Cognitive Performance in Hypertensive and

Normotensive Older Subjects

Frances Harrington, Brian K. Saxby, Ian G. McKeith, Keith Wesnes, Gary A. Ford

Abstract—Longitudinal studies suggest that hypertension in midlife is associated with cognitive impairment in later life.
Cross-sectional studies are difficult to interpret because blood pressure can change with onset of dementia and the
inclusion of subjects on treatment and with hypertensive end-organ damage can make analysis difficult. We examined
cognitive performance in hypertensive and normotensive subjects without dementia or stroke ⱖ70 years of age.
Cognitive performance was determined with the use of a computerized assessment battery in 107 untreated
hypertensives (55 women, age 76⫾4 years, blood pressure, 164⫾9/89⫾7; range, 138 to 179/68 to 99 mm Hg) and 116
normotensives (51 female, age 76⫾4 years, 131⫾10/74⫾7; 108 to 149/60 to 89 mm Hg). Older subjects with
hypertension were significantly slower in all tests (reaction time, milliseconds; simple, 346⫾100 versus 318⫾56,
P⬍0.05; memory scanning, 867⫾243 versus 789⫾159, P⬍0.01; immediate word recognition, 947⫾261 versus
886⫾192, P⬍0.05; and delayed word recognition, 937⫾230 versus 856⫾184, P⬍0.05; picture recognition, 952⫾184
versus 894⫾137, P⬍0.01; spatial memory, 1390⫾439 versus 1258⫾394, P⬍0.01; excepting choice reaction time,
510⫾75 versus 498⫾72, P⫽0.08). Accuracy was also impaired in tests of number vigilance, 99.2⫾2.5% versus
99.9⫾0.9, P⬍0.01; delayed word recognition, 83.5⫾16 versus 87.9⫾9.8, P⬍0.01; and spatial memory 64⫾32 versus
79⫾20, P⬍0.001. Hypertension in older subjects is associated with impaired cognition in a broad range of areas in the
absence of clinically evident target organ damage. (Hypertension. 2000;36:1079-1082.)
Key Words: hypertension, arterial 䡲 blood pressure 䡲 aging 䡲 dementia

C ognitive impairment and dementia are becoming increas-

ingly prevalent because of demographic changes. The
mingham7 suggested no association between BP and cognitive
performance when measured concurrently; however, when data
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prevalence of dementia doubles with each 5-year age rise, from
2.8% at 70 to 74 years to 38.6% at 90 to 95 years.1 The annual
incidence of dementia in the age group 85 to 88 years is 9%.2
Dementia incidence in a population ⬎55 years of age was 10.7
per 1000 person-years, equating to a lifetime dementia risk for a
55-year-old woman of 0.33 and 0.16 for a man.3
The UK population ⬎60 years of age is projected to
increase by a third by the year 2026; the population with
cognitive impairment is projected to double by 2026.4 In this
context, population risk factors for the development of
dementia that are potentially modifiable are important to
identify. Cognitive impairment usually develops insidiously,
eventually reaching a stage where it becomes clinically and
functionally apparent. Studies of subjects with no or with
minor cognitive impairment have shown that neuropsycho-
logical tests can predict who is likely to proceed to dementia.5
Hypertension is common in elderly Western populations, with
a prevalence of 41% for men and 54% for women 75 years of
age, defined by single blood pressure (BP) reading of
⬎160 mm Hg systolic and/or ⬎95 mm Hg diastolic or any
treatment for hypertension.6 Epidemiological data from Fra-
were reanalyzed the average BP over 20 years was inversely
related to cognitive performance.8 Three further studies have
shown a link between midlife or later-life hypertension and
subsequent cognitive impairment.9 –11 Reasons for discrepancies
between cross-sectional and longitudinal studies may include the
tendency for BP levels to change with the onset of dementia,10
the inclusion of individuals with established cerebrovascular
disease in cross-sectional studies, and the effects of BP-lowering
therapy on cognitive function. Except for one small study in 25
older patients with severe hypertension there are no data on
cognitive function in older hypertensives where the effects of
cerebrovascular disease have been excluded.12
The hypothesis of the present study was that cognitive
performance in older adults without overt cerebrovascular
disease would be impaired in line with increasing BP level.
We determined cognitive performance in untreated older
hypertensives and normotensives without cerebrovascular
disease, target organ damage, or other vascular risk factors.
Methods
The study was performed in a community primary care population.
Subjects were recruited from 10 local general practices in the

