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From the Department of Geriatrics (L.K., M.B., L.H., H.L.), Uppsala, and
the Department of Clinical Neurosciences (H.N.), Karolinska Hospital,
Stockholm, Sweden.
Correspondence to Dr Lena Kilander, Department of Geriatrics, Kålsängsgränd 10 D, PO Box 609, S-751 25 Uppsala, Sweden.
Vascular Risk Factors
Cognitive Function
Potential Confounders
Statistics
Interrelationships Between Risk Factors
Vascular Risk Factors and Cognitive Function
Longitudinal Measurements
Cross-sectional Measurements
There was an inverse relationship between 24-hour ambulatory SBP
and DBP at age 70 years and cognitive score, NDBP showing the strongest
linear relationship (r=-.15, P<.0001). Mean HR
during 24 hours was also inversely related to cognitive z
score (r=-.12, P=.0015). Cognitive score by
tertiles of 24-hour DBP are shown in Fig 2
Nondipping and BP Variability
Mean cognitive score was lower in nondippers (n=59, -0.22, SD
0.95), than in dippers (n=824, +0.04 [0.77], P=.04). In
multivariate analyses with cognitive score as a
continuous outcome variable, nondipping, mean 24-hour DBP, and mean
24-hour HR were all significantly and inversely related to cognitive
performance, independent of each other. Cognitive
performance in men with high NBP variability as measured by the
quotient between SD (of NSBP) divided by mean (of NSBP), and in extreme
dippers (
Insulin Resistance and Diabetes
As shown in Fig 3
Multivariate Analysis
In a logistic regression model, cognitive function was treated as
a dichotomous variable with the cutoff level for low
performance set at the lowest quintile. In
univariate analysis, men with low cognitive
function had higher 24-hour DBP and higher plasma glucose (Table 3
Stroke Patients
This group was a healthy cohort in which only a minority of the
participants scored below 27 points in the MMSE. It consisted of
approximately half of the survivors from the baseline examination only,
but nonresponse to health surveys has, on the other hand, been shown to
be associated both with a higher vascular risk and with cognitive
impairment.13 Those who declined to participate
in the cognitive testing had a lower level of education and higher
office BP and serum insulin than the participants, ie, factors with
positive relationship to the outcome. Furthermore, in our study cohort,
the risk factor pattern has been blunted not only by selection but also
by the effects of preventive treatment. Special efforts to prevent
cardiovascular disease were taken since the 50-year
survey, in which primary preventive measures were instituted in men who
were found to be hypertensive, hyperlipidemic, or had
an impaired glucose tolerance. Thus, we believe that the inference of
the relationships to the general population of community-living elderly
males might rather be underestimated.
The most convincing evidence of a relationship between
hypertension and cognitive deterioration is derived from a prospective
study in the 1960s, when antihypertensive treatment was still
infrequent.14 The authors suggested that "the
basis for the cognitive decline associated with aging should be
considered secondary to some pathologic processes and not merely as a
`normal' aging process." Results from other studies assessing
longitudinally measured BP point in the same direction. In the
Honolulu-Asia Aging Study, high midlife SBP was a predictor of reduced
cognitive function in later life, when stroke cases were
included.15 Similarly, in the Framingham study,
untreated BP levels and chronicity of hypertension were inversely
related to the composite cognitive score.17
Diabetes in the elderly has been linked to cognitive impairment in
cross-sectional case-control studies,18 and
impaired cognitive performance in diabetic subjects has been
related to poorer metabolic
control.19 In a cohort study, diabetes and
impaired glucose tolerance were associated with lower results in the
MMSE; however, this relationship was independent of other factors
associated with insulin resistance.20 In other
studies, the combinations of hypertension and
hyperinsulinemia,21
hypercholesterolemia, or diabetes, as defined
by a questionnaire,22 were related to impaired
cognitive function. To our knowledge, ours is the first cohort study
showing that cognitive impairment is related to metabolic
disturbances linked to the syndrome of insulin resistance,
together with hypertension.
