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1.  Cognitive Functioning in Adults Aging with HIV: A Cross-Sectional Analysis of Cognitive Subtypes and Influential Factors 
This cross-sectional study examined cognitive subtypes and influential factors in HIV-positive (HIV+) adults.
Two-step cluster analysis was conducted on a neurocognitive test battery in a sample (N = 78) of adults and older adults with HIV (Mage = 46.1). Next, cognitive, functional, and mental and physical health differences were compared between the HIV+ clusters and an HIV- reference group (N = 84; Mage = 47.9).
A two-cluster solution emerged, with a lower performing cluster exhibiting poorer performance across all domains except psychomotor speed, and a “normal” cluster displaying similar performance as the HIV- group. The most influential factors to classification in the lower performing cluster were older age and presence of stroke and hypertension. There were trends for longer duration of HIV-infection, higher unemployment rates, and greater prevalence of Hepatitis C co-infection in the lower performing cluster.
These findings suggest that there are not unique cognitive subtypes in HIV, but rather a subset of individuals who exhibit globally normal performance and those with below average performance. Older age and the related cardiovascular comorbidities of both aging and HIV medications may be key influential factors to variability in neurocognitive functioning in this population and thus should be considered in future studies. Implications for research and practice are provided.
PMCID: PMC4224145  PMID: 25386565
Cluster analysis; HIV/AIDS; older adults; Neurocognitive impairment
2.  Age Differences in the Association of Obstructive Sleep Apnea Risk with Cognition and Quality of Life 
Journal of sleep research  2013;23(1):69-76.
Using a sample of 2925 stroke-free participants drawn from a national population-based study, we examined cross-sectional associations of obstructive sleep apnea risk (OSA) with cognition and quality of life and whether these vary with age, while controlling for demographics and co-morbidities. Included participants from the REasons for Geographic And Racial Differences in Stroke Study were aged 47-93. OSA risk was categorized as high or low based on responses to the Berlin Sleep Questionnaire. Cognitive function was assessed with standardized fluency and recall measures. Depressive symptoms were assessed with the four-item Center for Epidemiologic Studies Depression Scale. Health-related Quality of Life (HRQoL) was assessed with the Medical Outcomes Study Short Form-12 (SF-12). MANCOVA statistics were applied separately to the cognitive and quality of life dependent variables while accounting for potential confounders (demographics, co-morbidities). In fully adjusted models, those at high risk for OSA had significantly lower cognitive scores (Wilks’ Lambda = 0.996, F(3, 2786) = 3.31, p < .05) and lower quality of life (depressive symptoms and HRQoL) (Wilks’ Lambda = 0.989, F(3, 2786) = 10.02, p < .0001). However, some of the associations were age-dependent. Differences in cognition and quality of life between those at high and low obstructive sleep apnea risk were most pronounced during middle age, with attenuated effects after age 70.
PMCID: PMC4147721  PMID: 24033751
Obstructive sleep apnea; Berlin Sleep Questionnaire; cognitive function; depression; health related quality life; age differences
3.  Lower Hippocampal Volume Predicts Decrements in Lane Control among Drivers with Amnestic MCI 
There are few methods to discern driving risks in patients with early dementia and Mild Cognitive Impairment (MCI). We aimed to determine whether structural MRI of the hippocampus – a biomarker of probable Alzheimer pathology and a measure of disease severity in those affected – is linked to objective ratings of on-road driving performance in older adults with and without amnestic MCI.
49 consensus-diagnosed participants from an Alzheimer's Disease Research Center (15 diagnosed with amnestic MCI and 34 demographically similar controls) underwent structural MRI and on-road driving assessments.
Mild atrophy of the left hippocampus was associated with less-than-optimal ratings in lane control but not with other discrete driving skills. Decrements in left hippocampal volume conferred higher risk for less-than-optimal lane control ratings in the MCI patients (B = −1.63, SE = .74, Wald = 4.85, P = .028), but not in controls (B = 0.13, SE = .415, Wald = 0.10, P = .752). The odds ratio (OR) and 95% confidence interval (CI) for below optimal lane control in the MCI group was 4.41 (1.18, 16.36), which was attenuated to 3.46 (0.88, 13.60) after accounting for the contribution of left hippocampal volume.
