Postural hypotension and mental function in the elderly MARTIN G. MYERS,* MD, FRCP[C]; PATRICIA M. KEARNS, M SC N. RALPH SHEDLETSKY, PH D. ANTHONY A. LYSAK, BA; RORY H. FISHER, MB, FRCP[C]
The effect of 3 hours of ambulatory activity on the mental function of 12 elderly persons with postural hypotension was examined. There was little difference between the mean combined mental status and set test scores when the subjects were supine (42.3) and when they were erect after 3 hours of ambulatory activity (42.2). A control group of persons of similar age and health who did not have hypotension also exhibited little difference in mean scores (49.9 v. 51.5 respectively). The mean scores of the two groups of subjects did not differ significantly. After 6 months the mean scores of the two groups were 40.9 and 44.7 respectively. It appears that elderly individuals with postural hypotension do not exhibit any appreciable deterioration in mental function with ambulation or after a 6-month period. L'effet de 3 heures d'actlvite ambulatoire sur Ia fonction mentale de 12 personnes igees souffrant d'hypotension orthostatique a ete etudie. On a observe peu de difference entre les scores combines moyens pour le test de statut mental et le "set test" que les sujets aient ete couches (42.3) ou debout apres 3 heures d'activite ambulatoire (42.2). Un groupe temoin de personnes de mime Age et de mime sante qui ne souffraient pas d'hypotension montra aussi peu de difference entre les scores moyens (49.9 et 51.5 respectivement). Les scores moyens des deux groupes ne differalent pas significativement. Apres 6 mois les scores moyens des deux groupes etaient de 40.9 et de 44.7 respectivement. II semble que les personnes igees souffrant d'hypotension orthostatique ne presentent aucune deterioration appreciable de Ia fonction mentale pendant Ia marche ou apres une periode de 6 mois.
Postural hypotension is relatively common in the elderly population. About 10% of persons over the age of 65 years exhibit a fall of 30 mm Hg or more in systolic blood pressure From the departments of medicine and psychology, Sunnybrook Medical Centre, Toronto Reprint requests to: Dr. Martin G. Myers, Sunnybrook Medical Centre, 2075 Bayview Ave., Toronto, Ont. M4N 3M5
on arising from the supine position.1'2 Various investigators have concentrated on the pathogenesis of this phenomenon in the elderly, directing little attention towards its possible adverse effects on neurologic function. Some evidence favours a relation between postural hypotension and certain disorders of brain function. Gross3'4 has reported that patients with known cerebrovascular disease have a higher frequency of postural hypotension than a matched control group. The converse may also be true, in that elderly individuals with documented postural decreases in blood pressure may have an increased frequency of cerebrovascular disease.1 These findings have been supported by the recent observation that in elderly persons given antihypertensive therapy disturbances in cerebral function may develop in association with relatively low standing blood pressures.3 Although a clear causal relation between postural hypotension and cerebral dysfunction in the elderly remains to be proven, it is possible that these individuals not only may suffer strokes more frequenfly but also may experience decreases in mental function if they stand or sit for relatively long periods. The study described below was therefore undertaken to examine the possible relation between excessive postural falls in blood pressure and changes in mental function in the elderly.
Methods Of 477 residents of a veterans' geriatric unit and domiciliary institution 12 were found during a blood pressure survey to have persistent postural hypotension - a fall in mean blood pressure (diastolic blood pressure plus one third of the difference between the systolic and diastolic pressures) of at least 15 mm Hg on two occasions several weeks apart. In all 12 the standing mean blood pressure was less than 85 mm Hg. The mean blood pressure was studied because it provided the best
measurement of perfusion pressure. The criteria for postural hypotension were arbitrarily selected to provide a reasonable number of severely affected subjects for the study. Blood pressures were recorded with a Hawksley random-zero sphygmomanometer, an instrument that effectively blinds the observer to the pressure readings,6 thus greatly reducing observer bias. Measurements were taken after the subjects had been recumbent for a minimum of 5 minutes in a quiet room and after they had been standing (or sitting, in four instances in which the subject could not stand unsupported) for 2 minutes. A control group of 10 residents who showed no excessive falls in blood pressure and were similar in age and health was selected (Table I). Mental status testing was performed on members of both groups by an experienced examiner (A.A.L.) who was unaware of each individual's blood pressures. Each subject was tested between 8 and 9 am, before arising from bed. The blood pressure was then recorded with the subject in the two positions. The mental status was reassessed after 3 hours of ambulatory activity with the subject sitting or erect; immediately before, the 'blood pressure was again taken with the subject standing. The daily medications of the subjects were continued except for sedatives to be taken at night-time, which were omitted the evening before the study. The mental and intellectual status of each subject was assessed quantitatively by means of the mental status test7 and the set test.8 These tests are particularly sensitive in subjects with confusion, disorientation or memory impairment. For the results to be more comparable, the same questions were asked after 3 hours of activity as during the initial test. The large number of items in the tests and the absence of any positive reinforcement as to the correct answers minimized any learning effect between the two examinations. Furthermore, the con-
trol group was similarly evaluated to determine if a bias in the testing methodology was present. The mental
CMA JOURNAL/NOVEMBER 4, 1978/VOL. 119
1061
status and set test scores were combined to obtain a mental test score for each subject. The significance of changes in the mental test scores before and after ambulation was assessed with the use of Student's paired t-test. Differences between the scores in the two groups were evaluated with the use of Student's unpaired t-test. A one-tail test was used since one would expect the hypotensive subjects' mental function to be poorer. Coefficients of correlation were computed to determine if there was a relation between mean blood pressure and performance during mental testing. Mental status testing was repeated 6 months later in 21 of the 22 subjects; the remaining subject died in the interval.
