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Psychosomatic Medicine 66:291-297 (2004)
© 2004 American Psychosomatic Society

ORIGINAL ARTICLES

The Relationship Between Blood Pressure and Cognitive Performance in the Third National Health and Nutrition Examination Survey (NHANES III)

Julie A. Suhr, PhD, Jesse C. Stewart, PhD and Christopher R. France, PhD

From the Department of Psychology (J.A.S., C.R.F.), Ohio University, Athens, OH; and the Department of Psychiatry (J.C.S.), University of Pittsburgh School of Medicine, Pittsburgh, PA.

Address correspondence and reprint requests to Julie A. Suhr, PhD, Department of Psychology, 200 Porter Hall, Ohio University, Athens, OH 45701. E-mail suhr{at}ohio.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: The present study examined the relationship between blood pressure and cognitive performance in 2727 healthy men and women between the ages of 20 and 59 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III).

METHODS: Participants were selected from a subsample of 5662 NHANES III respondents who completed an initial home interview, a medical examination, and a series of computerized cognitive tests of visuomotor reaction time, complex psychomotor speed (ie, symbol digit substitution), and verbal learning/attention (ie, serial digit learning).

RESULTS: Hierarchical regressions tested the contribution of resting blood pressure to the prediction of performance on each of the cognitive tests. Results indicated that, after controlling for demographic variables (age, sex, race/ethnicity, education) and resting blood pressure, the interaction of systolic blood pressure by age was a significant predictor of performance on the test of verbal learning/attention. Follow-up analyses revealed that higher systolic blood pressure was associated with poorer performance in those younger than 40 years.

CONCLUSIONS: Expanding on findings from previous epidemiological studies, the present study reports a small but significant relationship between resting blood pressure and cognitive performance that is particularly evident in younger healthy adults.

Key Words: blood pressure, • cognition, • hypertension.

Abbreviations: NHANES III = Third National Health and Nutrition Examination Survey;; NES = Neurobehavioral Evaluation System;; CNS = central nervous system;; SBP = systolic blood pressure;; DBP = diastolic blood pressure.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Many case-control studies have demonstrated the presence of subtle neuropsychological impairments in untreated hypertensives before the development of hypertension-related cerebrovascular complications. Deficits have frequently been observed in verbal and visual memory (1–6), abstract reasoning and executive functioning (7–10), attention/working memory (2,3,9,11), psychomotor speed (2,3,5,7,9,10,12), and visuoperceptual/constructional skills (1–3,9,12). Relative deficits in memory, mental flexibility, motor speed, and visuospatial/constructional skills have also been observed in individuals at increased risk for hypertension, including those with a parental history of the disorder and/or high-normal resting blood pressure (13,14). These findings suggest that cognitive differences may be present before the development of hypertensive blood pressure levels. Consistent with this notion, results of epidemiological studies suggest that there is a continuous inverse relationship between blood pressure and cognitive performance (15–25). Glynn et al. (26), however, reported a curvilinear relationship, with diminished cognitive performance found among older adults with the highest and lowest blood pressure levels. It should be noted that the vast majority of epidemiological studies addressing this question have focused on individuals in their mid 50s and older, leaving open the question of the nature of the blood pressure/cognition relationship in a younger and healthier population.

It has been hypothesized that the mild neuropsychological impairments associated with hypertension are related to hypertrophic changes of central nervous system (CNS) blood vessels resulting from recurrent autoregulation of blood pressure within the brain (27). These vascular changes may result in small but significant decreases in blood flow to the CNS, and, perhaps more importantly, may render blood vessels less efficient at producing dilatory responses required to enhance blood flow to focal brain regions in response to specific cognitive tasks. In line with this explanation, Jennings et al. (27,28) reported that hypertensive individuals (with a mean age of 60 years) exhibit a general reduction of cerebral blood flow relative to those with normal blood pressure and show smaller increases in cerebral blood flow to active areas of the brain during completion of cognitive tasks. Interestingly, evidence from cognitive testing suggests that this effect may be more pronounced in younger adults. For example, in two epidemiological studies that included individuals with a much wider range of ages (ie, from the 20s to the 80s), an interaction between blood pressure and age was detected, with a stronger relationship between blood pressure and cognitive performance observed among younger adults (29,30). Similarly, at least one case-control study has demonstrated that differences in cognitive performance between individuals with and without hypertension are more pronounced in younger cohorts (10).

