Gregory A. Dore

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.

Hypertension and Cognitive Functioning: A Perspective in Historical Context

Our objective is to characterize the development of the literature on hypertension and cognitive functioning from a historical perspective. This goal was stimulated by the review on “Historical Trends and Milestones in Hypertension Research” in the October 2012 issue of Hypertension .1 Our specific aims are threefold: (1) to trace and describe the history of this area of research; (2) to identify milestones in knowledge and methods; and (3) to discuss briefly how this literature translates into patient care. The topic is of major relevance to research and practice because hypertension is a well-known risk factor for decline in cognitive performance within the normal range of cognitive functioning, mild cognitive impairment (MCI) and dementia. It is important to emphasize 3 features of the review: (1) it is not designed as a critical review of the literature, but rather to describe the historical influences on our current knowledge base (poor, mediocre and outstanding papers from the past have all shaped our present); (2) word-count limitations require that we omit statistical detail except to emphasize effect sizes in pivotal papers; and (3) each milestone topic is addressed by noting the earliest work then followed by examples of papers representing pivotal events. A number of comprehensive reviews of this literature are available,2–6 including a seminal paper summarizing the formative years of this research.7 Please see http://hyper.ahajournals.org for citations to additional reviews of the literature and papers published in Hypertension . We recognize the importance of the emerging literature on hypotension and cognitive function, but refer the readers to previous reviews which include this topic.8–10 ### Measurement of Cognitive Functioning In this paper, the term cognitive performance is used to describe the outcome of studies measuring a full range of ability from low to high. The term cognitive functioning is used …

Relation Between Central Adiposity and Cognitive Function in the Maine-Syracuse Study: Attenuation by Physical Activity

BackgroundPrevious 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.PurposeThe 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.MethodsParticipants 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.ResultsWaist 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.ConclusionsWaist 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.

Decline in renal functioning is associated with longitudinal decline in global cognitive functioning, abstract reasoning and verbal memory

BACKGROUND Decreased estimated glomerular filtration rate (eGFR) and higher serum creatinine (sCR) levels have been associated with longitudinal decline in global mental status measures. Longitudinal data describing change in multiple domains of cognitive functioning are needed in order to determine which specific abilities are most affected in individuals with impaired renal function. METHODS We conducted a 5-year longitudinal study with 590 community-living individuals (mean age 62.1 years, 60.2% female, 93.2% white, 11.4% with diabetes mellitus, mean eGFR 78.4 mL/min/1.73 m²) free from dementia, acute stroke and end-stage renal disease. To measure longitudinal change-over-time, cognitive performance measures were regressed on eGFR adjusting for baseline eGFR and cognitive performance, comorbidity and vascular risk factors. Outcome measures were scores from 17 separate tests of cognitive abilities that were used to index 5 theoretically relevant domains: verbal episodic memory, visual-spatial organization and memory, scanning and tracking, working memory and similarities (abstract reasoning). RESULTS Declines in eGFR values were associated with cognitive declines, when adjusted for eGFR and cognitive function scores at baseline. Change in renal functioning over time was related to change observed in global cognitive ability [b=0.21SD decline per unit ln(eGFR), 95% CI: 0.04-0.38, P=.018], verbal episodic memory [b=0.28 SD decline per unit ln(eGFR), 95% CI: 0.02-0.54, P=0.038] and abstract reasoning [b=0.36 SD decline per unit ln(eGFR), 95% CI: 0.04-0.67, P=0.025]. Decline in cognitive functioning in association with declining renal functioning was observed despite statistical adjustment for demographic variables and CVD risk factors and the exclusion of persons with dementia or a history of acute stroke. CONCLUSIONS Early detection of mild to moderate kidney disease is an important public health concern with regard to cognitive decline.

