Life-Space Mobility: Normative Values From a National Cohort of U.S. Older Adults.

BACKGROUND: Life-space mobility, which measures the distance, frequency, and independence achieved as individuals move through their community, is one of the most important contributors to healthy aging. The University of Alabama at Birmingham Life-Space Assessment (LSA) is the most commonly used measure of life-space mobility in older adults, yet U.S. national norms for LSA have not previously been reported. This study reports such norms based on age and sex among community-dwelling older adults. METHODS: A cross-sectional analysis using data from the national REasons for Geographic and Racial Disparities in Stroke cohort study. LSA data were available for 10 118 Black and White participants over age 50, which were grouped by age (in 5-year increments) and sex, weighted for the U.S. national population. Correlations were calculated between LSA and measures of functional and cognitive impairment and physical performance. RESULTS: The weighted mean LSA ranged from 102.9 for 50-54-year-old males to 69.5 for males aged 85 and older, and from 102.1 for 50-54-year-old females to 60.1 for females aged 85 and older. LSA was strongly correlated with measures of timed walking, activities of daily living, cognition, depressive symptoms, and quality of life (all p < .001). CONCLUSIONS: We report U.S. national norms for LSA among community-dwelling Black and White older adults. These norms can serve as a reference tool for determining if clinical and research samples have greater or lesser life-space mobility than typical older adults in the United States for their age and sex.

Cognitive prescriptions for reducing dementia risk factors among Black/African Americans: feasibility, acceptability, and preliminary efficacy.

OBJECTIVES: Black/African Americans (B/AAs) have double the risk of Alzheimer's disease and related dementia than Whites, which is largely driven by health behaviors. This study examined the feasibility, acceptability, and preliminary efficacy of a pilot randomized clinical trial of an individualized multidomain health behavior intervention among middle-aged and older B/AAs (dubbed Cognitive Prescriptions [CogRx]). DESIGN: Thirty-nine community-dwelling B/AA participants aged 45-65 without significant cognitive impairment were randomized to one of three groups: CogRx, Psychoeducation, or no-contact control. The Psychoeducation and CogRx groups received material on dementia prevalence, prognosis, and risk factors, while the CogRx group additionally received information on their risk factor profile across the five CogRx domains (physical, cognitive, and social activity, diet, sleep). This information was used for developing tailored 3-month goals in their suboptimal areas. RESULTS: The CogRx program had high retention (all 13 CogRx participants completed the 3-month program and 97% of the full sample completed at least 1 follow-up) and was well-received as exhibited by qualitative and quantitative feedback. Themes identified in the positive feedback provided by participants on the program included: increased knowledge, goal-setting, personalization, and motivation. The COVID-19 pandemic was a consistent theme that emerged regarding barriers of adherence to the program. All three groups improved on dementia knowledge, with the largest effects observed in CogRx and Psychoeducation groups. Increases in cognitive, physical, and overall leisure activities favored the CogRx group, whereas improvements in sleep outcomes favored Psychoeducation and CogRx groups as compared to the control group. CONCLUSION: The CogRx program demonstrated feasibility, acceptability, and preliminary efficacy in increasing dementia knowledge and targeted health behaviors. Further refinement and testing of the implementation and effectiveness of similar person-centered dementia prevention approaches are needed on a larger scale in diverse populations. Such findings may have implications for clinical and public health recommendations. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03864536.

A 2-year longitudinal randomized controlled trial examining the transfer of speed of processing training to secondary cognitive domains in middle-aged and older adults with HIV-associated neurocognitive disorder: Results of the think fast study.

OBJECTIVE: As people with HIV (PWH) age, they are at-risk of developing cognitive impairments compared to their seronegative counterparts. Although speed of processing (SOP) training may help improve this cognitive ability, less work has examined transfer to other cognitive domains. This study examined the effect of SOP training has on secondary cognitive domains in PWH aged 40+ years. METHOD: In this 3-group 2-year longitudinal study, 216 PWH with HIV-associated neurocognitive disorder (HAND) or borderline HAND were randomized to either: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73); or (3) 10 h of an active control training (n = 73). Participants completed a comprehensive cognitive battery at baseline, immediately after training, and at 1 and 2 years. This battery yielded global and domain specific T-scores as well as a cognitive impairment variable. Generalized linear mixed-effect models were fitted to estimate between-group mean differences at the follow-up time-points adjusted for baseline. RESULTS: No clinically or statistically significant improvements in any of the cognitive outcomes were observed. A sensitivity analysis was conducted; conclusions replicated those of the main analysis, with two exceptions: Global Function T and Psychomotor Speed T showed relevant training improvements among the intervention groups over the control group at the immediate post time point. CONCLUSIONS: Although SOP training has been shown to improve cognitive abilities that correspond to driving and mobility, such training has limited therapeutic utility in improving cognition in other domains in PWH with HAND.

