Chronic kidney disease, creatinine and cognitive functioning.

BACKGROUND: Non-dialysis-dependent chronic kidney disease (CKD) is related to cognitive impairment. Previous studies have not explored the extent of impairment across multiple cognitive domains. We examined the range of specific cognitive abilities affected by CKD and whether the associations of CKD with cognition were eliminated by statistical control for cardiovascular disease correlates of CKD. METHODS: We performed a community-based cross-sectional study with 923 individuals free from dementia and end-stage renal disease. Two groups were defined based on estimated glomerular filtration rate (eGFR): eGFR<60 mL/min/1.73 m(2) versus eGFR >or= 60 mL/min/1.73 m(2). Outcome measures were scores from multiple clinical tests of specific cognitive abilities. The GFR classifications and serum creatinine levels were related to measures of cognitive performance using logistic and linear regression analyses with three sets of covariates: (1) basic (age, education, gender and race); (2) basic+risk factors for cardiovascular disease (CVD) and (3) basic+risk factors for CVD+stroke. RESULTS: An eGFR <60 mL/min/1.73 m(2) was present in 142 (15.4%) individuals; the mean (SD) eGFR in this subgroup was 49.7 (10.7). CKD was related to lower cognitive performance despite adjustment for CVD risk factors (CVD-RF). Adjusting for CVD-RF and stroke, odds ratios and 95% confidence intervals associated with performing in the lowest quartile of the distribution of the Global, Visual-Spatial Organization/Memory and Scanning and Tracking scores for the eGFR < 60 group were 1.97 (1.25, 3.10); 1.88 (1.21, 2.93) and 1.83 (1.56, 2.87), P < 0.01 with eGFR >or= 60 group as the reference group. CONCLUSIONS: Global performance and specific cognitive functions are negatively affected early in CKD. Targeted screening for cognitive deficits in kidney disease patients early in their disease course may be warranted.

Homocysteine and cognitive performance: modification by the ApoE genotype.

We hypothesized that the magnitude of the association between plasma homocysteine concentration and cognitive performance is larger for ApoE-epsilon4 carriers than for non-carriers. Nine hundred eleven dementia-free and stroke-free subjects (59% women) from the Maine-Syracuse study (26-98 years old) were stratified into no-ApoE-epsilon4 (n=667) and ApoE-epsilon4 carrier (n=244) cohorts. Employing a cross-sectional design and multiple regression analyses, plasma homocysteine was related to multiple domains of cognitive performance within these cohorts. When unadjusted, and with adjustment for age, education, gender, ethnicity, and previous cognitive examinations, homocysteine concentrations were inversely related to cognitive performance within both ApoE cohorts, with higher magnitude of associations within the ApoE-epsilon4 cohort. With adjustment for cardiovascular disease risk factors, cardiovascular disease, and B-vitamin concentrations, the higher magnitude of associations between plasma homocysteine and cognitive performance within the ApoE-epsilon4 cohort relative to the no-ApoE-epsilon4 cohort persisted; but associations of plasma homocysteine and cognitive performance were attenuated and no longer significant within the no-ApoE-epsilon4 cohort. Presence of the ApoE-epsilon4 allele modifies the relation between plasma homocysteine and cognitive performance.

Relation between central adiposity and cognitive function in the Maine-Syracuse Study: attenuation by physical activity.

BACKGROUND: Previous studies have demonstrated a relationship between central adiposity and cognitive function. However, only some of these studies have adjusted for cardiovascular risk factors and cardiovascular disease, and none have also adjusted for physical activity level. PURPOSE: The purpose of the study was to examine the association between anthropometric measures of central adiposity (waist circumference and waist/hip ratio) and cognitive functioning with adjustment for cardiovascular disease risk factors and physical activity. METHODS: Participants were 917 stroke- and dementia-free community-dwelling adults (59% women) in the Maine-Syracuse Study. The design was cross-sectional. Outcome measures included tests from the Wechsler Adult Intelligence Scale, the Halstead-Reitan Neuropsychological Battery, the Wechsler Memory Scale Revised, and the Mini-Mental State Examination. RESULTS: Waist circumference and waist/hip ratio were inversely related to multiple cognitive domains with adjustment for age, education, gender, and number of prior exams. For example, a 20-cm increment in waist circumference was associated with a 0.14 SD decrement in the Global Composite score. These relations were attenuated with adjustment for cardiovascular disease risk factors. However, with further adjustment for physical activity level, only waist circumference remained significantly associated with performance on the Similarities test. CONCLUSIONS: Waist circumference and waist/hip ratio are inversely related to cognitive function. Measures of central adiposity predict cognitive function independently of associated cardiovascular risk factors and events; however, the association between central adiposity and cognitive function is attenuated, to a large extent, by adjustment for physical activity level. Physical activity is an important covariate in studies relating measures of central adiposity to cognition.