Received March 30, 2000; first decision April 19, 2000; revision accepted June 5, 2000.
From the Institute for the Health of the Elderly, University of Newcastle Upon Tyne (F.H., B.K.S., I.G.M., G.A.F.); and Cognitive Drug Research
(K.W.), Reading, United Kingdom.
Correspondence to Prof G.A. Ford, Wolfson Unit of Clinical Pharmacology, University of Newcastle Upon Tyne, Newcastle Upon Tyne, NE2 4HH,
United Kingdom. E-mail g.a.ford@ncl.ac.uk
© 2000 American Heart Association, Inc.
Hypertension is available at http://www.hypertensionaha.org

1079
 1080 Hypertension December 2000

Tyneside area. BP readings over the last 5 years, current drug Results of Cognitive Assessment Battery in Hypertensive and
therapy, and concomitant disease from all persons in the 70- to Normotensive Groups
89-year age group were recorded from general practitioner case
records. Subjects who were not taking BP-lowering drugs, had no ms (%) Hypertensive Normotensive P
serious concomitant disease (dementia, malignancy, or advanced Simple reaction time 346 (100) 318 (56) ⬍0.05
renal failure), and had BP readings recorded in the notes were
contacted by letter and invited to attend the screening clinic; 1213 Choice reaction time 510 (75) 498 (72) 0.08
subjects attended. Hypertensive subjects were first recruited through Number vigilance accuracy 99.2 (2.5) 99.9 (0.9) ⬍0.01
screening of subjects with average recorded BP readings of ⬎160 Memory scanning reaction time 867 (243) 789 (159) ⬍0.01
and/or 90 mm Hg. Normotensive subjects were subsequently re-
cruited by screening of subjects with average BP readings of Immediate word recognition
⬍150/90 mm Hg. BP was measured with a mercury sphygmoma- Reaction time 947 (261) 886 (192) ⬍0.05
nometer 3 times on each of 3 occasions, each separated by 2 weeks.
Accuracy 88.8 (11) 89.3 (9.7) 0.68
Baseline BP was defined as the mean of the second and third
readings on the last of these 3 visits. Two cohorts of subjects were Delayed word recognition
recruited: hypertensives with systolic BP 160 to 179 mm Hg and/or Reaction time 937 (230) 856 (184) ⬍0.05
diastolic BP 90 to 99 mm Hg and normotensives with BP⬍150/
90 mm Hg. Subjects were excluded if they were receiving any Accuracy 83.5 (16) 87.9 (9.8) ⬍0.01
BP-lowering therapy, had atrial fibrillation, diabetes mellitus, previ- Picture recognition
ous stroke or transient ischemic attack (defined by clinical history or Reaction time 952 (184) 894 (137) ⬍0.01
physical examination), carotid bruits on auscultation, peripheral
vascular disease (symptomatic claudication or absent foot pulses), Accuracy 88 (13) 89.1 (10.4) 0.29
angina or previous myocardial infarction (defined by clinical history Spatial memory
or ECG changes), or dementia. Dementia was defined as mini mental Reaction time 1390 (439) 1258 (394) ⬍0.01
state examination (MMSE) ⬍24 and/or significant decline in cogni-
tive function; this was assessed by interview with a close friend or Accuracy 64 (32) 79 (20) ⬍0.0001
relative and completion of Clinical Dementia Rating13 and IQ Data are mean and SD.
Code.14 Subjects taking psychotropic medication were also excluded
because these drugs can interfere with cognitive function. Educa-
tional level was assessed by number of years at school and verbal IQ 50 women) were studied. Mean age (76⫾4 years), years in
using number of errors in the New Adult Reading Test15 (NART). education (10⫾2), and MMSE score (29⫾1) were identical in
Subjects were screened for the presence of depressive disorder by the both groups. There was no significant difference in hyperten-
30-point Geriatric Depression Scale16 (GDS). Studies were approved sive and normotensive group NART scores (19.3⫾9.2 versus
by the Newcastle Joint Ethics committee. All subjects gave in-
formed, written consent. 17.5⫾8.6) or GDS scores (5.4⫾4.6 versus 5.0⫾4.5). Ten
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subjects in each group were taking aspirin. Results of the