12) showed little alteration in mental function from early morning. The four individuals who were unable to stand unsupported also did not exhibit intellectual deterioration on the test day. The postural fall in mean blood pressure during the screening period was not significantly correlated with the changes in the mental test scores in the 12 subjects (r = 0.067). Similarly, the postural falls in pressure before and after ambulation correlated poorly with the changes in the mental test scores (r = 0.039 and 0.122 respectively). The mean mental test scores of the 12 subjects with hypotension (42.3 while supine and 42.2 while erect) were lower than the scores in the control group (49.9 and 51.5 respectively) but the differences were not significant (P > 0.1). Results There was a significant correlation The mean blood pressures of the (r = 0.978, P < 0.01) between the two groups are shown in Table II. 22 subjects' mental test scores Although before inclusion in the supine and the scores obtained while hypotensive group all subjects satis- ambulation. Similarly, within theafter hyfied the criteria for postural hypoten- potensive and control groups respectsion, on the day of testing three sub- ively there was a good correlation bejects (nos. 2, 11 and 12) had either tween the mental status and set test an insufficient fall in mean pressure scores for each subject for both the or a mean pressure while erect great- supine (r = 0.901, P < 0.01; r = er than 85 mm Hg. Similarly, at the end of 3 hours of ambulation not all the hypotensive subjects had a mean pressure of less than 85 mm Hg. Of the eight individuals who were fully ambulatory (nos. S to 12), one (no. 10) did not have severe hypotension while erect. Of the subjects who were unable to stand unsupported (nos. 1 to 4), two (nos. 1 and 4) had mean pressures greater than 85 mm Hg. The mean score on the mental tests done initially in the hypotensive group was similar to that on the tests done after 3 hours of sitting and walking (Table I). There did not appear to be any appreciable learning effect associated with repeat testing, since the control group also did not show any significant change (P> 0.1) in mental function after 3 hours of ambulation (Table I). The three subjects who fulfilled the criteria for postural hypotension on all screening and test days (nos. 5, 7 and 8) had comparable mean mental test scores before and after ambulation. Similarly, the five individuals who remained severely hypotensive at the end of the ambulatory period (nos. 5, 7, 8, 11 and 1062 CMA JOURNAL/NOVEMBER 4, 1978/VOL. 119
0.785, P < 0.01) and the erect (r 0.743, P < 0.01; r = 0.819, P < 0.01) positions. Repeat mental status testing at 6 months showed no significant difference (P > 0.1) between the mean mental test scores in the hypotensive group (40.9) and the control group (44.7) while the subjects were supine. At this time the mean blood pressure (± one standard error of the mean) in the hypotensive group fell from 84.6 ± 3.1 mm Hg while the subjects were supine to 63.7 ± 2.6 mm Hg while they were standing. For the control group there was no difference between the mean blood pressure while the subjects were supine (88.6 ± 5.5 mm Hg) and erect (89.2 ± 6.9 mm Hg). Discussion The evidence for a causal relation between postural hypotension and mental dysfunction in the elderly is mainly circumstantial. Several authors have observed disturbances in balance,9 confusion'0'11 and clouding of consciousness" in elderly individuals, but there have been few attempts to quantitate the degree of mental impairment. The possibility that a decrease in
blood flow to the brain may produce cerebral dysfunction in the elderly has been the subject of a recent Lancet editorial.12 which noted that increases in heart rate and cardiac output in older persons with pre-existing heart block may substantially improve cerebral blood flow. Also, persons with a low cardiac output may exhibit electroencephalographic abnormalities that disappear following cardiac pacing. It is conceivable that mental dysfunction may occur when a low systemic blood pressure reduces cerebral blood flow to a critical level. Whether this occurs in clinical situations, especially in elderly persons with postural hypotension, is unknown. In younger individuals Lassen13 and Olesen14 have shown that the mean systemic blood pressure must fall below 60 mm Hg before there is an appreciable decrease in cerebral
blood flow. Since elderly persons are more likely to have stenoses of cerebral vessels both proximally and distally, inadequate regional perfusion may occur with systemic pressures exceeding 60 mm Hg. Hence, regional decreases in cerebral blood flow could be one explanation for the purported high frequency of strokes and other neurologic disturbances in older persons with recurrent postural hypotension. In our study we tried to determine the possible effects of prolonged hypotension on mental function in the elderly. The results suggest that 3 hours of ambulatory activity while the person is hypotensive produces no demonstrable deterioration in intellectual performance. There are at least two possible explanations for these negative findings. It may be that the 3-hour observation period was too short to obtain a clinically detectable change
