Download Blood pressure and intellectual function in elderly subjects

Age and Ageing 1997; 26: 91 - 9 8
Blood pressure and intellectual
function in elderly subjects
VINCENZO PALOMBO, ROSA SCURTI, ANTONIO MUSCARJ1, GIOVANNI MARIA PUDDU, ANGELO D I IORIO,
MICHELE
Zrro, GIUSEPPE ABATE
Cattedra di Geriatria, Universrta 'G. D'Annunzio1, Via N. Nicolini, 2, 1-66100 Chieti, Italy
1
Istituto di Patologia Speciale Medica e Metodologia Qinica, Universrta degli studi Bologna, Italy
Address correspondence to: G. Abate. Fax (+39) 871 358851.
Abstract
Objective: to assess the relationship between hypertension and cognitive function in elderly subjects.
Methods: 17 subjects with uncomplicated hypertension (nine male, eight female) and 27 control subjects with
similar educational level and age (18 male, nine female) were studied. These individuals were recruited, according
to strict selection criteria, from a random sample of 120 elderly subjects living in the community, who had a normal
Mini Mental State score. An extensive neuropsychological test battery, sensitive to mild cognitive impairment, was
administered in standard conditions to measure attention, concentration and judgement, psychomotor speed,
memory and learning. Affective disorders were also evaluated. In all patients a computed tomography scan was
performed.
Results: subjects with high blood pressure had lower mean levels of performance in attentional measures: tapping
test (inhibition of incorrect answers), three words-three shapes test (attempts; incidental memory) and reaction
time to multiple stimuli. They also scored worse in clusters 1 and 2 of the Hamilton rating scale for depression.
Confluent white matter lesions were found in nine hypertensive subjects (52.9%) and five controls (18.5%;
P = 0.0170). Lacunes were demonstrated in 11 hypertensive (64.7%) and four normotensive people (14.8%;
P — 0.0007). In a multivariate analysis (logistic regression), three cognitive variables (tapping, Hamilton cluster 2
and Hamilton total score) remained significantly associated with hypertension, independently of the presence of
cerebral lesions.
Conclusions: in elderly otherwise normal hypertensive subjects, an attentional impairment may occur, which
appears to be functional and possibly reversible rather than structural and progressive.
Keywords: hypertension, psychometric impairment elderty patients
Introduction
Hypertension can lead to cognitive impairment by
producing cerebral ischaemic lesions and is the most
powerful risk factor for vascular dementia [1]. Some
deficits in cognitive performance (attention, perception,
memory, reasoning, visuo-spatial organiration, cognition)
have also been observed in hypertensive patients free
from symptomatic infarctions [2-6]. In elderly people,
however, the reports on the relationship between
hypertension and psychomotor impairment are conflicting. Some authors report significant impairment in
elderly hypertensive subjects [7-10], while others
suggest that mild hypertension may prevent age-related
decline in cognitive performance [11, 12].
The pathogenesis of the supposed hypertensionrelated impairment is also still debated. Several
mechanisms have been proposed; altered cerebral
metabolic processes, cerebral blood flow autoregulation
or other physiological changes leading to, or resulting
from, hypertension [13-16]; or confluent white matter
lesions (leukoaraiosis), whose prevalence is higher in
hypertensive than in normotensive subjects of the same
age. However, it is not known whether white matter
lesions relate to psychomotor impairment [17-20].
This study assesses the relationship between hypertension and psychomotor impairment in elderly subjects,
as well as the possible role played by white matter
lesions. For this purpose we studied a selected population of elderly subjects, normotensive and with uncomplicated hypertension, with computed tomography
(CT) and an extensive neuropsychometric evaluation.
Subjects and methods
In order to avoid a Berkson's bias, the subjects were
91
V. Palombo et al.
recruited from 120 elderly relatives of patients
hospitalized in our department. The resulting sample,
compared with previous demographic data, was
representative of the elderly population living in the
community with regard to disease, self-sufficiency and
socio-cultural conditions. Inclusion criteria were: (i)
age > 60 years, (ii) educational level (3-10 years of
schooling) and (iii) score > 23 on the Mini Mental State
Examination [21].
