Journal of Gerontology 1976, Vol. 31, No. 1, 23-28
Effects of Hyperbaric Oxygen on Behavioral and Physiological Measures in Elderly Demented Patients1 Larry W. Thompson, PhD, 2 Glenn C. Davis, MD, 3 Walter D. Obrist, PhD, 4 and Albert Heyman, MD5 This study tested the effects of repeated exposures to hyperbaric oxygen (HBO) on psychological, electroencephalographic, and cerebral blood flow measures in 8 patients with cerebrovascular disease and 13 patients with cortical atrophy. Patients were exposed to 100% oxygen at 2.5 atmospheres absolute twice daily for 90 min. for 15 days. No significant changes were observed in any of the measures in either group. Level of initial functioning was not associated with change due to treatment. Results suggest that HBO has no therapeutic effect in patients with moderate to severe dementia.
N recent years considerable attention Ihyperbaric has been focused on the possible value of oxygen as a treatment for dementia in the elderly. This interest stems from a report by Jacobs, Winter, Alvis, and Small (1969) that patients with chronic organic brain syndrome showed improvement in cognitive function following 15 days of intermittent exposure to high pressure oxygen, i.e., 100% oxygen at 2.5 atmospheres for 90 min. twice daily. Thirteen patients in their treatment group showed improvement, whereas 5 control patients failed to show any change in intellectual function. Improvement was observed, however, in the latter group with subsequent hyperbaric treatment. Later investigations by these workers suggested that the beneficial effects of such treatment may persist for 7 to 10 days (Jacobs, Alvis, & Small, 1972; Jacobs, Small, Winter, & Alvis, 1971). Similar therapeutic results in age-related dementia have been reported by other investigators (Ben-Yishay, 1967, 1972; Boyle, 1972; Edwards, 1972; Edwards & Hart, 1974) following hyperbaric oxygenation, but the use of control subjects was notably lacking or the 'This investigation was carried out at Duke Univ. Medical Center and was supported in part by NIH research grants HD-00668, HL-07896 and NS 06233, and by RR-30 from the General Clinical Research Centers Program, NIH. 'Andrus Gerontology Center, Univ. of Southern California, Los Angeles 90007. J Dept. of Psychiatry, Duke Univ. Medical Center, Durham 27710. 'Division of Neurosurgery, Hospital of the Univ. of Pennsylvania, Philadelphia 19104. "Division of Neurology, Duke Univ. Medical Center, Durham 27710.
treatment was combined with other types of therapy. In contrast, Goldfarb, Hochstadt, Jacobson, and Weinstein (1972) found no significant changes in cognitive function following hyperbaric oxygenation in elderly patients with organic brain syndrome. The present investigation was designed to repeat the studies of Jacobs and her colleagues in patients with dementia secondary either to cerebrovascular disease or to cortical atrophy. METHODS
Subjects The case material consisted of 21 patients with dementia, ages 50-80 years (Table 1). Thirteen of them had a diagnosis of cortical atrophy and 8 had evidence of cerebrovascular disease. Each of the patients in the latter group had a history and physical findings of recurrent hemiparesis or other focal neurologic deficits. Most of them also had hypertension and clinical or laboratory evidence of arteriosclerotic cardiovascular disease. The 13 patients with a diagnosis of cortical atrophy had a history of progressive dementia for 2 years or more with no focal neurologic signs suggestive of cerebrovascular disease. Other degenerative neurologic disorders, e.g., Parkinsonism, Huntington's chorea, etc., were excluded. In 10 cases, the diagnosis of cortical atrophy was verified by pneumoencephalography. This type 23
THOMPSON, DA VIS, OBRIST, ANDHEYMAN
24
of dementia is usually designated organic brain syndrome associated with senile or presenile brain disease, although it is sometimes erroneously attributed to cerebral arteriosclerosis. Procedures All patients in the study were admitted to the Neurology Service of Duke Hospital or the Durham VA Hospital for careful diagnostic screening, following which pre-treatment evaluations were carried out. Eight consecutive patients were randomly assigned to the control or treatment group (4 each). The remaining 13 were assigned only to the treatment group (Fig. 1). Table 1. Mean Age, IQ, and Educational Level for the Two Patient Groups. Cortical Atrophy
Cerebrovascular Disease
13(3)-
8(1)-
59 (50-67)
64(51-80)
9 4
7
Lowest education
6th grade
6th grade
Highest education
No. cases Mean age (range) Male Female
1
Graduate degree
Graduate degree
Mean full scale IQ (range)
70(45-91)
Mean verbal IQ (range)
76(45-96)
83(55-125) 89(60-140)
Mean performance IQ (range)
67(53-85)
77(55-100)
"Parentheses indicate number of control patients.
RESEARCH PLAN Screening Evaluation Pre-Treatment Evaluation CONTROL
TREATMENT Treatment- 15 days
Control-15 days
I
I
Post-Treatment Evaluation
Post-Control Evaluation T Treatment -15 days
Post-Treotment Evaluation
Hospital Discharge Follow-Up Evaluation (2wks,4wks,8wks)
Fig. 1. General outline of the research plan.