The finding that diastolic BP in middle age predicts later
cognitive performance suggests a causal relationship. However,
the data from the ABPM are cross-sectional, and causal mechanisms can
only remain speculative. The causation might be reverse, ie, cognitive
impairment and altered BP regulation may both be secondary to silent
cerebrovascular lesions. In cross-sectional studies, silent lacunar
infarctions23 and vascular dementia characterized
by extensive white matter lesions or by multiple lacunar
infarctions24 have been related to the absence of
NBP decrements. Changes in BP circadian variability indicate
alterations of central nervous regulatory systems, mediated by
sympathetic activation. However, on the other hand, sympathetic
overreactivity could also be etiologically linked to the syndrome of
hypertension and insulin resistance25 and
primarily affect cognitive function by vasoconstriction and cerebral
small-vessel lesions. The TMT reflects subcorticofrontal functions,
among others, and impaired performance in the TMT has
previously been associated with subcortical small-vessel
lesions.26 27
Is low BP always desirable, or is there a lower limit below which
too-aggressive antihypertensive treatment might be hazardous? It has
been hypothesized that low systemic BP might primarily contribute to
dementia via impaired cerebral perfusion and incomplete white matter
infarctions in areas supported by stenosed
vessels.28 Extreme dipping, as well as
nondipping, was associated with silent cerebrovascular disease
identified by magnetic resonance imaging.23
Moderate or severe dementia is accompanied by lower BP levels, but in
advanced stages, this is most likely a secondary
phenomenon.29 A previous study showed that
cognitive changes in hypertensive subjects, hypothetically mediated
through metabolic or hemodynamic
mechanisms, could be restored by treatment.30 In
our cohort, there existed no J-shaped relationship between BP and
cognitive function, and there were also indications of a positive
effect of treatment. This latter finding should be interpreted with
caution, because it may be due to selection.
To summarize, our results support the hypothesis that cerebral
target-organ damage in hypertension contributes to cognitive
impairment. Cognitive deterioration denotes an impaired quality of life
and is also a predictor of dementia and
mortality.31 Actions to prevent further decline
must be considered as early in the course of the disease as possible,
ie, before clinical manifest dementia. Because a linkage with risk
factors for vascular disease has been established, it is urgent to
investigate whether further cognitive decline can be postponed by a
more intensive preventive treatment. There is convincing evidence of
the importance of adequate antihypertensive treatment in primary
prevention of cerebrovascular disease even in higher
ages,32 and there are no indications of treatment
causing cognitive deterioration.33 Our findings
suggest that treatment with pharmacological agents that maintain the
normal 24-hour BP profile and have no metabolic side
effects should be preferred in the management of elderly persons with
hypertension.
Received May 20, 1997;
first decision June 30, 1997;
accepted October 6, 1997.
2.
Skoog I, Nilsson L, Palmertz B, Andreasson L-A,
Svanborg A. A population-based study of dementia in 85-year-olds.
N Engl J Med. 1993;328:153–158.
3.
Skoog I, Lernfelt B, Landahl S, Palmertz B, Andreasson
L-A, Nilsson L, Persson G, Odén A, Svanborg A. 15-year
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Hedstrand H. A Study of Middle-Aged Men with
Particular Reference to Risk Factors for Cardiovascular
Disease. Uppsala, Sweden: Faculty of Medicine,
Uppsala University; 1975. Thesis.
5.
Lithell H, Åberg H, Selinus I, Hedstrand H. The
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Skarfors E. Risk Factors for Development of
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Uppsala University; 1989. Thesis.
7.
Pollare T, Lithell H, Selinus I, Berne C. Application
of prazosin is associated with an increase of insulin sensitivity in
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Folstein MF, Folstein SE, McHugh PR. `Mini-Mental
State': a practical method for grading the cognitive state of patients
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Lezak M. Neuropsychological Assessment. 3rd
ed. New York, NY: Oxford University Press; 1995.
11.
Kuusisto J, Mykkänen L, Pyörälä
K, Laakso M. Non–insulin-dependent diabetes and its
metabolic control are important predictors of stroke in
elderly subjects. Stroke. 1994;25:1157–1164.[Abstract]
12.
