of persons with Alzheimer's Disease and Related Dementias in Uganda.

Background: Alzheimer's disease and related dementia (ADRD) present growing global health challenges, especially in aging populations such as Uganda. In Uganda, familial caregiving, predominantly undertaken by female relatives, is the primary form of support for patients with ADRD. Cultural stigma around dementia and limited access to support services amplify caregivers' challenges. This study examined psychological distress, depression, and quality of life (QoL) among family caregivers of patients with ADRD in Wakiso District, Uganda. Methods: This cross-sectional study involved 90 caregivers from three sub-counties in Wakiso selected through purposive sampling to capture diverse experiences. Data were collected using the Kessler Psychological Distress Scale, Caregiver Dementia Quality of Life Measurement Scale, and Center for Epidemiologic Studies Depression Scale, with an 80% response rate achieved through local collaboration. Statistical analyses focused on psychological distress, QoL, and depression. Results: The study included 82.2% females and 17.8% males, with a median age of 52 years for females and 35 years, respectively. Females were more likely to be single or widowed, whereas males were more likely to be married. The study revealed a high prevalence of psychological distress and depression among caregivers (64.4%) regardless of sex. The analysis indicated that having children was a significant predictor of better QoL (OR 3.04, 95% CI 1.79-5.66, p=0.034) and lower risk of depression (OR 0.10, 95% CI 0.01-0.86, p=0.036). No other sociodemographic factor was significantly associated with health outcomes across the models. Conclusion: Our findings revealed a heavy burden of psychological distress and depression among Ugandan caregivers of patients with ADRD, highlighting the need for structured support systems, including mental health services and gender-responsive interventions, in low-resource settings.

Construct validation of NIH Toolbox Cognition Battery premorbid cognitive functioning scores in Black and White older Americans with and without mild cognitive impairment.

OBJECTIVE: Valid estimates of premorbid cognitive functioning (PMIQ) are crucial for the assessment of older adults at risk for Alzheimer's disease. We investigated the relationship between the NIH Toolbox-Cognition Battery's (NIHTB-CB) Oral Reading Recognition (ORR) subtest and Wechsler Test of Adult Reading scores (WTAR, convergent validity). We also compared ORR to NIHTB-CB Flanker scores, where null relationships were expected (discriminant validity). METHODS: The WTAR and NIHTB-CB were administered to 130 cognitively normal (CN) and 113 participants with mild cognitive impairment (MCI). Participants were community-dwelling, older Black and White adults, ages 55-88 years. Data analysis used uncorrected standard scores and Bayesian bivariate correlations. Supplemental materials include intraclass correlations. RESULTS: ORR and WTAR scores were strongly positively associated, while ORR and Flanker scores were unrelated. This pattern held when restricting analyses to the two cognitive status groups, the two racial groups, and the four race-by-diagnosis subgroups. CONCLUSION: The findings demonstrate convergent and discriminant validity and support NIHTB-CB ORR scores as valid estimates of scores on a PMIQ measure in older Black and White adults with and without MCI.

Novel methodology for detection and prediction of mild cognitive impairment using resting-state EEG.

BACKGROUND: Early discrimination and prediction of cognitive decline are crucial for the study of neurodegenerative mechanisms and interventions to promote cognitive resiliency. METHODS: Our research is based on resting-state electroencephalography (EEG) and the current dataset includes 137 consensus-diagnosed, community-dwelling Black Americans (ages 60-90 years, 84 healthy controls [HC]; 53 mild cognitive impairment [MCI]) recruited through Wayne State University and Michigan Alzheimer's Disease Research Center. We conducted multiscale analysis on time-varying brain functional connectivity and developed an innovative soft discrimination model in which each decision on HC or MCI also comes with a connectivity-based score. RESULTS: The leave-one-out cross-validation accuracy is 91.97% and 3-fold accuracy is 91.17%. The 9 to 18 months' progression trend prediction accuracy over an availability-limited subset sample is 84.61%. CONCLUSION: The EEG-based soft discrimination model demonstrates high sensitivity and reliability for MCI detection and shows promising capability in proactive prediction of people at risk of MCI before clinical symptoms may occur.

