Hemostasis biomarkers and incident cognitive impairment: the REGARDS study.

Essentials Cognitive disorders are increasing and vascular risk factors play a role in this. We performed a nested case control study of hemostasis biomarkers and cognitive impairment (CI). Higher baseline fibrinogen, factor VIII and D-dimer were related to incident CI over 3.5 years. Adjusted for other risk factors, 2+ abnormal markers (but not single ones) led to higher risk. SUMMARY: Background Vascular risk factors are associated with cognitive impairment, a condition that imposes a substantial public health burden. We hypothesized that hemostasis biomarkers related to vascular disease would be associated with the risk of incident cognitive impairment. Methods We performed a nested case-control study including 1082 participants with 3.5 years of follow-up in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study, a longitudinal cohort study of 30 239 black and white Americans aged ≥ 45 years. Participants were free of stroke or cognitive impairment at baseline. Baseline D-dimer, fibrinogen, factor VIII and protein C levels were measured in 495 cases who developed cognitive impairment during follow-up (based on abnormal scores on two or more of three cognitive tests) and 587 controls. Results Unadjusted odds ratios (ORs) for incident cognitive impairment were 1.32 (95% confidence interval [CI] 1.02-1.70) for D-dimer > 0.50 µg mL-1 , 1.83 (95% CI 1.24-2.71) for fibrinogen > 90th percentile, 1.63 (95% CI 1.11-2.38) for FVIII > 90th percentile, and 1.10 (95% CI 0.73-1.65) for protein C < 10th percentile. There were no differences in associations by race or region. Adjustment for demographic, vascular and health behavior risk factors attenuated these associations. However, having at least two elevated biomarkers was associated with incident cognitive impairment, with an adjusted OR of 1.73 (95% CI 1.10-2.69). Conclusion Elevated D-dimer, fibrinogen and FVIII levels were not associated with the occurrence of cognitive impairment after multivariable adjustment; however, having at least two abnormal biomarkers was associated with the occurrence of cognitive impairment, suggesting that the burden of these biomarkers is relevant.

Lexical factors and cerebral regions influencing verbal fluency performance in MCI.

OBJECTIVE: To evaluate assumptions regarding semantic (noun), verb, and letter fluency in mild cognitive impairment (MCI) and Alzheimer disease (AD) using novel techniques for measuring word similarity in fluency lists and a region of interest (ROI) analysis of gray matter correlates. METHOD: Fifty-eight individuals with normal cognition (NC, n=25), MCI (n=23), or AD (n=10) underwent neuropsychological tests, including 10 verbal fluency tasks (three letter tasks [F, A, S], six noun categories [animals, water creatures, fruits and vegetables, tools, vehicles, boats], and verbs). All pairs of words generated by each participant on each task were compared in terms of semantic (meaning), orthographic (spelling), and phonemic (pronunciation) similarity. We used mixed-effects logistic regression to determine which lexical factors were predictive of word adjacency within the lists. Associations between each fluency raw score and gray matter volumes in sixteen ROIs were identified by means of multiple linear regression. We evaluated causal models for both types of analyses to specify the contributions of diagnosis and various mediator variables to the outcomes of word adjacency and fluency raw score. RESULTS: Semantic similarity between words emerged as the strongest predictor of word adjacency for all fluency tasks, including the letter fluency tasks. Semantic similarity mediated the effect of cognitive impairment on word adjacency only for three fluency tasks employing a biological cue. Orthographic similarity was predictive of word adjacency for the A and S tasks, while phonemic similarity was predictive only for the S task and one semantic task (vehicles). The ROI analysis revealed different patterns of correlations among the various fluency tasks, with the most common associations in the right lower temporal and bilateral dorsal frontal regions. Following correction with gray matter volumes from the opposite hemisphere, significant associations persisted for animals, vehicles, and a composite nouns score in the left inferior frontal gyrus, but for letter A, letter S, and a composite FAS score in the right inferior frontal gyrus. These regressions also revealed a lateralized association of the left subcortical nuclei with all letter fluency scores and fruits and vegetables fluency, and an association of the right lower temporal ROI with letter A, FAS, and verb fluency. Gray matter volume in several bihemispheric ROIs (left dorsal frontal, right lower temporal, right occipital, and bilateral mesial temporal) mediated the relationship between cognitive impairment and fluency for fruits and vegetables. Gray matter volume in the right lower temporal ROI mediated the relationship between cognitive impairment and five fluency raw scores (animals, fruits and vegetables, tools, verbs, and the composite nouns score). CONCLUSION: Semantic memory exerts the strongest influence on word adjacency in letter fluency as well as semantic verbal fluency tasks. Orthography is a stronger influence than pronunciation. All types of fluency task raw scores (letter, noun, and verb) correlate with cerebral regions known to support verbal or nonverbal semantic memory. The findings emphasize the contribution of right hemisphere regions to fluency task performance, particularly for verb and letter fluency. The relationship between diagnosis and semantic fluency performance is mediated by semantic similarity of words and by gray matter volume in the right lower temporal region.

Vascular risk factors and cognitive impairment in a stroke-free cohort.

