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(Stroke. 1998;29:2334-2340.)
© 1998 American Heart Association, Inc.
Original Contributions |
Systolic Blood Pressure Tracking Over 25 to 30 Years and Cognitive Performance in Older Adults
From the Center for Health Sciences, SRI International (G.E.S., D.C.) Menlo Park, Calif, and the University of New Mexico Medical Center (A.L.), Albuquerque, NM.
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Abstract |
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Objective—To determine the extent to which individual changes in systolic blood pressure (SBP) over a 30-year interval are associated with differential neuropsychological outcomes in old age.
Methods—Seven hundred seventeen survivors from the Western
Collaborative Group Study, a longitudinal study of
cardiovascular risk factors now in its 38th year of
follow-up, with blood pressures measured in middle age (mean=45 years)
and in old age (mean=75 years) and neuropsychological tests
administered at follow-up were included in this analysis.
Participants were grouped according to 30-year change in SBP
(increased, decreased, or "normal"). Analyses focused on
comparisons of neuropsychological performance of "high SBP
trackers" (ie, those with persistent SBP
140 mm Hg
throughout adult life) and of SBP "decreasers" with the
performance of those whose SBP was either stable or changed in
an expected way over time.
Results—Only 7.5% of participants had elevated SBP in middle age, but 43.8% of participants had elevated SBP in old age. After adjustment for age, education, depression, clinically defined stroke, and use of antihypertensive medications and after exclusion of individuals with impaired cognitive performance at follow-up, high SBP trackers, 5.0% (n=36), performed consistently less well than the "normal" SBP subgroups on a composite measure of verbal learning and memory (P=0.04). When compared with the "normal" SBP subgroup, the SBP decreasers, 5.3% (n=38), performed less well on speeded performance (P=0.03).
Conclusions—There is a relatively small group of people who maintain elevated SBP throughout their adult lives. These persons are at increased risk for reduced verbal learning and memory function. There is also a group of individuals who experience a decrease in SBP and who are at risk for decreased psychomotor speed. Delineation of these 2 SBP subgroups may lead to further clarification of the effects of SBP on neurobehavioral function in older adults.
Key Words: aging • blood pressure • cognition • neuropsychology
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Elevated systolic blood pressure (SBP) is associated with reduced levels of cognitive performance and increased cognitive decline in the majority of investigations of this issue.1 2 3 4 5 6 7 8 9 10 11 12 13 14 In a reanalysis of data reported originally as not being supportive of the SBP-cognition association,13 14 higher baseline SBP levels and increased chronicity of hypertension were found to be associated with lower cognitive performance measured 12 to 14 years later for measurements taken when few, if any, participants were on antihypertensive medication.15 16 17 The long-term impact of elevated midlife SBP on reduced cognitive performance has been extended from the 14-year interval first reported by Elias et al15 16 17 to 25 years18 and to 30 years.19 The primary implication of these findings is that SBP in middle age that is elevated but not necessarily hypertensive may exert a measurable deleterious effect on the function of the brain over intervals as long as 3 decades. This could suggest the need for more aggressive management, beginning in middle age, of SBP in these individuals.18
Although the long-term consequences of elevated midlife SBP for cognitive function now appear indisputable, 1 of the unanswered questions in this area is the extent to which individual differences in SBP tracking throughout adult life result in different neurobehavioral consequences. For example, the functional consequences of persistently elevated SBP over periods of as much as 30 years may be different from those associated with persistently low or moderate levels or those that occur as a result of gradually increasing SBP associated with aging. Under the assumption that the cumulative neurobehavioral consequences of SBP are more severe the longer the interval over which it is elevated, we hypothesized that the high SBP trackers would perform less well on neuropsychological tests taken at the end of the 25- to 30-year observation period than would any of the other tracking subgroups.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Subjects
The Western Collaborative Group Study is a prospective cardiovascular epidemiological study that began in 1960–61 with 3152 healthy white men drawn from 10 large California corporations in the San Francisco Bay Area and Los Angeles.20 21 22 23 At intake, the age of the subjects ranged from 39 to 59, and all subjects were determined to be healthy and free of heart disease. Seven examinations occurred between 1960 and 1970 to monitor the incidence of cardiovascular disease in this cohort. During 1982 and 1983, the first long-term mortality follow-up of this cohort was conducted; from 1986 through 1988 and again from 1992 through 1994, subsequent follow-up examinations were conducted in a large subgroup of survivors of this cohort.
At the 1986 to 1988 follow-up (see Figure 1
), 967 subjects (31% of the total
cohort) were deceased. Five hundred seventy-three subjects (26% of all
surviving subjects) participated by questionnaire only; 250 (11%) were
unable to participate or refused, and 130 (6%) subjects were lost to
follow-up.24 A total of 1232 subjects
participated in the examination, which included blood pressure (BP)
measurements, anthropometric measures, and neuropsychological
assessment. Extensive health histories were obtained by questionnaire
and interview and later validated by review of medical records.
Mean age of participants at this examination was 70.6 years (range, 60
to 86 years).