On the basis of history, physical observation,
medical recordings and, if needed, supplementary
laboratory or instrumental examinations, the following
conditions were excluded: (i) dementia (DSM-IH-R
criteria) [22]; (ii) previous stroke or transient ischaemic attack; (iii) neurological diseases (Parkinson's
disease, epilepsy, etc.); (iv) psychiatric disorders; (v)
poorly controlled diabetes; (vi) renal insufficiency
(creatinine > 2.5mg/dl); (vii) severe chronic diseases,
such as liver cirrhosis, respiratory insufficiency, heart
failure, malignancy, anaemia (Hb < 10g/dI), endocrine
disorders, etc.; (viii) sensory or motor impairments
influencing the ability to perform the tests in the
protocol; and (Ls) alcohol abuse or regular intake of
drugs interfering with cerebral function.
On the basis of these criteria, 44 healthy subjects
(27 males and 17 females) were included in the study.
Informed consent was obtained from all the patients
according to the Helsinki declaration.
Blood pressure and vascular risk factors
All patients were submitted to blood pressure evaluation with at least three measurements performed in
standard conditions, on two different occasions. For
each patient, the mean of these measurements was
used in the subsequent assessments.
Blood pressure was measured by the auscultatory
method, with the patient sitting upright and the arm
held in the horizontal position, using a random zero
sphygmomanometer. The diagnosis of hypertension
was made in patients with an established history of
hypertension, or who were treated with anti-hypertensive drugs or had systolic values > 165 mmHg and/or
diastolic values > 95 mmHg on sphygmomanometric
measurements. On the basis of these criteria the
original sample was subdivided in two groups: (i)
normotensive group, 27 patients (61.3%), 18 males
(66.6%) and nine females (333%), mean age 77.3 ± 5.5
years; (ii) hypertensive group, 17 patients (38.6%),
nine males (52.9%) and eight females (47.0%), mean
age 75.1 ± 5.5 years.
Of these patients, only five had newly
diagnosed hypertension, with ranges of systolic and
diastolic blood pressure of 180-196 and 85-100
mmHg respectively.
The sample was also dichotomized according
to hypercholesterolaemia (> 6.22 mmol/I) and/or
hypertriglyceridaemia (> 1.94mmol/I), smoking (> 5
92
cigarettes/day), diabetes mellitus (history and treatment) and being overweight (body mass index > 30).
Psychometric evaluation
This was performed in all cases by a skilled psychogeriatrician blind to the blood pressure status of the subjects
in a single morning session lasting about 90 min.
In treated hypertensive patients (seven out of 17)
all drugs were discontinued for 2 weeks and placebos
used to reduce the anxiety associated with discontinuation of treatment. Since both groups consisted of
substantially healthy subjects, the only drugs given
during the study period were oral hypoglycaemic
agents for diabetic patients.
Beverages containing caffeine and alcohol were
restricted from the evening before testing. A range of
cognitive functions, including attention and concentration, psychomotor speed, memory and learning,
was assessed. The tests were selected from standard
neuropsychological test batteries as being sensitive
enough to detect mild cerebral dysfunction.
Attentional capacity was assessed by several tests,
exploring specific and differential aspects of this
cerebral function: digit span from the Wechsler adult
intelligence scale, for vigilance and concentration [23,
24], word list generation for perseveration [25, 26],
tapping and reaction times for ability of inhibition of
incorrect answers and susceptibility to interference
[27, 28] and visual research for selective attention [25].
The structure of memory function was assessed
according to Buschke-Fuld [29] and incidental
memory was tested by the three words-three shapes
test [27]. Abstraction and conceptual reasoning skills
were assessed by the Weigl sorting test [25] and
depression evaluated by the Hamilton rating scale [30].
Short summaries of the tests follow.
Digit span
Sequences of numbers are read to the subject, who
must repeat them to the observer. This continues with
sequences of increasing length until two consecutive
errors are made for a given sequence length, hi the
second part, the subject must repeat numbers in
reverse sequence. The maximum score is 10.
Word list generation test
The task is to generate words of the same category (e.g.
animals). Normal adults with high-school education
can produce an average of 36 words over 3 min.
Tapping
The examiner asks the patient to place the hand on the
table and to raise the index finger in response to a
single tap, while holding still in response to two taps.
The score ranges from 0 to 12.
Blood pressure and cognitivity in the elderly
Simple visual reaction time
After practice trials, subjects are informed which of
four coloured lights (blue, green, red, white) will be
displayed on a screen and are asked to turn the light off
as quickly as possible by pressing a button. Five trials of
each colour are administered. Mean reaction times are
averaged across the colour conditions.