Cognitive Assessment
Subjects were administered the Cognitive Drug Research Comput-
erized Assessment Battery.17,18 The subject sits in front of a laptop
computer; a series of words, pictures, and numbers appear on the
screen and the subject responds by pressing “yes” or “no” on a button
box in front of them. The battery comprises 8 tests and takes 20
minutes to administer.
Simple reaction time is a test of attention, alertness, and power of
concentration. Choice reaction time is similar to simple reaction time
with an element of stimulus discrimination and response. Immediate
and delayed word recognition time test the ability to store and
retrieve verbal information and discriminate novel from previously
presented words. Picture recognition time tests the ability to store
and retrieve pictorial information and discriminate novel from
previously presented pictures. Number vigilance is a test of attention,
requiring intensive vigilance and the ability to ignore distraction.
Spatial memory tests the ability to store and retrieve visuospatial
information. Memory scanning tests the ability to store information
in the working memory and rapidly retrieve it, testing subvocal
rehearsal of digit sequences.
The computerized battery was administered once as a training
session before baseline. Preliminary studies with a subgroup estab-
lished that 1 training session was sufficient to familiarize the subjects
with the test system.
Statistical Analysis
Data were analyzed with SPSS for Windows. Statistical significance
was set at the 5% level. Means were analyzed by means of the
independent samples t test.
Results
One hundred seven untreated hypertensives (164⫾9/89⫾7;
range, 138 to 179/68 –99 mm Hg, 55 women) and 116
normotensives (131⫾10/74⫾7; 108 to 149/60 – 89 mm Hg,
cognitive assessment battery in hypertensive and normoten-
sive groups are shown in the Table. The hypertensive group
was significantly slower in all tests except for choice reaction
time, in which the slower response was of borderline signif-
icance. Accuracy of response in hypertensive subjects was
also impaired for number vigilance, delayed word recogni-
tion, and spatial memory.
Discussion
We have shown by using a cognitive assessment instrument
that has been well validated in the elderly17,18 that older
subjects with hypertension but without clinical evidence of
vascular disease have impaired cognition in a broad range of
tests of attention and short- and long-term memory. Hyper-
tensives were on average ⬇10% slower in psychomotor tests
compared with normotensive peers. The decrement seen in
the hypertensive subjects is one-third to one-half that seen in
mild dementia. A study using the CDR battery in subjects
with mild Alzheimers dementia (MMSE 24) and healthy
age-matched control subjects without dementia (MMSE 29)
found the dementia group to be slower by 13% to 44% in the
tests.19
These differences may not be sufficient to interfere with
activities of daily living and would not be recognized in
routine clinical practice because of wide interindividual
variability. However, many studies have observed that pre-
morbid cognitive function levels are associated with in-
creased risk of developing dementia.5,20,21 The public health
implications of relatively small individual declines in cogni-
 Harrington et al
tion are large when applied to a population. The presence of
vascular risk factors in some population subgroups was
associated with a left shift of the normal distribution of
MMSE scores and a large increase in numbers of individuals
falling below the cutoff score for probable dementia.22
The majority of studies examining the effect of BP on
cognition have looked at BP levels very much higher than
those in the present study. We have found important impair-
ments in cognitive function in a group of older hypertensives
with only moderately increased BP. This has implications for
the large numbers of elderly people with only minimally
raised BP. Results from this study agree with those from a
previous smaller study12 of more severe hypertensives (mean
age, 70.6 years; mean BP, 192/112) and normotensives (mean
age, 70.4 years; mean BP, 143/80). The hypertensives were
rigorously screened to exclude those with end-organ damage,
although the majority of hypertensives had been on treatment
and were tested off treatment. This study found the hyperten-
sives to be significantly slower in tests of attention and
psychomotor speed. The present study confirms these obser-
vations and extends the findings to older subjects with lesser
