Clin Auton Res (2003) 13 : 427432 DOI 10.

1007/s10286-003-0124-4

RESEARCH ARTICLE

Stefan Duschek Nathan Weisz Rainer Schandry

Reduced cognitive performance and prolonged reaction time accompany moderate hypotension

Received: 31 October 2002 Accepted: 9 July 2003

S. Duschek Prof. Dr. R. Schandry () Dept. of Psychology Ludwig-Maximilians-Universitt Leopoldstr. 13 80802 Munich, Germany Tel.: +49-89/2180-5176 Fax: +49-89/2180-5233 E-Mail: schandry@psy.uni-muenchen.de N. Weisz Dept. of Psychology Universitt Konstanz Konstanz, Germany

s Abstract The aim of the present study was to investigate the impact of hypotension on attentional and motor performance. Twentysix moderately hypotensive subjects (mean systolic blood pressure = 108.8 mmHg) were compared to 29 normotensive controls (mean systolic blood pressure = 123.5 mmHg). The participants were presented with two standard German tests of attention (Aufmerksamkeits-Belastungs-Test, Test d2; Zahlen-VerbindungsTest, ZVT). Additionally, reaction times to acoustic signals were measured. The hypotensive group showed significantly prolonged reaction times (p = 0.007) as well as reduced performance speed (p = 0.004) and lower concentration capacity (p = 0.014) in the test d2. In the ZVT as well a slightly poorer performance in hypotensives was

observed (p = 0.088). Moreover, significant partial correlations between systolic blood pressure and the performance measures with age as covariate were found (performance speed: r = 0.28; concentration capacity: r = 0.22; reaction time: r = 0.33). A lowered cerebral perfusion in hypotensives and an altered activity of baroreceptors located in the carotid sinus are discussed as possible underlying psychophysiological processes mediating the relationship between blood pressure and cognitive performance. This study is the first to provide empirical evidence for the relation between attentional deficits and even moderately lowered blood pressure. s Key words blood pressure hypotension cognitive performance attention reaction time

Introduction
Hypotension is defined as a systolic blood pressure level (SBP) below 100 mmHg for females and 110 mmHg for males, regardless of the diastolic blood pressure (DBP) [1, 2]. By convention however, the DBP should not exceed 6070 mmHg [3, 4]. Different types of hypotension can be distinguished [3]: primary or essential, secondary (e. g., due to blood loss, shock or medication) and orthostatic hypotension (caused by circulatory problems, when assuming a standing position). The most common form is essential hypotension, a chronic

state of lowered blood pressure, independent of the presence of any other pathological factors. The prevalence of hypotension has to be considered as relatively high with especially younger women being affected (1020 % of the female population between 20 and 40 years of age [5]). Hypotension was found to have caused approximately 4.8 million days of work absence in Western Germany (data from the year 1978), nearly two million more days than hypertension (3.1 million days of work absence) [4]. In contrast to elevated blood pressure hypotension is commonly not regarded as a medical condition. It was even shown that chronically lowered blood pressure might be cardioprotective re-

CAR 124

428

sulting in higher live expectancy compared to normotension and hypertension [6, 7]. Nevertheless, the impact of hypotension on personal well-being and quality of life should not be underestimated. Early studies in the 1920s [8, 9] associated hypotension to neurasthenic symptoms, such as tiredness, weakness, dizziness and a tendency to faint. Contemporary studies reported symptoms like dizziness, headache, lack of appetite, palpitations, reduced drive and concentration, drop in performance, enhanced urge for sleep, cold limbs and problems getting started in the morning (see e. g. [4, 10, 11]). A possible association between hypotension, especially the orthostatic form, and the chronic fatigue syndrome is discussed in the literature (see e. g. [12, 13]). Orthostatic symptoms were reported in a substantial portion of patients suffering from this disease. Furthermore, chronic fatigue syndrome symptoms seem to improve in a subset of patients using therapy directed against orthostatic hypotension [14]. In studies on typical personality traits [15, 16] higher scores in neuroticism and depression were found to be associated with hypotension. In contrast to the large number of studies investigating cognitive performance in hypertension [e. g., 1719], a comparable investigation on hypotensive subjects was lacking until recently. A pioneering study devoted to cognitive deficits in hypotension was presented by Stegagno et al. [20]. Here, a poorer performance of hypotensive subjects (females, mean SBP = 96.0 mmHg) both in a verbal short-term memory test and in a mental arithmetic task as well as prolonged reaction times to acoustic stimuli were observed as compared to normotensive controls. A second study was conducted by Costa et al. [21], also comparing hypotensive (mean SBP = 98.3 mmHg) to normotensive females. In the hypotensive group they found significantly lower scores on two standard German tests measuring attentional performance with a high load on speed of cognitive processing (Aufmerksamkeits-Belastungs-Test, Test d2 [22]; ZahlenVerbindungs-Test, ZVT [23]). As in the Stegagno et al. [20] study, poorer performance in a verbal recognition task was observed. In a recent study from our lab [24], hypotensive subjects (female participants with mean SBP = 101.8 mmHg) performed significantly poorer than controls in a computer test assessing attentional flexibility [25].
Table 1 Gender distribution, age, SBP and DBP in the sample (SD in parentheses) Hypotensives Normotensives Total m male; f female n 26 29 55