Choice visual reaction time (multiple stimuli)
This test is administered in a similar fashion to the
simple reaction time task, except that the subjects are
not informed which of the four coloured lights will be
illuminated. Mean reaction times in ms are computed
for the 20 test trials across the four colour conditions.
Visual search test
The subject must find and cancel a number from a
random array of numbers on a page. This isfollowedby
two other tests which involve cancelling two or three
numbers simultaneously. The test is scored for
accuracy and speed of completion.
Selective verbal reminding according to
Buscbke-Fuld
A 10 word list is presented over a series of 18 trials, or
until all the words are successfully recalled on two
consecutive trials. The entire list is shown only in the
first trial. Subsequently, only those words that were not
recalled in the immediately preceding trial are presented. Words that are remembered in two consecutive
trials without further presentation are presumed to be
in long-term storage; words recalled only after 'reminding' are assumed to be retrieved from short-term
storage. No cues are given during the test, so all the
subjects are free to adopt their own encoding
strategies. After a 15 min interval, during which a
non-verbal task is performed, the subject is invited to
recall as many words as possible without further
reminding. The selectiveretrievalat the end of learning
is a clear demonstration of retrieval efficiency.
In the Buscke-Fuld test the following parameters
were considered: (i) the total number of different items
recalled without further reminding at least once during
the task (long-term storage); (ii) the number of items
recalled on successive trials without presentation
(retrieval from long-term storage), divided into total,
consistent and delayed.
Three words-three shapes test
The patient is first asked to copy the six test stimuli,
without being told that memory is to be tested.
Immediately after copying, the stimuli are removed
and the patient is asked to reproduce them from
memory (incidental memory). Patients who do not
succeed are allowed a 30 s examination of the six
stimuli, this time being told that their memory will be
tested (immediate memory). Patients who again fail in
the task are allowed repeated study periods, either
until the criterion of five or six items is reached or until
five study periods have elapsed. Delayedrecallis tested
after 30 s and 15 min.
Weigl sorting test
In this test, the examiner displays to the patient 12
wooden pieces of different form (circles, squares,
triangles); colour (red, yellow, blue, green); suit
(hearts, flowers, squares); thickness (4-12 mm);
dimension (30-120 mm). In the first step (active) the
patient is invited to group the wooden pieces into one
category (i.e. all for the same colour). If the patient is
not able to find any possibility for grouping the
examiner passes to the second step. In the second
step (passive) the grouping of pieces is done by the
examiner and the patient is invited to explain the
criterion adopted for categorization.
Hamilton rating scale for depression
This is a questionnaire of 21 items, subdivided in four
clusters, which explore: (0 retarded depression, (ii)
agitated depression, (iii) anxiety reaction and (iv)
abnormal personalities. In normal subjects the score
ranges from 0 to 18.
Neuroradiological evaluation
In all patients a CT scan was performed without contrast
medium, with standard axial 5 mm slices. Leukoaraiosis
was denned as the presence of ill-denned, patchy or
diffuse, white matter periventricular hypodensities.
Lacunes were denned as well demarcated lesions,
following specific vascular territories and usually
involving the internal capsule, basal ganglia, corona
radiata or thalamus, with a maximum diameter < 1 cm2.
Each CT scan was analysed independently and blindly
by two experienced neuroradiologists, with full agreement in distinguishing leukoaraiosis and infarcts [17].
Statistical analysis
Unless otherwise stated, all deviations from the mean
were expressed as one standard deviation. Since many
variables had a non-Gaussian distribution, non-parametric tests were used: the Mann-Whitney test for the
comparison between groups, the \2 test for the
comparison between percentages and Spearman's
correlation coefficient for simple correlation analysis.
