Abstract
Background
Little is known about what specific cognitive functions are affected by elevated blood pressure (BP) and how orthostatic BP change is related to cognitive impairment. The aim of this study was to determine the effect of BP and its postural change on cognitive functions in otherwise healthy elders.
Methods
In 70 healthy persons (mean age, 72 ± 4 years), supine systolic BP (SBP) was assessed 3 times using a sphygmomanometer, and the average values were obtained for the analysis. After 1, 3, and 5 minutes of standing, 3 BP measurements were obtained and the orthostatic SBP changes were determined by subtracting these values from the supine average. Neuropsychological tests were administered to assess short-term and long-term verbal and visual memory, visuospatial skills, and frontal-executive functions. Participants were considered impaired in the specific cognitive performance if their scores fell below the 25th percentile of the study population. Multiple logistic regression models were used to evaluate the relation of SBP and the magnitude of orthostatic SBP decline to risk for impairment in each of the cognitive tests.
Results
Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31-fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in psychomotor speed and set shifting as measured using the Trailmaking Part-B test. There was no significant association between cognitive functions and orthostatic SBP decline at 1, 3, and 5 minutes of standing.
Conclusion
Elevation of BP is associated with a selective impairment in executive function in otherwise healthy community-dwelling elders.
Both hypertension and cognitive impairment increase in prevalence with advancing age, and their relation to each other is attracting significant research interest. Several recent studies have shown an association between hypertension and impairment in global cognition, attention, memory, visuospatial performance, or frontal-executive function (1,2). Controversy still exists regarding what specific cognitive domains are affected by elevated blood pressure (BP).
Normal aging is also associated with orthostatic hypotension (3), an important risk factor for syncope (4), falls (5), and stroke (6). An association between orthostatic hypotension and decreased cerebral blood flow has been shown in some studies (7,8), suggesting that orthostatic BP decline may contribute to cognitive impairment. However, very few studies have explored the relationship between postural BP change and cognitive function (9,10).
The aim of this cross-sectional study was to determine the relationship between BP and different cognitive domains, and to analyze the relation between orthostatic BP decline and cognitive functions in a group of relatively healthy elders.
Methods
Study Population
Seventy persons aged 65 years or older were recruited through the Harvard Cooperative Program on Aging registry. Exclusion criteria included congestive heart failure, severe valvular heart disease, stroke, dementia, carotid stenosis, coronary artery disease, chronic lung disease, smoking within 10 years, diabetes, Parkinson's disease, a cardiac pacemaker, severe hypertension (systolic BP > 200 mmHg, diastolic BP > 110 mmHg, or both or were taking more than 2 antihypertensive medications), peripheral vascular disease, hormone replacement therapy, or beta-blockers. Participants with chronic stable hypertension were included. The institutional review board of the Hebrew Rehabilitation Center for Aged approved the study.
Blood Pressure Measurements
During a visit to the clinical research laboratory, participants' BPs were assessed 3 times after 5 minutes of supine quiet rest, with 2 minutes between each measure using a Random-zero mercury sphygmomanometer (Hawksley, U.K.). The average systolic BP (SBP) was used for this study. Then the participants were asked to stand. After 1, 3, and 5 minutes of standing, BPs were measured and the orthostatic SBP changes were determined by subtracting these values from the supine average.
Neuropsychological Tests
After the BP measurements, a trained research nurse administered a battery of neuropsychological tests to each participant in the following order: Logical Memory-I (short-term verbal memory), Visual Reproductions-I (short-term visual memory), Trailmaking Parts-A&B and Word Fluency (frontal-executive function), Logical Memory-II (long-term verbal memory), and Visual Reproductions-II (long-term visual memory). Logical Memory and Visual Reproductions were administrated and scored using the Wechsler Memory Scale, Third Edition (11). Each test score was transformed to a standardized z-score using the formula z = X − X̅/SD if the distribution was normal. If the score was not normally distributed, its log-value was used for analysis. A composite z-score was obtained for different cognitive domains by summing z-scores whenever appropriate (see the footnote to Table 2). Participants were considered impaired in the specific cognitive performance if their z-score or composite z-score fell below the 25th percentile of the study population.