Changes in Adiposity and Cognitive Function in Older Adults: The REGARDS Study.

OBJECTIVES: Adiposity may have a role in the risk of dementia. Fewer studies have focused on the relationship between change in adiposity and cognitive decline. Our study aimed to explore the association between the change in adiposity and cognitive function in Black and White older adults. METHODS: The participants were 12,204 older adults without cognitive impairment (62.8 ±â€…8.0 years) in the United States. The percent body mass index change (%BMI change) and percent waist circumference change (%WC change) were measured at 2 in-home visits (first: 2003-2007, second: 2013-2016). Cognitive status was assessed by the Six-Item Screener annually. Memory and executive function were measured by word list learning, MOCA recall and orientation, and letter and animal fluency every 2 years. Logistic regression or linear regression models were used to estimate the relationship between percent change in adiposity and cognitive function. RESULTS: After 12.7 ±â€…1.7 years, a greater decrease in %BMI change or %WC change was significantly associated with a higher risk of cognitive impairment. Compared to older adults with -5% ≤ change ≤ 5% from baseline, a significantly higher risk of cognitive impairment and greater loss in memory and executive function were found among those who experienced more than a 10% decline in %BMI change or %WC change. Older adults who experienced a 5%-10% decrease in %BMI change had a higher risk of cognitive impairment and greater loss of memory compared to those with -5% ≤ change ≤ 5%. DISCUSSION: A greater decrease in %BMI (>5%) and %WC (>10%) change was associated with greater cognitive loss observed over time.

The role of caregiving in cognitive function and change: The REGARDS study.

Chronic stress is associated with negative health outcomes, including poorer cognition. Some studies found stress from caregiving associated with worse cognitive functioning; however, findings are mixed. The present study examined the relationship between caregiving, caregiving strain, and cognitive functioning. We identified participants in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study who were family caregivers at baseline assessment and used propensity matching on 14 sociodemographic and health variables to identify matched noncaregivers for comparison. Data included up to 14 years of repeated assessments of global cognitive functioning, learning and memory, and executive functioning. Our results showed that when compared to noncaregivers, caregivers had better baseline scores on global cognitive functioning and word list learning (WLL). Among caregivers, a lot of strain was associated with better WLL and delayed word recall in the unadjusted model only. Caregivers with a lot of strain had higher depressive symptoms but not significantly higher high-sensitivity c-reactive protein (hsCRP) at baseline compared to caregivers with no or some strain after covariate adjustment. Although caregiving can be highly stressful, we found caregiving status and caregiving strain were not associated with cognitive decline. More methodologically rigorous studies are needed, and conclusions that caregiving has negative effects on cognition should be viewed with caution. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Two-year clinical trial examining the effects of speed of processing training on everyday functioning in adults with human immunodeficiency virus-associated neurocognitive disorder (HAND) and borderline HAND in the U.S. Deep South: Findings of the Think Fast Study.

Many people living with human immunodeficiency virus (HIV) (PLWH) experience cognitive decline that impairs everyday functioning. Cognitive training approaches, such as speed of processing (SOP) training, may reduce the impact of HIV-Associated Neurocognitive Disorder (HAND) on everyday functioning. In this experimental design study called the Think Fast Study, 216 participants age 40 and older with HAND or borderline HAND were randomized to one of three groups: (1) 10 h of SOP training (n = 70); (2) 20 h of SOP training (n = 73); or (3) 10 h of Internet Navigation Control Training (a contact control group; n = 73). Participants completed several everyday functioning measures at baseline, posttest, and year 1 and year 2 follow ups, which included: (a) Modified Lawton and Brody Activities of Daily Living (ADL) Questionnaire; (b) Timed Instrumental Activities of Daily Living (TIADL) Test; (c) Patient's Assessment of Own Functioning (PAOFI); (d) Medication Adherence Questionnaire (MAQ); and (e) Medication Adherence Visual Analog Scale (VAS). Linear mixed-effect models and generalized estimating equation models were fitted to estimate between group differences at all follow-up time points. At follow-up timepoints, those in the 10-h and 20-h training groups had better scores on medication adherence measures (MAQ and VAS) than those in the control group, with effects (Cohen's d) ranging 0.13-0.41 for MAQ and 0.02-0.43 for VAS. In conclusion, SOP training improved some indicators of everyday functioning, specifically medication adherence; however, the therapeutic effects diminished over time. Implications for practice and research are posited.