Computerized Cognitive Training and 24-Month Mortality in Heart Failure.

BACKGROUND: Cognitive dysfunction predicts mortality in heart failure (HF). Computerized cognitive training (CCT) has shown preliminary efficacy in improving cognitive function. However, the relationship between CCT and mortality is unclear. Aims were to evaluate (1) long-term efficacy of CCT in reducing 24-month mortality and (2) age, HF severity, global cognition, memory, working memory, depressive symptoms, and health-related quality of life as predictors of 24-month mortality among patients with HF. METHODS: In this prospective longitudinal study, 142 patients enrolled in a 3-arm randomized controlled trial were followed for 24 months. Logistic regression was used to achieve the aims. RESULTS: Across 24 months, 16 patients died (CCT, 8.3%; control groups, 12.8%). Computerized cognitive training did not predict 24-month mortality (odds ratio [OR], 0.65). Older age (OR, 1.08), worse global cognition (OR, 0.73), memory (OR, 0.81), and depressive symptoms (OR, 1.10) at baseline predicted 24-month mortality. CONCLUSIONS: Efficacious interventions are needed to improve global cognition, memory, and depressive symptoms and reduce mortality in HF.

Evaluation of the Uniform Data Set version 3 teleneuropsychological measures.

OBJECTIVE: Few studies have evaluated in-home teleneuropsychological (teleNP) assessment and none, to our knowledge, has evaluated the National Alzheimer's Coordinating Center's (NACC) Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 t-cog). The current study evaluates the reliability of the in-home UDS v3.0 t-cog with a prior in-person UDS v3.0 evaluation. METHOD: One hundred and eighty-one cognitively unimpaired or cognitively impaired participants from a longitudinal study of memory and aging completed an in-person UDS v3.0 and a subsequent UDS v3.0 t-cog evaluation (∼16 months apart) administered either via video conference (n = 122) or telephone (n = 59). RESULTS: We calculated intraclass correlation coefficients (ICCs) between each time point for the entire sample. ICCs ranged widely (0.01-0.79) but were generally indicative of "moderate" (i.e., ICCs ranging from 0.5-0.75) to "good" (i.e., ICCs ranging from 0.75-0.90) agreement. Comparable ICCs were evident when looking only at those with stable diagnoses. However, relatively stronger ICCs (Range: 0.35-0.87) were found between similarly timed in-person UDS v3.0 evaluations. CONCLUSIONS: Our findings suggest that most tests on the UDS v3.0 t-cog battery may serve as a viable alternative to its in-person counterpart, though reliability may be attenuated relative to the traditional in-person format. More tightly controlled studies are needed to better establish the reliability of these measures.

In utero/peripartum antiretroviral therapy exposure and mental health outcomes at 8-18 years old: A longitudinal comparative study of children with perinatally acquired HIV, children perinatally HIV exposed but uninfected, and children unexposed uninfected from Uganda.

In utero/peripartum antiretroviral therapy (IPA) exposure type was examined in relationship to mental health symptoms among 577 children with perinatally acquired HIV (CPHIV), children perinatally HIV exposed but uninfected (CHEU), and children HIV unexposed uninfected (CHUU). IPA exposure was categorized for CPHIV and CHEU as none, single-dose nevirapine with or without zidovudine (sdNVP±AZT), sdNVP+AZT+lamivudine (3TC), or combination antiretroviral therapy (cART). Anxiety and depressive symptoms were reported at baseline, 6-, and 12-month follow-up per behavioral assessment system for children. Multivariable linear mixed models were used to estimate differences (b) with 95% confidence intervals (95% CI) for IPA exposure types versus CHEU without IPA exposure. Depressive and anxiety symptoms were lower in CHUU relative to CHEU and CPHIV but did not differ between CPHIV and CHEU. CHEU with sdNVP±AZT exposure had greater anxiety (b = 0.51, 95% CI: [0.06, 0.96]) and depressive symptoms (b = 0.48, 95% CI: [0.07, 0.89]) than CHEU without IPA exposure. CHEU with sdNVP+AZT+3TC exposure had higher anxiety (b = 0.0.45, 95% CI: [0.03, 0.86]) and depressive symptoms (b = 0.72, 95% CI: [0.27, 1.17]) versus CHEU without IPA exposure. Depressive and anxiety symptoms were not different for CHEU and CPHIV exposed to cART (b = 0.12-0.60, 95% CI: [-0.41, 1.30]) and CHEU and CHUU (b = -0.04 to 0.08, 95% CI: [-0.24, 0.29]) without IPA exposure. Among CHEU, peripartum sdNVP±AZT and sdNVP+AZT+3TC but not cART compared to no IPA exposure was associated with clinically important elevations in anxiety and depressive symptoms. Monitoring of mental health trajectory of HIV-affected children considering IPA is needed to inform mental health interventions. Patient Contribution: Caregivers and their dependents provided consent for participation and collaborated with study team to identify mutually convenient times for protocol implementation.