Table 2. Odd Ratios and 95% Confidence Intervals for Performing Below the 25th Percentile on Cognitive Tests for Each 10 mmHg Increase in Supine Systolic Blood Pressure.
| Cognitive Measures | Odds Ratio | 95% Confidence Interval | p Value |
|---|---|---|---|
| Frontal-executive | |||
| Trailmaking Part A | 1.09 | 0.68–1.76 | 0.72 |
| Trailmaking Part B | 2.31 | 1.14–4.66 | 0.019 |
| Verbal fluency | 0.69 | 0.39–1.21 | 0.20 |
| Naming fluency | 1.07 | 0.65–1.74 | 0.80 |
| Memory | |||
| Logical memory I* | 0.84 | 0.52–1.36 | 0.47 |
| Logical memory II* | 1.06 | 0.67–1.68 | 0.79 |
| Visual reproduction I recall | 1.40 | 0.76–2.59 | 0.28 |
| Visual reproduction II recall | 0.98 | 0.60–1.59 | 0.93 |
| Visuospatial tests | |||
| Copy and discrimination† | 1.21 | 0.77–1.90 | 0.40 |
Notes:
Composite z-score from recall score and thematic score.
Composite z-score form copy score and discrimination score.
Statistical Analyses
Logistic regression was used to evaluate the relation of SBP or magnitude of orthostatic SBP decline to impairment in each cognitive measure, controlling for age, sex, ethnicity, education level, alcohol consumption, body mass index, total cholesterol level, and use of medications, including antihypertensives, antidepressants, antipsychotics, and sedatives. Data management and analyses were performed using STATA 7.0 software (STATA Corp., College Station, TX).
Results
Table 1 summarizes the participants' characteristics and cognitive scores. Table 2 shows the results of logistic regression analyses for the effects of supine SBP on different cognitive impairments. BP elevation was selectively associated with impairment in frontal-executive function, as measured by the Trailmaking Part-B test. Controlling for potential confounders, each 10 mmHg increase in supine SBP was associated with a 2.31-fold increase (95% confidence interval, 1.14 to 4.66) in risk for impairment in the Trailmaking Part-B test, which measures psychomotor speed and set shifting. Increased SBP was not associated with other cognitive measures including immediate/delayed verbal and visual memory and visuospatial performance.
Table 1. Characteristics and Cognitive Test Scores of Study Subjects (N = 70, 31 Women).
| Characteristics | Range | Mean ± SD or Percentage |
|---|---|---|
| Age (y) | 65–85 | 72.0 ± 4.4 |
| Female | NA | 44.3% |
| Education (y) | 12–20 | 15.4 ± 2.8 |
| Body mass index (kg/m2) | 18.7–30.8 | 24.8 ± 3.0 |
| Alcohol consumption (drinks/wk) | 0–25 | 2.4 ± 4.4 |
| Antihypertensive treatment | NA | 58.6% |
| Use of antidepressants or sedatives | NA | 5.7% |
| Supine systolic blood pressure (mmHg) | 100–185 | 134.4 ± 16.3 |
| Standing systolic blood pressure, 1 min (mmHg) | 94–184 | 131.1 ± 17.4 |
| Standing systolic blood pressure, 3 min (mmHg) | 96–176 | 133.3 ± 16.9 |
| Standing systolic blood pressure, 5 min (mmHg) | 96–174 | 135.1 ± 16.6 |
| Total cholesterol level (mg/dL) | 125–297 | 210.4 ± 39.1 |
| Cognitive test scores | ||
| Frontal-executive tests | ||
| Trail A time (s) | 36–132 | 67.6 ± 20.6 |
| Trail A score | 1–10 | 5.5 ± 2.2 |
| Trail B time (s) | 46–302 | 111.0 ± 54.0 |
| Trail B score | 0–9 | 3.4 ± 2.2 |
| Verbal fluency | 15–83 | 41.6 ± 14.4 |
| Naming fluency | 8–41 | 21.3 ± 6.1 |
| Memory tests | ||
| Logical memory I recall total score | 10–54 | 36.9 ± 8.5 |
| Logical memory I thematic total score | 5–23 | 15.4 ± 3.4 |
| Logical memory II recall total score | 6–39 | 22.4 ± 6.8 |
| Logical memory II thematic total score | 2–14 | 9.6 ± 2.6 |
| Visual reproduction I recall total score | 22–101 | 70.2 ± 17.2 |
| Visual reproduction II recall total score | 0–100 | 52.5 ± 23.4 |
| Visuospatial tests | ||
| Copy total score | 86–104 | 99.2 ± 4.7 |
| Discrimination total score | 5–7 | 6.8 ± 0.4 |
SD = standard deviation.