Multivariate analysis was carried out by stepwise
unconditional logistic regression models. A backward
elimination procedure was adopted to ascertain which
variables remained independently associated with
hypertension. Two-tailed tests were used throughout
93
V. Palombo et al.
Table I. Relevant features of the two study groups
Group
Normotensive (n = 27)
77.3 ± 5.5
Age (years)
Mini Mental State score
26.7 ± 2.0
Educational level (years)
4.3 ± 1.4
Distribution of characteristics (no and % of subjects)
Male sex
18 (66.7%)
Smoking
12 (44.4%)
Hyperlipidaemia
3(11.1%)
Overweight
9 (33.3%)
Diabetes mellitus
2 (7-4%)
Lacunes
4 (14.8%)
Leukoaraiosis
5 (18.5%)
Blood pressure (mmHg)
Systolic
140.8 ± 12.9
Diastolic
74.2 ± 10.7
Hypertensive (n = 17)
P value
75.1 ± 5.5
25.8 ± 1.7
3.9 ± 0.9
0.2781
0.1695
0.3670
9 (52.9%)
8(47.1%)
3 (17.6%)
9 (52.9%)
5 (29.4%)
11 (64.7%)
9 (52.9%)
0.3626
0.8653
0.5385
0.1977
0.0520
0.0007
0.0170
174.6 ± 16.0
91.1 ±6.8
Deviations from means arc 1 standard deviation.
and P values less than 0.05 were considered significant.
All tests were performed with BMDP software [31].
Results
The main clinical and computed tomographic characteristics of hypertensive and normotensive subjects
are summarized in Table 1. The two groups did not
differ in age, sex distribution, Mini Mental State score,
educational level, smoking habit, blood lipids or body
mass. In hypertensive patients the prevalence of
lacunes and leukoaraiosis was significantly greater
than in normotensive subjects. The prevalence of
diabetes was also greater in those with high blood
pressure, with a P value close to significance.
In psychometric evaluation, the following significant differences were observed between hypertensive
and normotensive subjects (Tables 2 and 3):
1. More inhibition and attentional errors on the
tapping test, revealing a trend towards an attention
defect;
2. More attempts and worse scores in incidental
memory (P close to significance) in the three
words-three shapes test;
3. Higher scores in the Hamilton rating scale for
depression, which were significant in clusters 1 and 2;
Table 2. Psychometric evaluation: attention
Group
Attention
Digit span
Forward
Backward
Word production test
Tapping (no. of errors)
Inhibition
Attentional
Visual search test
No. of correct answers
Accuracy
Normotensive (n = 27)
94
P value
4.4 ± 0.7
2.8 ± 0.7
12.8 ±2.1
4.2 ± 0.8
2.5 ± 0.9
12.6 ± 3.1
0.3922
0.3114
0.5230
2.1 ± 1.5
0.1 ± 0.3
3.2 ± 1.9
0.5 ± 0.7
0.0553
0.0827
34.4 ± 8.5
0.3609 ± 0.2226
Deviation from means are 1 standard deviation.
Hypertensive (n = 17)
30.9 ± 12.6
0.3336 ± 0.2137
0.2912
0.4765
Blood pressure and cognitivity in the elderly
Table 3. Psychometric evaluation: memory, depression, abstraction and judgement, speed of reaction
Group
Normotensive (n = 27)
Memory
Buschke-Fuld
ITS
1033 ± 24.2
LTRt
77.8 ± 24.7
LTRc
33.4 ± 24.6
LTRd
6.6 ± 2 . 1
Three words-three shapes
Incidental
4.7 ± 1.2
5.4 ± 0.6
Immediate
0.4 ± 0.8
Attempts
30 s
5.4 ± 0.7
15 min
4.9 ± 1.1
Depression (Hamilton rating scale)
Total score
5-9 ± 7.0
Cluster 1
1.1 ± 1.8
Cluster 2
3.1 ± 3.6
3.0 ± 4.0
Cluster 3
Cluster 4
1.6 ± 2 . 2
Abstraction and judgement
Weigl sorting test
9-7 ± 2.8
Reaction time
Simple stimuli
391.5 ± 126.4
Multiple stimuli
525.3 ± 141.3
Hypertensive (n = 17)
P value
102.3 ±
78.2 ±
28.9 ±
6.6 ±
36.4
32.3
24.2
2.0
0.8505
0.8802
0.4510
0.8901
3.8
4.9
0.9
5.2
5.0
±
±
±
±
±
1.7
1.1
0.8
0.8
1.1
0.0652
0.2101
0.0349
0.5549
0.7449
8.8
1.8
5.5
4.7
2.6
±
±
±
±
±
6.8
1.5
4.2
4.7
2.8
0.0745
0.0454
0.0454
0.1252
0.1515
9.3 ± 3.2
0.7540
434.5 ± 123.5
600.1 ± 113.4
0.3000
0.0329
Deviation from means are 1 standard deviation.