Mild Cognitive Impairment Subtype Performance in Comparison to Healthy Older Controls on the NIH Toolbox and Cogstate.

BACKGROUND: Early detection is necessary for the treatment of dementia. Computerized testing has become more widely used in clinical trials; however, it is unclear how sensitive these measures are to early signs of neurodegeneration. We investigated the use of the NIH Toolbox-Cognition (NIHTB-CB) and Cogstate-Brief computerized neuropsychological batteries in the identification of mild cognitive impairment (MCI) versus healthy older adults [healthy control (HC)] and amnestic (aMCI) versus nonamnestic MCI (naMCI). Exploratory analyses include investigating potential racial differences. METHODS: Two hundred six older adults were diagnosed as aMCI (n = 58), naMCI (n = 15), or cognitively healthy (HC; n = 133). RESULTS: The NIH Toolbox-CB subtests of Flanker, Picture Sequence Memory, and Picture Vocabulary significantly differentiated MCI from HC. Further, subtests from both computerized batteries differentiated patients with aMCI from those with naMCI. Although the main effect of race differences was noted on tests and in diagnostic groups was significant, there were no significant race-by-test interactions. CONCLUSIONS: Computer-based subtests vary in their ability to help distinguish MCI subtypes, though these tests provide less expensive and easier-to-administer clinical screeners to help identify patients early who may qualify for more comprehensive evaluations. Further work is needed, however, to refine computerized tests to achieve better precision in distinguishing impairment subtypes.

Metacognition in Community-Dwelling Older Black and African American Adults During the COVID-19 Pandemic.

BACKGROUND: Cognitive assessment of older adults typically includes symptom reports and objective evaluations. However, there is often poor agreement between these measures. Cultural norms, stress, and anxiety may also influence cognitive self-appraisal and performance. Little research describes how other factors affect the self-report/objective test discrepancies noted in the literature. OBJECTIVE: This study investigated whether the disparity between subjective cognitive concerns and objective cognitive performance is related to measures of anxiety and stress in older Black and African American adults. METHODS: Telephone screenings were administered to 206 older adults (ages 64-94) during the first year of the pandemic. Demographic data, objective memory (Telephone Interview for Cognitive Status [TICS-m]), an adaptation of the subjective memory measure, the Cognitive Change Questionnaire, emphasizing executive functioning in everyday life [CCQ-e]), Generalized Anxiety Disorder-7 (GAD-7), and Perceived Stress Scale-4 (PSS4) were measured. Metacognition Discrepancy Index (MDI) was calculated from the standardized residual after regressing TICS-m on CCQ-e scores to quantify the discrepancy between cognitive self-appraisal and objective cognitive functioning. RESULTS: Neither GAD-7 nor PSS-4 moderated the relationship between TICS-m and CCQ-e, and TICS-m scores weakly predicted subjective CCQ-e scores (F(1, 197)=4.37, p = 0.038, R2 = 0.022). The MDI correlated with stress and anxiety (rs = 0.294, 0.396, ps < 0.001). CONCLUSION: Discrepancies exist between objectively measured and self-evaluated cognition. Elevations in stress and anxiety are associated with greater overestimation of cognitive difficulties relative to objective performance. Pandemic-related stressors may have worsened anxiety and diminished self-appraisal of cognitive abilities for some individuals, while others may remain reluctant to acknowledge impairments. Social and emotional factors are meaningful considerations in assessing cognitive difficulties.