Reaven G. Role of insulin resistance in human disease.
Diabetes. 1988;37:1595–1607.[Abstract]
13.
Launer LJ, Wind AW, Deeg DJH. Nonresponse pattern and
bias in a community-based cross-sectional study of cognitive
functioning among the elderly. Am J Epidemiol. 1994;139:803–812.
14.
Wilkie F, Eisdorfer C. Intelligence and blood pressure
in the aged. Science. 1971;172:959–962.
15.
Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ.
The association between midlife blood pressure and late-life cognitive
function: the Honolulu-Asia Aging Study. JAMA. 1995;274:1846–1851.
17.
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.
18.
Tun PA, Nathan DM, Perlmuter LC. Cognitive and
affective disorders in elderly diabetics. Clin Geriatr Med. 1990;6:731–746.[Medline]
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19.
Reaven GM, Thompson LW, Nahum D, Haskins E.
Relationship between hyperglycemia and cognitive function in older
NIDDM patients. Diabetes Care. 1990;13:16–21.[Abstract]
20.
Kalmijn S, Feskens EJM, Launer LJ, Stijnen T, Kromhout
D. Glucose intolerance, hyperinsulinaemia and
cognitive function in a general population of elderly men.
Diabetologia. 1995;38:1096–1102.[Medline]
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21.
Kuusisto J, Koivisto K, Mykkänen L, Helkala E-L,
Vanhanen M, Hänninen T, Pyörälä K, Riekkinen P,
Laakso P. Essential hypertension and cognitive function: the role of
hyperinsulinemia. Hypertension. 1993;22:771–779.
22.
Desmond DW, Tatemichi TK, Paik M, Stern Y. Risk factors
for cerebrovascular disease as correlates of cognitive function in a
stroke-free cohort. Arch Neurol. 1993;50:162–166.
23.
Kario K, Matsuo T, Kobayashi H, Imiya M, Matsuo M,
Shimada K. Nocturnal fall of blood pressure and silent cerebrovascular
damage in elderly hypertensive patients. Hypertension. 1996;27:130–135.
24.
Tohgi H, Chiba K, Kimura M. Twenty-four-hour variation
of blood pressure in vascular dementia of the Binswanger type.
Stroke. 1991;22:603–608.
25.
Reaven G, Lithell H, Landsberg L. Hypertension and
associated metabolic abnormalities: the role of insulin
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Med. 1996;334:374–381.
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lesions on magnetic resonance imaging. Stroke. 1994;25:1109–1115.[Abstract]
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© 1998 American Heart Association, Inc.
Scientific Contributions
Hypertension Is Related to Cognitive Impairment
A 20-Year Follow-up of 999 Men
Abstract
Top
Abstract
Introduction
Methods
Results
Discussion
References
Abstract—Recent findings of a
linkage between high blood pressure (BP) and later development of
dementia have given new prospects on cerebral target-organ damage in
hypertension and have added substance to the concept of "preventable
senility." The aim of this study was to analyze the impact of
hypertension, circadian BP profile, and disturbed glucose
metabolism on cognitive function. The study population
consisted of 999 seventy-year-old men from a population-based cohort
study in Uppsala, Sweden, followed with respect to
cardiovascular risk factors since the age of 50 years.
At the age of 70, 24-hour ambulatory BP was monitored together with
measurements of insulin sensitivity, glucose tolerance, serum lipids,
and lipoproteins. Cognitive function was assessed by the Mini-Mental
State Examination and the Trail-Making Test. High diastolic
BP at baseline predicted later impaired cognitive performance,
even after excluding men with a previous stroke (n=70). Cross-sectional
measurements at age 70 showed that high 24-hour BP, nondipping, insulin
resistance, and diabetes all were related to low cognitive function.
The relationships between hypertension and cognitive impairment were
strongest in untreated men. These data from a general population of
healthy elderly men indicate that hypertension and associated
metabolic disturbances might be susceptibility
factors for cognitive disorders. The findings add support to
possibilities of intervention in early stages in cognitive decline, ie,
before manifest dementia.