In summary, these results can be regarded as a first indication of cognitive deficits related to essential hypotension, especially in the field of attention. The present study aimed at the question whether an impairment in attention processes can also be found in subjects with only mild hypotension. Therefore we assessed subjects with SBP < 115 mmHg using nearly the same tests as Costa et al. [21], comparing the attentional performance of this sample to that in normotensive controls.

Material and methods

s Subjects A total of 55 subjects participated in the study. The gender distribution as well as the means for age, SBP and DBP in the sample are given in Table 1. All of the participants were students at the University of Munich who were recruited through advertisements throughout the campus. Severe physical diseases, psychiatric disorders, and the use of medication affecting the cardiovascular system or psychoactive drugs were defined as exclusion criteria. s Material The Aufmerksamkeits-Belastungs-Test (Test d2) [22] as well as the Zahlen-Verbindungs-Test (ZVT) [23] were applied. Both of these paper-pencil tests are widely in use in the German speaking countries to assess visual selective attention and speed of cognitive processing. Aufmerksamkeits-Belastungs-Test (Test d2) This test consists of a task in which a target stimulus has to be identified among a variety of distracter items. The target stimulus is defined as the letter d with two apostrophe marks each of which may be located above or below the letter. The letters p and q with different numbers of apostrophe marks as well as the letter d with one, three or four apostrophe marks serve as distracters. The stimuli are arranged in 14 rows containing 47 letters each. For each row the subject has 20 seconds to work, then she/he is instructed to immediately move on to the next row. Attentional performance can be quantified as performance speed (total number of processed items), concentration capacity (number of correct responses) and percentage of mistakes. Zahlen-Verbindungs-Test (ZVT) The ZVT is a variant of the Trail Making-Test,the latter being widely used in Anglo-American countries. Numbers from 1 to 90, distributed pseudorandomly on a page, have to be connected sequentially as fast as possible. The test consists of four of these matrices. The time needed to complete each of the matrices is measured and a total score is calculated as the average of the four results.

Gender distribution 1 m, 25 f 10 m, 19 f 11 m, 44 f

Mean age in years 27.77 (8.20) 24.59 (5.12) 26.09 (6.88)

Mean SBP in mmHg 108.77 (4.83) 123.45 (7.61) 116.51 (9.78)

Mean DBP in mmHg 69.50 (4.63) 80.00 (5.85) 75.04 (7.46)

429

Motor reaction task Simple reaction times (RT) to acoustic signals (approx. 60 dB) were measured. Stimulus generation and RT recording were carried out automatically. The subjects were instructed to press a button as quickly as possible after the tone. Each participant completed 15 trials. s Procedure In a screening session, blood pressure was assessed in each of the subjects approximately one week before the actual experiment. It was recorded sphygmomanometically after a resting period of ten minutes.A second blood pressure reading took place a few minutes before the experiment. Based on the mean SBP of these two assessments, participants were assigned to one of the two experimental groups: mean SBP-values below or equal 115 mmHg were regarded as moderately hypotensive, values above 115 mmHg as normotensive. Subjects with SBP above 140 mmHg were classified as hypertensives and therefore excluded from the study. The experiment was conducted as follows: after the Riva-Rocci assessment of blood pressure, the RT task was carried out. Then the test d2 and the ZVT were presented. Throughout the experiment SBP and DBP were recorded continuously using a Finapres BP Monitor, Ohmeda 2300 (for reviews of this method see [26] and [27]). In order to evaluate task-induced changes of BP baseline measurements (rest periods of 10 min) were taken preceding both of the cognitive tests as well as the RT task. s Data analysis To compare the scores on the cognitive tests and the reaction times of hypotensives and controls, a multivariate analysis of variance (MANOVA) was computed.Age and gender were used as covariates in order to control for their effects on performance.Additionally, partial correlations between SBP and the performance measures were calculated over the total sample with age being partialed out. The continuously recorded SBP and DBP were averaged over each of the rest periods and phases of cognitive testing. The resulting means were compared using t-tests for independent samples (hypotensives vs. normotensives).