Patient Cognitive Status and Physician Recommendations for Cardiovascular Disease Treatment: Results of Two Nationwide, Randomized Survey Studies.

BACKGROUND: Clinical guidelines recommend that older patients (65+) with mild cognitive impairment (MCI) and early-stage dementia receive similar guideline-concordant care after cardiovascular disease (CVD) events as those with normal cognition (NC). However, older patients with MCI and dementia receive less care for CVD and other conditions than those with NC. Whether physician recommendations for guideline-concordant treatments after two common CVD events, acute myocardial infarction (AMI) and acute ischemic stroke (stroke), differ between older patients with NC, MCI, and early-stage dementia is unknown. OBJECTIVE: To test the influence of patient cognitive status (NC, MCI, early-stage dementia) on physicians' recommendations for guideline-concordant treatments for AMI and stroke. DESIGN: We conducted two parallel, randomized survey studies for AMI and stroke in the US using clinical vignettes where the hypothetical patient's cognitive status was randomized between physicians. PARTICIPANTS: The study included cardiologists, neurologists, and generalists who care for most patients hospitalized for AMI and stroke. MAIN MEASURES: The primary outcome was a composite quality score representing the number of five guideline-concordant treatments physicians recommended for a hypothetical patient after AMI or stroke. KEY RESULTS: 1,031 physicians completed the study (58.5% response rate). Of 1,031 respondents, 980 physicians had complete information. After adjusting for physician factors, physicians recommended similar treatments after AMI and stroke in hypothetical patients with pre-existing MCI (adjusted ratio of expected composite quality score, 0.98 [95% CI, 0.94, 1.02]; P = 0.36) as hypothetical patients with NC. Physicians recommended fewer treatments to hypothetical patients with pre-existing early-stage dementia than to hypothetical patients with NC (adjusted ratio of expected composite quality score, 0.90 [0.86, 0.94]; P < 0.001). CONCLUSION: In these randomized survey studies, physicians recommended fewer guideline-concordant AMI and stroke treatments to hypothetical patients with early-stage dementia than those with NC. We did not find evidence that physicians recommend fewer treatments to hypothetical patients with MCI than those with NC.

Vitamin D and Probability of Developmental Disorders among Perinatally HIV-Affected and Unaffected Ugandan Children.

We tested the hypothesis that vitamin D deficiency (VDD) is associated with higher developmental disorder probability in 604 children with perinatal HIV infection (CPHIV, n = 199), HIV exposed and uninfected (CHEU, n = 196), and HIV unexposed uninfected (CHUU, n = 201). Children at 6-18 years old and their adult caregivers were assessed at enrollment, 6, and 12-month follow-ups. Serum 25-hydroxyvitamin-D (25OHD) levels in children quantified per the NHANES protocol were used to define VD categories as VDD (25OHD < 20 ng/mL), VD insufficient (VDI, 20 ≤ 25OHD ≤ 25 ng/mL), and VD sufficient (VDS = reference group if 25OHD > 25 ng/mL). Perinatal HIV status per DNA polymerase chain reaction/HIV rapid diagnostic tests included: CPHIV, CHEU, and CHUU. Developmental stage was defined as pre-adolescent (age < 11) vs. adolescent (age ≥ 11) years. Caregiver responses to standardized questions from Behavioral Assessment System for Children, Third Edition (BASC-3), were used to calculate probability scores for four disorders, namely: autism (ASD), attention deficit & hyperactivity (ADHD), emotional behavioral disorder (EBD), functional impairment (FI), and resiliency at 0, 6 and 12 months. Multivariable longitudinal models estimated VD-associated standardized mean difference (SMD) and corresponding 95% confidence intervals (95% CI) in respective probability scores in Statistical Analysis Software (v.9.4). Baseline VDD vs. VDS predicted higher probability scores of moderate clinical importance for ASD, ADHD, EBD, and higher FI among pre-adolescents (SMD = 0.32 to 0.40, 95% CI: 0.00 to 0.74). VDD was not associated with resiliency or any developmental disorders among adolescents. VDD predicted higher developmental disorder and FI scores over 12 months in a developmental stage-dependent manner. This relationship requires further understanding to appropriately target future interventions.