in mental function. Alternatively, the degree of hypotension may not have been sufficient to reduce cerebral perfusion to a level at which changes in the mental test scores would become apparent. The first possibility is not supported by the results of repeat testing at 6 months in 21 of the 22 subjects. At this time there was no appreciable alteration in the mental test scores even though the mean blood pressure when these individuals were erect remained low. Similarly, if severe hypotension reduces cerebral blood flow to a level at which mental function is impaired, then this highly selected group of individuals with hypotension should have exhibited some deterioration in intellectual performance. The 12 members of the hypotensive group were obtained from a total of 477 elderly persons and therefore represented a severely affected segment of the elderly population with postural hypotension. Two subjects in this group (nos. 3 and 10) had substantially lower mental test scores than the other participants. Although in neither individual had a diagnosis of stroke been made, one cannot exclude the possibility that the low level of intellectual function resulted from permanent brain damage secondary to postural hypotension before entry into the study. The blood pressures of the 12 subjects with hypotension illustrate an interesting aspect of this condition. In spite of documented severe postural falls in blood pressure on two occasions during the screening period, a number of individuals did not always satisfy the criteria for postural hypotension subsequently. Numerous factors, including medication, degree of activity, observer bias and changing disease processes may have influenced the pressure recordings. However, these factors were minimized by the lack of alteration in the subjects' treatment, the restriction of their activity to 2 and at least 5 minutes in the standing and supine positions respectively, and the use of a specially designed sphygmomanometer that reduces observer bias. Changes in disease process were unlikely since none of the participants had a major illness between the time of blood pressure screening and the days of mental testing. Blood pressure often varies from minute to minute, and one could expect fluc-
CMA JOURNAL/NOVEMBER 4, 1978/VOL. 119 1063
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indications Urogenital infections (cystitis, prostatitis, pyelitis end urethritis) and soft tisaue infections, due to sulfonsmide sensitive organisms. Contralndicatlons Sensitivity to sulfonamides. Severe liver damage; pregnancy at term end during the nursing period or in newborn or premature intents during the first few weeks of life. Precautions Perform blood counts during prolonged therapy; discontinue therapy on signs of headache, nausea, vomiting, urticaria, raah, fever or hematurla. With caution in patients with impaired renal or liver function. Adverse reactions Discontinue therapy on the appearance of one or more of the following adverse reactions: * Blood dyscrasias: agranulocytosis, apleatic or hemolytic anemia, thrombocytopenia, hypoprothrombinemia, leukopenia, purpura or methemoglobinemia. * Allergic reactions: generalized skin eruptions, urticaria, pruritus, epidermal necrolysis, erythema multiforme, exfoliative dermatitis or other possible allergic reactions. * Gastrointestinal: nausea, vomiting, abdominal pain, diarrhea, anorexia, pancreatitis, stomatitis or hepatitis. * Central nervous system: headache, ataxia, hallucinationS, vertigo, tinnitus. Dosage Adults: 2 g initially, then 1 g every 12 hours. Children: 50 to 60 mg/kg initially, then 25 to 30 mg/kg every 12 hours. In severe infections, maintenance dose may be given three times daily. Continue therapy for 5 to 7 days or until patient is asymptomatic for 48 hours. Supply Pale green, cylindrical, biplane tablet, ROCHE engraved on one face, cross-scored on other with C in upper right and lower left quadrant; contains suifamethoxazole 500 mg. Bottles of 100 and 500. Cherry flavoured suspension containing sulfamethoxazole -500 mg/5 ml. Bottles of 100 and 400 ml. 'Gantanol' Duplex Pack Containing 28 tablets Gantanol' and 14 tablets Uro Gantanol.
Uro Gantanol®
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indications Urogenital infections (cystitis, prostatitis, pyalitis and urethritis), particularly those where pain exists. Contraindications Sensitivity to sulfonamides or phenazopyridine. Severe liver damage; pregnancy at term and during the nursing period or in newborn or premature infants during the first few weeks of life. Phenazopyridine is contraindicated in glomerular nephritie, pyelonephritis, uremia and severe hepatitis with gastrointestinal disturbances. Precautions Perform blood counts during prolonged therapy; discontinue therapy on signs of headache, nausea, vomiting, urticaria, rash, fever or hematurla. With caution in patients with impaired renal or liver function. Adverse reactions Discontinue therapy on the appearance of one or more of the following adverse reactions: * Blood dyscrasias: agranulocytosis, aplastic or hemolytic anemia, thrombocytopenia, hypoprothrombinemia, leukopenia, purpura or methemoglobinemia. * Allergic reactions: generalized skin eruptions, urticaria, pruritus, epidermal necrolysis, erythema multiforme, exfoliative dermatitis or other possible allergic reactions. * GastroIntestinal: nausea, vomiting, abdominal pain, diarrhea, anorexia, pancreatitis, stomatitis or hepatitis. *Central nervoussystem: headacheataxia, hallucinations, vertigo, tinnitus. Dosage Adults: 4 tablets initially, then 2 tablets every 12 hours. Children (up to 36 kg): 2 tablets per 18 kg body weight initially, then 1 tablet per 18 kg body weight every 12 hours. After relief of pain, continued treatment with Gantanol' may be considered. Note: Phenazopyridine will colour urine orange-red. Supply Red, cylindrical, biconvex, film-coated tablet, engraved Roche II; contains sulfamethoxazole -500 mg, and phenazopyridine HCI -100 mg. Bottles of 100 and 500. Complete prescribing information available on request.