LTS, long-term storage; LTR, long-term retrieval (t = total; c = consistent; d = delayed).
4. Longer reaction time to multiple stimuli, which
expresses a slower psychomotor speed.
The structure of memory (Buschke-Fuld), abstraction and judgement (Weigl) were unimpaired in
hypertensive patients.
The psychomotor performance of those subjects
who were receiving drug treatment for hypertension
prior to the placebo run-in period was similar to that of
newly-diagnosed hypertensive patients who had never
previously been treated for hypertension.
In order to ascertain which variables were independently associated with hypertension, a multiple
logistic regression was performed, which included as a
dependent variable hypertension and, as possible
independent variables, all the variables which differed
between hypertensive and normotensive subjects with
P values less than 0.10 (Table 4). This analysis was
Table 4. Variables independently associated with hypertension in multiple logistic regression
Independent variable
1
Lacunes
Tapping (no. of attentional errors)
Hamilton cluster 2
Hamilton total score
P value
Correlation coefficient ± SE
3.892
2.531
0.852
0.508
±
±
±
±
1.196
1.015
0.356
0.215
0.2135
0.1376
0.1281
0.1254
0.0011
0.0126
0.0167
0.0181
*0 = no, 1 = yes.
The initial model also included the following variables, which were removed according to a backward elimination procedure: diabetes,
leultoaraiosis, tapping (no. of inhibition errors; reaction time to multiple stimuli), Hamilton cluster 1, three words-three shapes (incidental;
attempts).
95
V. PaJombo et al.
perfonned only to test associations, not cause-effect
relationships. Eleven variables were included in the
initial model: diabetes, lacunes, leukoaraiosis, tapping
(number of inhibition errors and number of attentional
errors), reaction time to multiple stimuli, three wordsthree pictures (incidental and attempts) and Hamilton
rating scale (total score, cluster 1 and cluster 2). After a
backward elimination procedure, only lacunes and
three psychometric tests—tapping (number of attentional errors), Hamilton cluster 2 and Hamilton total
score—remained significantly associated with hypertension.
When a similar analysis was perfonned without
lacunes and leukoaraiosis in the initial model, the same
three psychometric tests remained significandy associated with hypertension.
Discussion
The relationship between hypertension and psychomotor impairment in elderly people has been
addressed in several studies with conflicting results
[32]. A significant and progressive cognitive decline
has been reported [7, 8, 20, 33] in elderly hypertensive
patients. Other investigators have shown that older
people with hypertension exhibit only subtle changes
in psychomotor performance [34, 35] or that such an
impairment is less evident and non-progressive, compared with that in younger people [6, 36-40]. It has
even been suggested that mild hypertension may
prevent age-related decline of psychomotor performance [11, 12].
Several factors may account for these discrepancies
[35]. Studies have used different selection criteria and
sample characteristics, such as age, gender, education,
health habits, medical disorders, neurological disorders
or psychopathology; others are related to hypertension
characteristics, such as blood pressure levels, duration,
target organ damage and treatment. Moreover, the
methods used for neuropsychological evaluation have
varied widely, making a comparison of results difficult.
In the present study strict selection criteria were
used. Participants were self-sufficient and cognitively
competent, randomly selected from the general
population; medical, neurological or psychiatric disorders were excluded; psychometric evaluation was
carried out in standard conditions, with a battery of
tests validated in elderly people. Age, gender, educational level and drug treatment were also excluded as
confounding variables.
Our results show that hypertension does not
interfere with the structure of memory (long-term
storage and retrieval are unaffected) or with the
abilities of abstraction and judgement. On the contrary,
attentional abilities are clearly impaired in hypertensive
patients compared with normotensive subjects, as
shown by the higher number of inhibition and
96
attentional errors on the tapping test and from the
worse scores in incidental memory (which is strictly
dependent on attention).
The association found in previous studies between
hypertension and poor performance in psychomotor
tests might have been due to changes in mental activity
variables (attention, arousal, activity rate), radier than
to a true impairment of intellectual function (receptivity, thinking, memory, expressiveness). The presence
of low-level deficits (e.g. in attention) needs to be
taken into account when interpreting performance in
higher level tasks, such as diose involving memory
[41].
Unfortunately, few studies have followed a hierarchical approach to psychomotor testing, so that the
interpretation of results is often difficult [42].
