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.

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.

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.

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.

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.

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.

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.

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.

Quality of Education and Late-Life Cognitive Function in a Population-Based Sample From Puerto Rico.

BACKGROUND AND OBJECTIVES: We examined quality of education, literacy, and years of education in relation to late-life cognitive function and decline in older Puerto Ricans. RESEARCH DESIGN AND METHODS: Our sample consisted of 3,385 community-dwelling adults aged 60 years and older from the Puerto Rican Elderly: Health Conditions study. Quality of education was based on principal component analysis of variables gathered from Department of Education and Census reports. Literacy (yes/no) and years of education were self-reported. Cognitive function was assessed in participants' homes at baseline and 4 years later using a previously validated Spanish-language 20-point global screening measure for dementia, the minimental Cabán. Regression models were adjusted for sociodemographic and life course covariates. RESULTS: Quality of education was positively correlated with both educational attainment and cognitive performance. Independent of years of education, literacy, childhood economic hardship, and adult economic hardship, compared to participants in the lowest quartile of education quality, those in the highest quartile had significantly better baseline cognitive performance (ß = 0.09, p < .001). Quality of education did not consistently show an association with change in cognitive function over 4 years. Literacy and greater educational attainment were each independently associated with better cognitive function at baseline and less cognitive decline. DISCUSSION AND IMPLICATIONS: Quality of education, literacy, and years of education, while interrelated, also show independent associations with cognitive functioning in older Puerto Ricans. The downstream factors of literacy and years of education were more closely related to age-related cognitive decline than quality of education.

Trajectory of Cognitive Decline After Sepsis.

OBJECTIVES: Cognitive impairment is an important consequence of sepsis. We sought to determine long-term trajectories of cognitive function after sepsis. DESIGN: Prospective study of the Reasons for Geographic and Racial Differences in Stroke cohort. SETTING: United States. PATIENTS: Twenty-one thousand eight-hundred twenty-three participants greater than or equal to 45 years, mean (sd) age 64.3 (9.2) years at first cognitive assessment, 30.9% men, and 27.1% Black. MEASUREMENTS AND MAIN RESULTS: The main exposure was time-dependent sepsis hospitalization. The primary outcome was global cognitive function (Six-Item Screener range, 0-6). Secondary outcomes were incident cognitive impairment (Six-Item Screener score ≤ 4 [impaired] vs ≥5 [unimpaired]), new learning (Consortium to Establish a Registry for Alzheimer Disease Word List Learning range, 0-30), verbal memory (word list delayed recall range, 0-10), and executive function/semantic fluency (animal fluency test range, ≥ 30). Over a median follow-up of 10 years (interquartile range, 6-12 yr), 840 (3.8%) experienced sepsis (incidence 282 per 1,000 person-years). Sepsis was associated with faster long-term declines in Six-Item Screener (-0.02 points per year faster [95% CI, -0.01 to -0.03]; p < 0.001) and faster long-term rates of incident cognitive impairment (odds ratio 1.08 per year [95% CI, 1.02-1.15]; p = 0.008) compared with presepsis slopes. Although cognitive function acutely changed after sepsis (0.05 points [95% CI, 0.01-0.09]; p = 0.01), the odds of acute cognitive impairment (Six-Item Screener ≤ 4) immediately after sepsis was not significant (odds ratio, 0.81 [95% CI, 0.63-1.06]; p = 0.12). Sepsis hospitalization was not associated with acute changes or faster declines in word list learning, word list delayed recall, or animal fluency test. CONCLUSIONS: Sepsis is associated with accelerated long-term decline in global cognitive function.

Can Individualized-Targeted Computerized Cognitive Training Benefit Adults with HIV-Associated Neurocognitive Disorder? The Training on Purpose Study (TOPS).