book of Geriatric Medicine and Gertuations in the degree of postural ontology, BROCKLEHURST JC (ed), hypotension in the 12 subjects. Churchill Livingstone, London, 1973, The possible adverse effects of p 137 postural hypotension are of some 11. WOLLNER L, SPALDING JMK: The clinical relevance to the management autonomic nervous system, ibid, p 235 of older patients. Numerous medica- 12. Cardiogenic dementia (E). Lancet 1: 27, 1977 tions that may produce postural falls NA: Cerebral blood flow and in blood pressure are commonly pre- 13. LASSEN oxygen consumption in man. Pliysiol scribed to the elderly; examples inRev 39: 183, 1959 clude phenothiazine tranquillizers, 14. OLESEN J: Quantitative evaluation of normal and pathologic cerebral blood antihypertensive drugs, levodopa and flow regulation to perfusion pressure. vasodilators. If postural hypotension Neurol 28: 143, 1973 alone were sufficient to cause an 15. Arch HACHINSKI VC, LASSEN NA, MARacute deterioration in mental funcSHALL J: Multi-infarct dementia: a tion, then it would be potentially cause of mental deterioration in the elderly. Lancet 2: 207, 1974 harmful to treat any older patient with these drugs. The above data do not support this belief and instead suggest that a low ambulatory blood pressure is not likely to produce a permanent loss of intellectual function, at least not during a 6-month observation period. None the less, it continued from page 1043 is conceivable that a longer period of CELL RECEPTOR DISORDERS. Theodore hypotension could result in recurrent Melnechuk. Based on a workshop held on March 3-5, 1977, planned and cochaired strokes or multi-infarct dementia,15 with Jon N. Lindstrom, Floyd E. Bloom with a worsening of mental perfor- and John D. Baster. Written with the mance. Care should therefore be aid of notes taken by 12 graduate stuscribes. Revised and updated by taken to ensure that long-term drug dent workshop speakers in March and April, therapy in the elderly is not accom- 1978. 215 pp. lIlust. Western Behavioral panied by chronic postural hypoten- Sciences Institute, La Jolla, California, 1978. $10, paperbound sion. DRUGS OF CHOICE 1978-1979. Edited Dr. Myers is the recepient of a senior by Walter MadeIl. 824 pp. Illust. The research fellowship from the Ontario C.V. Mosby Company, Saint Louis, Missouri, 1978. $35.75. ISBN 0-8016-3442-3 Heart Foundation.
BOOKS
References 1. JOHNSON RH, SMITH AC, SPALDING
JMK, Ct al: Effect of posture on blood-pressure in the elderly. Lancet 1: 731, 1965 2. CAIRD Fl, ANDREWS GR, KENNEDY RD: Effect of posture on blood pressure in the elderly. Br Heart J 35: 527, 1973 3. GRoss M: The effect of posture on subjects with cerebrovascular disease. Q J Med 39: 485, 1970 4. Idem: Circulatory reflexes in cerebral ischaemia involving different vascular territories. Clin Sci Mci Med 38: 491, 1970 5. JACKSON G, PIERsCIANOWSKI TA, MAHON W, et al: Inappropriate antihypertensive therapy in the elderly.
Lancet 2: 1317, 1976 6. WRIGHT BM, DORE CF: A randomzero sphygmomanometer. Lancet 1: 337, 1970 7. HoDIuNsoN HM: Mental impairment
in the elderly. J R Coil Physicians Lend 7: 305, 1973 8. IsAACs B, AKHTAR AJ: The set test: a rapid test of mental function in old people. Age Ageing 1: 222, 1972 9. Postural hypotension in the elderly
(E). Br Med J 4: 246, 1973 mann-La Roche Limited Vaudreull,Qu6bec J7V 6B3
®Reg. Trade Mark
10. CAIRD Fl, DALL JLC: The significance of heart disease in old age, in Text-
HEALTH IMPLICATIONS OF NUCLEAR POWER PRODUCTION. Report of a Working Group. Brussels, 1-5 December 1975. WHO Regional Publications European series no 3. 75 pp. Illust. World Health Organization, Regional Office for Europe, Copenhagen, 1978. $4, paperbound. ISBN 92-9020-103-7 MANUAL OF NEUROLOGIC THERAPEUTICS WITH ESSENTIALS OF DIAGNOSIS. Edited by Martin A. Samuals. 436 pp. Illust. Little, Brown and Company, Boston, 1978. $12.50, spiralbound. ISBN 0-31676990-8 MEDICAL COMPUTING SERIES. Vol 2. Computers for the Physician's Office. Joan Zimmerman and Alan Rector. Edited by D.W. Hill. 305 pp. Research Studies Press, Forest Grove, Oregon, 1978. Price not stated. ISBN 0-89355-007-8 NUTRITION IN THE CLINICAL MANAGEMENT OF DISEASE. Edited by John W.T. Dickerson and H.A. Lee. 409 pp. IIlust. Edward Arnold (Publishers) Ltd., London; Year Book Medical Publishers, Inc., Chicago, 1978. Price not stated. ISBN 0-8151-2451-1 PROCEEDINGS OF THE JAMES C. KIMBROUGH UROLOGICAL SEMINAR. Vol 11, 25th Annual Meeting, 6-11 November 1977, Denver, Colorado. Edited by H.G. Stevenson and S. Christian. 344 pp. Norwich-Eaton Pharmaceuticals, Norwich, New York, 1978. $10, paperbound
continued on page 1076
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The effect of 3 hours of ambulatory activity on the mental function of 12 elderly persons with postural hypotension was examined. There was little difference between the mean combined mental status and set test scores when the subjects were supine (42.3) and when they were erect after 3 hours of ambulatory activity (42.2). A control group of persons of similar age and health who did not have hypotension also exhibited little difference in mean scores (49.9 v. 51.5 respectively). The mean scores of the two groups of subjects did not differ significantly. After 6 months the mean scores of the two groups were 40.9 and 44.7 respectively. It appears that elderly individuals with postural hypotension do not exhibit any appreciable deterioration in mental function with ambulation or after a 6-month period. L'effet de 3 heures d'actlvite ambulatoire sur Ia fonction mentale de 12 personnes igees souffrant d'hypotension orthostatique a ete etudie. On a observe peu de difference entre les scores combines moyens pour le test de statut mental et le "set test" que les sujets aient ete couches (42.3) ou debout apres 3 heures d'activite ambulatoire (42.2). Un groupe temoin de personnes de mime Age et de mime sante qui ne souffraient pas d'hypotension montra aussi peu de difference entre les scores moyens (49.9 et 51.5 respectivement). Les scores moyens des deux groupes ne differalent pas significativement. Apres 6 mois les scores moyens des deux groupes etaient de 40.9 et de 44.7 respectivement. II semble que les personnes igees souffrant d'hypotension orthostatique ne presentent aucune deterioration appreciable de Ia fonction mentale pendant Ia marche ou apres une periode de 6 mois.