Why is cognitive function disturbed in essential
hypertension? Some suggest that a hypertensionrelated reduction in cerebral blood flow or dysfunctions in autoregulatory mechanisms might adversely
affect neuropsychological functioning [13, 14, 43].
According to other studies neurochemical alterations
in prefrontal, limbic or hypodialamic regions could be
responsible for both die development of hypertension
and the impairment of a variety of neuropsychological
functions [15, 16]. Finally, according to Kuusisto et al.
[33], hyperinsulinaemia seems to identify a subgroup
of hypertensive subjects with a particularly poor
performance in neuropsychological tests requiring
complex cognition, such as semantic memory, problem solving and abstraction.
The role played by silent cerebral lesions is another
unresolved question. The prevalence of lacunar brain
infarcts, caused by occlusion of perforating arteries,
and of white matter hypodensities, associated with
ischaemia in deep watershed areas, is higher in
hypertensive subjects tiian in normotensive people of
die same age [17, 44]. However, the clinical significance of these tomographic findings remains unclean
some authors report diat in elderly subjects diey are
associated with neuropsychological deficits [18, 20,
45, 46], while others have failed to find any relationship between white matter changes and cognitive
abnormalities [19, 47-50].
In our study the prevalence of subclinical lesions in
CT scan was found to be higher in hypertensive
patients. However, in multivariate analysis, which
included tomographic findings, psychometric tests
remained significantly associated widi hypertension,
suggesting diat cognitive impairment is linked to high
blood pressure independendy of the presence of
cerebral lesions. This in turn might indicate diat such
an impairment is functional and reversible rather than
structural and progressive. The lack of correlation of
die changes in psychomotor performance widi die
duration and severity of hypertension would be in
agreement widi die functional hypodiesis [5,37, 38, 51].
In diis perspective, depressed mood could play a
Blood pressure and cognitivity in the elderly
relevant role. Depression is a frequent finding in
hypertension and it may be associated with an
impairment of cognitive function [2, 35, 37, 52-54].
It could therefore be the primary determinant of the
attentional impairment and related incidental memory
defects and of the slower psychomotor reaction, as
illustrated by our hypertensive patients. The significant
relationship found between depression scores and
other psychometric tests is in agreement with this
hypothesis.
The functional nature of cognitive impairment in
hypertension suggests that an improvement may be
achieved with adequate control of blood pressure,
provided that the drugs used do not interfere with
psychomotor performance [10, 55].
Key points
• Hypertension in older people does not affect longterm memory or abstraction/judgement ability.
• Hypertension is associated with depression and
defects in attention and incidental memory.
• The cognitive impairment associated with depression is independent of the presence of cerebral
lesions.
References
1. Forette F, Boiler F. Hypertension and the risk of dementia
in the elderly. Am J Med 1991; 90 (Suppl. 3A): 14S.
2. Waldestein SR, Manuck SB, Ryan CM, Parkinson DK,
Bromet FJ. Learning and memory function in men with
untreated blood pressure elevation. J Consult Clin Psychol
1991; 59: 513.
11. Obrist WD. Cerebral ischemia and the senescent
electroencephalogram. In: Simonson E, McGavack TH, eds.
Cerebral Ischemia. Springfield, IL Charles C. Thomas, 1964; 71.
12. Wang HS, Busse EW. Heart disease and brain impairment
among aged persons, hi: Palmore E, ed. Normal Ageing n.
Durham, NC: Duke University Press, 1974: 132.
13. Rodriguez G, Arvigo F, Marenco S, Nobili F, Romano P,
Sandini G, et al. Regional cerebral blood flow in essential
hypertension. Data evaluation by a mapping system. Stroke
1987; 18: 13.
14. Baumbach GL, Heistad DD. Cerebral circulation in
chronic arterial hypertension. Hypertension 1988; 12: 89.
15. Brody MJ, O'Neill TP, Porter JR Role of central catecholaminergic systems in pathogenesis and treatment of hypertension. J Cardiovasc Pharmacol 1984; 9 (SuppL 5): 727.
16. Kruglikov RI. Basic trends in research into the neurochemical mechanisms of learning and memory. Neurosci
BehavPhysiol 1987; 17: 192.
17. Steigard A, Hachinski VC, Lau C. Cognitive and
neurologic findings in subjects •with diffuse white matter
lucencies on computed tomographic scan (leuko-araiosis).
Arch Neurol 1987; 44: 32.