Key Words: cognition • blood pressure monitoring, ambulatory • diabetes • insulin resistance
Introduction
Top
Abstract
Introduction
Methods
Results
Discussion
References
The question of
whether some degree of cognitive deterioration is an inevitable part of
aging or should be considered as a pathological prestage of dementia is
currently debated. This is a field in need of
research1 because further decline in cognition
might be preventable in the early stages of "cognitive impairment
nondementia." Vascular dementia is a common form of dementia; in the
oldest elderly patients it is as frequent as Alzheimer's
disease.2 Recently, a 15-year follow-up study
showed that high BP predicted dementia in the oldest elderly patients,
irrespective of subtype.3 Little is known about
how cognitive function is affected by vascular risk factors in the
general population. The aim of the present study was to
analyze the associations between BP, diurnal BP variation,
disturbances in glucose and lipid metabolism, and
cognition. We examined cognitive functions in a population-based cohort
of 70-year-old men in which longitudinal measurements of vascular risk
factors were available.
Methods
Top
Abstract
Introduction
Methods
Results
Discussion
References
The study population consisted of 999 men. They were
participants in a health survey focusing on
cardiovascular risk factors that was started in the
beginning of the 1970s in Uppsala, Sweden. The original cohort
was defined as all men born in 1920 to 1924, who resided in the
municipality of Uppsala in 1970 to 1973 (n=2841). A total of
2322 (81.7%) men participated in the baseline examination at 50 years
of age.4 As a result of this first survey,
medical and/or dietary treatment were offered to 126 men with
hypertension, to 363 men with hyperlipidemia, and to
112 men with impaired glucose tolerance.5 A new
examination was carried out when they were 60 years of age, in which
1860 of the 2130 remaining men from the original study cohort
participated. In January of 1991, 422 subjects from the 50-year study
had died. Of the 1900 men still alive, those who lived in
Uppsala county (n=1681) were invited to a more extensive health
examination, in which 1221 men (72.6%) took part. These men were also
invited to a psychometric testing, in which 999 men (82%) took part.
Their mean age was 72.4 years (range, 69 to 75 years).
From the baseline examination at age 50 years, data for the
following measurements were collected: office SBP and DBP measured in
the supine position after 10 minutes rest with a mercury manometer to
the nearest 0 or 5 mm Hg; BMI calculated as weight (in kilograms)
divided by the height squared (in meters); and fasting concentrations
of blood glucose, serum insulin (n=815), HDL cholesterol
(n=801), and serum triglycerides. The study protocol has
previously been described in detail.6 Values of
serum lipids and lipoproteins were later standardized to correspond to
the methods used for the 70-year survey. From the 60-year survey, data
on office BP, measured as described above, and antihypertensive
treatment from a questionnaire were collected. At the 70-year survey,
the investigations included office SBP and DBP in the supine position,
measured with a sphygmomanometer to the nearest 2 mm Hg (mean of two
measurements), calculation of BMI, analyses of fasting plasma
concentrations of insulin and glucose, and serum lipids and
lipoproteins.7 Twenty-four-hour ABPMs were
completed in 950 of the participants in the cognitive study, using the
Accutracker 2 equipment (Suntech Medical Instruments Inc). BP
recordings were made every 20 minutes during daytime (6:00
AM to 11:00 PM) and every 20 or 60 minutes
during nighttime (11:00 PM to 6:00 AM). The
following variables were used in the analyses: MAP, SBP,
DBP, and HR during 24 hours; DSBP and DDBP; and NSBP and NDBP. The
difference between mean DSBP and mean NSBP was calculated. Nondipping
was defined as 
(DSBP-NSBP) of 
0 mm Hg. SBP variability was
estimated as the quotient between the mean standard deviation SBP
divided by the mean SBP. An OGTT was carried out (n=976), and subjects
were classified as having normal or impaired glucose tolerance or
diabetes according to the criteria of the National Diabetes Data
Group.8 A hyperinsulinemic
euglycemic clamp7 was performed
(n=965) and the M/I was calculated as glucose uptake per minute divided
by mean insulin concentration during the clamp, 60 to 120 minutes.