Postural hypotension is relatively common in the elderly population. About 10% of persons over the age of 65 years exhibit a fall of 30 mm Hg or more in systolic blood pressure From the departments of medicine and psychology, Sunnybrook Medical Centre, Toronto Reprint requests to: Dr. Martin G. Myers, Sunnybrook Medical Centre, 2075 Bayview Ave., Toronto, Ont. M4N 3M5
on arising from the supine position.1'2 Various investigators have concentrated on the pathogenesis of this phenomenon in the elderly, directing little attention towards its possible adverse effects on neurologic function. Some evidence favours a relation between postural hypotension and certain disorders of brain function. Gross3'4 has reported that patients with known cerebrovascular disease have a higher frequency of postural hypotension than a matched control group. The converse may also be true, in that elderly individuals with documented postural decreases in blood pressure may have an increased frequency of cerebrovascular disease.1 These findings have been supported by the recent observation that in elderly persons given antihypertensive therapy disturbances in cerebral function may develop in association with relatively low standing blood pressures.3 Although a clear causal relation between postural hypotension and cerebral dysfunction in the elderly remains to be proven, it is possible that these individuals not only may suffer strokes more frequenfly but also may experience decreases in mental function if they stand or sit for relatively long periods. The study described below was therefore undertaken to examine the possible relation between excessive postural falls in blood pressure and changes in mental function in the elderly.
Methods Of 477 residents of a veterans' geriatric unit and domiciliary institution 12 were found during a blood pressure survey to have persistent postural hypotension - a fall in mean blood pressure (diastolic blood pressure plus one third of the difference between the systolic and diastolic pressures) of at least 15 mm Hg on two occasions several weeks apart. In all 12 the standing mean blood pressure was less than 85 mm Hg. The mean blood pressure was studied because it provided the best
measurement of perfusion pressure. The criteria for postural hypotension were arbitrarily selected to provide a reasonable number of severely affected subjects for the study. Blood pressures were recorded with a Hawksley random-zero sphygmomanometer, an instrument that effectively blinds the observer to the pressure readings,6 thus greatly reducing observer bias. Measurements were taken after the subjects had been recumbent for a minimum of 5 minutes in a quiet room and after they had been standing (or sitting, in four instances in which the subject could not stand unsupported) for 2 minutes. A control group of 10 residents who showed no excessive falls in blood pressure and were similar in age and health was selected (Table I). Mental status testing was performed on members of both groups by an experienced examiner (A.A.L.) who was unaware of each individual's blood pressures. Each subject was tested between 8 and 9 am, before arising from bed. The blood pressure was then recorded with the subject in the two positions. The mental status was reassessed after 3 hours of ambulatory activity with the subject sitting or erect; immediately before, the 'blood pressure was again taken with the subject standing. The daily medications of the subjects were continued except for sedatives to be taken at night-time, which were omitted the evening before the study. The mental and intellectual status of each subject was assessed quantitatively by means of the mental status test7 and the set test.8 These tests are particularly sensitive in subjects with confusion, disorientation or memory impairment. For the results to be more comparable, the same questions were asked after 3 hours of activity as during the initial test. The large number of items in the tests and the absence of any positive reinforcement as to the correct answers minimized any learning effect between the two examinations. Furthermore, the con-
trol group was similarly evaluated to determine if a bias in the testing methodology was present. The mental
CMA JOURNAL/NOVEMBER 4, 1978/VOL. 119
1061
status and set test scores were combined to obtain a mental test score for each subject. The significance of changes in the mental test scores before and after ambulation was assessed with the use of Student's paired t-test. Differences between the scores in the two groups were evaluated with the use of Student's unpaired t-test. A one-tail test was used since one would expect the hypotensive subjects' mental function to be poorer. Coefficients of correlation were computed to determine if there was a relation between mean blood pressure and performance during mental testing. Mental status testing was repeated 6 months later in 21 of the 22 subjects; the remaining subject died in the interval.