degrees of BP elevation. Interpretation of cross-sectional
studies is difficult for a number of reasons, including use of
wide age ranges,23–25 use of tests not validated in the elderly,
use of combinations of treated and untreated subjects,25
subjects with likely end organ damage,26 inclusion of subjects
with probable dementia,27 and too few BP readings to
adequately define BP status and level.28,29 However, repeated
BP measurements in this study to clearly characterize partic-
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ipants BP status may have had the disadvantage of “labeling”
subjects, which may have led subjects who were aware that
they were hypertensive to perform less well. However, it is
also possible that low levels of anxiety, generated by “label-
ing” of subjects as hypertensive, may have enhanced some
aspects of cognitive performance.
The differences seen in our study are likely to be due to a
direct effect of hypertension. The groups are well matched for
other factors known to influence cognitive function: age,
educational level, depressive disorder, and psychotropic med-
ication. There are a number of possible mechanisms through
which hypertension might directly impair cognitive function.
Ischemic stroke increases the risk of dementia.30 –32 The
hypertensive subjects in our study had no clinical evidence of
cerebrovascular disease or other target organ damage from
hypertension. However, an increased prevalence of asymp-
tomatic cerebrovascular disease may have been present in the
hypertensive subjects. Multiple small infarcts can lead to
dementia, depending on volume of brain affected,33,34 loca-
tion of infarcts, and bilateralality. White matter lesions that
consist of areas of demyelination and narrowing of small
arteriolar lumen size have been associated both with hyper-
tension and with cognitive dysfunction. The presence of brain
MRI white matter lesions is associated with impaired cogni-
tive functioning in subjects with and without dementia.35,36
Other possible mechanisms are changes in cerebral auto-
regulation37 and cerebral blood flow38 associated with hyper-
tension. Kalra et al39 reported improvements in tests of
attention and psychomotor speed when 25 elderly hyperten-
sive subjects were treated with BP-lowering therapy (n⫽20)
Cognitive Performance in Hypertension 1081
or placebo (n⫽5). These observations require confirmation,
but such reversibility would suggest that psychomotor im-
pairment is a direct consequence of hypertension, most likely
mediated through effects on cerebral blood flow or
metabolism.
Genotypic influences that contribute to hypertension could
influence cognition through common or separate mecha-
nisms. A potential genetic link factor between hypertension
and cognitive impairment is the apolipoprotein E allele,
which has been linked to vascular risk factors,40 coronary
artery disease,41,42 and stroke,43 as well as Alzheimer’s
dementia.44,45 In postmortem studies,46,47 an increased ⑀4
allele frequency has been reported in subjects with hyperten-
sion or critical coronary artery disease and an increased
number of senile plaques and neurofibrillary tangles in the
brains of apo⑀4-positive hypertensives who were not de-
mented. Further work is needed to explore the link between
apo⑀4 and hypertension and cognitive impairment in older
people.
Our observations do not necessarily imply that treatment of
hypertension will reduce cognitive decline. However, the
SystEur Vascular Dementia project48 reported treatment of
hypertension in the elderly with the calcium channel blocker
nitrendipine reduced incidence of dementia by 50%. A recent
longitudinal observational study also suggests that treatment
of hypertension in older individuals may reduce cognitive
decline.49 Hypertension was associated with cognitive decline
during 4 years of follow-up, with the highest risk in untreated
patients. If treating hypertension reduces the rate of cognitive
decline, the benefits of treating hypertension would extend
beyond the prevention of stroke and myocardial infarction to
primary prevention of dementia. The present findings support
undertaking further studies to elucidate the mechanisms
through which hypertension is associated with cognitive
impairment and intervention studies to determine whether
treatment of hypertension prevents dementia.
Acknowledgments
This work was funded by the Astra Foundation, United Kingdom.
We thank Helene Poppleton for assistance with cognitive testing.
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