These findings suggest that there may be a link between hippocampal atrophy and difficulties with lane control in persons with amnestic MCI. Further study appears warranted to better discern patterns of brain atrophy in MCI and AD and whether these could be early markers of clinically meaningful driving risk.
PMCID: PMC4114386  PMID: 24212246
MCI (mild cognitive impairment); Volumetric MRI; Driving performance
4.  Family Caregiving and All-Cause Mortality: Findings from a Population-based Propensity-matched Analysis 
American Journal of Epidemiology  2013;178(10):1571-1578.
Previous studies have provided conflicting evidence on whether being a family caregiver is associated with increased or decreased risk for all-cause mortality. This study examined whether 3,503 family caregivers enrolled in the national Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study showed differences in all-cause mortality from 2003 to 2012 compared with a propensity-matched sample of noncaregivers. Caregivers were individually matched with 3,503 noncaregivers by using a propensity score matching procedure based on 15 demographic, health history, and health behavior covariates. During an average 6-year follow-up period, 264 (7.5%) of the caregivers died, which was significantly fewer than the 315 (9.0%) matched noncaregivers who died during the same period. A proportional hazards model indicated that caregivers had an 18% reduced rate of death compared with noncaregivers (hazard ratio = 0.823, 95% confidence interval: 0.699, 0.969). Subgroup analyses by race, sex, caregiving relationship, and caregiving strain failed to identify any subgroups with increased rates of death compared with matched noncaregivers. Public policy and discourse should recognize that providing care to a family member with a chronic illness or disability is not associated with increased risk of death in most cases, but may instead be associated with modest survival benefits for the caregivers.
PMCID: PMC3888278  PMID: 24091890
caregiving; cohort studies; mortality; propensity scores
5.  Report of stroke-like symptoms predicts incident cognitive impairment in a stroke-free cohort 
Neurology  2013;81(2):113-118.
The present study characterizes the relationship between report of stroke symptoms (SS) or TIA and incident cognitive impairment in the large biracial cohort of the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study.
The REGARDS Study is a population-based, biracial, longitudinal cohort study that has enrolled 30,239 participants from the United States. Exclusion of those with baseline cognitive impairment, stroke before enrollment, or incomplete data resulted in a sample size of 23,830. Participants reported SS/TIA on the Questionnaire for Verifying Stroke-free Status at baseline and every 6 months during follow-up. Incident cognitive impairment was detected using the Six-item Screener, which was administered annually.
Logistic regression found significant association between report of SS/TIA and subsequent incident cognitive impairment. Among white participants, the odds ratio for incident cognitive impairment was 2.08 (95% confidence interval: 1.81, 2.39) for those reporting at least one SS/TIA compared with those reporting no SS/TIA. Among black participants, the odds ratio was 1.66 (95% confidence interval: 1.45, 1.89) using the same modeling. The magnitude of impact was largest among those with fewer traditional stroke risk factors, particularly among white participants.
Report of SS/TIA showed a strong association with incident cognitive impairment and supports the use of the Questionnaire for Verifying Stroke-free Status as a quick, low-cost instrument to screen for people at increased risk of cognitive decline.