12) showed little alteration in mental function from early morning. The four individuals who were unable to stand unsupported also did not exhibit intellectual deterioration on the test day. The postural fall in mean blood pressure during the screening period was not significantly correlated with the changes in the mental test scores in the 12 subjects (r = 0.067). Similarly, the postural falls in pressure before and after ambulation correlated poorly with the changes in the mental test scores (r = 0.039 and 0.122 respectively). The mean mental test scores of the 12 subjects with hypotension (42.3 while supine and 42.2 while erect) were lower than the scores in the control group (49.9 and 51.5 respectively) but the differences were not significant (P > 0.1). Results There was a significant correlation The mean blood pressures of the (r = 0.978, P < 0.01) between the two groups are shown in Table II. 22 subjects' mental test scores Although before inclusion in the supine and the scores obtained while hypotensive group all subjects satis- ambulation. Similarly, within theafter hyfied the criteria for postural hypoten- potensive and control groups respectsion, on the day of testing three sub- ively there was a good correlation bejects (nos. 2, 11 and 12) had either tween the mental status and set test an insufficient fall in mean pressure scores for each subject for both the or a mean pressure while erect great- supine (r = 0.901, P < 0.01; r = er than 85 mm Hg. Similarly, at the end of 3 hours of ambulation not all the hypotensive subjects had a mean pressure of less than 85 mm Hg. Of the eight individuals who were fully ambulatory (nos. S to 12), one (no. 10) did not have severe hypotension while erect. Of the subjects who were unable to stand unsupported (nos. 1 to 4), two (nos. 1 and 4) had mean pressures greater than 85 mm Hg. The mean score on the mental tests done initially in the hypotensive group was similar to that on the tests done after 3 hours of sitting and walking (Table I). There did not appear to be any appreciable learning effect associated with repeat testing, since the control group also did not show any significant change (P> 0.1) in mental function after 3 hours of ambulation (Table I). The three subjects who fulfilled the criteria for postural hypotension on all screening and test days (nos. 5, 7 and 8) had comparable mean mental test scores before and after ambulation. Similarly, the five individuals who remained severely hypotensive at the end of the ambulatory period (nos. 5, 7, 8, 11 and 1062 CMA JOURNAL/NOVEMBER 4, 1978/VOL. 119
0.785, P < 0.01) and the erect (r 0.743, P < 0.01; r = 0.819, P < 0.01) positions. Repeat mental status testing at 6 months showed no significant difference (P > 0.1) between the mean mental test scores in the hypotensive group (40.9) and the control group (44.7) while the subjects were supine. At this time the mean blood pressure (± one standard error of the mean) in the hypotensive group fell from 84.6 ± 3.1 mm Hg while the subjects were supine to 63.7 ± 2.6 mm Hg while they were standing. For the control group there was no difference between the mean blood pressure while the subjects were supine (88.6 ± 5.5 mm Hg) and erect (89.2 ± 6.9 mm Hg). Discussion The evidence for a causal relation between postural hypotension and mental dysfunction in the elderly is mainly circumstantial. Several authors have observed disturbances in balance,9 confusion'0'11 and clouding of consciousness" in elderly individuals, but there have been few attempts to quantitate the degree of mental impairment. The possibility that a decrease in
blood flow to the brain may produce cerebral dysfunction in the elderly has been the subject of a recent Lancet editorial.12 which noted that increases in heart rate and cardiac output in older persons with pre-existing heart block may substantially improve cerebral blood flow. Also, persons with a low cardiac output may exhibit electroencephalographic abnormalities that disappear following cardiac pacing. It is conceivable that mental dysfunction may occur when a low systemic blood pressure reduces cerebral blood flow to a critical level. Whether this occurs in clinical situations, especially in elderly persons with postural hypotension, is unknown. In younger individuals Lassen13 and Olesen14 have shown that the mean systemic blood pressure must fall below 60 mm Hg before there is an appreciable decrease in cerebral
blood flow. Since elderly persons are more likely to have stenoses of cerebral vessels both proximally and distally, inadequate regional perfusion may occur with systemic pressures exceeding 60 mm Hg. Hence, regional decreases in cerebral blood flow could be one explanation for the purported high frequency of strokes and other neurologic disturbances in older persons with recurrent postural hypotension. In our study we tried to determine the possible effects of prolonged hypotension on mental function in the elderly. The results suggest that 3 hours of ambulatory activity while the person is hypotensive produces no demonstrable deterioration in intellectual performance. There are at least two possible explanations for these negative findings. It may be that the 3-hour observation period was too short to obtain a clinically detectable change