Homocysteine, folate, and vitamins B6 and B12 blood levels in relation to cognitive performance: the Maine-Syracuse study.

OBJECTIVE: Our objective was to examine associations among plasma homocysteine concentrations (tHcy), the tHcy-cofactors (folate, vitamins B6 and B12), and multiple domains of cognitive performance, with statistical adjustment for possible confounds, including cardiovascular disease risk factors (CVD-RF) and cardiovascular disease (CVD). METHODS: Subjects were 812 participants (58% women) of the Maine-Syracuse study who were free of dementia and stroke. Employing a cross-sectional design and multiple regression analyses, fasting concentrations of tHcy and its vitamin cofactors (folate, B6, and B12) were related to multiple domains of cognitive performance. RESULTS: With adjustment for age, education, gender, ethnicity, and the vitamins, tHcy was inversely associated with visual-spatial organization, working memory, scanning-tracking, and abstract reasoning. The same results were found with adjustment for age, education, gender, ethnicity, CVD-RF, and CVD. Vitamin cofactors were positively related to cognitive performance, but with adjustment for CVD-RF and CVD, only vitamin B6 was related to multiple cognitive domains. CONCLUSIONS: The inverse association of tHcy with multiple domains of cognitive functioning is not necessarily dependent on vitamin levels, vitamin deficiency, prevalent CVD risk factors, and manifest CVD. Serum folate, serum B12, and plasma B6 vitamin concentrations are positively associated with cognitive performance. Investigation of other possible mechanisms (e.g., tHcy neurotoxicity) mediating tHcy associations with cognitive performance is important, as are clinical trials examining the efficacy of folate, vitamin B6, and vitamin B12 for maintenance of cognitive functioning.

Atrial fibrillation is associated with lower cognitive performance in the Framingham offspring men.

The purpose of this study was to investigate the association of atrial fibrillation (AFIB) with multiple measures of cognitive performance in a large community-based sample extensively characterized for vascular risk factors. Our primary analysis included 1011 Framingham Offspring Study (Framingham, Mass) men, mean age = 61.0 (37-89) years, free of clinical stroke and dementia. Using multivariable linear regression models, we related the presence (n = 59) versus absence (n = 952) of AFIB in men to a global measure of performance and multiple measures of specific cognitive abilities assessed an average of 8 months after the AFIB surveillance period. Adjusting for age, education, multiple cardiovascular risk factors, and cardiovascular disease, men with AFIB exhibited significantly lower mean levels of cognitive performance compared with men in normal sinus rhythm. Men with AFIB exhibited lower performance on global cognitive ability and cognitive abilities including Similarities (abstract reasoning), Visual Reproductions-Immediate Recall, Visual Reproductions-Delayed Recall, Visual Organization, Logical Memory-Delayed Recall, and Trail Making A (scanning and tracking) and Trail Making B (scanning, tracking, and executive functioning). Further studies leading to a better understanding of the mechanisms underlying the relation between AFIB and cognitive performance are important.

Obesity, diabetes and cognitive deficit: The Framingham Heart Study.

OBJECTIVE: To determine the independent effects of obesity on cognitive performance and to examine interactions between obesity and non-insulin dependent diabetes mellitus (NIDDM). METHODS: Using a prospective design, male (n=551) and female (n=872) participants of the Framingham Heart Study were classified as obese (yes/no), diabetic (yes/no), and the number of diabetes-years was determined by data collected over an 18-year surveillance period. All subjects were free from dementia, stroke, and clinically diagnosed cardiovascular disease up to the time of cognitive testing. Statistical models were adjusted for age, education, occupation, native language, and cardiovascular disease risk factors. Body mass index status (non-obese or obese) and NIDDM status (diabetic/non-diabetic) were related to cognitive performance on multiple cognitive measures. RESULTS: Adverse effects of obesity on cognitive performance were observed for men only. Diabetes-years related to poorer cognitive performance, but only when men and women were combined for analyses. Neither diabetes nor diabetes-years by obesity interactions were observed. CONCLUSIONS: The gender-specific results for obesity, but not for diabetes, suggests that the underlying mechanisms linking them to cognition may be different.