PMCID: PMC3770175  PMID: 23783751
Heart failure (HF) is associated with an overall stroke rate that is too low to justify anticoagulation in all patients. This study was conducted to determine if vascular risk factors can identify a subgroup of individuals with heart failure with a stroke rate high enough to warrant anticoagulation. The REGARDS study is a population-based cohort of US adults aged ≥45 years. Participants are contacted every six months by telephone for self- or proxy-reported stroke and medical records are retrieved and adjudicated by physicians. Participants were characterized into three groups: HF without atrial fibrillation (AF), AF with or without HF, and neither HF nor AF. Cardiovascular risk factors at baseline were compared between participants with and without incident stroke in HF and AF. Stroke incidence was assessed in risk factor subgroups in HF participants. Of the 30,239 participants, those with missing/anomalous data were excluded. Of the remaining 28,832, 1,360 (5%) had HF without AF, 2,528 (9%) had AF, and 24,944 (86%) had neither. Prior stroke/TIA (p=0.0004), diabetes (DM) (p=0.03) and higher systolic blood pressure (p=0.046), were associated with increased stroke risk in participants with HF without AF. In participants with HF without AF, stroke incidence was highest in those with prior stroke/TIA and DM (2.4 [1.1, 4.0] per hundred personyears). The combination of prior stroke/TIA and DM increases the incidence of stroke in participants with HF without AF. No analyzed subgroup had a stroke rate high enough to make it likely that the benefits of warfarin would outweigh the risks.
PMCID: PMC3326204  PMID: 22142776
7.  Caregiving Strain and All-Cause Mortality: Evidence From the REGARDS Study 
Using a large, national sample, this study examined perceived caregiving strain and other caregiving factors in relation to all-cause mortality.
The REasons for Geographic and Racial Differences in Stroke (REGARDS) study is a population-based cohort of men and women aged 45 years and older. Approximately 12% (n = 3,710) reported that they were providing ongoing care to a family member with a chronic illness or disability. Proportional hazards models were used for this subsample to examine the effects of caregiving status measures on all-cause mortality over the subsequent 5-year period, both before and after covariate adjustment.
Caregivers who reported high caregiving strain had significantly higher adjusted mortality rates than both no strain (hazard ratio [HR] = 1.55, p = .02) and some strain (HR = 1.83, p = .001) caregivers. The mortality effects of caregiving strain were not found to differ by race, sex, or the type of caregiving relationship (i.e., spouse, parent, child, sibling, and other).
High perceived caregiving strain is associated with increased all-cause mortality after controlling for appropriate covariates. High caregiving strain constitutes a significant health concern and these caregivers should be targeted for appropriate interventions.
PMCID: PMC3674731  PMID: 23033358
Caregiving; Mortality; Strain.
8.  The American Heart Association Life's Simple 7 and Incident Cognitive Impairment: The REasons for Geographic And Racial Differences in Stroke (REGARDS) Study 
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.
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.
PMCID: PMC4309046  PMID: 24919926
cardiovascular disease prevention; cardiovascular disease risk factors; cognitive impairment; cognitive tests; lifestyle
9.  Nondisease-Specific Problems and All-Cause Mortality in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study 
Problems that cross multiple domains of health are frequently assessed in older adults. We evaluated the association between six of these nondisease-specific problems and mortality among middle-aged and older adults.
Prospective, observational cohort
U.S. population sample
Participants included 23,669 black and white US adults ≥ 45 years of age enrolled in the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
Nondisease-specific problems included cognitive impairment, depressive symptoms, falls, polypharmacy, impaired mobility and exhaustion. Age-stratified (<65, 65-74, and ≥ 75 years) hazard ratios for all-cause mortality were calculated for each problem individually and by number of problems.
Among participants < 65, 65-74, ≥ 75 years old, one or more nondisease-specific problems occurred in 40%, 45% and 55% of participants, respectively. Compared to those with none of these problems the multivariable adjusted hazard ratios and 95% confidence intervals for all-cause mortality associated with each additional nondisease-specific problem was 1.34 (1.23–1.46), 1.24 (1.15–1.35) and 1.30 (1.21–1.39), among participants < 65, 65 – 74 years, ≥ 75 years of age, respectively.
Nondisease-specific problems were associated with mortality across a wide age spectrum. Future studies should determine if treating these problems will improve survival and identify innovative healthcare models to address multiple nondisease-specific problems simultaneously.
PMCID: PMC3656135  PMID: 23617688
nondisease-specific problems; geriatrics; mortality
10.  Effect of duration and age at exposure to the Stroke Belt on incident stroke in adulthood 
Neurology  2013;80(18):1655-1661.