in mental function. Alternatively, the degree of hypotension may not have been sufficient to reduce cerebral perfusion to a level at which changes in the mental test scores would become apparent. The first possibility is not supported by the results of repeat testing at 6 months in 21 of the 22 subjects. At this time there was no appreciable alteration in the mental test scores even though the mean blood pressure when these individuals were erect remained low. Similarly, if severe hypotension reduces cerebral blood flow to a level at which mental function is impaired, then this highly selected group of individuals with hypotension should have exhibited some deterioration in intellectual performance. The 12 members of the hypotensive group were obtained from a total of 477 elderly persons and therefore represented a severely affected segment of the elderly population with postural hypotension. Two subjects in this group (nos. 3 and 10) had substantially lower mental test scores than the other participants. Although in neither individual had a diagnosis of stroke been made, one cannot exclude the possibility that the low level of intellectual function resulted from permanent brain damage secondary to postural hypotension before entry into the study. The blood pressures of the 12 subjects with hypotension illustrate an interesting aspect of this condition. In spite of documented severe postural falls in blood pressure on two occasions during the screening period, a number of individuals did not always satisfy the criteria for postural hypotension subsequently. Numerous factors, including medication, degree of activity, observer bias and changing disease processes may have influenced the pressure recordings. However, these factors were minimized by the lack of alteration in the subjects' treatment, the restriction of their activity to 2 and at least 5 minutes in the standing and supine positions respectively, and the use of a specially designed sphygmomanometer that reduces observer bias. Changes in disease process were unlikely since none of the participants had a major illness between the time of blood pressure screening and the days of mental testing. Blood pressure often varies from minute to minute, and one could expect fluc-
CMA JOURNAL/NOVEMBER 4, 1978/VOL. 119 1063
Rx Summary
Gantanol (sulfamethoxezole 'Roche')
indications Urogenital infections (cystitis, prostatitis, pyelitis end urethritis) and soft tisaue infections, due to sulfonsmide sensitive organisms. Contralndicatlons Sensitivity to sulfonamides. Severe liver damage; pregnancy at term end during the nursing period or in newborn or premature intents during the first few weeks of life. Precautions Perform blood counts during prolonged therapy; discontinue therapy on signs of headache, nausea, vomiting, urticaria, raah, fever or hematurla. With caution in patients with impaired renal or liver function. Adverse reactions Discontinue therapy on the appearance of one or more of the following adverse reactions: * Blood dyscrasias: agranulocytosis, apleatic or hemolytic anemia, thrombocytopenia, hypoprothrombinemia, leukopenia, purpura or methemoglobinemia. * Allergic reactions: generalized skin eruptions, urticaria, pruritus, epidermal necrolysis, erythema multiforme, exfoliative dermatitis or other possible allergic reactions. * Gastrointestinal: nausea, vomiting, abdominal pain, diarrhea, anorexia, pancreatitis, stomatitis or hepatitis. * Central nervous system: headache, ataxia, hallucinationS, vertigo, tinnitus. Dosage Adults: 2 g initially, then 1 g every 12 hours. Children: 50 to 60 mg/kg initially, then 25 to 30 mg/kg every 12 hours. In severe infections, maintenance dose may be given three times daily. Continue therapy for 5 to 7 days or until patient is asymptomatic for 48 hours. Supply Pale green, cylindrical, biplane tablet, ROCHE engraved on one face, cross-scored on other with C in upper right and lower left quadrant; contains suifamethoxazole 500 mg. Bottles of 100 and 500. Cherry flavoured suspension containing sulfamethoxazole -500 mg/5 ml. Bottles of 100 and 400 ml. 'Gantanol' Duplex Pack Containing 28 tablets Gantanol' and 14 tablets Uro Gantanol.
Uro Gantanol®
(sulfamethoxazole/phenazopyridine HCI Roche')
indications Urogenital infections (cystitis, prostatitis, pyalitis and urethritis), particularly those where pain exists. Contraindications Sensitivity to sulfonamides or phenazopyridine. Severe liver damage; pregnancy at term and during the nursing period or in newborn or premature infants during the first few weeks of life. Phenazopyridine is contraindicated in glomerular nephritie, pyelonephritis, uremia and severe hepatitis with gastrointestinal disturbances. Precautions Perform blood counts during prolonged therapy; discontinue therapy on signs of headache, nausea, vomiting, urticaria, rash, fever or hematurla. With caution in patients with impaired renal or liver function. Adverse reactions Discontinue therapy on the appearance of one or more of the following adverse reactions: * Blood dyscrasias: agranulocytosis, aplastic or hemolytic anemia, thrombocytopenia, hypoprothrombinemia, leukopenia, purpura or methemoglobinemia. * Allergic reactions: generalized skin eruptions, urticaria, pruritus, epidermal necrolysis, erythema multiforme, exfoliative dermatitis or other possible allergic reactions. * GastroIntestinal: nausea, vomiting, abdominal pain, diarrhea, anorexia, pancreatitis, stomatitis or hepatitis. *Central nervoussystem: headacheataxia, hallucinations, vertigo, tinnitus. Dosage Adults: 4 tablets initially, then 2 tablets every 12 hours. Children (up to 36 kg): 2 tablets per 18 kg body weight initially, then 1 tablet per 18 kg body weight every 12 hours. After relief of pain, continued treatment with Gantanol' may be considered. Note: Phenazopyridine will colour urine orange-red. Supply Red, cylindrical, biconvex, film-coated tablet, engraved Roche II; contains sulfamethoxazole -500 mg, and phenazopyridine HCI -100 mg. Bottles of 100 and 500. Complete prescribing information available on request.