Serum cholesterol and cognitive performance in the Framingham Heart Study.

OBJECTIVE: The objective of this study was to examine the relationship between total cholesterol (TC) and cognitive performance within the context of the Framingham Heart Study, a large, community-based, prospective investigation of cardiovascular risk factors. METHODS: Participants were 789 men and 1105 women from the Framingham Heart Study original cohort who were free of dementia and stroke and who received biennial TC determinations over a 16- to 18-year surveillance period. Cognitive tests were administered 4 to 6 years subsequent to the surveillance period and consisted of measures of learning, memory, attention/concentration, abstract reasoning, concept formation, and organizational abilities. Statistical models were adjusted for multiple demographic and biological covariates. RESULTS: There was a significant positive linear association between TC and measures of verbal fluency, attention/concentration, abstract reasoning, and a composite score measuring multiple cognitive domains. Performance levels for three clinically defined groups were examined. Participants with "desirable" TC levels (<200 mg/dL) performed less well than participants with borderline-high TC levels (200-239 mg/dL) and participants with high TC levels (there exists 240 mg/dL). CONCLUSIONS: Lower naturally occurring TC levels are associated with poorer performance on cognitive measures, which place high demands on abstract reasoning, attention/concentration, word fluency, and executive functioning.

Blood pressure and cognitive function in an African-American and a Caucasian-American sample: the Maine-Syracuse Study.

OBJECTIVE: The primary purpose of this study was to examine associations between indices of blood pressure (BP) and cognitive function for African-American participants in the Maine-Syracuse Longitudinal Study (MSLS). Corresponding data for the Caucasian-American MSLS participants were included to provide a basis for comparison. Interactions of age with BP indices were also assessed in relation to cognitive function. METHODS: Data were drawn from the baseline MSLS questionnaires, medical interviews and examinations, Wechsler Adult Intelligence Scale subtests, and measurements of BP for 1563 participants, of whom 147 were African American. Multiple linear regression analyses were employed to examine the relationship between several BP predictors and cognitive outcomes with statistical adjustment for demographic, psychosocial, and cardiovascular risk factors. RESULTS: Significant inverse associations between BP indices and cognitive performance were obtained for both racial cohorts but were generally of higher magnitude for the African-American cohort. Interactions of BP with age were not obtained for any of the cognitive test scores. CONCLUSIONS: Elevations in BP are associated with poorer cognitive function for African-American and Caucasian-American cohorts. These associations are similar for younger and older participants.

Framingham stroke risk profile and lowered cognitive performance.

BACKGROUND AND PURPOSE: The primary objective of this work was to describe the relationships between 10-year risk for stroke and multiple measures of cognitive performance for a large community-based sample of individuals who were free of clinical stroke and dementia at the time of risk assessment. METHODS: Participants were 1011 men and 1164 women from the Framingham Offspring Study. The Framingham Stroke Risk Profile was used to assess 10-year risk of stroke. Using a cross-sectional design, we assessed 10-year risk of stroke, the predictor variable, and cognitive performance, the outcome variable, at examination 7 of the Framingham Offspring Study. Multivariable linear regression models were used to relate 10-year risk of stroke to cognitive tests measuring multiple domains of cognitive functioning. RESULTS: With statistical adjustment for age, education, sex, and other correlates of both stroke and cognitive ability, an inverse association between increments in 10-year risk of stroke and cognitive performance level was observed for tests indexing visual-spatial memory, attention, organization, scanning, and abstract reasoning. CONCLUSIONS: In stroke- and dementia-free individuals, higher 10-year risk for stroke is associated with performance decrements in multiple cognitive domains.

From blood pressure to physical disability: the role of cognition.