Fig. 1 SBP in mmHg during the course of the experiment

ing results: in the test d2 performance speed (quantified as the number of processed items) was substantially lower in the hypotensive group (m = 523.23; SD = 64.91) as compared to the normotensive controls (m = 572.69; SD = 67.32; see also Figs. 2a and b). This finding is confirmed by a highly significant difference between the two means (F = 4.97; df = 3; p = 0.004). A similar result was obtained for concentration capacity (number of correct responses), again with hypotensives performing significantly poorer than normotensives (hypotensives: m = 196.42; SD = 44.24; normotensives: m = 221.38; SD = 47.73; F = 3.92; df = 3; p = 0.014). The percentage of
a)

Results
s Blood pressure
Fig. 1 displays the course of SBP throughout the experiment in both the hypotensive and the normotensive sample. The mean SBP turned out to be significantly lower in hypotensives measured at the beginning of the experiment as well as during the execution of each of the cognitive tests and the respective resting phases (all p < 0.05). Similar results were achieved for the DBP. These data confirm that the difference in SBP between hypotensives and normotensive remained almost stable during the entire experiment.

b)

s Cognitive tests
The ANCOVA concerning attentional performance with age and gender being controlled for revealed the followFig. 2 a Test d2: Performance speed. b Test d2: Concentration capacity

430

mistakes in the test d2 differed only to a small extent between the groups (hypotensives: 6.51 %; normotensives: 5.44 %; F = 1.81; df = 3; p = 0.16). In the ZVT, a slightly poorer performance in hypotensives was also observed (normotensives: m = 59.31 s; SD = 12.19 s; hypotensives: m = 62.34 s; SD = 13.55 s). However, this difference reached only a significance level of p < 10 % (F = 2.31; df = 3; p = 0.088).

s Reaction time
The difference between the RTs of the two groups was highly significant (F = 4.49; df = 3; p = 0.007). As displayed in Fig. 3 the mean RT in the hypotensive sample (m = 367.47 ms; SD = 54.75 ms) was far longer than in normotensives (m = 328.07 ms; SD = 30.21 ms).

s Correlations between SBP and the performance measures

The relation between lowered blood pressure and reduced attentional performance is confirmed by substantial correlations between SBP and the performance measures. The calculated partial correlations of SBP to the test d2-measures performance speed and concentration capacity with age being held constant both turned out to be significant (performance speed: r = 0.28; p = 0.022; concentration capacity: r = 0.22; p = 0.045). This was also true for the correlation between SBP and the RTs (r = 0.33; p = 0.005). In contrast to this, no considerable association was found between SBP and either the percentage of mistakes in the test d2 or the ZVT score.

Discussion
The results point towards reduced attentional performance related to arterial hypotension confirming the earlier findings by Stegagno et al. [20] and Costa et al. [21]. Moreover, this study is the first to demonstrate cog-

Fig. 3 Simple motor reaction times

nitive deficits in a group of subjects with only comparatively mild hypotension (systolic blood pressure below 115 mmHg). The test d2 as well as the ZVT were also employed in the Costa et al. [21] study. The results in the test d2 could be replicated almost exactly in our sample. In contrast to this, the significant difference between hypotensive and normotensive subjects in the ZVT found by Costa et al. [21] was only seen as a slight tendency towards poorer performance in hypotensives. This may be due to the different degree of hypotension in the samples of the two studies (mean systolic pressure = 108.8 mmHg in our sample vs. 98.3 mmHg in Costa et al. [21]). Furthermore, it seems interesting to look at the attentional deficits from a taxonomic point of view. In most of the common neuropsychological theories, attention is not regarded as a single cognitive function. Based on numerous experimental studies generally at least four distinct components of attention are distinguished, which can be assigned to different neuronal systems (see e. g. [28, 29]): general alertness (arousal), selective or focused attention, divided attention and sustained attention. The prolonged simple RTs in hypotensives primarily refer to the component of alertness. They reflect a reduced general state of vigilance as well as decreased readiness to respond to significant environmental stimuli. The test d2 requires attention focused on one class of relevant stimuli to the exclusion of irrelevant (distracter) stimuli, and thus has a high load on selective attention. The results of the experiment point towards a possible blood pressure-related deficit in this area. In their theory of attention, van Zomeren and Brouwer [29] proposed two key features of attention: intensity and selectivity. While alertness and sustained attention primarily refer to the aspect of intensity, tasks involving focused or divided attention relate to the dimension of selectivity. The reduced performance of hypotensives in the alertness component as well as in selective attention indicates an impairment related to both of these aspects. Thus, the attentional deficits in hypotension seem to exceed a simple reduction of general arousal. The components of sustained and divided attention have not yet been specifically assessed in hypotensives.According to subjectively described daily experiences of many hypotensives, especially sustained attention is thought to be strongly affected and therefore would surely be worth investigating at a quantitative level. Nevertheless, one problem concerning the interpretation of our results is that both of the cognitive tests we used have a certain load on motor speed. The extent to which the poorer performance of hypotensives is due to possible deficits in fine motor functions can not be determined based on the studies presented to date. Tests assessing specific processes of attention which put less emphasis on motor speed have to be employed.