Rural versus Urban Residence in Adulthood and Incident Cognitive Impairment.

INTRODUCTION: Rural versus urban living is a social determinant of cognitive health. We estimated the association of rural versus urban residence in the USA with incident cognitive impairment (ICI) and assessed effect heterogeneity by sociodemographic, behavioral, and clinical factors. METHODS: The Reasons for Geographic and Racial Differences in Stroke Study (REGARDS) is a population-based prospective observational cohort of 30,239 adults, 57% female, 36% Black, aged 45+ years, sampled from 48 contiguous states in the USA in 2003-2007. We analyzed 20,878 participants who at baseline were cognitively intact with no history of stroke and had ICI assessed on average 9.4 years later. We classified participants' home addresses at baseline as urban (population ≥50,000), large rural (10,000-49,999), or small rural (≤9,999) by Rural-Urban Commuting Area codes. We defined ICI as ≥1.5 SD below the mean on at least 2 of the following tests: word list learning, word list delayed recall, and animal naming. RESULTS: Participants' home addresses were 79.8% urban, 11.7% large rural, and 8.5% small rural. ICI occurred in 1,658 participants (7.9%). Small rural residents had higher odds of ICI than urban residents, adjusted for age, sex, race, region, and education (OR = 1.34 [95% CI: 1.10, 1.64]), and after further adjustment for income, health behaviors, and clinical characteristics (OR = 1.24 [95% CI: 1.02, 1.53]). Former smoking versus never, nondrinking versus light alcohol drinking, no exercise versus ≥4 times/week, CES-D depressive symptom score of 2 versus 0, and fair versus excellent self-rated health had stronger associations with ICI in small rural areas than in urban areas. For example, in urban areas, lack of exercise was not associated with ICI (OR = 0.90 [95% CI: 0.77, 1.06]); however, lack of exercise combined with small rural residence was associated with 1.45 times the odds of ICI compared with ≥4 bouts of exercise/week in urban areas (95% CI: 1.03, 2.03). Overall, large rural residence was not associated with ICI; however, black race, hypertension, and depressive symptoms had somewhat weaker associations with ICI, and heavy alcohol drinking a stronger association with ICI, in large rural areas than in urban areas. CONCLUSION: Small rural residence was associated with ICI among USA adults. Further research to better understand why rural residents are at higher risk for developing ICI and mechanisms to ameliorate that risk will support efforts to advance rural public health.

Nonalcoholic fatty liver disease and cognitive impairment: A prospective cohort study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase). METHODS: In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples. RESULTS: NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age. CONCLUSIONS: A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health.

Can individualized-targeted computerized cognitive training improve everyday functioning in adults with HIV-associated neurocognitive disorder?

Half of people with human immunodeficiency virus (HIV) have HIV-associated neurocognitive disorder (HAND). Fortunately, cognitive training programs can improve function across cognitive domains, which may translate to everyday functioning. The Training on Purpose (TOPS) Study was designed to reverse HAND by targeting cognitive training to specific cognitive impairments that contributed to the diagnosis. A secondary aim of TOPS was to determine whether such cognitive training improved subjective and objective everyday functioning. In this two-group pre-post experimental design study, 109 adults with HAND were randomized to either: (1) a no-contact control group (no training) or (2) the Individualized-Targeted Cognitive Training group. Each participant received approximately 10 hours of cognitive training in two selected cognitive domains based on her/his individual baseline cognitive performance. Thus, 20 hours of individualized training on these two cognitive domains occurred over a course of 12 weeks in 1-2 hour sessions. Specific to the secondary aim of TOPS, measures of everyday functioning were administered before and after cognitive training to examine transfer effects. The analyses revealed that in general, speed of processing training produced benefits in everyday functioning as measured by the medication adherence visual analogue scale and the Timed Instrumental Activities of Daily Living test. Inconsistent findings were found for the other seven cognitive training protocols in either improving everyday functioning or reducing perceived everyday functioning; however, there may be other contributing factors that obscured such effects needing further research. This study demonstrated that some training protocols vary in efficacy in altering both objective and subjective everyday functioning ability.