We examined the hypothesis that lowered cognitive performance plays a role in the relation between elevated blood pressure and physical disability in performing basic physical tasks. A community-based sample (N=1025) free from stroke and dementia (mean age: 61.1 years; SD: 13.0 years; 59.8% women) was used. Using path analysis, systolic and diastolic blood pressures (predictor variable) measured over multiple longitudinal examinations were averaged and related to multiple measures of cognition (intermediate variable) and physical ability (PA; outcome variable) measured at wave 6 of the Maine-Syracuse Study. PA was indexed by time required to execute standing, walking, and turning tests. A best-fit path model including blood pressure and multiple demographic and cardiovascular disease covariates was used. Paths from systolic blood pressure to global performance, verbal memory, and abstract reasoning (Similarities test) were significant (P<0.05), as were paths from diastolic blood pressure to global performance, executive functioning, visual spatial organization/memory, verbal memory, working memory, and abstract reasoning. Regardless of the blood pressure predictor, lower cognitive performance (intermediate variable) was related to lower PA (outcome) in the path from blood pressure to PA. The direct path from blood pressure to PA was significant only for systolic blood pressure. Cognitive performance mediates between blood pressure and PA. As compared with systolic blood pressure, more domains of cognitive functioning intervene between diastolic blood pressure and PA.

Arterial pulse wave velocity and cognition with advancing age.

We hypothesized that carotid-femoral pulse wave velocity (PWV), a marker of arterial stiffness, interacts with age such that the magnitude of associations between PWV and cognitive performance are greater with increasing age and that this interaction is observed despite adjustments for demographic variables, mean arterial pressure, and cardiovascular risk factors. PWV was estimated using applanation tonometry in 409 dementia- and stroke-free participants of the Maine-Syracuse Longitudinal Study (24 to 92 years of age; 62.3% women). Using linear regression analyses in a cross-sectional design, associations between PWV and age and the interaction of PWV and age were examined in relation to a global composite score, the Wechsler Adult Intelligence Scale Similarities test (abstract reasoning), and 4 cognitive domains indexed by multiple cognitive measures. Adjusting for age, gender, education, height, weight, heart rate, mean arterial pressure, and antihypertensive treatment, PWV-by-age interactions were obtained for the global, visual-spatial organization and memory, scanning and tracking, and verbal episodic memory composites, as well as similarities. The combination of higher PWV and age resulted in progressively lower cognitive performance. This finding was the same with an extended model, which also included adjustment for cardiovascular risk factors and other confounds. PWV interacts with age in a multiplicative way to exert a negative influence on cognitive performance level. Early interventions to prevent an increase in arterial stiffness could possibly play an important role in the preservation of cognitive ability.

Cognitive performance and age: norms from the Maine-Syracuse Study.

The primary objective of this study was to provide contemporary normative data on aging and cognition from an ongoing community-based study. This dementia and stroke-free sample (age range = 20-79; mean = 53) consisted of 623 women and 322 men participating in the Maine-Syracuse Longitudinal Study at waves 4 to 6 (1993 to 2003). We employed a battery of 22 widely utilized cognitive tests. A 5 (age) x 3 (education) x 2 (gender) analysis of variance indicated that, in general, higher educated and younger participants exhibited better performance on cognitive tests. We found education group to be the strongest, and gender to be the weakest, predictor of cognitive performance. However, education cohort was not significantly associated with every cognitive outcome, nor was age cohort membership. The addition of cardiovascular disease health variables to a model including age, education, and gender groupings provided statistically significant, but modest, increases in prediction of performance on some tests. Results are discussed in relation to findings for previous studies presenting normative data on cognitive ability as a function of age, education, and gender.

Left ventricular mass, blood pressure, and lowered cognitive performance in the Framingham offspring.