The present study sought to replicate and extend previous findings by assessing the relationship between blood pressure and cognitive function in 2727 men and women between the ages of 20 and 59 years who participated in the Third National Health and Nutrition Examination Survey (NHANES III). The specific goals of this study were to reexamine the previously reported linear relationship between blood pressure and cognitive performance in a larger and more diverse sample of young to middle-aged adults who were carefully screened for alternative medical explanations for cognitive impairment and to determine whether the relationship between blood pressure and cognition, if observed, is more pronounced in younger versus older adults.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Population and Procedures
The data examined in the present study were collected as part of the NHANES III, conducted from 1988 through 1994 on a civilian, noninstitutionalized population of the United States (31–33). Nearly 34,000 people completed an extensive interview in their homes, and approximately 31,000 of the interviewees subsequently underwent a medical examination. Blood pressure readings were obtained from each respondent during the household interview and the medical evaluation. In addition, a representative sample of respondents between the ages of 20 and 59 years were selected to complete a battery of computerized cognitive tests from the Neurobehavioral Evaluation System (NES) (34).

The sample for this study was taken from all respondents between the ages of 20 and 59 years who completed the Household Adult Questionnaire, the medical evaluation, and the NES tests (N = 5662). From this sample, 283 respondents were excluded because they had incomplete NES data. To control for potential alternative causes of cognitive impairment, we also excluded, in the following order, respondents who reported a history of stroke (N = 29), who reported taking 3 or more prescription medications (N = 412), who reported taking any prescription medications other than antihypertensive medications (N = 1530), who reported being exhausted on the questionnaire administered immediately before the cognitive tests (N = 69), who reported consuming 2 or more alcoholic drinks in the 3 hours directly preceding administration of the cognitive tests (N = 9), who reported putting forth no effort on the cognitive tests (N = 85), and who did not take the cognitive tests in English (N = 495). It should be noted that another 23 respondents who were statistical outliers on the measures of cognitive performance were excluded from analyses (see below), leaving a final sample of 2727 individuals. Also of note, we planned to exclude individuals with a self-reported diagnosis of diabetes, but other exclusionary criteria above eliminated all such individuals from the sample.

Measures
Resting Blood Pressure
A total of 6 blood pressure readings were obtained from each respondent. The procedures for the blood pressure assessments as well as the specific instrumentation are described in detail elsewhere (31). Briefly, using a Baumanometer Gravity Rx sphygmomanometer with calibrated V-Lok cuff, 3 seated blood pressure readings were taken by a trained interviewer during the household interview after administration of the Household Adult Questionnaire. Respondents were asked to refrain from smoking or drinking coffee or alcohol during the interview, and they were instructed to remain relaxed during the blood pressure measurements. During a subsequent medical examination, a physician recorded 3 more seated blood pressure readings using a Baumanometer wall model standard sphygmomanometer with a calibrated V-lok cuff. Because blood specimens were also obtained during the medical examination, respondents were instructed to fast for at least 6 hours before their examination.

Mean blood pressure readings obtained in the home and at the medical examination were significantly correlated for both systolic blood pressure (SBP, r = 0.74, p < .001) and diastolic blood pressure (DBP) (r = 0.61, p < .001), and differed by less than 2 mm Hg between settings (SBPhome, mean = 119.2, SD = 14.4; SBPexam, mean = 117.0, SD = 14.7; DBPhome, mean = 74.9, SD = 11.9; DBPexam, mean = 73.8, SD = 11.8). As can be seen in Table 1, simple correlations between blood pressure and cognitive variables were similar for both the home and medical examination blood pressure readings. As a result, to provide a single, reliable estimate of resting blood pressure levels for all participants, the mean of all six blood pressure readings (home + medical examination) was used in the subsequent analyses.


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  		TABLE 1. Simple Correlations Between Systolic (SBP) and Diastolic Blood Pressure (DBP) and the Cognitive Tests of Reaction Time, Symbol Digit, and Serial Digit Learning for the Entire Sample (N = 2727)
 
Neurobehavioral Tests
Three computerized cognitive tests from the NES were administered to NHANES participants, including a visual reaction time test, a symbol digit substitution test, and a serial digit learning test. NES testing occurred as part of the mobile examination center evaluation. The visual reaction time test assessed an individual’s response time to presentation of visual targets on a computer screen. The symbol digit substitution task measured the speed with which an individual identified a matching single digit with a symbol presented on the computer screen, when a symbol to digit code was displayed at the top of the screen. This task is often thought to tap visual attention and psychomotor speed (35). The serial digit learning task assessed an individual’s ability to learn an eight-digit numerical sequence, and involved presenting the eight-digit sequence visually, one digit at a time, on the computer screen. Respondents were required to enter the correct sequence on two consecutive trials. Although the task is described as a verbal learning task (34), research shows it can generally be regarded as a general attention/concentration task (36). Details regarding the selection of respondents to complete the cognitive tests, the administration of the cognitive tests, the training of the administrators, and the normative data for the NES tests are described in more detail elsewhere (34).