431

Even if the studies presented to date clearly support the hypothesis of reduced cognitive or psychomotor performance in hypotension, the experimental designs used do not allow definite inferences of causality. The psychophysiological processes mediating the relationship between blood-pressure and performance remain a matter of speculation. One hypothesis is that hypotension is accompanied by a lowered cerebral perfusion and a reduced metabolic rate. This explanation is not at all trivial insofar as cerebral autoregulation keeps the blood flow constant within wide range of arterial pressure [30, 31]. Possible disturbances of autoregulatory processes in essential hypotension have not been investigated so far. A second possible explanation includes an altered activity of baroreceptors in hypotension. Baroreceptors in the carotid sinus are primarily engaged in the regulation of arterial blood pressure. It was shown that in hypotension the threshold for baroreceptor activity is reduced, thus, stabilizing blood pressure at a lower level [32]. Additionally, baroreceptors play a major role in mediating cardiovascular influences on brain activity: their excitation and inhibition are known to have modulating effects on cortical activation with increased receptor activity being related to reduced cortical arousal [33, 34]. Assuming a hypersensitivity of the baroreceptors to increasing blood-pressure in hypotensives, the resulting receptor-hyperactivity could lead to a generally reduced

level of cortical arousal explaining the prolonged reaction times and poorer performance in cognitive tasks. Another putative explanation for our results is that reduced personal well-being in hypotensives affects their cognitive performance. Studies on orthostatic hypotension [35] as well as on the essential form [4, 10, 11] reported subjective symptoms of a considerable degree. This potential confound was not controlled in our study. A number of studies concerned with elevated blood pressure also showed reduced performance in various cognitive and psychomotor tests [1719]. Taking the results from these studies on hypertension together with our findings, an inverted U-shaped relationship between blood pressure and cognitive function may be hypothesized with a presumably optimal performance at the normotensive level (c. f. [21]). This resembles the inverted U-shaped relationship between arousal and cognitive performance as formulated in the so-called Yerkes-Dodson-Law [36, 37]. In both cases the mediating physiological process could be the sympathetic tonus. However, to substantiate this assumption, studies manipulating sympathetic outflow, for example through pharmacological interventions, would be necessary.
s Acknowledgment The authors would like to thank Barbara Wiese and Michael Kleinhenz for their assistance during data collection. We are also grateful to Julia Knig for help with the translation of the manuscript into English.