RELATIONS BETWEEN DAIRY FOOD INTAKE AND ARTERIAL STIFFNESS: PULSE WAVE VELOCITY AND PULSE PRESSURE

Modifiable risk factors, such as diet, are becomingly increasingly important in the management of cardiovascular disease, one of the greatest major causes of death and disease burden. Few studies have examined the role of diet as a possible means of reducing arterial stiffness, as measured by pulse wave velocity, an independent predictor of cardiovascular events and all-cause mortality. The aim of this study was to investigate whether dairy food intake is associated with measures of arterial stiffness, including carotid-femoral pulse wave velocity and pulse pressure. A cross-sectional analysis of a subset of the Maine-Syracuse Longitudinal Study sample was performed. A linear decrease in pulse wave velocity was observed across increasing intakes of dairy food consumption (ranging from never/rarely to daily dairy food intake). The negative linear relationship between pulse wave velocity and intake of dairy food was independent of demographic variables, other cardiovascular disease risk factors, and nutrition variables. The pattern of results was very similar for pulse pressure, whereas no association between dairy food intake and lipid levels was found. Further intervention studies are needed to ascertain whether dairy food intake may be an appropriate dietary intervention for the attenuation of age-related arterial stiffening and reduction of cardiovascular disease risk.

Kidney disease and cognitive function.

UNLABELLED We provide a brief review of research on chronic kidney disease and cognitive performance, including dementia. We touch briefly on the literature relating end-stage-renal disease to cognitive function, but focus on studies of modest and moderate forms of chronic kidney disease (CKD) that precede dialysis and transplantation. We summarize previous reviews dealing with case control studies of patients but more fully examine community-based studies with large samples and necessary controls for demographic risk factors, cardiovascular variables, and other confounds such as depression. In addition we suggest potential biological and social-psychological mediators between CKD and cognition. Studies follow in two categories of design: (1) cross-sectional studies, and (2) longitudinal studies. In each, CKD is related to a wide range of deficits in cognitive functioning including verbal and visual memory and organization, and components of executive functioning and fluid intellect. In general, prior to the need to treat with hemodialysis (HD) or kidney transplant (KT), magnitude of effect with relation to CKD and function are small or modest in persons free from acute stroke and dementia. However, HD and KT can result in major impairment. We discuss needed controls, the greater demand on controls after the start of HD and KT, and suggest that mechanisms intervening relations between hypertension, or diabetes, and cognitive performance may be similar to those intervening between hypertension and cognitive performance and the hypertension and diabetes literature on cognition provides a good model for the study of early stage kidney disease and cognitive ability. We posit that the mechanisms linking CKD and cognition may be similar to those linking hypertension or diabetes to cognition. We identify the need for more studies with multiple cognitive test batteries, measures of every-day cognitive abilities relevant to patient understanding of the disease and treatments, and more studies with prevalent and incident dementia outcomes. DESCRIPTORS kidney disease, chronic kidney disease, cognitive function, dementia and cardiovascular risk factors.

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.

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.

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) × 3 (education) × 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.

Deterioration in Renal Function Is Associated With Increased Arterial Stiffness

BACKGROUND Higher levels of baseline pulse wave velocity (PWV) have been associated with longitudinal decline in renal function in patients with kidney disease. We examined longitudinal decline in renal function in relation to levels of PWV. We hypothesized that longitudinal decline in renal function in a community-based, nonclinic sample would be associated with higher levels of PWV. METHODS We conducted a 4-5 year longitudinal study with 482 community-living individuals free from acute stroke, dementia, and end-stage renal disease (mean age = 60.9 years; 59% women; 93.2% white; 10% with diabetes mellitus; mean estimated glomerular filtration rate (eGFR) = 79.2 ml/min/1.73 m2). Multiple linear regression analyses were used to examine the association between changes in renal function (eGFR and serum creatinine) from baseline to follow-up and PWV levels at follow-up, the outcome measure. Regression coefficients were adjusted for age, sex, education, race/ethnicity, weight, activity level, mean arterial pressure, treatment of hypertension, and cardiovascular risk factors. RESULTS With adjustment for covariables, decline in renal function was associated with higher levels of PWV over a mean follow-up of 4.68 years. CONCLUSIONS Decline in renal functioning from baseline levels measured 4-5 years before measurement of PWV is related to higher levels of PWV in a community sample.