Reproducibility was tested in 21 subjects. The coefficients of
variation were 24-hour DBP, 5%; plasma glucose, 6%; M/I, 14%; serum
triglycerides, 15%; and plasma insulin, 20%.
The psychometric testing included the
MMSE9 (n=891) (MMSE was added to the protocol
after the start) and the TMT-A (n=998) and TMT-B
(n=996).10 Standardized procedures from published
manuals were used in the administration and evaluation. The maximal
time set for TMT-B was 240 seconds. MMSE is a widely used instrument in
the screening for cognitive disorders, and the TMT was selected to
assess psychomotor speed and shifting capacity. The testing was
performed in connection with the ABPM in some cases, but in others the
time interval was longer (mean, 18 months). After a logarithmic
transformation of the test results, a z transformation was
applied, and a composite cognitive score was calculated for each
subject as the mean sum of the test scores. Cognitive score was treated
both as a continuous outcome variable and as a dichotomous
variable, setting the cutoff level for low results at the lowest
quintile.
All pharmacological treatment with agents affecting BP,
irrespective of indication (ie, ß-blockers, calcium
antagonists, angiotensin-converting enzyme
inhibitors, diuretics, and 
-blockers), was
recorded in a questionnaire at age 70 years. Educational level was
stratified as low (elementary school only, 6 to 7 years, n=530), medium
(secondary school, n=309), or high (university studies, n=160). Main
previous occupational level was divided into three categories: low
(manual workers, n=406), medium (foremen, clerks, salesmen, n=388), and
high (major professionals, business managers, n=193). The following are
diagnoses of stroke according to the ICD-8 or ICD-9 before the
cognitive testing results were collected from the Swedish National
Inpatient Register and cover all diagnoses in hospitalized patients
from 1970 and onward: intracerebral hemorrhage
(431), thromboembolic stroke (433 to 434), transient ischemic
attack (435), and acute "ill-defined" cerebrovascular disease
(436). Informed consent was obtained from the participants after the
nature of the procedures had been fully explained. The study was
approved by the Ethics Committee at Uppsala University.
A logarithmic transformation was applied to all variables
not normally distributed. Student's unpaired t test was
applied for comparisons between independent groups, the
2 test was used for analysis of
relationships between categorical variables, and linear
relationships were examined with Pearson's correlation coefficient. In
the analyses of determinants of cognitive function, adjustment
was made for potential confounders, ie, socioeconomic factors
(educational and occupational levels) and age. ANCOVA was applied in
multivariate models with continuous dependent
variables, and logistic regression was used when the outcome
variable was binary. The odds ratio for continuous explaining
variables was calculated per increase with 1 SD within a 95%
confidence interval or per year (age). Testing for trend was performed
according to Spearman.
Results
Top
Abstract
Introduction
Methods
Results
Discussion
References
Description of the Population
Characteristics of the participants (n=999) are shown in Table 1
. Diabetes according to the OGTT was
present in 139 subjects (14.2%), and a total of 5.3% were treated
with peroral antidiabetic agents or insulin. Thirty-four percent were
treated with drugs affecting BP, irrespective of indication, mainly
ß-blockers and/or diuretics (26%), and the rate of treatment
with lipid-lowering agents was 9.4%. The correlation coefficient
between MMSE and TMT-A was r=.32; between MMSE and TMT-B it
was r=.40; and between TMT-A and TMT-B it was
r=.66. Seventy men had had a previous stroke, and they were
excluded from the main part of the analyses. Excluding stroke
patients, a large majority had high scores in the MMSE: 462 men scored
29 to 30 points; 287 men scored 27 to 28 points, and 77 men scored 26
points or below. The nonparticipants in the cognitive testing (n=222)
differed from the participants (n=999) with regard to a higher rate of
low education (72%, P<.0001 compared with participants).
In addition, they had higher office DBP at age 50 and higher plasma
concentrations of insulin at age 70 (both P<.05). The
distributions of 24-hour DBP were equal in participants and
nonparticipants.