The purpose of this study was to determine whether echocardiographic left ventricular mass is related to cognitive performance beyond casual blood pressure adjusting for the influence of other vascular risk factors. We used multivariable regression analyses to relate left ventricular mass assessed at a routine examination (1995-1998) to measures of cognitive ability obtained routinely (1998-2001) in 1673 Framingham Offspring Study participants (56% women; mean age: 57 years) free from stroke, transient ischemic attack, and dementia. We adjusted for the following covariates hierarchically: (1) age, education, sex, body weight, height, interval between left ventricular mass measurement and neuropsychological testing (basic model); (2) basic model+blood pressure+treatment for hypertension; and (3) basic model+blood pressure+treatment for hypertension+vascular risk factors and prevalent cardiovascular disease. For the basic model, left ventricular mass was inversely associated with abstract reasoning (similarities), visual-spatial memory and organization, and verbal memory. For the basic model+blood pressure+treatment for hypertension, left ventricular mass was inversely associated with similarities and visual-spatial memory and organization. For the basic+blood pressure+treatment for hypertension+risk factors+cardiovascular disease model, no significant associations were observed. Echocardiographic left ventricular mass is associated with cognitive performance beyond casual and time-averaged systolic blood pressure, but this association is attenuated and rendered nonsignificant with additional adjustment for cardiovascular risk factors and cardiovascular disease, thus suggesting that these variables play an important role in mediating the association between left ventricular mass and cognition.

Homocysteine, type 2 diabetes mellitus, and cognitive performance: The Maine-Syracuse Study.

Type 2 diabetes mellitus and higher total plasma homocysteine concentrations are each associated with an increased incidence of cardiovascular disease and with diminished cognitive performance. Relations between homocysteine concentrations and cardiovascular disease incidence are stronger in the presence of type 2 diabetes mellitus. Therefore, we hypothesized that relations between homocysteine concentrations and cognitive performance would be stronger in the presence of type 2 diabetes. We related homocysteine concentrations and cognitive performance on the Mini-Mental State Examination in 817 dementia- and stroke-free participants of the Maine-Syracuse Study, 90 of whom were classified with type 2 diabetes mellitus. Regardless of statistical adjustment for age, sex, gender, vitamin co-factors (folate, vitamin B6, vitamin B12), cardiovascular disease risk factors, and duration and type of treatment for type 2 diabetes mellitus, statistically significant inverse associations between homocysteine concentrations and cognitive performance were observed for diabetic individuals. The weaker inverse associations between homocysteine concentrations and cognitive performance obtained for non-diabetic individuals were not robust to statistical adjustment for some covariates. Interactions between homocysteine concentrations and type 2 diabetes mellitus are observed such that associations between homocysteine and cognitive performance are stronger in the presence of diabetes.

Homocysteine and cognitive performance in the Framingham offspring study: age is important.

Plasma total homocysteine (tHcy) concentrations are associated with deficits in cognitive performance in persons free from dementia. The extent to which age modifies these associations is in need of further investigation in large, community-based, prospective studies combining the following elements: 1) multiple cognitive tests; 2) statistical adjustment for the role of the vitamin cofactors folate, vitamin B6, and vitamin B12; and 3) adjustment for the presence of risk factors for cardiovascular disease and stroke. Using data collected between 1991 and 2002, the authors investigated the associations between tHcy and multiple measures of cognitive performance in 2,096 dementia- and stroke-free participants of the Framingham Offspring Study, who were stratified into three age groups (40-49 years, 50-59 years, 60-82 years), after findings of statistically significant tHcy-by-age interactions for multiple cognitive measures. Regardless of statistical adjustment for age, sex, gender, the vitamin cofactors, and cardiovascular risk factors, statistically significant inverse associations between tHcy and multiple cognitive domains were observed for individuals aged 60 or more years; no such associations were observed for participants aged less than 60 years. Early preventive interventions may be important, because the inverse association between tHcy and cognitive performance is observed beyond middle age.

Blood pressure-related cognitive decline: does age make a difference?

Systolic and diastolic blood pressures have been inversely related to cognitive performance in prospective and cross-sectional studies. However, in large, community-based samples, these findings have been limited to older adults. In this 20-year longitudinal study, we examined the relationship between baseline blood pressure and cognitive decline for 529 participants using 2 age groups (18 to 46 years and 47 to 83 years). Cognitive performance was measured over multiple examinations with the Wechsler Adult Intelligence Scale from which 4 scores were derived by factor analysis. A 2-stage growth curve method of analysis was used to model cognitive change. Results indicated that higher levels of baseline systolic blood pressure, diastolic blood pressure, mean arterial pressure, and blood pressure categories as defined by the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were significantly associated with decline in Visualization/Fluid abilities in both younger and older age groups. Young adults are as susceptible to blood pressure-related longitudinal decline in cognitive performance as are older adults.