To assess whether there are differences in the strength of association with incident stroke for specific periods of life in the Stroke Belt (SB).
The risk of stroke was studied in 24,544 black and white stroke-free participants, aged 45+, in the Reasons for Geographic and Racial Differences in Stroke study, a national population-based cohort enrolled 2003–2007. Incident stroke was defined as first occurrence of stroke over an average 5.8 years of follow-up. Residential histories (city/state) were obtained by questionnaire. SB exposure was quantified by combinations of SB birthplace and current residence and proportion of years in SB during discrete age categories (0–12, 13–18, 19–30, 31–45, last 20 years) and entire life. Proportional hazards models were used to establish association of incident stroke with indices of exposure to SB, adjusted for demographic, socioeconomic (SES), and stroke risk factors.
In the demographic and SES models, risk of stroke was significantly associated with proportion of life in the SB and with all other exposure periods except birth, ages 31–45, and current residence. The strongest association was for the proportion of the entire life in SB. After adjustment for risk factors, the risk of stroke remained significantly associated only with proportion of residence in SB in adolescence (hazard ratio 1.17, 95% confidence interval 1.00–1.37).
Childhood emerged as the most important period of vulnerability to SB residence as a predictor of future stroke. Improvement in childhood health circumstances should be considered as part of long-term health improvement strategies in the SB.
PMCID: PMC3716470  PMID: 23616168
11.  Adherence to a Mediterranean diet and risk of incident cognitive impairment 
Neurology  2013;80(18):1684-1692.
We sought to determine the relationship of greater adherence to Mediterranean diet (MeD) and likelihood of incident cognitive impairment (ICI) and evaluate the interaction of race and vascular risk factors.
A prospective, population-based, cohort of individuals enrolled in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study 2003–2007, excluding participants with history of stroke, impaired cognitive status at baseline, and missing data on Food Frequency Questionnaires (FFQ), was evaluated. Adherence to a MeD (scored as 0–9) was computed from FFQ. Cognitive status was evaluated at baseline and annually during a mean follow-up period of 4.0 ± 1.5 years using Six-item-Screener.
ICI was identified in 1,248 (7%) out of 17,478 individuals fulfilling the inclusion criteria. Higher adherence to MeD was associated with lower likelihood of ICI before (odds ratio [lsqb]OR[rsqb] 0.89; 95% confidence interval [lsqb]CI[rsqb] 0.79–1.00) and after adjustment for potential confounders (OR 0.87; 95% CI 0.76–1.00) including demographic characteristics, environmental factors, vascular risk factors, depressive symptoms, and self-reported health status. There was no interaction between race (p = 0.2928) and association of adherence to MeD with cognitive status. However, we identified a strong interaction of diabetes mellitus (p = 0.0134) on the relationship of adherence to MeD with ICI; high adherence to MeD was associated with a lower likelihood of ICI in nondiabetic participants (OR 0.81; 95% CI 0.70–0.94; p = 0.0066) but not in diabetic individuals (OR 1.27; 95% CI 0.95–1.71; p = 0.1063).
Higher adherence to MeD was associated with a lower likelihood of ICI independent of potential confounders. This association was moderated by presence of diabetes mellitus.
PMCID: PMC3716473  PMID: 23628929
12.  Indicators of Childhood Quality of Education in Relation to Cognitive Function in Older Adulthood 
The association between years of education and cognitive function in older adults has been studied extensively, but the role of quality of education is unknown. We examined indicators of childhood educational quality as predictors of cognitive performance and decline in later life.
Participants included 433 older adults (52% African American) who reported living in Alabama during childhood and completed in-home assessments of cognitive function at baseline and 4 years later. Reports of residence during school years were matched to county-level data from the 1935 Alabama Department of Education report for school funding (per student), student–teacher ratio, and school year length. A composite measure of global cognitive function was utilized in analyses. Multilevel mixed effects models accounted for clustering of educational data within counties in examining the association between cognitive function and the educational quality indices.