18. Kobari M, Meyer JS, Ichijo M. Leukoaraiosis: correlation
of MR and CT findings with blood flow, atrophy and
cognition. Am J Neuroradiol 1990; 11: 274.
19. Schmidt R, Fazekas F, Offenbacher H. Magnetic resonance imaging white matter lesions and cognitive impairment in hypertensive individuals. Arch Neurol 1991; 48: 417.
20. Van Swieten JC, Geyskes GG, Derix MMA, Peeck BM,
Ramos LMP, Van Latum JC, et al. Hypertension in the elderly is
associated with white matter lesions and cognitive decline.
Ann Neurol 1991; 30: 825.
21. Folstein MF, Folstein SE, McHugh PR. 'Mini Mental State':
a practical method for grading the cognitive state of patients
for the clinician. J Psychiatr Res 1975; 12: 189.
3. Shapiro AP, Miller RE, King HE, Ginchereau EH, Fitzgibbon
K. Behavioural consequences of mild hypertension. Hypertension 1982; 4: 355.
22. American Psychiatric Association. DSM-m-R Diagnostic
and Statistical Manual of Mental Disorders, 3rd ed, revised.
Washington, DC: American Psychiatric Association, 1987.
4. light K. Slowing of response time in young and middle
aged hypertensive patients. Exp Aging Res 1975; 1: 209-
23. Wechsler D. Manual for the Wechsler Adult Intelligence
Scale. New York: The Psychological Corporations, 1955.
5. Franceschi M, Tancredi O, Smirne S, Merdnelli A, Canal N.
Cognitive processes in hypertension. Hypertension 1992; 4:
226.
24. Matarazzo JD. Wechsler's Measurement and Appraisal of
Adult Intelligence, 5th ed. Baltimore: Williams & Wilkins,
1972.
6. Pentz C, Elias M, Wood W, Schultz N, Dineen J. Relationship of age and hypertension to neuropsychological test
performance. Exp Aging Res 1979; 5: 351.
25. Spinnler H, Tognoni G. Standardizzazione e taratura
italiana di tests neuropsicologici. Ital J Neurol Sci 1987;
Suppl. 8; 6.
7. Wilkie N, Eisdorfer C. Intelligence and blood pressure in
the aged. Science 1971; 172: 959.
26. Spreen O, Benton AL. Neurosensory Center Comprehensive Examination for Aphasia. Neuropsychological
Laboratory, Department of Psychology, University of Victoria,
Victoria, BC, Canada, 1969.
8. Wilkie F, Eisdorfer C, Nowiin J. Memory and blood
pressure in the aged. Exp Aging Res 1976; 2: 39. Starr JM, Whalley LJ, Inch S, Shering PA- Blood pressure
and cognitive function in healthy old people. J Am Geriatric
Soc 1993; 41: 75310. Starr JM, Whalley LJ. Senile hypertension and cognitive
impairment: an overview. J Hypertens 1992; 10 (Suppl. 2):
S31.
27. Marsel Mesulam M, Weintraub S. Mental assessment of
young and elderly adults in behavioral neurology. In:
Principles of Behavioural Neurology, Contemporary Neurology Series. Philadelphia; FA Davis Company, 1985.
28. Luria AR. Human Brain and Psychological Processes.
New York: Harper & Row, 1966.
97
V. Palombo et al.
29. Buschke H, Fuld PA. Evaluating storage, retention and
retrieval in disordered memory and learning. Neurology
1974; 24: 1019.
30. Hamilton M. A rating scale for depression. J Neurol
Neurosurg Psychiat I960; 23: 56.
31. Hintze JL. SOLO Statistical System. Los Angeles: BMDP
Statistical Software, 1991.
32. Waldstein SR, Manuck SB, Ryan CM, Muldoon ME
Neuropsychological correlates of hypertension: review and
methodologic considerations. Psychol Bull 1991; 110: 451.
33. Kuusisto J, Koivisto K, Mykkanen L, Helkala EL,
Vanhanen M, Hannlnen T, et al. Essential hypertension and
cognitive function. The role of hyperinsulinemia. Hypertension 1993; 22: 771.
34. Kalra L, Jackson SHD, Swift CG. Review: neuropsychological test performance as an indicator of silent
cerebrovascular disease in elderly hypertensives. Age Ageing
1994; 23: 517.