Mild Cognitive Impairment in African Americans Is Associated with Differences in EEG Theta/Beta Ratio.

BACKGROUND: Identification of older individuals with increased risk for cognitive decline can contribute not only to personal benefits (e.g., early treatment, evaluation of treatment), but could also benefit clinical trials (e.g., patient selection). We propose that baseline resting-state electroencephalography (rsEEG) could provide markers for early identification of cognitive decline. OBJECTIVE: To determine whether rsEEG theta/beta ratio (TBR) differed between mild cognitively impaired (MCI) and healthy older adults. METHODS: We analyzed rsEEG from a sample of 99 (ages 60-90) consensus-diagnosed, community-dwelling older African Americans (58 cognitively typical and 41 MCI). Eyes closed rsEEGs were acquired before and after participants engaged in a visual motion direction discrimination task. rsEEG TBR was calculated for four midline locations and assessed for differences as a function of MCI status. Hemispheric asymmetry of TBR was also analyzed at equidistant lateral electrode sites. RESULTS: Results showed that MCI participants had a higher TBR than controls (p = 0.04), and that TBR significantly differed across vertex location (p < 0.001) with the highest TBR at parietal site. MCI and cognitively normal controls also differed in hemispheric asymmetries, such that MCI show higher TBR at frontal sites, with TBR greater over right frontal electrodes in the MCI group (p = 0.003) and no asymmetries found in the cognitively normal group. Lastly, we found a significant task aftereffect (post-task compared to pre-task measures) with higher TBR at posterior locations (Oz p = 0.002, Pz p = 0.057). CONCLUSION: TBR and TBR asymmetries differ between MCI and cognitively normal older adults and may reflect neurodegenerative processes underlying MCI symptoms.

Association Between Acute Myocardial Infarction and Cognition.

Importance: The magnitude of cognitive change after incident myocardial infarction (MI) is unclear. Objective: To assess whether incident MI is associated with changes in cognitive function after adjusting for pre-MI cognitive trajectories. Design, Setting, and Participants: This cohort study included adults without MI, dementia, or stroke and with complete covariates from the following US population-based cohort studies conducted from 1971 to 2019: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, Multi-Ethnic Study of Atherosclerosis, and Northern Manhattan Study. Data were analyzed from July 2021 to January 2022. Exposures: Incident MI. Main Outcomes and Measures: The main outcome was change in global cognition. Secondary outcomes were changes in memory and executive function. Outcomes were standardized as mean (SD) T scores of 50 (10); a 1-point difference represented a 0.1-SD difference in cognition. Linear mixed-effects models estimated changes in cognition at the time of MI (change in the intercept) and the rate of cognitive change over the years after MI (change in the slope), controlling for pre-MI cognitive trajectories and participant factors, with interaction terms for race and sex. Results: The study included 30 465 adults (mean [SD] age, 64 [10] years; 56% female), of whom 1033 had 1 or more MI event, and 29 432 did not have an MI event. Median follow-up was 6.4 years (IQR, 4.9-19.7 years). Overall, incident MI was not associated with an acute decrease in global cognition (-0.18 points; 95% CI, -0.52 to 0.17 points), executive function (-0.17 points; 95% CI, -0.53 to 0.18 points), or memory (0.62 points; 95% CI, -0.07 to 1.31 points). However, individuals with incident MI vs those without MI demonstrated faster declines in global cognition (-0.15 points per year; 95% CI, -0.21 to -0.10 points per year), memory (-0.13 points per year; 95% CI, -0.22 to -0.04 points per year), and executive function (-0.14 points per year; 95% CI, -0.20 to -0.08 points per year) over the years after MI compared with pre-MI slopes. The interaction analysis suggested that race and sex modified the degree of change in the decline in global cognition after MI (race × post-MI slope interaction term, P = .02; sex × post-MI slope interaction term, P = .04), with a smaller change in the decline over the years after MI in Black individuals than in White individuals (difference in slope change, 0.22 points per year; 95% CI, 0.04-0.40 points per year) and in females than in males (difference in slope change, 0.12 points per year; 95% CI, 0.01-0.23 points per year). Conclusions: This cohort study using pooled data from 6 cohort studies found that incident MI was not associated with a decrease in global cognition, memory, or executive function at the time of the event compared with no MI but was associated with faster declines in global cognition, memory, and executive function over time. These findings suggest that prevention of MI may be important for long-term brain health.