Hyperbaric therapy consisted of the same procedures used by Jacobs and her coworkers, i.e., exposure to 100% oxygen at 2.5 atmospheres absolute pressure for 90 min. twice daily over a 15-day period. The controls received identical treatment, except that they were given room air instead of 100% oxygen. In order to simulate pressure conditions, the controls were initially pressurized to a depth of 20 feet. The pressure was then slowly reduced to a minimal level sufficient to keep the doors of the chamber closed. Following 15 days of sham treatment, the 4 control patients were "crossed over" into the treatment group. With one exception, none of the patients or the staff was aware of the form of therapy at the time of the post-treatment evaluation. Although the procedure was generally well tolerated, one patient with cerebrovascular disease developed acute hemiparesis 4 weeks after hospital discharge, while another sustained a stroke during the treatment period which necessitated his removal from the study. Two patients (one with cerebrovascular disease and one with cortical atrophy) manifested transient mild paranoid reactions that required the attention of a psychiatrist. Oxygen was administered via a semi-closed respiratory assembly and plastic hood, tightly affixed to the upper thorax. The gaseous environment within the hood was monitored continuously. A high internal circulation rate, an effective CO2 removal system, and continuous replenishment of oxygen resulted in measured O2 concentrations of 96-99% and CO2 concentrations below 0.2%. Measurements of arterial blood revealed comparable or higher pO2 values than those obtained by other delivery systems under similar circumstances. Behavioral and physiological evaluations were performed over a 2-day period immediately before and immediately after the treatment and control conditions. These included a battery of psychological tests, measurements of regional cerebral blood flow, and both routine and special electroencephalographic examinations. Two rating scales were employed to evaluate behavior on the ward and at home, i.e., the Stockton Geriatric Scale used by nurses on the ward and an Activities of Daily Living Scale used by both nurses and the patient's family. Portions of the psychological battery, as well as the behavioral ratings, were repeated at 2,4 and 8 weeks post-treatment.
HYPERBARIC OXYGEN IN ELDERL Y PA TIENTS
25
The specific psychological procedures were:
aminations were performed on 16 subjects in which a special effort was made to prevent 1. Wechsler Memory Scale. This is a test of recent drowsiness and reduce muscle tension by enlearning and memory. Subscales include personal and curvironmental manipulation. This was conrent information, orientation, mental control, logical memory, digits forward and backward, paired associate sidered necessary, since interpretation of testlearning, and visual retention. retest changes assumes comparable levels of 2. Benton Visual Retention Test. This test requires that arousal, not easily achieved by routine clinical the patient draw from memory outlines of familiar shapes methods. The EEGs were read independently presented for 10 sec. 3. Raven's Progressive Matrices (children's form). This by two electroencephalographers. Agreement between observers was high; the few instances test requires the patient to find the missing part of a design from an array of six possible selections. It reflects spatial of disagreement were resolved by consultation.
reasoning and is thought by some psychologists to be a measure of "g" factor intelligence. RESULTS 4. Hooper Visual Organization Test. This is a complex Psychological Tests visual perception task in which the patient has to identify an Fig. 2 presents the results of the object by looking at disassembled parts. 5. Tiens Organic Integrity Test. This is a test of psychological tests administered before and abstracting ability which involves matching objects ac- after treatment. The values shown in these bar cordingjo color or structure. graphs are mean scores. None of the eight tests 6. Word Naming. This procedure requires that the pawas statistically significant by the Wilcoxon tient name as many words as he can beginning with " C " or matched pairs signed-ranks test. "S" in successive two-min. periods. 7. Tapping Test. This is a simple motor task adapted There were no discernible trends either befrom the Halstead Reitan battery in which the patient taps a tween or within subjects. Intercorrelations of key as fast as possible. Five 10-sec. samples with left and pre- and post-treatment changes in the psychoright index fingers were obtained.
Regional cerebral blood flow was determined by the noninvasive xenon-133 inhalation method developed by Obrist, Thompson, Wang, and Wilkinson (1975). Studies were carried out on 13 of the patients (4 with cerebrovascular disease and 9 with cortical atrophy) within 48 hours of the onset and termination of treatment. Blood flow measurements were not obtained on the remaining subjects for technical reasons, lack of cooperation, or marked hyperventilation during the procedures. Radioactivity was monitored for 10 min. from 4 extracranial detectors (15 mm diameter), following a one-min. inhalation of air containing tracer amounts of xenon-133. Computer analysis of the resulting clearance curves yielded grey matter blood flow in ml/100 gm/min for the frontal and parietal regions, bilaterally. Additional measurements were available for the temporal areas in 6 of the patients. Appropriate blood flow corrections were made in 5 subjects who showed inter-test differences in arterial pCO2, estimated capnographically. Pre- and post-treatment clinical EEGs were recorded on 18 patients (7 with cerebrovascular disease and 11 with cortical atrophy). Standard monopolar and bipolar techniques were employed, with electrodes placed according to the International System. Additional EEG ex-
logical measures were small and variable, with no consistent pattern in evidence. Thus, a patient who showed a positive change on a given test did not necessarily have a positive change on another test. Table 2 presents the Pearson productmoment correlations between initial WAIS full PSYCHOLOGICAL TESTS BEFORE ANO AFTER HYPERBARIC EXPOSURE 80 60
I I Pre-Exposure • • Post-Exposure
Corticol Atrophy-13
40 20
Irin
80
Cerebrovascular-8
60 > 40
20 80 60 40 20
nnn
1
Wch.M S. Benton Raven's Hooper
Controls-4
Tien's
Word Noming
Finger Tapping Right Left
Fig. 2. Mean values for the 8 behavioral tests administered before and after exposure to hyperbaric oxygenation.