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At the 1992 to 1994 follow-up, an additional 363 (12% of the total cohort) were deceased. Four hundred twenty-one subjects (23% of all surviving subjects) participated by questionnaire only; 287 (16%) were unable or refused, and 381 subjects (21%) were lost to follow-up. A total of 733 subjects participated in the examination, which included many of the same components as the 1986 to 1988 follow-up (see below for a complete description of measures used in this analysis).
Risk Factor Assessment
In addition to age and neuropsychological status (see below),
the following variables were assessed at the 1986 to 1988 and 1991
to 1993 exams. (1) Education: subjects indicated the amount of
education they had acquired, on a 7-point scale (1=less than 8th grade,
7=doctoral level). (2) Stroke and transient ischemic attacks
(TIAs) were determined by physician-validated self-reports. With the
use of hospital records and physician reports, cerebrovascular
diagnoses encompassing stroke and TIA were coded as International
Classification of Diseases, 9th Revision (ICD-9) 430 to
438.9.25 (3) SBP and diastolic blood
pressure (DBP; in millimeters of mercury) were measured by a trained
technician according to published guidelines while the subject was in
the seated position.26 (4) Antihypertensive
medication status at follow-up was determined through coding of current
medications as determined by physical inspection at the time of
examination. The recorded BP medication was then categorized into
therapeutic categories as either ß-blocker,
angiotensin-converting enzyme (ACE) inhibitor,
calcium channel blocker, or diuretic. ](5)
Cardiovascular disease (CVD): This variable
encompassed review of electrocardiograms and physician
validation of self-reports of ischemic heart disease and
myocardial infarction. With the use of hospital records, physician
reports, and an ECG, we assigned cardiovascular
diagnoses (ICD-9 codes 410 to 414, 427.5, and
428)25 according to published
criteria.27 Information was reviewed by 2
physicians without knowledge of the participant's cognitive status.
(6) Depression: A score of greater than 5 on the Geriatric Depression
Scale28 was the definition of probable
depression. Total scores on this scale can range up to 15. (7) Body
mass index (BMI) was determined from measured height (in meters) and
weight (in kilograms) and calculated as kilograms per meters squared.
(8) Diabetes was determined by physician-validated self-report. With
the use of subsequent hospital and physician records, the diagnosis
of diabetes was coded as ICD-9 250 to
250.9.25
Neuropsychological Measures
The follow-up examination of the surviving subjects also
included the following neuropsychological tests. (1) The Iowa Screening
Battery for Mental Decline29,30: This battery is
composed of 3 tests assessing orientation to time, visuospatial skills
and visual memory, and word-list generation (associative word fluency).
(2) Mini-Mental State Examination31: This
30-point test includes questions on orientation to time and place,
registration, attention, calculations, recall, language, and visual
construction. Scores of less than 23 have been used previously to
indicate significant cognitive impairment.32
(3) Wechsler Adult Intelligence Scale–Revised Digit Symbol
Substitution33: This task required the subject to
copy, over a 90-second period, a series of letter-like symbols paired
with specific numbers. Adequate performance entails several
cognitive and perceptual functions, including attention, visual
perceptual and visuoconstructive abilities, sequencing, and short-term
memory. (4) Color Trail Making Test34: Like the
traditional Trail Making Test,35 Color Trails is
a brief psychomotor speeded task presented in 2 trials
(hereafter referred to as Trails 1 and 2). The test measures sustained
visual attention, visual scanning, and graphomotor skills in adults.
Both trails entail drawing a line to connect in correct
numerical sequence numbers scattered across a page; some numbers are
circled in yellow and others in pink. In Color Trails 2, consecutive
numbers of alternating color must be selected, and alternative color
options must be ignored. All participants were assessed for color
blindness before administration. Those reporting difficulty with color
perception were not given the Color Trails or the Color-Word
Interference Test. (5) Color-Word Interference
Test36,37: This test provides an index of a
person's ability to inhibit an overlearned response. Three stimulus
cards are presented for which the subject must read printed
color words, then identify color patches, and then name the color of
ink for words that have been printed in conflicting colors (eg, the
word "red" printed in green ink). (6) California Verbal Learning
Test (CVLT)38,39: The CVLT is a test of
multi-trial verbal free cued recall. A meta-analysis of the
literature40 found the CVLT to be among the most
sensitive of all tests for cognitive deficits associated with abnormal
aging. Test responses were scored with personal computer–based
software.41
Statistical Methods
Midlife SBP was defined as the mean of 7 SBP measurements taken
over the span of 1960–61 through 1969–70. Each of the 7 measurements
was itself a mean of 3 SBP measurements taken 5 minutes apart.
Late-life SBP was defined as the mean of 2 SBP measurements taken
during the follow-up exams from 1986 through 1988 (mean age=71 years)
and from 1992 through 1994 (mean age=75 years). Each of the 2 SBP
measures was itself a mean of 2 SBP measurements taken 5 minutes
apart.
All the available BP measurements taken between 1960 and 1970 were used to calculate an overall mean of midlife BP. Subjects participating in fewer than 3 of the 7 annual exams between 1960 and 1970 were excluded. Subjects participating in 1 or both of the follow-up exams were included in the calculation of late-life BP.