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[in a new window]
Table 1. Description of Participants (n=999)
The correlation coefficients between office and 24-hour
measurements were r=.58 for SBP and r=.62 for
DBP. There were only weak linear relationships between BP and
metabolic measurements. The correlation coefficients
between metabolic measurements and 24-hour DBP were as
follows: plasma glucose, r=.12 (P=.003); plasma
insulin, r=.08 (P=.05); M/I, r=-.12
(P=.003); and BMI, r=.13 (P=.0007).
Serum lipids were not significantly related to 24-hour DBP.
Concentrations of serum triglycerides were closely related
to M/I (r=-.39) and to plasma glucose (r=.27).
Plasma glucose was significantly higher in nondippers (6.3 mmol/L)
than in dippers (5.7 mmol/L), independent of 24-hour DBP
(P=.008, logistic regression).
The mean cognitive z score in the entire cohort was
±0.00 (SD 0.82; range, -5.19 to +2.00). Cognitive score was equal in
men with missing results from the ABPM, the clamp, or the OGTT compared
with the others. Stroke patients (n=70) were excluded from the
analyses of determinants of cognitive function. Their results
are shown separately. In all analyses, adjustment was made for
age and educational and occupational levels. The relationships with the
composite cognitive score described below were unchanged when separate
analyses between risk factors and the single test results
(MMSE, TMT-A, TMT-B) were performed.
Office DBP at baseline (age 50) was inversely related to cognitive
function 20 years later. In the analysis, participants were
split into five DBP categories. Cognitive performance at age 70
was highest in men with the lowest baseline BP, DBP70 mm Hg
(n=147), and lowest in men with DBP
105 mm Hg (n=36), adjusted
value for trend P=.0040 (Table 2). Rates of antihypertensive treatment
and office DBP at age 60 and 70 years in each BP category are also
shown in Table 2. Only 3 men with DBP105 mm Hg were not treated
20 years later; their mean cognitive score was -1.24. Serum
concentrations of insulin at age 50 were also inversely related to
cognitive results at follow-up (Fig 1).
Men within the lowest tertile of s-insulin had higher
results than those in the highest tertile; the difference was, however,
not significant when DBP was adjusted for. High systolic BP,
BMI, or high levels of blood glucose or serum lipids at baseline were
not associated with later impaired performance.
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[in a new window]
Table 2. DBP at Age 50 Years in Relation to Cognitive
Function at Age 70 Years
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[in a new window]
Figure 1. Tertiles of serum insulin at age 50 years relative
to cognitive score 20 years later. Cognitive score in tertile 1 versus
tertile 3, ANCOVA: P1 (adjusted for age,
education, occupation)=.031; P2 (as
P1+DBP at age 50)=.145.
Blood Pressure , with separate analyses for
untreated men (n=594) and treated men (n=289). The inverse relationship
between BP and cognitive score was similar in both categories but
significant for untreated men only (P=.014 for trend). Mean
cognitive score did not differ between men with and without treatment
(+0.03 versus +0.02, respectively, P=.941), despite higher
mean 24-hour DBP in the latter group (75 versus 78 mm Hg,
respectively, P<.0001). This finding is discussed further
in the following sections. Isolated systolic hypertension was
not related to impaired cognitive function.
View larger version (17K):
[in a new window]
Figure 2. Cognitive score by tertiles of 24-hour DBP at age
70. Tests for trend according to Spearman, adjusted for age, education,
occupation, and M/I. P for trend=.014 in untreated men;
P for trend=.272 in treated men. [DSBP-NSBP] of 20 mm Hg), was equal to the rest
of the cohort. There was no relationship between the number of missing
single measurements due to technical reasons and cognitive
performance. , measurements of
M/I was negatively related to cognitive results (P=.048 for
trend). When adjustment was made for 24-hour DBP and treatment, the
value for trend was P=.055. Men with diabetes according to
the OGTT (n=130) performed worse than nondiabetic men (n=779, -0.16
[0.90] versus +0.06 [0.75]), independent of 24-hour DBP
(P=.005). In a multivariate model (n=868),
diabetes, nondipping, and 24-hour DBP were all independently and
inversely related to cognitive score as a continuous outcome
variable. In diabetic men, performance was equal in men
with and without pharmacological treatment. Stratifying for diabetes
did not alter the relationship between high DBP and low cognitive
results.