Validity of the NIH toolbox cognitive battery in a healthy oldest-old 85+ sample.

OBJECTIVE: To evaluate the construct validity of the NIH Toolbox Cognitive Battery (NIH TB-CB) in the healthy oldest-old (85+ years old). METHOD: Our sample from the McKnight Brain Aging Registry consists of 179 individuals, 85 to 99 years of age, screened for memory, neurological, and psychiatric disorders. Using previous research methods on a sample of 85 + y/o adults, we conducted confirmatory factor analyses on models of NIH TB-CB and same domain standard neuropsychological measures. We hypothesized the five-factor model (Reading, Vocabulary, Memory, Working Memory, and Executive/Speed) would have the best fit, consistent with younger populations. We assessed confirmatory and discriminant validity. We also evaluated demographic and computer use predictors of NIH TB-CB composite scores. RESULTS: Findings suggest the six-factor model (Vocabulary, Reading, Memory, Working Memory, Executive, and Speed) had a better fit than alternative models. NIH TB-CB tests had good convergent and discriminant validity, though tests in the executive functioning domain had high inter-correlations with other cognitive domains. Computer use was strongly associated with higher NIH TB-CB overall and fluid cognition composite scores. CONCLUSION: The NIH TB-CB is a valid assessment for the oldest-old samples, with relatively weak validity in the domain of executive functioning. Computer use's impact on composite scores could be due to the executive demands of learning to use a tablet. Strong relationships of executive function with other cognitive domains could be due to cognitive dedifferentiation. Overall, the NIH TB-CB could be useful for testing cognition in the oldest-old and the impact of aging on cognition in older populations.

Post-Processing Automatic Transcriptions with Machine Learning for Verbal Fluency Scoring.

Objective: To compare verbal fluency scores derived from manual transcriptions to those obtained using automatic speech recognition enhanced with machine learning classifiers. Methods: Using Amazon Web Services, we automatically transcribed verbal fluency recordings from 1400 individuals who performed both animal and letter F verbal fluency tasks. We manually adjusted timings and contents of the automatic transcriptions to obtain "gold standard" transcriptions. To make automatic scoring possible, we trained machine learning classifiers to discern between valid and invalid utterances. We then calculated and compared verbal fluency scores from the manual and automatic transcriptions. Results: For both animal and letter fluency tasks, we achieved good separation of valid versus invalid utterances. Verbal fluency scores calculated based on automatic transcriptions showed high correlation with those calculated after manual correction. Conclusion: Many techniques for scoring verbal fluency word lists require accurate transcriptions with word timings. We show that machine learning methods can be applied to improve off-the-shelf ASR for this purpose. These automatically derived scores may be satisfactory for some applications. Low correlations among some of the scores indicate the need for improvement in automatic speech recognition before a fully automatic approach can be reliably implemented.

A comparison of techniques for deriving clustering and switching scores from verbal fluency word lists.

Objective: To compare techniques for computing clustering and switching scores in terms of agreement, correlation, and empirical value as predictors of incident cognitive impairment (ICI). Methods: We transcribed animal and letter F fluency recordings on 640 cases of ICI and matched controls from a national epidemiological study, amending each transcription with word timings. We then calculated clustering and switching scores, as well as scores indexing speed of responses, using techniques described in the literature. We evaluated agreement among the techniques with Cohen's κ and calculated correlations among the scores. After fitting a base model with raw scores, repetitions, and intrusions, we fit a series of Bayesian logistic regression models adding either clustering and switching scores or speed scores, comparing the models in terms of several metrics. We partitioned the ICI cases into acute and progressive cases and repeated the regression analysis for each group. Results: For animal fluency, we found that models with speed scores derived using the slope difference algorithm achieved the best values of the Watanabe-Akaike Information Criterion (WAIC), but with good net reclassification improvement (NRI) only for the progressive group (8.2%). For letter fluency, different models excelled for prediction of acute and progressive cases. For acute cases, NRI was best for speed scores derived from a network model (3.4%), while for progressive cases, the best model used clustering and switching scores derived from the same network model (5.1%). Combining variables from the best animal and letter F models led to marginal improvements in model fit and NRI only for the all-cases and acute-cases analyses. Conclusion: Speed scores improve a base model for predicting progressive cognitive impairment from animal fluency. Letter fluency scores may provide complementary information.