Half of people with HIV (PWH) have HIV-associated neurocognitive disorder (HAND). This study examined whether cognition can be improved using a framework targeting impaired individual cognitive domains in PWH with HAND. In this two-group pre-post experimental design study, 88 adults with HAND were randomized to either: (1) a no-contact control group (n = 40) or (2) the Individualized-Targeted Cognitive Training group (n = 48). Baseline cognitive performance was assessed on eight cognitive domains. A theoretical framework was used to determine the two cognitive domains selected for training. With priority on speed of processing (SOP) and attention impairments, participants received SOP and/or attention training if such impairments were detected; if not, participants were assigned to cognitive training in one/two of the least impaired cognitive domains contributing to their HAND diagnosis. Global cognitive score was slightly improved following training (p = 0.256; d = - 0.21), but it was not significant. Significant improvements were observed on SOP following training in that domain (SOP; d = - 0.88; p = 0.011). SOP training also improved functioning in other cognitive domains. This individualized cognitive intervention did not change HAND status, but it did result in improved SOP, in turn yielding improvement in other cognitive domains.

Executive function in individuals with clinically significant weight loss via behavioral intervention.

BACKGROUND: Executive function (EF) is associated with obesity development and self-management. Individuals who demonstrate or self-report poorer EF performance tend to have poorer short-term outcomes in obesity treatment. There may be distinct behavioral self-management strategies and EF domains related to initial weight loss as compared to weight loss maintenance. OBJECTIVE: To characterize EF in individuals who achieved clinically significant weight loss via behavioral intervention and examine potential differences in EF between those who maintained versus regained lost weight. METHODS: Participants who previously achieved ≥5% weight loss via lifestyle intervention were included (N = 44). "Maintainers" (n = 16) maintained this minimum level of weight loss for ≥1 year. "Regainers" (n = 28) regained some or all initially lost weight. Performance-based EF, intelligence quotient, health literacy, depression, anxiety, binge eating, demographics, and medical/weight history were assessed using a cross-sectional design. Descriptive statistics and age-, gender-, education-adjusted reference ranges were used to characterize EF. Analyses of covariance were conducted to examine EF differences between maintainers and regainers. RESULTS: The sample consisted primarily of females with obesity over age 50. Approximately half self-identified as African-American. Decision-making performance was better in maintainers than regainers (p = 0.003, partη2 = 0.19). There were no differences between maintainers and regainers in inhibitory control, verbal fluency, planning/organization, cognitive flexibility, or working memory (ps > 0.05, partη2s = 0.003-0.07). At least 75% of the sample demonstrated average-above average EF test performance, indicated by scaled scores ≥13 or t-scores > 60. CONCLUSIONS: Most individuals with obesity who achieved clinically significant weight loss via behavioral intervention had average to above average EF. Individuals who maintained (vs. regained) their lost weight performed better on tests of decision-making.

The relationship of cognitive change over time to the self-reported Ascertain Dementia 8-item Questionnaire in a general population.

OBJECTIVE: The aim of the study was to examine the relationship between longitudinally assessed cognitive functioning and self-reported dementia status using the Ascertain Dementia 8-item questionnaire (AD8) in a national population-based sample. METHODS: The analysis included 14,453 participants from the REasons for Geographic and Racial Differences in Stroke study. A validated cutoff of ≥2 symptoms endorsed on the AD8 (administered 10 years after enrollment) represented positive AD8 status. Incident cognitive impairment was defined as change from intact to impaired status in the Six-Item Screener score, and cognitive decline was defined by trajectories of Letter "F" Fluency from the Montreal Cognitive Assessment, and Animal Fluency, Word List Learning, and Word List Delayed recall, all from the Consortium to Establish a Registry for Alzheimer's Disease battery. Logistic regression models controlled for demographics, health variables, and depressive symptoms. RESULTS: Sensitivity and specificity of the AD8 to detect incident cognitive impairment were 45.2% and 78.4%, respectively. Incident cognitive impairment and a one-word decline in WLL increased the odds of self-reported positive AD8 by 96% (95% CI: 1.68-2.28) and 27% (95% CI: 1.17-1.37), respectively. There was a strong association between high depression risk and self-reported positive AD8 in sensitivity analyses. CONCLUSIONS: Incident cognitive impairment and high depression risk were the strongest predictors of self-reported positive AD8 in this population-based sample. Our results inform the utility of the AD8 as a self-report measure in a large, national sample that avoids selection biases inherent in clinic-based studies. The AD8 is screening measure and should not be used to diagnose dementia clinically.