The following categories of SBP level were created for this
analysis: low (<120 mm Hg), medium (120 to 139
mm Hg), and high (140 mm Hg). An individual was considered to
be "normal" if his SBP was consistently low or medium at
both midlife and at follow-up or if his SBP increased over follow-up
(eg, those whose SBPs increased from the low to the medium or high
category or from the medium to the high category). If his SBP was
consistently high at midlife and at follow-up, he was
categorized as a "high tracker." Those whose SBPs decreased (eg,
those whose SBPs decreased from the high to the medium or low BP
category or from the medium to the low category) were classified as
"SBP decreasers." Univariate comparisons of participant
characteristics in the different SBP tracking subgroups were evaluated
using 
2 tests for categorical response
variables and ANOVA tests for continuous response
variables.42 The analytical sample included
717 individuals with complete BP data from the 1960s, either of
the 2 long-term follow-up exams, and neurobehavioral data from the 1992
through 1994 follow-up. The distribution of individuals within the 3
tracking subgroups without neurobehavioral data was not significantly
different from that found in those with neurobehavioral data in the
period 1992 to 1994,
2(2)=0.76,
P=0.69.
We conducted a principal components analysis (PCA) followed by
a varimax rotation,42 to reduce complexity and
redundancy among the cognitive measures used in this study. The minimum
eigenvalue for retention of a component was set to
1.43 PCA identified 3 orthogonal components
(eigenvalues were 5.9, 2.5, and 1.0, respectively) accounting
for a total of 67.1% of the total intermeasure covariance.
After rotation, the first factor, accounting for 32% of total
covariance, was marked by very high correlations with measures
of verbal memory (List A total, short- and long-delay cued and free
recall from the CVLT). Factor loadings ranged from 0.93 for long-delay
free recall to 0.86 for List A total learning. Loadings on the first
factor for the other cognitive measures were low and ranged from 0.04
(Trails A) to 0.23 (Color-Word Interference). This factor was
labeled "verbal memory."
The second rotated factor, accounting for 26.4% of total covariance, was marked by high correlations with the tests of speeded performance (Trail Making A and B, Color Trail Making 1 and 2, Color-Word Interference, and Digit Symbol Substitution). Factor loadings for these variables ranged from a high of 0.71 for Trails B to -0.51 for Color Word Interference performance. Loadings for the remaining cognitive measures were moderate to low, ranging from -0.11 for short-delay cued verbal recall to -0.13 for verbal fluency. This factor was labeled "psychomotor speed."
The third rotated factor, accounting for 9% of the total variance, was marked by a very high correlation with verbal fluency (r=0.81) and small to moderate correlations with the other tests of neurobehavioral function. Accordingly, this factor was labeled as "verbal fluency."
Eigenvalues for the remaining 11 principal components identified in the initial PCA fell below the conventional cutoff of 1.0 and ranged from 0.90 to 0.09. The proportion of variance accounted for by each individual component was small and ranged from 6% to 1%.
Standardized scoring coefficients from each of the 3 factors were then used to generate 3 composite standardized scores (mean=0, SD=1) for verbal memory, speeded performance, and verbal fluency, for each subject included in this analysis. After the exclusion of 7 persons who scored below 23 on the Mini-Mental State Examination, the tracking subgroups' 3 composite scores were then compared, using the general linear model to adjust for the effects of age, education, depression, clinically defined stroke, and the use of antihypertensive medications.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Distribution of SBP in Midlife and Late-Life
Table 1
shows the joint
distribution of SBP categories in the 717 participants with both
midlife and late-life measurements. In midlife, only 7.5% of this
group of survivors had SBP in the high category. The percentage of
individuals with elevated SBP in late-life was 43.8%. Overall, 31.8%
"tracked," ie, remained stable throughout the period of follow-up
with respect to their SBP level. Ten percent of participants were low
SBP trackers, and 5% were high SBP trackers. Sixty-three percent of
the sample showed an increase in SBP over the follow-up, and 5.3%
showed a decrease in SBP over the follow-up.
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Characteristics of Tracking Subgroups
Table 2 presents characteristics
of the 3 SBP tracking subgroups defined for this analysis.
There were no significant differences between the tracking subgroups
with respect to age, F(2,714)=1.72,
P=0.18; education, F(2,714)=2.27,
P=0.10; or BMI, F(2,681)=0.28,
P=0.76. There were also no significant associations observed
between tracking subgroup membership and prevalence of stroke,
2(2)=3.27, P=0.20;
TIA, 2(2)=1.95,
P=0.38; or coronary heart disease,
2(2)=4.60,
P=0.10.
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As expected, significant group differences were observed between
midlife (1960 through 1970) SBP,
F(2,714)=234.56, P=0.0001, follow-up
SBP in 1988, F(2,611)=20.12, P=0.0001,
and follow-up SBP in 1992, F(2,706)=34.48,
P=0.0001; all pair-wise comparisons were considered
significant at P
0.05. Persons in the normal SBP trajectory subgroup
experienced an average increase of 24 mm Hg (a 20.1% increase in
SBP over the life span), whereas those in the high tracking subgroup
increased an average of 16.6 mm Hg (an 11.2% increase over the
follow-up interval). An average decrease of 9.1 mm Hg (a change
of -6.7%) was observed in persons experiencing a reduction in SBP
over the follow-up interval.