OBJECTIVE: To examine vascular risk factors, as measured by the Framingham Stroke Risk Profile (FSRP), to predict incident cognitive impairment in a large, national sample of black and white adults age 45 years and older. METHODS: Participants included subjects without stroke at baseline from the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study with at least 2 cognitive function assessments during the follow-up (n = 23,752). Incident cognitive impairment was defined as decline from a baseline score of 5 or 6 (of possible 6 points) to the most recent follow-up score of 4 or less on the Six-item Screener (SIS). Subjects with suspected stroke during follow-up were censored. RESULTS: During a mean follow-up of 4.1 years, 1,907 participants met criteria for incident cognitive impairment. Baseline FSRP score was associated with incident cognitive impairment. An adjusted model revealed that male sex (odds ratio [OR] = 1.59, 95% confidence interval [CI] 1.43-1.77), black race (OR = 2.09, 95% CI 1.88-2.35), less education (less than high school graduate vs college graduate, OR = 2.21, 95% CI 1.88-2.60), older age (10-year increments, OR = 2.11, per 10-year increase in age, 95% CI 2.05-2.18), and presence of left ventricular hypertrophy (LVH, OR = 1.29, 95% CI 1.06-1.58) were related to development of cognitive impairment. When LVH was excluded from the model, elevated systolic blood pressure was related to incident cognitive impairment. CONCLUSIONS: Total FSRP score, elevated blood pressure, and LVH predict development of clinically significant cognitive dysfunction. Prevention and treatment of high blood pressure may be effective in preserving cognitive health.

Association of higher diastolic blood pressure levels with cognitive impairment.

BACKGROUND: We evaluated the cross-sectional relationship of blood pressure (BP) components with cognitive impairment after adjusting for potential confounders. METHODS: Reasons for Geographic and Racial Differences in Stroke (REGARDS) is a national, longitudinal population cohort evaluating stroke risk in 30,228 black and white men and women >or=45 years old. During the in-home visit, BP measurements were taken as the average of 2 measurements using a standard aneroid sphygmomanometer. Excluding participants with prior stroke or TIA, the present analysis included 19,836 participants (enrolled from December 2003 to March 2007) with complete baseline physical and cognitive evaluations. Incremental logistic models examined baseline relationships between BP components (systolic blood pressure [SBP], diastolic blood pressure [DBP], and pulse pressure [PP]) and impaired cognitive status (score of

The impact of speed of processing training on cognitive and everyday performance.

The purpose of the present investigation was to examine the impact of speed of processing training on the cognitive and everyday abilities of older adults with initial processing speed or processing difficulty. Participants were randomized to either a speed of processing intervention or a social- and computer-contact control group. Results indicate that speed of processing training not only improves processing speed, as indicated by performance on the Useful Field of View test (UFOV), but also transfers to certain everyday functions, as indicated by improved performance on Timed Instrumental Activities of Daily Living (Timed IADL). Transfer of speed of processing training to other cognitive domains was not evident. This study provides additional evidence that speed of processing training has the potential to enhance everyday functions that maintain independence and quality of life, particularly when the training is targeted toward individuals who most need it. Further study is needed to learn about the long-term effects of such training in relation to everyday abilities.

Linking depressive symptoms and functional disability in late life.

We hypothesized that the relationship of depressive symptoms to functional disability might be mediated by cognitive processes such as memory and problem-solving. The study sample consisted of 147 community-dwelling older adults (mean age = 74.0 years, SD = 5.9). In regression models that included terms for age, gender, and years of education, depressive symptoms were significantly inversely associated with two performance-based measures of functioning: everyday problems test (beta = -0.15, p = 0.04) and observed tasks of daily living (beta = -0.14, p = 0.02). When memory and problem-solving ability were added to the model, the relationship of depressive symptoms with function was attenuated. A structural equation model based on our conceptual framework revealed that both memory and problem-solving abilities were important mediators in the relationship of depressive symptoms and functional disability. The results suggest that intervention studies intended to limit functional disability secondary to depression among older adults may need to consider the effect of depression on cognition.

Association of life events and psychological distress in family caregivers of dementia patients.

Relationships between life events and psychological distress were investigated for 197 dementia caregivers and 218 non-caregivers. Participants indicated which events on the Louisville Older Persons Events Scale they had experienced over the past six months. Life events were then classified as associated or unassociated with care-giving using differences in incidence rates between caregivers and non-caregivers. Primary care-giving stressors and associated life events were most predictive of psychological distress among caregivers. Among non-caregivers, unassociated negative life events were the strongest predictors of depression and life satisfaction. Implications for the assessment of life events and caregiver interventions are discussed.

Diagnostic attributions versus labeling: impact of Alzheimer's disease and major depression diagnoses on emotions, beliefs, and helping intentions of family members.

Labeling theory suggests that applying disease labels to behavior may serve to medicalize deviance and produce stigma. In contrast, attribution theory suggests that this practice may evoke sympathetic responses. Female undergraduates (N = 221) read vignettes describing an older parent exhibiting inappropriate behavior in a social situation, with diagnostic label (Alzheimer's disease, major depression, no label), personal congruence of the behavior (congruent, incongruent, no information), and parent gender manipulated across participants. Participants rated their emotional responses, attributions, and willingness to help. The Alzheimer's disease label, and to a lesser extent the major depression label, produced more sympathy toward the parent, less blame, and greater willingness to help, indicating that the provision of these labels may facilitate compassionate attitudes and enhanced caregiving toward older adults. However, participants reported greater anger and higher personality attributions toward fathers than mothers, suggesting that the influence of parent gender on potential caregivers' reactions warrants further attention.

Psychological, social, and health impact of caregiving: a comparison of black and white dementia family caregivers and noncaregivers.

Psychological, social, and health variables were compared in 175 Black and White family caregivers of patients with dementia and 175 Black and White noncaregivers. Caregivers and noncaregivers did not differ within race on demographic variables. Caregiving was associated with increased depression and decreased life satisfaction only in White families. However, caregiving appears to have similar social consequences for Black and White families, including restriction of social activity and increased visits and support by family from outside of the home. Race, but not caregiving, was associated with physical health variables. Methodological issues in comparing well-being in Black and White caregivers, in particular the importance of including noncaregiving comparison subjects are discussed.