Because the measures of performance on the cognitive tests were not normally distributed, they were transformed to approximate a normal distribution. Specifically, the performance measures on the visual reaction time test (ie, mean latency to respond to a visual stimulus across 50 trials) and the symbol digit substitution test (ie, mean latency to complete a trial across five trials) were inverse transformed such that lower scores on the transformed variables were indicative of worse performance. The performance measure on the serial digit learning test (ie, total number of errors across trials required to learn the criterion) was square root transformed such that higher scores were indicative of worse performance. As noted above, seven statistical outliers on the symbol digit substitution test and 16 outliers on the visual reaction time test were excluded from all analyses.

Data Analysis
As an initial exploration of the NES data and to compare performance in our smaller sample to that obtained in larger NHANES III reports (34), we examined the relation of demographic characteristics (age, education, sex, self-reported racial/ethnic background) to the NES variables using simple correlation and t tests or one-way analysis of variance, where appropriate. To test specific hypotheses regarding 1) the relation of blood pressure to cognitive performance and 2) interaction between blood pressure and age in explaining cognitive performance, we first conducted three hierarchical regression analyses (one for each NES performance measure) with age, race/ethnicity, education, and sex entered on the initial step as control variables. Resting SBP was then offered as a potential predictor on the second step of the regression. The age by blood pressure interaction was offered on step three. Finally, SBP by sex and SBP by self-reported race/ethnicity interactions were entered on step 4. Significant blood pressure by age interactions were examined using hierarchical regressions for separate age groups (ie, 20–29, 30–39, 40–49, and 50–59 years). In addition, significant hierarchical regressions were followed up with parallel hierarchical logistic regression analyses, using clinical impairment on cognitive tests as the dependent variable. Clinical impairment was defined as a score that might be interpreted as clinically meaningful in a testing setting (performance falling 1.5 SD or greater from the mean for the task based on data from the entire sample).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Characteristics of Respondents
The final sample of respondents consisted of 1384 men (50.8%) and 1343 women (49.2%) with a mean age of 35.7 years (SD = 10.5 years). The sample included 1054 whites (38.7%), 1017 blacks (37.2%), and 566 Mexican-Americans (20.8%), based on self-reported race/ethnicity (of note, 109 persons were coded in the NHANES III data set as "other," and included Hispanics who were not Mexican-American and individuals who did not specify a particular racial/ethnic background). The average level of education of respondents in the sample was 12.5 years (SD = 2.5 years). Mean resting SBP and DBP levels for respondents were 118.1 mm Hg (SD = 13.7) and 74.5 mm Hg (SD = 10.5), respectively.

Demographic Variables and Neurobehavioral Test Performance
Consistent with prior research (34), significant correlations were observed between age, education, and performance on the three NES tests. Higher age and lower educational level were related to worse performance on all three tests (age rs = –0.04 to –0.43, education rs = 0.17 to 0.44). Males performed better than females on all three tasks, and self-reported non-Hispanic whites performed better than individuals in the three other self-reported racial-ethnic groups. Thus, age, education, sex, and self-reported race-ethnicity (recoded as non-Hispanic/white vs. all other groups, given the above findings) were entered on the first step of each of the regression analyses.

Blood Pressure and Neurobehavioral Test Performance
As Table 1 demonstrates, elevations in SBP or DBP were significantly related to worse performance on both the symbol digit substitution task (r = –0.16 to –0.23, p < .001) and the serial digit learning task (r = 0.11 to 0.13, p < .001). The following regression analyses use SBP as a predictor; however, it should be noted that a similar pattern of relationships was observed when the analyses were repeated using DBP instead of SBP.

Visual Reaction Time
As can be seen in Table 2, the demographic control variables of age, race/ethnicity, education, and sex combined to account for 9% of the variance in performance on the visual reaction time test. Neither SBP nor the blood pressure by age interaction significantly added to the variance explained in test performance. The interactions between sex and SBP as well as race/ethnicity and SBP also did not add significantly to variance explained in performance on this task.


