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.

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.

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.

The American Heart Association Life's Simple 7 and incident cognitive impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) study.

BACKGROUND: Life's Simple 7 is a new metric based on modifiable health behaviors and factors that the American Heart Association uses to promote improvements to cardiovascular health (CVH). We hypothesized that better Life's Simple 7 scores are associated with lower incidence of cognitive impairment. METHODS AND RESULTS: For this prospective cohort study, we included REasons for Geographic And Racial Differences in Stroke (REGARDS) participants aged 45+ who had normal global cognitive status at baseline and no history of stroke (N=17 761). We calculated baseline Life's Simple 7 score (range, 0 to 14) based on smoking, diet, physical activity, body mass index, blood pressure, total cholesterol, and fasting glucose. We identified incident cognitive impairment using a 3-test measure of verbal learning, memory, and fluency obtained a mean of 4 years after baseline. Relative to the lowest tertile of Life's Simple 7 score (0 to 6 points), odds ratios of incident cognitive impairment were 0.65 (0.52, 0.81) in the middle tertile (7 to 8 points) and 0.63 (0.51, 0.79) in the highest tertile (9 to 14 points). The association was similar in blacks and whites, as well as outside and within the Southeastern stroke belt region of the United States. CONCLUSIONS: Compared with low CVH, intermediate and high CVH were both associated with substantially lower incidence of cognitive impairment. We did not observe a dose-response pattern; people with intermediate and high levels of CVH had similar incidence of cognitive impairment. This suggests that even when high CVH is not achieved, intermediate levels of CVH are preferable to low CVH.

The relationship between long-term sunlight radiation and cognitive decline in the REGARDS cohort study.

Sunlight may be related to cognitive function through vitamin D metabolism or circadian rhythm regulation. The analysis presented here sought to test whether ground and satellite measures of solar radiation are associated with cognitive decline. The study used a 15-year residential history merged with satellite and ground monitor data to determine sunlight (solar radiation) and air temperature exposure for a cohort of 19,896 cognitively intact black and white participants aged 45+ from the 48 contiguous United States. Exposures of 15, 10, 5, 2, and 1-year were used to predict cognitive status at the most recent assessment in logistic regression models; 1-year insolation and maximum temperatures were chosen as exposure measures. Solar radiation interacted with temperature, age, and gender in its relationships with incident cognitive impairment. After adjustment for covariates, the odds ratio (OR) of cognitive decline for solar radiation exposure below the median vs above the median in the 3rd tertile of maximum temperatures was 1.88 (95 % CI: 1.24, 2.85), that in the 2nd tertile was 1.33 (95 % CI: 1.09, 1.62), and that in the 1st tertile was 1.22 (95 % CI: 0.92, 1.60). We also found that participants under 60 years old had an OR = 1.63 (95 % CI: 1.20, 2.22), those 60-80 years old had an OR = 1.18 (95 % CI: 1.02, 1.36), and those over 80 years old had an OR = 1.05 (0.80, 1.37). Lastly, we found that males had an OR = 1.43 (95 % CI: 1.22, 1.69), and females had an OR = 1.02 (0.87, 1.20). We found that lower levels of solar radiation were associated with increased odds of incident cognitive impairment.

Nondisease-specific problems and all-cause mortality in the REasons for Geographic and Racial Differences in Stroke study.

OBJECTIVES: To evaluate the association between six nondisease-specific problems (problems that cross multiple domains of health) and mortality in middle-aged and older adults. DESIGN: Prospective, observational cohort. SETTING: U.S. population sample. PARTICIPANTS: Participants included 23,669 black and white U.S. adults aged 45 and older enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study. MEASUREMENTS: Nondisease-specific problems included cognitive impairment, depressive symptoms, exhaustion, falls, impaired mobility, and polypharmacy. Age-stratified (<65, 65-74, ≥ 75) hazard ratios for all-cause mortality were calculated for each problem individually and according to number of problems. RESULTS: One or more nondisease-specific problems occurred in 40% of participants younger than 65, 45% of those aged 65 to 74, and 55% of those aged 75 and older. Compared with participants with none of these problems, the multivariable adjusted hazard ratio for all-cause mortality associated with each additional nondisease-specific problem was 1.34 (95% confidence interval (CI) = 1.23-1.46) for participants younger than 65, 1.24 (95% CI = 1.15-1.35) for those aged 65 to 74, and 1.30 (95% CI = 1.21-1.39) for those aged 75 and older. CONCLUSION: Nondisease-specific problems were associated with mortality across a wide age spectrum. Future studies should explore whether treating these problems will improve survival and identify innovative healthcare models to address multiple nondisease-specific problems simultaneously.

Short- and long-term sunlight radiation and stroke incidence.