Higher student–teacher ratio was associated with worse cognitive function and greater school year length was associated with better cognitive function. These associations remained statistically significant in models adjusted for education level, age, race, gender, income, reading ability, vascular risk factors, and health behaviors. The observed associations were stronger in those with lower levels of education (≤12 years), but none of the education quality measures were related to 4-year change in cognitive function.
Educational factors other than years of schooling may influence cognitive performance in later life. Understanding the role of education in cognitive aging has substantial implications for prevention efforts as well as accurate identification of older adults with cognitive impairment.
PMCID: PMC3598357  PMID: 22546959
Cognitive aging; Education; Health disparities
Rehabilitation psychology  2013;58(1):10.1037/a0031726.
Stroke is a leading cause of long-term disability in the United States. Family caregivers are susceptible to negative outcomes as a result of their caregiving role. A stress process model was utilized to identify characteristics of stroke caregivers who are at risk for poor physical and mental health-related quality of life (QOL).
Research Method
Individuals who experienced an incident stroke event within the previous year were identified from a larger epidemiologic study of stroke incidence. These stroke survivors were enrolled in the Caring for Adults Recovering from the Effects of Stroke (CARES) study along with their primary family caregivers (N=146 dyads). Caregivers completed a baseline telephone interview that assessed physical and mental health-related QOL, problems their family members were experiencing, appraisals of those problems, and caregiver resources.
Objective stressors, appraisals, and caregiver resources were related to caregiver physical and mental health-related QOL, p’s <.05. Objective stressors were found to have a stronger association with caregiver mental health than physical health. Hierarchical regression models showed the relative importance of each category of predictors. In the final models, older age and receiving more support were associated with worse physical health-related QOL while African American race and fewer stroke survivor problems were associated with better mental health.
The correlates of health-related QOL identified in this national sample of caregivers can help identify stroke caregivers who are at-risk for poor adjustment to the caregiving role and aid in identifying areas that can potentially be intervened upon for these caregivers.
PMCID: PMC3851300  PMID: 23437997
stroke caregiving; health disparities; health-related quality of life; stress process; social support
14.  Short and Long-Term Sunlight Radiation and Stroke Incidence 
Annals of neurology  2012;73(1):32-37.
Examine whether long and short-term sunlight radiation is related to stroke incidence.
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+ from the 48 contiguous United States. Fifteen, ten, five, two and one-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.
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 an HR=1.61 (95% 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=1.92 (1.27, 2.92).
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 if it is due to short or long-term exposures.
PMCID: PMC3563869  PMID: 23225379
15.  Does Caregiver Well-Being Predict Stroke Survivor Depressive Symptoms? A Mediation Analysis 
Topics in stroke rehabilitation  2013;20(1):10.1310/tsr2001-44.
Background and Purpose
Studies suggest that family caregiver well-being (ie,, depressive symptoms and life satisfaction) may affect stroke survivor depressive symptoms. We used mediation analysis to assess whether caregiver well-being might be a factor explaining stroke survivor depressive symptoms, after controlling for demographic factors and stroke survivor impairments and problems.
Caregiver/stroke participant dyads (N=146) completed measures of stroke survivor impairments and problems and depressive symptoms and caregiver depressive symptoms and life satisfaction. Mediation analysis was used to examine whether caregiver well-being mediated the relationship between stroke survivor impairments and problems and stroke survivor depressive symptoms.
As expected, more stroke survivor problems and impairments were associated with higher levels of stroke survivor depressive symptoms (P < .0001). After controlling for demographic factors, we found that this relationship was partially mediated by caregiver life satisfaction (29.29%) and caregiver depressive symptoms (32.95%). Although these measures combined to account for 40.50% of the relationship between survivor problems and impairments and depressive symptoms, the direct effect remained significant.
Findings indicate that stroke survivor impairments and problems may affect family caregivers and stroke survivors and a high level of caregiver distress may result in poorer outcomes for stroke survivors. Results highlight the likely importance of intervening with both stroke survivors and family caregivers to optimize recovery after stroke.