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  		TABLE 2. Results of Hierarchical Regression Analyses Using Age, Sex, Race/Ethnicity, Education, and Systolic Blood Pressure (SBP) to Predict Cognitive Performance
 
Symbol Digit Substitution
For the symbol digit substitution test, the set of demographic predictors accounted for 41% of the variance in performance (Table 2). Once again, neither SBP nor the blood pressure by age interaction was a significant predictor of test performance. Interactions between sex and SBP as well as race/ethnicity and SBP did not add significantly to variance explained in performance on this task.

Serial Digit Learning
For the serial digit learning test, the set of demographic predictors accounted for 20% the variance in performance (Table 2). Although SBP did not explain significant additional variance in performance on this task, the SBP by age interaction was significant. Neither the SBP by sex interaction nor the SBP by race/ethnicity interaction added to variance explained in performance on the serial digit learning task.

Blood Pressure by Age Interaction
To further examine the SBP by age interaction observed on the serial digit learning test, we conducted four additional hierarchical regressions, separately by age groups. In each regression analysis, education, sex, and race/ethnicity were entered on the first step, and SBP was entered on the second step. As can be seen in Table 3, SBP accounted for a significant amount of variance in test performance above and beyond the demographic predictors in the two younger age groups (ie, 20–29 years and 30–39 years). In contrast, for the two older age groups (ie, 40–49 years and 50–59 years), blood pressure was not a significant predictor of test performance after controlling for the demographic variables.


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  		TABLE 3. Results of Hierarchical Regression Models Using Sex, Race/Ethnicity, Education, and Systolic Blood Pressure (SBP) to Predict Serial Digit Learning Test Performance in Four Age Groups
 
Clinical Relevance of Findings
To examine the clinical relevance of the relationship between blood pressure and performance on the serial digit learning test, we analyzed whether blood pressure could predict likelihood of impaired performance on the task. We coded each individual as "normal" if their score was less than or equal to 1.5 SD above the mean for total errors and "impaired" if their score was greater than 1.5 SD above the mean for total errors, using the untransformed serial digit learning test total errors score and based on scores from the entire sample (428 individuals from the total sample fell in the "impaired" range using this definition). We then conducted a hierarchical logistic regression analysis for the whole sample, using "normal" or "impaired" on the serial digit learning test as the dependent variable. As can be seen in Table 4, on the first step, demographic variables (age, education, sex, and race/ethnicity) were entered. SBP was then entered on the second step, and the age by SBP interaction was entered on the third step. Results were consistent with previous analyses and showed that education, race, and age were significant predictors of the likelihood of being impaired on the test (sex was not a significant predictor and was excluded from the final model). According to the resulting odds ratios, each year decrease in total number years of schooling completed was associated with a 23% greater risk of impairment, each year increase in age was associated with 16% increased likelihood of impairment, and self-reported minority status (black, Mexican-American, Hispanic/Other) was related to a 2.7 times greater risk of impairment. SBP and the SBP by age interaction were also significant predictors of impairment.


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  		TABLE 4. Results of Hierarchical Logistic Regression Analyses Using Sex, Race/Ethnicity, Education, and Systolic Blood Pressure (SBP) to Predict the Likelihood of Impairment on the Serial Digit Learning Test
 
To follow up on the significant interaction, similar analyses were conducted within the four separate age groups listed above (Table 4). After controlling for the demographic variables, there was a significant relationship between increased SBP and membership in the impaired performance group in 30- to 39-year-old participants, as well as a nonsignificant trend (p = .07) in the 20- to 29-year-old group. In each of these groups, after controlling for demographic contributions to performance, each 10 mm Hg increase in SBP was associated with a 20% increase in likelihood of being in the impaired group.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Consistent with the results from previous studies of older samples, a significant inverse relationship between resting SBP and performance on a relatively nonspecific cognitive measure of attention/learning efficiency was found in the present study. The relationship observed in our sample is small and limited to one of the three cognitive tests administered; however, it is comparable in magnitude to that reported in previous epidemiological studies (15,16,21,23,25). In addition, the effect size that we found must be considered in the context of the statistical method employed; our hierarchical regression models controlled for demographic variables (age, sex, race/ethnicity, education) that share substantial variance with both blood pressure and cognitive performance, which resulted in reduced predictive power for blood pressure. Furthermore, results of logistical regression models suggested that blood pressure was related to clinically significant impairment on the serial digit learning task, as defined by performance at least 1.5 SD from the sample mean.