Compared with those with normal SBP over the follow-up, high SBP
trackers had a higher frequency of diabetes,
2(2)=9.75,
P=0.008; were more likely to be using antihypertensive
medication in 1988,
2(2)=55.80,
P=0.001, and in 1992,
2(2)=33.02,
P=0.001; and if taking BP medication, were more likely to be
using an ACE inhibitor,
2(2)=38.16,
P=0.001.
The SBP decreasers, on the other hand, when compared with those with a
normal SBP trajectory, were more likely to report a significant number
of depressive symptoms,
2(2)=7.50,
P=0.023; to exhibit cognitive impairment,
2(2)=14.12,
P=0.001; and to be use antihypertensive medication at the
1988 and 1992 follow-ups. SBP decreasers who were using BP medication
were more likely to be using ß-blockers,
2(2)=13.52,
P=0.001.
Neuropsychological Performance of Tracking
Subgroups
Figure 2 presents mean scores
and associated standard errors for each of the tracking subgroups after
adjustment for potential confounders and the exclusion of cognitively
impaired individuals. High SBP trackers performed significantly less
well on verbal memory (M=-0.29±0.18) than did those classified as
having a normal blood pressure trajectory (M=0.03±0.04),
P=0.039, 1-tailed test. High SBP trackers had lower
scores on the memory factor score than those whose SBP decreased over
the follow-up (M=-0.03±0.18), although this difference did not reach
significance.
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In addition, SBP decreasers performed significantly less well on speeded performance (M=-0.29±0.17) than did those exhibiting a normal SBP trajectory (M=0.03±0.04), P=0.03, 1-tailed test. High SBP trackers appeared to perform better than the SBP decreasers on speeded performance (M=-0.05±0.18), but, again, this difference did not reach significance.
No significant differences were observed in the adjusted verbal fluency factor score across the 3 SBP tracking groups.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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The relatively few longitudinal studies of SBP tracking from middle to older age suggest that individual differences in SBP tracking continue throughout the life span44 45 46 47 and that adult high SBP trackers encounter increased risk for stroke and diabetes44 and ischemic heart disease in late life.46 Whereas DBP tends to drop with increasing age, SBP continues to increase with age regardless of the initial level in early to middle adulthood. The plateauing of mean arterial pressure along with the concomitant increase in pulse pressure have led some investigators to conclude that large-artery stiffness (as opposed to peripheral vascular resistance) is the primary contributor to the rise in SBP in old age.47
Although the dynamic nature of BP is widely known in the literature on cardiovascular aging, it has rarely been taken into account in epidemiological investigations of the BP-cognition connection. The main findings from the present analysis are (1) despite the availability of BP medication, there remained a small group of persons (5% of the present sample) whose SBP was high in middle age and remained high when assessed again 25 to 30 years later, in late life; (2) these high tracking individuals appear to be at risk for reduced verbal learning and memory function when compared with other SBP subgroups; and (3) individuals whose SBP decreased over the life span (5.3% of the present sample) appear to be at risk for reduced psychomotor speed performance in old age.
The cumulative effect of high SBP tracking can be seen in the somewhat higher prevalence of stroke at follow-up in this subgroup relative to all other SBP tracking subgroups. It is interesting to note the very high prevalence of the use of antihypertensive medication in the group with consistently elevated SBP. This finding would suggest that despite the fact that the use of these medications may have been effective in reducing DBP to lower levels, their impact on SBP was less in magnitude.
Individuals whose SBPs declined over the follow-up interval of this study had a comparatively high prevalence of depression (16.2%) and coronary heart disease (44.7%), both of which are related to impaired cognitive function.48 Low SBP in the elderly has previously been shown to be related to the prevalence of heart failure, limitations in activities of daily living, and cognitive impairment,49 as well as to an increased risk of 5-year mortality.50 Declining SBP may result from dementing illness,51 cardiac insufficiency,49 or a number of other disease conditions.52
Although the high SBP trackers and the SBP decreasers both performed
less well on 2 of 3 measures of neurobehavioral function than did the
normal trajectory subgroup, they did not differ statistically with
respect to their level of verbal memory and psychomotor speed
performance. However, inspection of Figure 2
suggests a trend
in which the high SBP trackers appear to be at greatest risk for
decrements in verbal memory, and the SBP decreasers were most likely to
show reduced psychomotor speed. This pattern suggests that the causal
connection may well be reversed for the 2 groups. In the case of the
high SBP trackers, the deleterious effects of the elevated SBP are
focused specifically on memory functions. In the case of SBP
decreasers, chronic disease and systemic decline may operate to
influence declining SBP and psychomotor speed. In this context, we note
that a previous investigation of ours reported a relationship between
slower psychomotor speed and increased 5-year
mortality.53 Our previous finding, in concert
with the finding that low BP is also a predictor of 5-year mortality in
older adults,50 suggests to us that 1 of the next
steps for investigation of risk factors for mortality in older adults
should be the inclusion of decline in cognitive function and SBP in the
same predictive model. This approach would enable us to determine the
relative importance and independence of these 2 processes
vis-à-vis mortality.