PMCID: PMC3824614  PMID: 23340070
caregiver depressive symptoms; caregiver well-being; stroke depressive symptoms
16.  Fine Particulate Matter and Incident Cognitive Impairment in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Cohort 
PLoS ONE  2013;8(9):e75001.
Studies of the effect of air pollution on cognitive health are often limited to populations living near cities that have air monitoring stations. Little is known about whether the estimates from such studies can be generalized to the U.S. population, or whether the relationship differs between urban and rural areas. To address these questions, we used a satellite-derived estimate of fine particulate matter (PM2.5) concentration to determine whether PM2.5 was associated with incident cognitive impairment in a geographically diverse, biracial US cohort of men and women (n = 20,150). A 1-year mean baseline PM2.5 concentration was estimated for each participant, and cognitive status at the most recent follow-up was assessed over the telephone using the Six-Item Screener (SIS) in a subsample that was cognitively intact at baseline. Logistic regression was used to determine whether PM2.5 was related to the odds of incident cognitive impairment. A 10 µg/m3 increase in PM2.5 concentration was not reliably associated with an increased odds of incident impairment, after adjusting for temperature, season, incident stroke, and length of follow-up [OR (95% CI): 1.26 (0.97, 1.64)]. The odds ratio was attenuated towards 1 after adding demographic covariates, behavioral factors, and known comorbidities of cognitive impairment. A 10 µg/m3 increase in PM2.5 concentration was slightly associated with incident impairment in urban areas (1.40 [1.06–1.85]), but this relationship was also attenuated after including additional covariates in the model. Evidence is lacking that the effect of PM2.5 on incident cognitive impairment is robust in a heterogeneous US cohort, even in urban areas.
PMCID: PMC3783452  PMID: 24086422
17.  Prevalence and significance of stroke symptoms among patients receiving maintenance dialysis 
Neurology  2012;79(10):981-987.
The purpose of this cross-sectional study was to determine the prevalence and potential significance of stroke symptoms among end-stage renal disease (ESRD) patients without a prior diagnosis of stroke or TIA.
We enrolled 148 participants with ESRD from 5 clinics. Stroke symptoms and functional status, basic and instrumental activities of daily living (ADL, IADL), were ascertained by validated questionnaires. Cognitive function was assessed with a neurocognitive battery. Cognitive impairment was defined as a score 2 SDs below norms for age and education in 2 domains. IADL impairment was defined as needing assistance in at least 1 of 7 IADLs.
Among the 126 participants without a prior stroke or TIA, 46 (36.5%) had experienced one or more stroke symptoms. After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had lower scores on tests of attention, psychomotor speed, and executive function, and more pronounced dependence in IADLs and ADLs (p ≤ 0.01 for all). After adjustment for age, sex, race, education, language, diabetes, and cardiovascular disease, participants with stroke symptoms had a higher likelihood of cognitive impairment (odds ratio [OR] 2.47, 95% confidence interval [CI] 1.03–5.92) and IADL impairment (OR 3.86, 95% CI 1.60–9.28).
Stroke symptoms are common among patients with ESRD and strongly associated with impairments in cognition and functional status. These findings suggest that clinically significant stroke events may go undiagnosed in this high-risk population.
PMCID: PMC3430712  PMID: 22875090
18.  The association between self-reported tooth loss and cognitive function in the REasons for Geographic And Racial Differences in Stroke study 
Several mechanisms may associate tooth loss and related oral inflammation with cognitive impairment. The authors studied the relationship between tooth loss and cognitive function.
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.
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.
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.