References
1. World Health Organization (1978) Arterial hypertension (Technical Report Series No. 628). Author, Geneva 2. Brschneider M (1996) Kleines Diagnostikon Differentialdiagnose klinischer Symptome. Berlin, de Gruyter 3. Pschyrembel (1990) Klinisches Wrterbuch. Berlin, de Gruyter 4. Wei B, Donat K (1982) Arterielle Hypotonie. Fortschritte der Medizin 30:13961399 5. Baenkler HW, Fritze D, Fel HS (1999) Innere Medizin. Thieme, Stuttgart 6. Pilgrim JA (1994) Psychological aspects of high and low blood pressure. Psychol Med 24:924 7. Swales J (1979) Clinical Hypertension. London, Chapman & Hall 8388 8. Dally J (1928) Low Blood Pressure: Its Causes and Consequences. London, Heinemann 9. Friedlander A (1927) Hypotension. Med 6:143339 10. Heidemann BM (1988) Der hypotone Symptomenkomplex Ein typisches Krankheitsbild der Allgemeinpraxis. Frankfurt a. M., Haag & Herchen 11. Wessely S, Nickson J, Cox B (1990) Symptoms of low blood pressure: a population study. Br Med J 301: 362365 12. Wessely S (1995) Is neurally mediated hypotension an unrecognised cause of chronic fatigue? Lancet 345 (8957): 11121113 13. Streeten DH, Anderson GH (1998) The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res 8 (2):119124 14. Bou-Holaigah I, Rowe PC, Kan J, Calkins H (1995) The relationship between neurally mediated hypotension and the chronic fatigue syndrome. J Am Med Assoc 274 (12):961967 15. Davies M (1970) Blood pressure and personality. J Psychosom Res 14: 89104 16. Schalling D, Svensson J (1984) Blood pressure and personality. Personality and Individual Differences 5:4151 17. Blumental JA, Madden DJ, Pierce TW, Siegel W, Appelbaum M (1993) Hypertension affects neurobehavioral functioning. Psychosom Med 55:4450 18. Shapiro D, Miller RE, King HE, Ginchereau EH, Fitzgibbon K (1982) Behavioral consequences of mild hypertension. Hypertension 4:355360 19. Waldstein SR, Ryan CM, Manuck SB, Parkinson DK, Bromet EJ (1991) Learning and memory function in men with untreated blood pressure elevation. J Consult Clin Psychol 59: 513517 20. Stegagno L, Angrilli A, Costa M, Palomba D (1996) Deficit cognitivi e ipotensione arteriosa: Unindagine cronopsicofisiologica. Giornale Italiano di Psicologia 23:837859 21. Costa M, Stegagno L, Schandry R, Bitti PER (1998) Contingent negative variation and cognitive performance in hypotension. Psychophysiol 35:737744 22. Brickenkamp R (1994) Test d2, Aufmerksamkeits-Belastung-Test. Gttingen, Hofgrefe 23. Oswald WD, Roth E (1987) Der Zahlen-Verbindungs-Test (ZVT) Ein sprachfreier Intelligenz-Test zur Messung der kognitiven Leistungsgeschwindigkeit. Gttingen, Hofgrefe

432

24. Weisz N, Schandry R, Jacobs A, Mialet J, Duschek S (2002) Early contingent negative variation of the EEG and attentional flexibility are reduced in hypotension. Intern J Psychophysiol 45(3):253260 25. Mialet JP, Jacobs A, Bisserbe JC (1995) Computerized attentional and cognitive efficiency battery: preliminary results. European Journal of psychological assessment 11 (suppl. 1):111 26. Molhoek PG, Wesseling KH, Arntzenius AC, Settels JJM, van Vollenhoven E, Weeda H, de Wit B (1983) Initial results of noninvasive measurement of finger blood pressure according to Penaz. Automedica 4(4):241246 27. Pickering TG, Blank SG (1989) The measurement of blood pressure. In: Schneiderman N, Weiss SM, Kaufman P (eds) Handbook of Research Methods in Cardiovascular Behavioral Medicine. New York, Plenum, pp 6979

28. Posner MI, Rafal RD (1987) Cognitive theories of attention and the rehabilitation of attentional deficits. In: Meier MJ, Benton AL, Diller L (eds) Neuropsychological Rehabilitation. Edinburgh, Churchill Livingston, pp 182201 29. Van Zomeren AH, Brouwer WH (1994) Clinical neuropsychology of Attention. New York, Oxford University Press 30. Paulson OB, Waldemar G, Schmidt JF, Strandgaart S (1989) Cerebral circulation under normal and pathologic conditions. The American Journal of Cardiology 63:2c5c 31. Novak V, Novak P, Spies JM, Low PA (1998) Autoregulation of cerebral blood flow in orthostatic hypotension. Stroke 29:104111 32. Dembowsky K, Seller H (1995) Arterial baroreceptor reflexes. In: Vaitl D, Schandry R (eds) From the Heart to the Brain: the Psychophysiology of Circulation-Brain Interaction. Frankfurt a. M., Peter Lang, pp 3560

33. Lacey BC, Lacey JI (1980) Cognitive modulation of time-dependent primary bradycardia. Psychophysiol 17: 209221 34. Lacey JI (1992) The visceral systems in psychology. In: Koch S, Leary DE (eds) A Century of Psychology as Science. 2nd edition. Washington DC., American Psychological Association, pp 721736 35. Mathias CJ, Mallipeddi R, BleasdaleBarr K (1999) Symptoms associated with orthostatic hypotension in pure autonomic failure and multiple system atrophy. J Neurol 246:893898 36. Yerkes RM, Dodson JD (1908) The relation of strength of stimulus to rapidity of habit-formation. J Comparative and Neurological Psychol 18:459482 37. McClelland D (1995) Human Motivation. Cambridge, University Press

Reproduced with permission of the copyright owner. Further reproduction prohibited without permission.