35. Ellas ME Robbins MA, Shultz NR, Streeten DHP, Elias PK.
Clinical significance of cognitive performance by hypertensive patients. Hypertension 1987; 9: 192.
36. Schultz N, Dineen J, Elias M, Pentz C, Wood W. WAIS
performance for different age groups of hypertensive and
control subjects during the administration of a diuretic.
J Gerontol 1979; 34: 246.
37. Bias MF, Schultz NR, Robbins MA, Elias PK. A longitudinal study of neuropsychological performance by hypertensives and normotensives: a third measurement point.
J Gerontol 1989; 44: 25.
38. Schultz NR, Elias NR, Robbins MF, Streeten DHP, Blakeman N. A longitudinal comparison of hypertensives and
normotensives on the WAIS. Psychol Aging 1989; 4: 496.
39. Battersby C, Hartley K, Fletcher AE, Markowe HJL, Brown
RG, Styles W, et al. Cognitive function in hypertension: a
community based study. J Hum Hypertens 1993; 7: 117.
40. Scherr PA, Hebertle E, Smith LA, Evans DA. Relation of
blood pressure to cognitive function in the elderly. Am J
Epidemiol 1991; 134: 1303.
41. Miller RE, Shapiro AP, King EH, Ginchereau EH, Hosutt
JA. Effect of antihypertensive treatment on the behavioural
consequences of elevated blood pressure. Hypertension
1984; 6: 202.
42. Mayer JS, McClintic KL, Rogers RL, Sims P, Mortel KF.
Aetjological considerations for multi-infarct dementia.
J Neurol Neurosurg Psychiatry 1988; 51: 148943. Mentis MJ, Salerno I, Horwitz B, Grady C, Shapiro MB,
98
Murphy DG, et al. Reduction of functional neuronal
connectivity in long-term treated hypertension. Stroke
1994; 25: 601.
44. Van Swieten JC, Van Den Hout JHW, Van Ketel BA,
Hijdra A, Wokke JHJ, Van Gijn J. Periventricular lesions in the
white matter on magnetic resonance imaging in the elderly.
Brain 1991; 114: 761.
45. Boone KB, Miller BL, Lesser IH, Mehringer CM, HillGutierrez E, Goldberg MA, et al. Neuropsychological
correlates of white-matter lesions in healthy elderly subjects.
A threshold effect. Arch Neurol 1992; 49: 549.
46. Austrom MG, Thompson RF, Hendrie HC. Foci of
increased T2 signal intensity in MRI images of healthy elderly
subjects: a follow-up study. J Am Ger Soc 1990; 38: 1133.
47. Bernardin LJ, Rao SM, Haughton VM, Yetkin ZF,
Ellington LE. The neuropsychological significance of leukoaraiosis in a hypertensive population. J Clin Exp Neuropsychol
1991; 13: 78.
48. Fein G, Van Dyke C, Davenport L. Preservation on
normal cognitive functioning in elderly subjects with
extensive white-matter lesions of long duration. Arch Gen
Psychiatry 1990; 47: 220.
49. George AE, De Leon MJ, Gentes CI. Leukoencephalopathy in normal and pathologic aging, I: CT of brain
lucencies. Am J Neuroradiol 1986; 7: 561.
50. Rao SM, Mittenberg W, Bernardin L, Haughton V, Leo GJ.
Neuropsychological test findings in subjects with leukoaraiosis. Arch Neurol 1989; 46: 40.
51. Mazzucchi A, Mutti A, Poletti A, Ravanetti C, Novarini A,
Parma M. Neuropsychological deficits in arterial hypertension. Acta Neurol Scand 1986; 73: 619.
52. Bulpitt CJ, Hoffbrand BI, DoUery CT. Psychological
features of patients with hypertension attending hospital
follow-up clinics. J Psychosom Res 1976; 20: 403.
53. Williams JM, Little MM, Scates S, Blockman N. Memory
complaints and abilities among depressed older adults.
J Consult Clin Psychol 1987; 55: 595.
54. Bias MF, Robbins MA, Schultz NR, Pierce PW. Is blood
pressure an important variable in research on aging and
neuropsychological test performance? J Gerontol 1990; 45:
128.
55. Muldoon MF, Manuck SB, Shapiro AP, Waldstein SR.
Neurobehavioral effects of antihypertensive medications.
J Hypertens 1991; 9: 549.
Received in revised form 17 June 1996