OBJECTIVE: Examine whether long- and short-term sunlight radiation is related to stroke incidence. METHODS: Fifteen-year residential histories merged with satellite, ground monitor, and model reanalysis data were used to determine sunlight radiation (insolation) and temperature exposure for a cohort of 16,606 stroke and coronary artery disease-free black and white participants aged ≥45 years from the 48 contiguous United States. Fifteen-, 10-, 5-, 2-, and 1-year exposures were used to predict stroke incidence during follow-up in Cox proportional hazard models. Potential confounders and mediators were included during model building. RESULTS: Shorter exposure periods exhibited similar, but slightly stronger relationships than longer exposure periods. After adjustment for other covariates, the previous year's monthly average insolation exposure below the median gave a hazard ratio (HR) of 1.61 (95% confidence interval [CI], 1.15-2.26), and the previous year's highest compared to the second highest quartile of monthly average maximum temperature exposure gave an HR of 1.92 (95%, 1.27-2.92). INTERPRETATION: These results indicate a relationship between lower levels of sunlight radiation and higher stroke incidence. The biological pathway of this relationship is not clear. Future research will show whether this finding stands, the pathway for this relationship, and whether it is due to short- or long-term exposures.

Incident cognitive impairment is elevated in the stroke belt: the REGARDS study.

OBJECTIVE: To determine whether incidence of impaired cognitive screening status is higher in the southern Stroke Belt region of the United States than in the remaining United States. METHODS: A national cohort of adults age ≥45 years was recruited by the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from 2003 to 2007. Participants' global cognitive status was assessed annually by telephone with the Six-Item Screener (SIS) and every 2 years with fluency and recall tasks. Participants who reported no stroke history and who were cognitively intact at enrollment (SIS >4 of 6) were included (N = 23,913, including 56% women; 38% African Americans and 62% European Americans; 56% Stroke Belt residents and 44% from the remaining contiguous United States and the District of Columbia). Regional differences in incident cognitive impairment (SIS score ≤4) were adjusted for age, sex, race, education, and time between first and last assessments. RESULTS: A total of 1,937 participants (8.1%) declined to an SIS score ≤4 at their most recent assessment, over a mean of 4.1 (±1.6) years. Residents of the Stroke Belt had greater adjusted odds of incident cognitive impairment than non-Belt residents (odds ratio, 1.18; 95% confidence interval, 1.07-1.30). All demographic factors and time independently predicted impairment. INTERPRETATION: Regional disparities in cognitive decline mirror regional disparities in stroke mortality, suggesting shared risk factors for these adverse outcomes. Efforts to promote cerebrovascular and cognitive health should be directed to the Stroke Belt.

The association between self-reported tooth loss and cognitive function in the REasons for Geographic And Racial Differences in Stroke study: an assessment of potential pathways.

BACKGROUND: Several mechanisms may associate tooth loss and related oral inflammation with cognitive impairment. The authors studied the relationship between tooth loss and cognitive function. METHODS: The REasons for Geographic And Racial Differences in Stroke study is a national longitudinal study of more than 30,000 African American and white adults 45 years or older. Data for tooth loss, cognitive function and potential confounding variables were available for 9,853 participants at the time of analysis. The authors used incremental linear regression modeling to investigate the cross-sectional association between self-reported tooth loss and cognitive function. RESULTS: In unadjusted analysis (mean learning followed by recall; α level of significance of .05), the loss of six to 16 teeth and the loss of more than 16 teeth were associated with poorer cognitive function compared with the loss of no teeth. Attenuated associations persisted after the authors adjusted for demographic and systemic risk factors. The full model, which was adjusted for socioeconomic status (SES), revealed no association between tooth loss and cognitive function. CONCLUSION: Tooth loss may be associated with cognitive function; however, this association is mediated by age and SES. CLINICAL IMPLICATIONS: Tooth loss due to periodontal disease may be a marker for low SES, and the interplay of these factors with advanced age may confer risk of having poorer cognitive function. Further studies are needed to clarify these associations.

Cognitive status, stroke symptom reports, and modifiable risk factors among individuals with no diagnosis of stroke or transient ischemic attack in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

BACKGROUND AND PURPOSE: Vascular disorders that increase risk for stroke may be accompanied by decrements in cognitive functioning and by stroke symptoms in the absence of diagnosed stroke or transient ischemic attack. This study evaluates relationships among cognitive status, stroke symptom reports, and cardiovascular and behavioral factors. METHODS: REasons for Geographic and Racial Differences in Stroke (REGARDS), a prospective population study of stroke incidence, assesses stroke risk with telephone interviews and in-home physicals. Excluding subjects with a history of stroke or transient ischemic attack, this analysis includes 14,566 black and white men and women > or =45 years of age. Incremental logistic models examine baseline relationships among cognitive status (Six-item Screener scores), stroke symptom reports, demographics, health behaviors, cardiovascular indices, and depressive symptoms. RESULTS: A history of stroke symptoms was related to impaired cognitive status after adjusting for age, gender, race, and education but not after adjusting for poor health behaviors, vascular risk factors, and depressive symptoms. Odds of experiencing a stroke symptom increased 35% with each of five modifiable factors (hypertension, diabetes, smoking, lack of exercise, depressive symptoms), and odds of cognitive impairment increased an additional 12% with each modifiable factor. Lifelong abstinence from alcohol, lack of exercise, and depressive symptoms were independently related to impaired cognitive status. CONCLUSIONS: The increased likelihood of cognitive impairment among subjects reporting stroke symptoms in the absence of a diagnosed stroke or transient ischemic attack suggests that such symptoms are not benign and may warrant clinical evaluation that includes a cognitive assessment. Future studies that include brain imaging may clarify the etiology of these symptoms.