book of Geriatric Medicine and Gertuations in the degree of postural ontology, BROCKLEHURST JC (ed), hypotension in the 12 subjects. Churchill Livingstone, London, 1973, The possible adverse effects of p 137 postural hypotension are of some 11. WOLLNER L, SPALDING JMK: The clinical relevance to the management autonomic nervous system, ibid, p 235 of older patients. Numerous medica- 12. Cardiogenic dementia (E). Lancet 1: 27, 1977 tions that may produce postural falls NA: Cerebral blood flow and in blood pressure are commonly pre- 13. LASSEN oxygen consumption in man. Pliysiol scribed to the elderly; examples inRev 39: 183, 1959 clude phenothiazine tranquillizers, 14. OLESEN J: Quantitative evaluation of normal and pathologic cerebral blood antihypertensive drugs, levodopa and flow regulation to perfusion pressure. vasodilators. If postural hypotension Neurol 28: 143, 1973 alone were sufficient to cause an 15. Arch HACHINSKI VC, LASSEN NA, MARacute deterioration in mental funcSHALL J: Multi-infarct dementia: a tion, then it would be potentially cause of mental deterioration in the elderly. Lancet 2: 207, 1974 harmful to treat any older patient with these drugs. The above data do not support this belief and instead suggest that a low ambulatory blood pressure is not likely to produce a permanent loss of intellectual function, at least not during a 6-month observation period. None the less, it continued from page 1043 is conceivable that a longer period of CELL RECEPTOR DISORDERS. Theodore hypotension could result in recurrent Melnechuk. Based on a workshop held on March 3-5, 1977, planned and cochaired strokes or multi-infarct dementia,15 with Jon N. Lindstrom, Floyd E. Bloom with a worsening of mental perfor- and John D. Baster. Written with the mance. Care should therefore be aid of notes taken by 12 graduate stuscribes. Revised and updated by taken to ensure that long-term drug dent workshop speakers in March and April, therapy in the elderly is not accom- 1978. 215 pp. lIlust. Western Behavioral panied by chronic postural hypoten- Sciences Institute, La Jolla, California, 1978. $10, paperbound sion. DRUGS OF CHOICE 1978-1979. Edited Dr. Myers is the recepient of a senior by Walter MadeIl. 824 pp. Illust. The research fellowship from the Ontario C.V. Mosby Company, Saint Louis, Missouri, 1978. $35.75. ISBN 0-8016-3442-3 Heart Foundation.
BOOKS
References 1. JOHNSON RH, SMITH AC, SPALDING
JMK, Ct al: Effect of posture on blood-pressure in the elderly. Lancet 1: 731, 1965 2. CAIRD Fl, ANDREWS GR, KENNEDY RD: Effect of posture on blood pressure in the elderly. Br Heart J 35: 527, 1973 3. GRoss M: The effect of posture on subjects with cerebrovascular disease. Q J Med 39: 485, 1970 4. Idem: Circulatory reflexes in cerebral ischaemia involving different vascular territories. Clin Sci Mci Med 38: 491, 1970 5. JACKSON G, PIERsCIANOWSKI TA, MAHON W, et al: Inappropriate antihypertensive therapy in the elderly.
Lancet 2: 1317, 1976 6. WRIGHT BM, DORE CF: A randomzero sphygmomanometer. Lancet 1: 337, 1970 7. HoDIuNsoN HM: Mental impairment
in the elderly. J R Coil Physicians Lend 7: 305, 1973 8. IsAACs B, AKHTAR AJ: The set test: a rapid test of mental function in old people. Age Ageing 1: 222, 1972 9. Postural hypotension in the elderly
(E). Br Med J 4: 246, 1973 mann-La Roche Limited Vaudreull,Qu6bec J7V 6B3
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10. CAIRD Fl, DALL JLC: The significance of heart disease in old age, in Text-
HEALTH IMPLICATIONS OF NUCLEAR POWER PRODUCTION. Report of a Working Group. Brussels, 1-5 December 1975. WHO Regional Publications European series no 3. 75 pp. Illust. World Health Organization, Regional Office for Europe, Copenhagen, 1978. $4, paperbound. ISBN 92-9020-103-7 MANUAL OF NEUROLOGIC THERAPEUTICS WITH ESSENTIALS OF DIAGNOSIS. Edited by Martin A. Samuals. 436 pp. Illust. Little, Brown and Company, Boston, 1978. $12.50, spiralbound. ISBN 0-31676990-8 MEDICAL COMPUTING SERIES. Vol 2. Computers for the Physician's Office. Joan Zimmerman and Alan Rector. Edited by D.W. Hill. 305 pp. Research Studies Press, Forest Grove, Oregon, 1978. Price not stated. ISBN 0-89355-007-8 NUTRITION IN THE CLINICAL MANAGEMENT OF DISEASE. Edited by John W.T. Dickerson and H.A. Lee. 409 pp. IIlust. Edward Arnold (Publishers) Ltd., London; Year Book Medical Publishers, Inc., Chicago, 1978. Price not stated. ISBN 0-8151-2451-1 PROCEEDINGS OF THE JAMES C. KIMBROUGH UROLOGICAL SEMINAR. Vol 11, 25th Annual Meeting, 6-11 November 1977, Denver, Colorado. Edited by H.G. Stevenson and S. Christian. 344 pp. Norwich-Eaton Pharmaceuticals, Norwich, New York, 1978. $10, paperbound
continued on page 1076
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