PMCID: PMC3744362  PMID: 21454843
Cognitive function; tooth loss
19.  ACTIVE Cognitive Training and Rates of Incident Dementia 
Systematic cognitive training produces long-term improvement in cognitive function and less difficulty in performing activities of daily living. We examined whether cognitive training was associated with reduced rate of incident dementia. Participants were from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (n=2,802). Incident dementia was defined using a combination of interview- and performance-based methods. Survival analysis was used to determine if ACTIVE treatment affected the rate of incident dementia during 5 years of follow-up. A total of 189 participants met criteria for incident dementia. Baseline factors predictive of incident dementia were older age, male gender, African American race, fewer years of education, relationship other than married, no alcohol use, worse MMSE< worse SF-36 physical functioning, higher depressive symptomatology, diabetes, and stroke (all p<.05). A multivariable model with significant predictors of incident dementia and training group revealed that cognitive training was not associated with a lower rate of incident dementia. Cognitive training did not affect rates of incident dementia after 5 years of follow-up. Longer follow-up or enhanced training may be needed to fully explore the preventive capacity of cognitive training in forestalling onset of dementia.
PMCID: PMC3384749  PMID: 22400989
Cognitive training; Intervention; Aging; Dementia; Prevention; Cognition
20.  Albuminuria, Kidney Function, and the Incidence of Cognitive Impairment Among Adults in the United States 
Albuminuria and estimated glomerular filtration rate (eGFR) are each associated with increased risk for cognitive impairment, but their joint association is unknown.
Study Design
Prospective cohort study.
Setting and Participants
A US national sample of 19,399 adults without cognitive impairment at baseline participating in the REGARDS )REasons for Geographic And Racial Disparities in Stroke) study.
Albuminuria was assessed by the urine albumin-creatinine ratio (UACR) and GFR was estimated using the CKD-EPI (CKD Epidemiology Collaboration) equation.
Incident cognitive impairment was defined as a score of 4 or less on the Six-item Screener at the last follow-up visit.
Over a mean follow-up of 3.8 ± 1.5 years, UACR 30 – 299 and ≥300 mg/g were independently associated with 31% and 57% higher risk for cognitive impairment, respectively, relative to individuals with UACR <10 mg/g. This finding was strongest among those with high eGFR and attenuated at lower levels (P=0.04 for trend). Relative an eGFR ≥60 ml/min/1.73m2, eGFR <60 ml/min/1.73m2 was not independently associated with cognitive impairment. However, after stratifying by UACR, eGFR <60 ml/min/1.73m2 was associated with 30% higher risk for cognitive impairment among participants with UACR <10 mg/g but not higher UACR levels (P=0.04 for trend).
single measure of albuminuria and eGFR, screening test of cognition
When eGFR was preserved, albuminuria independently associated with incident cognitive impairment. When albuminuria was <10 mg/g, low eGFR independently associated with cognitive impairment. Albuminuria and low eGFR are complementary but not additive risk factors for incident cognitive impairment.
PMCID: PMC3199339  PMID: 21816528
albuminuria; chronic kidney disease; cognitive impairment
21.  Speed of Processing Training with Middle-Age and Older Adults with HIV: A Pilot Study 
Adults with HIV are at risk for deficits in speed of processing that can interfere with performing instrumental activities of daily living. In this pilot study, 46 middle-age and older adults with HIV were assigned to 10 hours of computerized speed of processing training (n = 22) or to a no-contact control condition (n = 24). ANCOVAs were used to examine treatment effects on a neurocognitive battery and the Timed Instrumental Activities of Daily Living (TIADL) Test. Treatment effects were detected on the Useful Field of View® Test, F(1, 43) = 4.29, p = .04 and the TIADL Test, F(1, 43) = 5.02, p = .03; those in the experimental condition improved on these measures. Many of the participants also indicated that they felt the training improved their cognitive functioning. This study demonstrated that speed of processing training may improve cognitive and everyday functioning in this growing population.
PMCID: PMC3422374  PMID: 22579081
aging; cognitive intervention; cognitive remediation therapy; cognitive training; instrumental activities of daily living; speed of processing training
Annals of neurology  2011;70(2):229-236.
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 U.S.
A national cohort of adults ≥ age 45 was recruited by the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study from 2003–2007. Participants’ global cognitive status was assessed annually by telephone with the Six-item Screener (SIS) and every two 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.
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 (OR = 1.18; 95% CI 1.07 – 1.30). All demographic factors and time independently predicted impairment.
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.