Verbal fluency response times predict incident cognitive impairment.

Introduction: In recent decades, researchers have defined novel methods for scoring verbal fluency tasks. In this work, we evaluate novel scores based on speed of word responses. Methods: We transcribed verbal fluency recordings from 641 cases of incident cognitive impairment (ICI) and matched controls, all participants in a large national epidemiological study. Timing measurements of utterances were used to calculate a speed score for each recording. Traditional raw and speed scores were entered into Cox proportional hazards (CPH) regression models predicting time to ICI. Results: Concordance of the CPH model with speed scores was 0.599, an improvement of 3.4% over a model with only raw scores and demographics. Scores with significant effects included animals raw and speed scores, and letter F speed score. Discussion: Novel verbal fluency scores based on response times could enable use of remotely administered fluency tasks for early detection of cognitive decline. Highlights:  The current work evaluates prognostication with verbal fluency speed scores. These speed scores improve survival models predicting cognitive decline. Cases with progressive decline have some characteristics suggestive of Alzheimer's disease. The subset of acute decliners is probably pathologically heterogeneous.

Rationale and protocol for a pilot randomized controlled trial of a cognitive prescription intervention for reducing dementia risk factors among African Americans.

BACKGROUND & PURPOSE: African Americans (AAs) are twice as likely to develop dementia than Whites, which may be driven by poorer dementia knowledge and lifestyle factors. This article provides the rationale and protocol for a pilot clinical trial examining a tailored multi-domain lifestyle modification intervention in middle-aged and older AAs. This study will explore the feasibility and efficacy of individualized Cognitive Prescriptions (CogRx) which target five domains: physical activity, cognitive activity, diet, sleep, and social activity. Theoretical underpinnings include Social Cognitive Theory and the Health Belief Model, which suggest that tailored risk factor information, goal-setting, and outcome expectations along with addressing self-efficacy and barriers will promote behavior change. STUDY DESIGN: This study plans to enroll 150 community-dwelling AA participants aged 45-65 without significant cognitive impairment. After baseline assessment including data-driven assessment of deficiencies in each of the five CogRx domains, participants are randomized with equal allocation to either: psychoeducation + CogRx, psychoeducation only, or no-contact control. The psychoeducation and CogRx groups receive general psychoeducation on dementia prevalence, prognosis, and risk factors, while the CogRx group also receives information on their risk factor profile and develops a tailored 3-month intervention plan, consisting of simple evidence-based strategies to implement. The CogRx condition receives text-messaging reminders and adherence queries and provides feedback on this program. CONCLUSION: This study tests a novel multi-domain dementia prevention intervention and has several strengths, including enrolling middle-aged AAs with a focus on prevention, assessing adherence and self-efficacy, tailoring the intervention, and examining dementia knowledge. The goal is to yield new perspectives on person-centered dementia prevention approaches in diverse populations, and ultimately impact clinical and public health recommendations for maintaining cognitive health, thereby reducing disparities in dementia. Modifications to study design due to COVID-19 and future directions are discussed.

Robust demographically-adjusted normative data for the Montreal Cognitive Assessment (MoCA): Results from the systolic blood pressure intervention trial.