Although the relationship between blood pressure and cognitive performance observed in this study was small in magnitude, it may nonetheless have important implications. One significant implication of the current findings is that blood pressure-related cognitive deficits may be observable in a wide range of the population, including young, healthy adults. Whereas previous findings were based largely on older populations with multiple medical conditions, the current results confirm a relationship between elevated blood pressure and diminished cognitive performance even among young adults who were screened for the presence of many potential confounding contributors to decrements in cognitive functioning (eg, medication use, neurological impairment, cardiovascular disease, diabetes, alcohol use, and fatigue and effort during testing).

An additional important finding is the blood pressure by age interaction. In line with prior studies (29,30), our analyses indicate that the most pronounced relationship between elevated blood pressure and diminished cognitive performance was observed among the younger individuals in our sample (ie, those under 40 years of age). Although the mechanism of this effect remains to be elucidated, one possibility is that this reflects increased severity of CNS autoregulatory responses to higher blood pressure in a subset of adults particularly vulnerable to development of hypertension and its future health consequences. Alternatively, our exclusion criteria may have introduced a selection bias such that older participants who show similar relationships between blood pressure and cognitive performance may have been excluded because they were more likely to have developed hypertension-related medical conditions (eg, stroke).

Yet another important implication of our findings is the nature of the blood pressure–cognitive performance relationship. Although most studies of older adults also report an inverse, linear relationship between SBP and cognitive performance (15–25), others have argued for a curvilinear relationship based on existing evidence that low blood pressure may be related to cognitive decline in adults over 65 (26,37–40). This may be particularly true for individuals with cardiovascular disorders such as stroke, myocardial infarction, carotid sinus syndrome, orthostatic hypotension, or vasovagal syndrome, due to the increased likelihood of microvascular pathology (38) or reduced CNS blood flow (41) associated with these conditions. Alternatively, it has also been argued that the apparent relationship between hypotension and cognitive impairment may arise from sample bias inherent in longitudinal studies of older populations (42). That is, participants with lower blood pressure are more likely to survive into a prolonged follow-up evaluation period and, therefore, will also have a greater opportunity to exhibit age-related cognitive impairment. Regardless of the accuracy of these explanations, in our relatively young and healthy sample, a linear relationship provided the best fit to the available data.

Even though our findings provide an interesting extension of the existing literature, there are several limitations that must be noted. First, because only three brief cognitive tests were administered as part of the NHANES III, it is impossible to provide a comprehensive assessment of cognitive abilities or to provide repeated assessment within a particular domain of function. It is important to note that the vast majority of prior epidemiological studies have assessed cognitive performance using measures such as the Mini-Mental State Examination, although at least one used measures of memory and attention (21). Second, the NES tests were not selected specifically for the purpose of assessing potential cognitive consequences of blood pressure and, consequently, are not measures that are frequently used in neuropsychological studies of the effects of hypertension. For example, in the Waldstein et al. (43) comprehensive review of the case-control study literature, few investigations used measures of basic reaction time and only one used a serial digit learning task. Digit symbol and symbol digit substitution tasks are often used in studies of the cognitive effects of hypertension, although consistent group differences have not been observed across studies. Indeed, some of the most consistent findings in the hypertension literature are changes in memory and attention (43), skills that are tapped, at least in part, by the serial digit learning task. Interestingly, prior research with the NES serial digit learning task suggests that it is sensitive to neurological dysfunction (44), and factor analysis suggests that it is more strongly related to performance on traditional neuropsychological instruments than the other two NES variables utilized in the present study, which were more consistently associated with a factor that was interpreted as "computer performance," rather than tapping specific cognitive skills per se (45).

Finally, while multiple blood pressure measurements were obtained on two different occasions, these readings may not be an accurate reflection of typical blood pressure in all participants. Blood pressure reactivity to medical assessment and the minimal control over possible environmental influences on blood pressure levels (eg, recent substance use, eating, drinking, and physical activity) are just two potential sources of variability. While our analyses of the home and medical examination data suggested relative stability of measurement and lack of "white coat" reactivity at the group level, it would be important to replicate findings using more stable measures of blood pressure, such as 24-hour ambulatory monitoring of blood pressure levels.

In conclusion, the findings from the present study provide evidence that increased resting SBP is related to poorer performance on an attentional/learning task in a large sample of young, healthy adults of diverse heritage. These findings provide an important extension to the existing literature on older adults and suggest that comprehensive testing with younger populations may provide important insights into the range and severity of cognitive deficits that can predate the development of hypertension.

Received for publication July 1, 2003.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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