Because of its epidemiologic nature, this study leaves open the question of potential mechanisms underlying the association between high SBP tracking and neurobehavioral function. Numerous possibilities exist including disturbed cerebral perfusion, with consequent negative impact on brain cell metabolism15,16; cerebral infarction; and/or the presence of diffuse white matter lesions.54 Even in mildly hypertensive subjects, regional cerebral blood flow is reduced in the frontal cortex and basal ganglia, compared with normotensive subjects. In moderate-to-severe hypertensives, cerebral oxygen metabolism is diminished, and there are higher prevalences of ventricular enlargement and white matter vascular lesions.55 56 57 58 Recent studies involving the use of MRI have found an association between hypertension and brain atrophy,59 leukoaraiosis,60 lacunae and periventricular hyperintensities,61 62 63 prevalence and severity of white matter hyperintensities,64 65 66 67 68 and cognitive decline.64 The presence of white matter hyperintensities in elderly adults free of disease has recently been shown to be related to elevated mean arterial pressures, as well as to poorer cognitive performance on tasks involving speed and complex mental processing.69 Recent studies of large samples of older subjects also found an association between MRI findings and cognition.56 70 These findings suggest that subclinical changes in brain morphology may underlie the previously observed associations between SBP and cognitive function.
In the present study, the high SBP trackers were more likely to be using ACE inhibitors, whereas the SBP decreasers were most likely to be using ß-blockers. The relationship of various classes of BP medication to differential neurobehavioral outcomes is inconsistent across a variety of studies.71 72 73 Although small sample size precludes the stratification of the sample based on type of BP medication, it is important to note that we included the use or nonuse of BP medication as an adjustment variable in the predictive models of neurobehavioral function. In none of the 3 models did the BP medication variable exhibit a significant association with cognitive outcomes.
The strong points of the present study include its use of a relatively large number of BP measurements to estimate BP in middle and late life, the long duration of follow-up, and a comprehensive assessment of neurobehavioral function in late life. A limitation of the study is its use of data from male participants only. Females were not available to this analysis for no reason other than that the study's inception (1960) occurred in an era when a lack of knowledge about gender differences in CVD risk factors led to the erroneous conclusion that males and females are similar in these respects. Because more recent findings suggest the presence of strong gender differences with respect to CVD risk factor profiles and the relationship of CVD to dementia, the results from the present analysis will need to be confirmed in older women.
Another limitation of the present study concerns the substantial attrition experienced by this cohort over the duration of the 25- to 30-year follow-up. The data actually used for analysis are based on testing of 39% of the original cohort from the period 1986 to 1988 and on 34% of the cohort from 1992 to 1994. Although this is not uncommon for a study of this length, the effect of attrition because of premature death, disease, or disability is most likely to have resulted in an underestimation of the true predictive relationship seen here.
On the basis of these results, it does appear that there is a relatively small group of individuals whose SBP remains elevated over the life span despite the use of antihypertensive medication. Whether the neurobehavioral differences in these individuals are associated with an increased incidence of brain morphologic changes, such as "silent" stroke, brain atrophy, or white matter disease, remains to be determined.
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Acknowledgments |
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This research was supported by Grant AG09341 from the National Institute on Aging (Bethesda, Md). The authors thank Mary McElroy, Sharyn Moore, Ann von Essen, Frances Hernandez, Susan Kotler-Cope, and Taryn Markee for their efforts in the collection of data and Ruth Krasnow for assistance with data analysis.
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Footnotes |
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Portions of this paper were presented at the 70th Scientific Sessions of the American Heart Association, Orlando, Fla, November 10, 1997.
Address correspondence to Gary E. Swan, PhD, Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA 94025.
Received March 23, 1998; revision received August 3, 1998; accepted August 3, 1998.
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References |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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1. Wilkie FL, Eisdorfer C. Intelligence and blood pressure in the aged. Science. 1971;172:959–962.
2. Elias MF, Schultz NR Jr, Robbins MA, Elias PK. A longitudinal study of neuropsychological performance by hypertensives and normotensives: a third measurement point. J Gerontol. 1989;45:25–28.
3. Schultz NR, Elias MF, Robbins, MA, Streeten DHP, Blakeman NA. A longitudinal study of the performance of hypertensive and normotensive subjects on the Wechsler Adult Intelligence Scale. Psychol Aging. 1989;4:496–499.[Medline] [Order article via Infotrieve]
4.
Elias MF, Robbins MA, Schultz NR, Streeten DHP, Elias
PK. Clinical significance of cognitive performance by
hypertensive patients. Hypertension. 1987;9:192–197.