We also analyzed the risk for impairment in the Trailmaking Part-B test according to quartiles of SBP. The risk for impairment in the Trailmaking Part-B test began to increase steeply when supine SBP exceeded the second quartile (>135 mmHg; Figure 1).
Figure 1.
The relationship between supine systolic blood pressure (SBP) quartiles and the risk for Trailmaking Part-B test performance below the 25th percentile. Participants with the lowest quartile of supine SBP were the reference group. Participants whose supine SBP measurements were in the third quartile and the highest quartile had nearly 4-fold and 9-fold risks for impairment in the Trailmaking Part-B test compared with the reference group. Participants whose supine SBPs were in the second quartile showed a similar risk compared with the reference group.
There was no significant association between orthostatic SBP decline and any of the cognitive measures, regardless of whether orthostatic SBP changes were evaluated at 1, 3, or 5 minutes after standing (data not shown).
Discussion
The results of this study indicate that elevated SBP is selectively associated with frontal-executive impairment among elderly persons. We also found that orthostatic SBP changes were not associated with impairments in any of the cognitive measures. These findings support and extend our previous study that evaluated the relationship between cardiovascular risk factors and frontal-executive dysfunction (12), in which cardiovascular risk factors had a specific deleterious effect on frontal-executive measures in elderly African Americans. The current study has the advantage of evaluating the independent role of BP on cognitive functions using a group of relatively healthy elders without other cardiovascular risk factors. Our findings are particularly important given the current controversy over whether to treat elevated SBP in the old-old (13).
The finding that there is no association between orthostatic BP decline and cognitive impairment is consistent with a recent longitudinal study (10) in which no association was found between orthostatic hypotension and cognitive deterioration. However, the Mini-Mental State Examination was used as a measure of global cognitive function, and individual cognitive domains were not assessed. Although our study has the strength of evaluating the relationship between orthostatic BP decline and different cognitive domains, we could not detect any significant association.
Frontal-executive dysfunction may be more common than expected in elderly persons because the prevalence of hypertension and other cardiovascular risk factors increases with age. Ischemic damage to small vessels in watershed areas of frontal-subcortical regions may selectively impair executive functions (14). Executive control functions are essential for the management of hypertension and other cardiovascular risk modifications that involve the administration of multiple medications, dietary and lifestyle changes, and self-monitoring of responses. Thus, patients with overlooked frontal-executive dysfunction are often labeled as noncompliant or unmotivated. Clinicians should learn to recognize signs of executive dysfunction, and, once identified, therapy should be prescribed in a simple step-by-step manner to achieve the best possible outcomes (15).
Our study has several limitations. First, because of the cross-sectional design, we cannot establish a causal relationship between BP elevation and frontal-executive dysfunction. Future studies should address this issue using a longitudinal design. Second, we may not have had sufficient power to detect a relationship between orthostatic BP changes and cognitive impairments.
Conclusion
Elevated BP is an independent correlate of frontal-executive dysfunction in otherwise healthy elders. There appears to be no association between orthostatic BP change and cognitive impairment. Once frontal-executive dysfunction develops, risk reduction programs should be tailored to enable patients to better comply with pharmocotherapy, diet, and lifestyle recommendations.
Acknowledgments
Dr. Kuo was supported by the Men's Associates Fellowship from the Hebrew Rehabilitation Center for Aged, Boston, Massachusetts. Dr. Lipsitz holds the Irving and Edyth S. Usen and Family Chair in Geriatric Medicine at the Hebrew Rehabilitation Center for Aged, Boston, Massachusetts.
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