PMCID: PMC3152671  PMID: 21618586
23.  The Geographic Distribution of Dementia Mortality: Elevated Mortality Rates for Black and White Americans By Place of Birth 
We hypothesized that patterns of elevated stroke mortality among those born in the US Stroke Belt (SB) states also prevailed for mortality related to all-cause dementia or Alzheimer Disease (AD). Cause specific mortality (contributing cause of death, including underlying cause cases) rates in 2000 for US-born African-Americans and whites aged 65–89 were calculated by linking national mortality records with population data based on race, sex, age, and birth state or state of residence in 2000. Birth in a SB state (North Carolina, South Carolina, Georgia, Tennessee, Arkansas, Mississippi, or Alabama) was cross-classified against SB residence at the 2000 Census. Compared to those who were not born in the SB, odds of all cause dementia mortality were significantly elevated by 29% for African-Americans and 19% for whites born in the SB. These patterns prevailed among individuals who no longer lived in the SB at death. Patterns were similar for AD-related mortality. Some non-SB states were also associated with significant elevations in dementia-related mortality. Dementia mortality rates follow geographic patterns similar to stroke mortality, with elevated rates among those born in the SB. This suggests important roles for geographically patterned childhood exposures in establishing cognitive reserve.
PMCID: PMC3383774  PMID: 21297428
Dementia; cerebrovascular disease/stroke; geography; Stroke Belt; lifecourse; racial disparities
24.  The Relationship Between Cognitive Function and Life Space: The Potential Role of Personal Control Beliefs 
Psychology and Aging  2011;27(2):364-374.
We examined the relationship of cognitive and functional measures with life space (a measure of spatial mobility examining extent of movement within a person’s environment) in older adults, and investigated the potential moderating role of personal control beliefs. Internal control beliefs reflect feelings of competence and personal agency, while attributions of external control imply a more dependent or passive point of view. Participants were 2,737 adults from the ACTIVE study, with a mean age of 74 years. Females comprised 76% of the sample, with good minority representation (27% African American). In multiple regression models controlling for demographic factors, cognitive domains of memory, reasoning, and processing speed were significantly associated with life space (p<.001 for each), and reasoning ability appeared most predictive (B=.117). Measures of everyday function also showed significant associations with life space, independent from the traditional cognitive measures. Interactions between cognitive function and control beliefs were tested, and external control beliefs moderated the relationship between memory and life space, with the combination of high objective memory and low external control beliefs yielding the highest life space (t=−2.07; p=.039). In conclusion, older adults with better cognitive function have a larger overall life space. Performance-based measures of everyday function may also be useful in assessing the functional outcome of life space. Additionally, subjective external control beliefs may moderate the relationship between objective cognitive function and life space. Future studies examining the relationships between these factors longitudinally appear worthwhile to further elucidate the interrelationships of cognitive function, control beliefs, and life space.
PMCID: PMC3302939  PMID: 21875217
aging; cognition; control beliefs; life space
25.  The Impact of Feedback on Self-rated Driving Ability and Driving Self-regulation Among Older Adults 
The Gerontologist  2010;51(3):367-378.
In 129 community-dwelling older adults, feedback regarding qualification for an insurance discount (based on a visual speed of processing test; Useful Field of View) was examined as a prospective predictor of change in self-reported driving ability, driving avoidance, and driving exposure over 3 months, along with physical, visual, health, and cognitive variables. Multiple regression models indicated that after controlling for baseline scores on the outcome measures, failure to qualify was a significant predictor of increased avoidance over 3 months (p = .02) but not change in self-rated driving ability or exposure. Female gender (p = .03) was a significant predictor of subsequent lower self-rated driving ability. Overall, the findings of this study provide support for the role of feedback in the self-monitoring of older adults’ driving behavior through avoidance of challenging driving situations but not through driving exposure or self-rated driving ability.
PMCID: PMC3095650  PMID: 21071621
Older drivers; Driving ability; Self-regulation; Self-rated driving; Driving exposure; Driving avoidance

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