5. Wallace RB, Lemke JA, Morris MC, Goodenberger M, Kohout F, Hinrichs JV. Relationship of free-recall memory to hypertension in the elderly: the Iowa 65+ Rural Health Study. J Chronic Dis. 1985;38:475–481.[Medline] [Order article via Infotrieve]
6. Waldstein SR, Manuck SB, Ryan CM, Muldoon MF. Neuropsychological correlates of hypertension: review and methodologic considerations. Psychol Bull. 1991;110:451–468.[Medline] [Order article via Infotrieve]
7. Battersby C, Hartley K, Fletcher AE, Markowe HJL, Brown RG, Styles W, Carne S, Jamieson T, Koppel I, Fraser S, Sapper H, Bulpitt CJ. Cognitive function in hypertension: a community based study. J Hum Hypertens. 1993;7:117–123.[Medline] [Order article via Infotrieve]
8. Kalra L, Jackson SHD, Swift CG. Psychomotor performance in elderly hypertensive patients. J Hum Hypertens. 1993;7:279–284.[Medline] [Order article via Infotrieve]
9. Sands LP, Meredith W. Blood pressure and intellectual functioning in late midlife. J Gerontol. 1992;47:P81–P84.
10.
Robbins MA, Elias MF, Croog SH, Colton T. Unmedicated
blood pressure levels and quality of life in elderly women.
Psychosom Med. 1994;56:251–259.
11. Starr JM, Whalley LJ, Inch S, Shering PA. Blood pressure and cognitive function in healthy old people. J Am Geriatr Soc. 1993;41:753–756.[Medline] [Order article via Infotrieve]
12.
Guo Z, Viitanen M, Winblad B, Fratiglioni L. Blood
pressure and performance on the Mini Mental State Examination
in the very old: cross-sectional and longitudinal data from the
Kungsholmen Project. Am J Epidemiol. 1997;145:1106–1113.
13.
Farmer ME, White LR, Abbott RD, Kittner SJ, Kaplan E,
Wolz MM, Brody JA, Wolf PA. Blood pressure and cognitive
performance: the Framingham Study. Am J
Epidemiol. 1987;126:1103–1114.
14. Farmer ME, Kittner SJ, Abbott RD, Wolz MM, Wolf PA, White LR. Longitudinally measured blood pressure, anti-hypertensive medication use, and cognitive performance: the Framingham Study. J Clin Epidemiol. 1990;43:475–480.[Medline] [Order article via Infotrieve]
15.
Elias MF, Wolf PA, D'Agostino RB, Cobb J, White LR.
Untreated blood pressure level is inversely related to cognitive
functioning: the Framingham Study. Am J Epidemiol. 1993;138:353–364.
16. Elias PK, D'Agostino RB, Elias MF, Wolf PA. Blood pressure, hypertension, and age as risk factors for poor cognitive performance. Exp Aging Res. 1995;21:393–417.[Medline] [Order article via Infotrieve]
17. Elias MF, D'Agostino RB, Elias PK, Wolf PA. Neuropsychological test performance, cognitive functioning, blood pressure, and age: the Framingham Heart Study. Exp Aging Res. 1995;21:369–391.[Medline] [Order article via Infotrieve]
18.
Launer LJ, Masaki K, Petrovich H, Foley D, Havlik RJ.
The association between mid-life blood pressure levels and late-life
cognitive function: the Honolulu-Asia Aging Study. JAMA. 1995;274:1846–1851.
19. Swan GE, Carmelli D, LaRue A. Relationship between blood pressure during middle age and cognitive impairment in old age: the Western Collaborative Group Study. Aging Neuropsychol Cognition. 1996;3:241–250.
20. Rosenman RH, Friedman M, Straus R, Wurm M, Kositchek R, Hahn W, Werthessen NT. A predictive study of coronary heart disease: the Western Collaborative Group Study. JAMA. 1964;189:113–120.
21. Rosenman RH, Freidman M, Straus R, Jenkins CD, Zyzanski SJ, Wurm M. Coronary heart disease in the Western Collaborative Group Study: a follow-up experience of 4 1/2 years. J Chronic Dis. 1970;23:173–190.[Medline] [Order article via Infotrieve]
22.
Rosenman RH, Brand RJ, Jenkins CD, Freidman M, Straus
R, Wurm M. Coronary heart disease in the Western Collaborative
Group Study: final follow-up experience of 8 1/2 years.
JAMA. 1975;233:872–877.
23. Rosenman RH, Brand RJ, Sholtz RI, Friedman M. Multivariate prediction of coronary heart disease during 8.5 year follow-up in the Western Collaborative Group Study. Am J Cardiol. 1976;37:903–910.[Medline] [Order article via Infotrieve]
24. Carmelli D, Halpern J, Swan GE, Dame A, McElroy M, Gelb AB, Rosenman RH. 27-year mortality in the Western Collaborative Group Study: construction of risk groups by recursive partitioning. J Clin Epidemiol. 1991;44:1341–1351.[Medline] [Order article via Infotrieve]
25. Schmidt KM, Aaron WS, eds. St. Anthony's ICD-9-CM Code Book. Reston, VA: St. Anthony Publishing; 1996.
26. Kirkendall WM, Feinleib M, Fries ED, Mark AL. Recommendations for human blood pressure determination by sphygmomanometers: Subcommittee of the AHA Postgraduate Education Committee. Circulation. 1980;62:1146A–1155A.
27. National Heart, Lung, and Blood Institute, National Institutes of Health. The ARIC Manuals of Operation. Chapel Hill, NC: ARIC Coordinating Center, School of Public Health, University of North Carolina; 1991.