To generate robust, demographically-adjusted regression-based norms for the Montreal Cognitive Assessment (MoCA) using a large sample of diverse older US adults.Baseline MoCA scores were examined for participants in the Systolic Blood Pressure Intervention Trial (SPRINT). A robust, cognitively-normal sample was drawn from individuals not subsequently adjudicated with cognitive impairment through 4 years of follow-up. Multivariable Beta-Binomial regression was used to model the association of demographic variables with MoCA performance and to create demographically-stratified normative tables.Participants' (N = 5,338) mean age was 66.9 ± 8.8 years, with 35.7% female, 63.1% White, 27.4% Black, 9.5% Hispanic, and 44.5% with a college or graduate education. A large proportion scored below published MoCA cutoffs: 61.4% scored below 26 and 29.2% scored below 23. A disproportionate number falling below these cutoffs were Black, Hispanic, did not graduate from college, or were ≥75 years of age. Multivariable modeling identified education, race/ethnicity, age, and sex as significant predictors of MoCA scores (p<.001), with the best fitting model explaining 24.4% of the variance. Model-based predictions of median MoCA scores were generally 1 to 2 points lower for Black and Hispanic participants across combinations of age, sex, and education. Demographically-stratified norm-tables based on regression modeling are provided to facilitate clinical use, along with our raw data.By using regression-based strategies that more fully account for demographic variables, we provide robust, demographically-adjusted metrics to improve cognitive screening with the MoCA in diverse older adults.

Racial Segregation and Cognitive Function Among Older Adults in the United States: Findings From the Reasons for Geographic and Racial Differences in Stroke Study.

OBJECTIVES: Residential segregation is one of the fundamental features of health disparities in the United States. Yet little research has examined how living in segregated metropolitan areas is related to cognitive function and cognitive decline with age. We examined the association between segregation at the metropolitan statistical area (MSA) level and trajectories of age-related cognitive function. METHOD: Using data from Black and White older adults in the REasons for Geographic and Racial Differences in Stroke study (n = 18,913), we employed linear growth curve models to examine how living in racially segregated MSAs at baseline, measured by the degree of non-Hispanic Black (NHB) isolation and NHB dissimilarity, was associated with trajectories of age-related cognitive function and how the associations varied by race and education. RESULTS: Living in MSAs with greater levels of isolation was associated with lower cognitive function (b = -0.093, p < .05) but was not associated with rates of change in cognitive decline with age. No effects of living in isolated MSAs were found for those with at least a high school education, but older adults with less than a high school education had lower cognitive function in MSAs with greater isolation (b = -0.274, p < .05). The degree of dissimilarity was not associated with cognitive function. The association between segregation and cognitive function did not vary by race. DISCUSSION: Metropolitan segregation was associated with lower cognitive function among older adults, especially for those with lower education living in racially isolated MSAs. This suggests complex associations between individual socioeconomic status, place, and cognitive health.

Effect of intensive blood pressure control on subtypes of mild cognitive impairment and risk of progression from SPRINT study.

BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of <120 mm Hg (intensive treatment; n = 4678) or <140 mm Hg (Standard treatment; n = 4683). Outcomes included adjudicated MCI, MCI subtype (amnestic, non-amnestic, multi-domain, single domain), and probable dementia. Multistate survival models were used to examine transitions in cognitive status accounting for the competing risk of death. RESULTS: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 640 participants met the protocol definition for MCI, with intensive treatment reducing the risk of MCI overall (hazard ratio [HR], 0.81 [95% confidence interval {CI}, 0.69-0.94]), as previously reported. This effect was largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66-0.92]) and multi-domain subtypes (HR, 0.78 [95% CI, 0.65-0.93]). An adjudication of MCI, as compared with normal cognitive function, substantially increased the probability of progressing to probable dementia (5.9% [95% CI: 4.5%-7.7%] vs. 0.6% [95% CI: 0.3%-0.9%]) and to death (10.0% [95% CI: 8.3%-11.9%] vs. 2.3% [95% CI: 2.0%-2.7%]) within 2 years. CONCLUSIONS: Intensive treatment reduced the risk for amnestic and multi-domain subtypes of MCI. An adjudication of MCI was associated with increased risk of progression to dementia and death, highlighting the relevance of MCI as a primary outcome in clinical and research settings.

A Randomized Clinical Trial on the Impact of Individually Targeted Computerized Cognitive Training on Quality of Life Indicators in Adults With HIV-Associated Neurocognitive Disorder in the Southeastern United States.