View larger version (10K):
[in a new window]
Figure 3. Cognitive score by tertiles of M/I (insulin
sensitivity index) at age 70. P1 for trend
(adjusted for age, education, occupation)=.048.
P2 for trend (as
P1+24-hour DBP and treatment)=.055. ). In a multivariate
model that included 24-hour DBP, p-glucose,
p-insulin, M/I, s-triglycerides, BMI,
HDL cholesterol, treatment, age, educational and
occupational levels, an increase of 24-hour DBP with 1 SD was
associated with an odds ratio of 1.45 (1.20 to 1.75) of cognitive
impairment. Despite higher DBP in treated men, antihypertensive
treatment was associated with a decreased risk, ie, treatment was a
negative confounder. As shown in Table 4,
the association between hypertension and cognitive impairment was
significant only in untreated men.
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[in a new window]
Table 3. Determinants of Low Cognitive Performance:
Cross-sectional Data at Age 70 Years
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[in a new window]
Table 4. Determinants of Low Cognitive Performance
Stratified for Antihypertensive Treatment
Men with a previous stroke (n=70) had lower cognitive results;
mean cognitive score (SD) was -0.43 (1.14) versus +0.02 (0.78) for
nonstroke subjects (P=.0001), and they had higher DBP at
baseline. When stroke cases were included in the analyses
previously described, the relationships between vascular risk factors
and low cognitive performance remained almost identical.
Discussion
Top
Abstract
Introduction
Methods
Results
Discussion
References
High DBP at the baseline examination at age 50 years was related
to impaired cognitive performance 20 years later, even after
exclusion of men with a previous stroke. Elevated concentrations of
serum insulin also predicted later low cognitive function, but not
independently of DBP. Cross-sectional measurements at age 70 showed
that high 24-hour DBP, a nondipping nocturnal BP pattern, insulin
resistance, and diabetes all were related to low cognitive function.
The relationships between hypertension and cognitive impairment were
strongest in men without antihypertensive treatment. High BP and
impaired glucose metabolism11 are
both independent predictors of cerebrovascular disease. We conclude
that hypertension and factors linked to the syndrome of insulin
resistance12 might contribute to cognitive
disturbances in the elderly, mediated through functional
changes, or by silent cerebral large- and small-vessel lesions.
Selected Abbreviations and Acronyms
ABPM
=
ambulatory blood pressure measurement
BMI
=
body mass index
BP
=
blood pressure
DBP
=
office diastolic blood pressure
DDBP
=
mean daytime diastolic blood pressure
DSBP
=
mean daytime systolic blood pressure
HR
=
heart rate
ICD
=
International Classification of Diseases
MAP
=
mean arterial pressure
M/I
=
insulin sensitivity index
MMSE
=
Mini-Mental State Examination
NBP
=
nocturnal blood pressure
NDBP
=
mean nocturnal diastolic blood pressure
NSBP
=
mean nocturnal systolic blood pressure
OGTT
=
oral glucose tolerance test
SBP
=
office systolic diastolic blood pressure
TMT
=
Trail-Making Test
Acknowledgments
The study was supported by grants from the Swedish Medical
Research Council (grant 5446), The King Gustav V and Queen Victoria
Foundation, The Foundation of Old Servants, The Alzheimer
Foundation, The Dementia Foundation in Sweden, the Swedish Stroke
Foundation, and The Swedish Hypertension Society. We are grateful to
Paul McKeigue, Senior Lecturer, London School of Hygiene & Tropical
Medicine, for valuable comments on the manuscript and to Gun-Britt
Ångman for excellent coordination and care of the study
participants.
References
Top
Abstract
Introduction
Methods
Results
Discussion
References
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