28. Yesavage JA. The use of self-rating depression scales in the elderly. In: Poon LW, ed. Handbook for Clinical Memory Assessment of Older Adults. Washington, DC: American Psychological Association; 1986:213–217.
29.
Eslinger PJ, Damasio AR, Benton AL, Van Allen M.
Neuropsychologic detection of abnormal mental decline in older persons.
JAMA. 1985;253:670–674.
30. Eslinger PJ, Damasio AR, Benton AL. The Iowa Screening Battery for Mental Decline. Iowa City, Iowa: Department of Neurology, The University of Iowa College of Medicine; 1984.
31. Folstein MF, Folstein SE, McHugh PR. Mini-Mental State: a practical method for grading the cognitive state of patients for clinicians. J Psychiatr Res. 1975;12:189–198.[Medline] [Order article via Infotrieve]
32. Anthony JC, LeResche L, Niaz U, von Korff MR, Folstein MF. Limits of the `Mini-Mental State' as a screening test for dementia and delirium among hospital patients. Psychol Med. 1982;12:397–408.[Medline] [Order article via Infotrieve]
33. Wechsler D. Wechsler Adult Intelligence Scale—Revised. New York, NY: Psychological Corporation; 1981.
34. D'Elia LF, Satz P, Uchiyama CL, White T. Color Trails Test Manual. Odessa, Fla: Psychological Assessment Resources, Inc; 1997.
35. Reitan RM. Validity of the Trail Making Test as an indicator of organic brain damage. Percept Mot Skills. 1958;8:271–276.
36. Stroop JR. Studies of inference in serial verbal reactions. J Exp Psychol. 1935;18:643–662.
37. Golden CJ. Stroop Color and Word Test: A Manual for Clinical and Experimental Uses. Chicago, Ill: Stoelling Co; 1978.
38. Delis DC, Kramer JH, Kaplan E, Ober BA. California Verbal Learning Test. New York, NY: Psychological Corporation; 1987.
39. Elwood RW. The California Verbal Learning Test: psychometric characteristics and clinical application. Neuropsychol Rev. 1995;5:173–201.[Medline] [Order article via Infotrieve]
40. Christensen H, Hadzi-Pavlovic D, Jacob P. The psychometric differentiation of dementia from normal aging: a meta-analysis. Psychol Assess. 1991;3:147–155.
41. Fridlund AJ, Delis DC. The California Verbal Learning Test, Scoring and Administration Software. New York, NY: Psychological Corporation; 1987.
42. SAS Institute, Inc. SAS/STAT Guide, Version 6. Cary, NC: SAS Institute; 1987.
43. Cattell RB. The scree test for the number of factors. Multivariate Behav Res. 1966;1:245–276.
44.
Tate R, Manfreda J, Krahn AD, Cuddy TE. Tracking of
blood pressure over a 40-year period in the University of Manitoba
Follow-up Study, 1948–1988. Am J Epidemiol. 1995;142:946–954.
45. Wilsgaard T. Tracking of blood pressure in adult men: the Tromso Study, 1974–1986. Can J Cardiol. 1997;13(suppl B):1249. Abstract.
46. Tate R, Manfreda J, Cuddy TE. Blood pressure tracking and ischemic heart disease in the Manitoba follow-up study. Can J Cardiol. 1997;13(suppl B):1325. Abstract.
47.
Franklin SS, Gustin W IV, Wong ND, Larson MG, Weber MA,
Kannel WB, Levy D. Hemodynamic patterns of age-related
changes in blood pressure: the Framingham Heart Study.
Circulation. 1997;96:308–315.
48. LaRue A, Jarvik LA. Old age and biobehavioral changes. In: Wolman B, ed. Handbook of Developmental Psychology. Englewood Cliffs, NJ: Prentice Hall; 1982:791–806.
49. Guo Z, Winblad B, Viitanen M. Clinical correlates of low blood pressure in very old people: the importance of cognitive impairment. J Am Geriatr Soc. 1997;45:701–705.[Medline] [Order article via Infotrieve]
50.
Guo Z, Winblad B, Viitanen M. Low blood pressure and
five-year mortality in a Stockholm cohort of the very old: Possible
confounding by cognitive impairment and other factors. Am J
Public Health. 1997;87:623–628.
51.
Guo Z, Viitanen M, Fratiglioni L, Winblad B. Low blood
pressure and dementia in elderly people: the Kungsholmen project.
BMJ. 1996;312:805–808.
52. Guo Z, Fratiglioni L, Winblad B, Viitanen M. Blood pressure and performance on the Mini-Mental State Examination in the very old. Am J Epidemiol. 1997;145:1106–1113.
53.
Swan GE, Carmelli D, LaRue A, McElroy MR.
Performance on the Digit Symbol Substitution Test and 5-year
mortality in the Western Collaborative Group Study. Am J
Epidemiol. 1995;141:32–40.
54.
Scheinberg P. Dementia due to vascular disease: a
multifactorial disorder. Stroke. 1988;19:1291–1299.
55. Fujishima M, Ibayashi S, Fujii K, Mori S. Cerebral blood flow and brain function in hypertension. Hypertens Res. 1995;18:111–117.[Medline] [Order article via Infotrieve]
56.