ABSTRACT: HIV-associated neurocognitive disorder (HAND) is experienced by 30% to 50% of people living with HIV (PLWH), potentially affecting their quality of life (QoL). In the Training on Purpose Study, we investigated whether targeted cognitive training can improve QoL in PLWH with HAND. Using a two-group experimental design, we randomized 109 adults with HAND to either (a) the Individualized-Targeted Cognitive Training group or (b) a no-contact control group. Those in the training group were assigned 10 hr of cognitive training per two selected cognitive domains (20 hr total) for which impairment was observed. Overall, two patterns emerged. First, significant improvements in measures of everyday cognitive complaints, depression, and mental health were consistently observed after the completion of many cognitive training protocols. Second, immediate and delayed spatial learning and memory training resulted in more significant indicators of QoL improvements compared with the other cognitive domain trainings. The findings suggest that some types of cognitive training may have advantages over others in improving aspects of QoL.

Depressive Symptoms and Risk of Stroke in a National Cohort of Black and White Participants From REGARDS.

OBJECTIVE: The purpose of this study was to examine depressive symptoms as a risk factor for incident stroke and determine whether depressive symptomatology was differentially predictive of stroke among Black and White participants. METHODS: The study comprised 9,529 Black and 14,516 White stroke-free participants, aged 45 and older, enrolled in the REasons for Geographic and Racial Differences in Stroke (2003-2007). Incident stroke was the first occurrence of stroke. Association between baseline depressive symptoms (assessed via the 4-item Center for Epidemiologic Studies Depression Scale [CES-D-4]: 0, 1-3, or ≥4) and incident stroke was analyzed with Cox proportional hazards models adjusted for demographics, stroke risk factors, and social factors. RESULTS: There were 1,262 strokes over an average follow-up of 9.21 (SD 4.0) years. Compared to participants with no depressive symptoms, after demographic adjustment, participants with CES-D-4 scores of 1-3 had 39% increased stroke risk (hazard ratio [HR] = 1.39, 95% confidence interval [CI] = 1.23-1.57), with slight attenuation after full adjustment (HR = 1.27, 95% CI = 1.11-1.43). Participants with CES-D-4 scores of ≥4 experienced 54% higher risk of stroke after demographic adjustment (HR = 1.54, 95% CI = 1.27-1.85), with risk attenuated in the full model similar to risk with 1-3 symptoms (HR = 1.25, 95% CI = 1.03-1.51). There was no evidence of a differential effect by race (p = 0.53). CONCLUSIONS: The association of depressive symptoms with increased stroke risk was similar among a national sample of Black and White participants. These findings suggest that assessment of depressive symptoms should be considered in primary stroke prevention for both Black and White participants.

Baseline Cognitive Impairment in Patients With Asymptomatic Carotid Stenosis in the CREST-2 Trial.

BACKGROUND AND PURPOSE: Studies of carotid artery disease have suggested that high-grade stenosis can affect cognition, even without stroke. The presence and degree of cognitive impairment in such patients have not been reported and compared with a demographically matched population-based cohort. METHODS: We studied cognition in 1000 consecutive CREST-2 (Carotid Revascularization and Medical Management for Asymptomatic Carotid Stenosis Trial) patients, a treatment trial for asymptomatic carotid disease. Cognitive assessment was after randomization but before assigned treatment. The cognitive battery was developed in the general population REGARDS Study (Reasons for Geographic and Racial Differences in Stroke), involving Word List Learning Sum, Word List Recall, and Word List fluency for animal names and the letter F. The carotid stenosis patients were >45 years old with ≥70% asymptomatic carotid stenosis and no history of prevalent stroke. The distribution of cognitive performance for the patients was standardized, accounting for age, race, and education using performance from REGARDS, and after further adjustment for hypertension, diabetes, dyslipidemia, and smoking. Using the Wald Test, we tabulated the proportion of Z scores less than the anticipated deviate for the population-based cohort for representative percentiles. RESULTS: There were 786 baseline assessments. Mean age was 70 years, 58% men, and 52% right-sided stenosis. The overall Z score for patients was significantly below expected for higher percentiles (P<0.0001 for 50th, 75th, and 95th percentiles) and marginally below expected for the 25th percentile (P=0.015). Lower performance was attributed largely to Word List Recall (P<0.0001 for all percentiles) and for Word List Learning (50th, 75th, and 95th percentiles below expected, P≤0.01). The scores for left versus right carotid disease were similar. CONCLUSIONS: Baseline cognition of patients with severe carotid stenosis showed below normal cognition compared to the population-based cohort, controlling for demographic and cardiovascular risk factors. This cohort represents the largest group to date to demonstrate that poorer cognition, especially memory, in this disease. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02089217.