Associations Between Vascular Risk Factor Levels and Cognitive Decline Among Stroke Survivors.

Importance: Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain. Objective: To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decline. Design, Setting, and Participants: Individual participant data meta-analysis of 4 US cohort studies (conducted 1971-2019). Linear mixed-effects models estimated changes in cognition after incident stroke. Median (IQR) follow-up was 4.7 (2.6-7.9) years. Analysis began August 2021 and was completed March 2023. Exposures: Time-dependent cumulative mean poststroke SBP, glucose, and LDL cholesterol levels. Main Outcomes and Measures: The primary outcome was change in global cognition. Secondary outcomes were change in executive function and memory. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Results: A total of 1120 eligible dementia-free individuals with incident stroke were identified; 982 (87.7%) had available covariate data and 138 (12.3%) were excluded for missing covariate data. Of the 982, 480 (48.9%) were female individuals, and 289 (29.4%) were Black individuals. The median age at incident stroke was 74.6 (IQR, 69.1-79.8; range, 44.1-96.4) years. Cumulative mean poststroke SBP and LDL cholesterol levels were not associated with any cognitive outcome. However, after accounting for cumulative mean poststroke SBP and LDL cholesterol levels, higher cumulative mean poststroke glucose level was associated with faster decline in global cognition (-0.04 points/y faster per each 10-mg/dL increase [95% CI, -0.08 to -0.001 points/y]; P = .046) but not executive function or memory. After restricting to 798 participants with apolipoprotein E4 (APOE4) data and controlling for APOE4 and APOE4 × time, higher cumulative mean poststroke glucose level was associated with a faster decline in global cognition in models without and with adjustment for cumulative mean poststroke SBP and LDL cholesterol levels (-0.05 points/y faster per 10-mg/dL increase [95% CI, -0.09 to -0.01 points/y]; P = .01; -0.07 points/y faster per 10-mg/dL increase [95% CI, -0.11 to -0.03 points/y]; P = .002) but not executive function or memory declines. Conclusions and Relevance: In this cohort study, higher poststroke glucose levels were associated with faster global cognitive decline. We found no evidence that poststroke LDL cholesterol and SBP levels were associated with cognitive decline.

Influence of mild cognitive impairment on patient and care partner decision-making for acute ischemic stroke.

GOALS: Evidence suggests that patients with mild cognitive impairment (MCI) receive fewer treatments for acute ischemic stroke and other cardiovascular diseases than patients with normal cognition. Little is known about how patient and care partner preferences for ischemic stroke treatment differ between the patient population with MCI and the population with normal cognition. This study aimed to understand how patient MCI diagnosis influences patient and care partner decision-making for acute ischemic stroke treatments. METHODS: Multi-center qualitative study using in-person semi-structured interviews with 20 MCI and normal cognition patient-care partner dyads using a standard guide. The present study reports results on patient and care partner preferences for a clinical vignette patient to receive three non-invasive treatments (intravenous tissue plasminogen activator, inpatient rehabilitation, and secondary preventive medications) and two invasive treatments (feeding tube and carotid endarterectomy) after acute ischemic stroke. We used qualitative content analysis to identify themes. FINDINGS: We identified three major themes: (1) Patients with MCI desired non-invasive treatments after stroke, similar to patients with normal cognition and for similar reasons; (2) Patients with MCI expressed different preferences than patients with normal cognition for two invasive treatments after stroke: carotid endarterectomy and feeding tube placement; and (3) Patients with MCI expressed more skepticism of the stroke treatment options and less decisiveness in decision-making than patients with normal cognition. CONCLUSIONS: These results suggest that patient MCI diagnosis may contribute to differences in patient and care partner preferences for invasive treatments after stroke, but not for non-invasive treatments.