Breteler, MM, van Sweiten JC, Bots ML, Grobbee DE,
Claus JJ, van den Hout JH, van Harskamp F, Tanghe HL, deJong PT, van
Gijn J, Hoffman A. Cerebral white matter lesions, vascular risk
factors, and cognitive function in a population-based study: the
Rotterdam Study. Neurology. 1994;44:1246–1252.
57. DeCarli C, Murphy DGM, Tranh M, Grady CL, Haxby JV, Gillette JA, Salerno JA, Gonzales-Aviles A, Horwitz B, Rapoport SI. The effect of white matter hyperintensity volume on brain structure, cognitive performance, and cerebral metabolism of glucose in 51 healthy adults. Neurology. 1995;45:2077–2084.[Abstract]
58.
Schmidt R, Fazekas F, Koch M, Kapeller P, Augustin M,
Offenbacher H, Fazekas G, Lechner H. Magnetic resonance imaging
cerebral abnormalities and neuropsychologic test performance in
elderly hypertensive subjects: a case-control study. Arch
Neurol. 1995;52:905–910.
59.
Salerno JA, Murphy DGM, Horwitz B, DeCarli C, Haxby JV,
Rapoport SI, Schapiro MB. Brain atrophy in hypertension: a volumetric
magnetic resonance imaging study. Hypertension. 1992;20:340–348.
60. Ogata J, Masuda J, Yutani C, Sawada T, Yamaguchi T. Is hypertension a cause of dementia in the elderly? A clinico-pathological study. Hypertens Res. 1994;17(suppl 1):S97–S101.
61. Shimada K, Kawamoto A, Matsubayashi K, Nishinaga M, Kimura S, Ozawa T. Silent cerebrovascular disease and ambulatory blood pressure in the elderly. Hypertens Res. 1994;17(suppl 1):S55–S58.
62. Kawamoto A, Shimada K, Matsubayashi K, Nishinaga M, Kimura S, Ozawa T. Factors associated with silent multiple lacunar lesions on magnetic resonance imaging in asymptomatic elderly hypertensive patients. Clin Exp Pharmacol Physilo. 1991;18:605–610.
63.
Shimada K, Kawamoto A, Matsubayashi K, Ozawa T. Silent
cerebrovascular disease in the elderly: correlation with ambulatory
pressure. Hypertension. 1990;16:692–699.
64. van Sweiten JC, Geyskes CG, Derix MMA, Peeck BM, Ramos LMP, van Latum JC, van Gijn J. Hypertension in the elderly is associated with white matter lesions and cognitive decline. Ann Neurol. 1991;30:825–830.[Medline] [Order article via Infotrieve]
65.
Kozachuck WE, DeCarli C, Schapiro MB, Wagner EE,
Rapoport SI, Horwitz B. White matter hyperintensities in dementia of
Alzheimer's type and in healthy subjects without
cerebrovascular risk factors. Arch Neurol. 1990;47:1306–1310.
66.
Fazekas F, Niederkorn K, Schmidt R, Offenbacher H,
Horner S, Bertha G, Lechner H. White matter signal abnormalities in
normal individuals: correlation with carotid ultrasonography, cerebral
blood flow measurements, and cerebrovascular risk factors.
Stroke. 1988;19:1285–1288.
67.
Lechner H, Schmidt R, Bertha G, Justich E, Offenbacher
H, Schneider G. Nuclear magnetic resonance image white matter and risk
factors for stroke in normal individuals. Stroke. 1988;19:263–265.
68.
Schmidt R, Fazekas F, Offenbacher H, Lytwyn H, Blemati
B, Niederkorn K, Horner S, Payer F, Freidl W. Magnetic resonance
imaging white matter lesions and cognitive impairment in hypertensive
individuals. Arch Neurol. 1991;48:417–420.
69.
Matsubayashi K, Shimada K, Kawamoto A, Ozawa T.
Incidental brain lesions on magnetic resonance imaging and
neurobehavioral functions in the apparently healthy elderly.
Stroke. 1992;23:175–180.
70.
Boone KB, Miller BL, Lesser IM, Mehringer CM, Hill E,
Berman N. Cognitive deficits with white-matter lesions in healthy
elderly. Arch Neurol. 1992;49:549–554.
71. Prince M, Lewis G, Bird A, Blizzard R, Mann A. A longitudinal study of factors predicting change in cognitive test scores over time in an older hypertensive population. Psychol Med. 1996;26:555–568.[Medline] [Order article via Infotrieve]
72. Starr JM, Deary IJ, Whalley LJ. The effects of antihypertensive treatment on cognitive function: results from the HOPE study. J Am Geriatr Soc. 1996;44:411–415.[Medline] [Order article via Infotrieve]
73.
Applegate WB, Perry HM Jr, Moye L, Hadley E, Greenlick
MR, Camel GH, Shekelle RB, Luhr J, Wittes J, Pressel S. Impact of the
treatment of isolated systolic hypertension on behavioral
variables: results from the Systolic Hypertension in the
Elderly Program. Arch Intern Med. 1994;154:2154–2160.
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