THOMPSON, DA VIS, OBRIST, AND HEYMAN
26
Table 2. Product-moment Correlations" Between WAIS Full Scale IQ and Changes in Psychological Test Scores with Hyperbaric Treatment (N = 21). Test
r
Test
r
Wechsler Memory Scale
-.128
Tien's Organic Int.
Benton Visual Retention
-.491*
Word Naming
-.019
Raven's Progressive Matrices
-.079
Finger Tap., Right
-.186
Hooper Visual Organization
+ .451*
Finger Tap., Left
-.284
+ .003
'A positive correlation indicates an association between high initial IQ and improvement in test performance. •p
Effects of Hyperbaric Oxygen on Behavioral and Physiological Measures in Elderly Demented Patients1 Larry W. Thompson, PhD, 2 Glenn C. Davis, MD, 3 Walter D. Obrist, PhD, 4 and Albert Heyman, MD5 This study tested the effects of repeated exposures to hyperbaric oxygen (HBO) on psychological, electroencephalographic, and cerebral blood flow measures in 8 patients with cerebrovascular disease and 13 patients with cortical atrophy. Patients were exposed to 100% oxygen at 2.5 atmospheres absolute twice daily for 90 min. for 15 days. No significant changes were observed in any of the measures in either group. Level of initial functioning was not associated with change due to treatment. Results suggest that HBO has no therapeutic effect in patients with moderate to severe dementia.
N recent years considerable attention Ihyperbaric has been focused on the possible value of oxygen as a treatment for dementia in the elderly. This interest stems from a report by Jacobs, Winter, Alvis, and Small (1969) that patients with chronic organic brain syndrome showed improvement in cognitive function following 15 days of intermittent exposure to high pressure oxygen, i.e., 100% oxygen at 2.5 atmospheres for 90 min. twice daily. Thirteen patients in their treatment group showed improvement, whereas 5 control patients failed to show any change in intellectual function. Improvement was observed, however, in the latter group with subsequent hyperbaric treatment. Later investigations by these workers suggested that the beneficial effects of such treatment may persist for 7 to 10 days (Jacobs, Alvis, & Small, 1972; Jacobs, Small, Winter, & Alvis, 1971). Similar therapeutic results in age-related dementia have been reported by other investigators (Ben-Yishay, 1967, 1972; Boyle, 1972; Edwards, 1972; Edwards & Hart, 1974) following hyperbaric oxygenation, but the use of control subjects was notably lacking or the 'This investigation was carried out at Duke Univ. Medical Center and was supported in part by NIH research grants HD-00668, HL-07896 and NS 06233, and by RR-30 from the General Clinical Research Centers Program, NIH. 'Andrus Gerontology Center, Univ. of Southern California, Los Angeles 90007. J Dept. of Psychiatry, Duke Univ. Medical Center, Durham 27710. 'Division of Neurosurgery, Hospital of the Univ. of Pennsylvania, Philadelphia 19104. "Division of Neurology, Duke Univ. Medical Center, Durham 27710.
treatment was combined with other types of therapy. In contrast, Goldfarb, Hochstadt, Jacobson, and Weinstein (1972) found no significant changes in cognitive function following hyperbaric oxygenation in elderly patients with organic brain syndrome. The present investigation was designed to repeat the studies of Jacobs and her colleagues in patients with dementia secondary either to cerebrovascular disease or to cortical atrophy. METHODS
Subjects The case material consisted of 21 patients with dementia, ages 50-80 years (Table 1). Thirteen of them had a diagnosis of cortical atrophy and 8 had evidence of cerebrovascular disease. Each of the patients in the latter group had a history and physical findings of recurrent hemiparesis or other focal neurologic deficits. Most of them also had hypertension and clinical or laboratory evidence of arteriosclerotic cardiovascular disease. The 13 patients with a diagnosis of cortical atrophy had a history of progressive dementia for 2 years or more with no focal neurologic signs suggestive of cerebrovascular disease. Other degenerative neurologic disorders, e.g., Parkinsonism, Huntington's chorea, etc., were excluded. In 10 cases, the diagnosis of cortical atrophy was verified by pneumoencephalography. This type 23
THOMPSON, DA VIS, OBRIST, ANDHEYMAN
24
of dementia is usually designated organic brain syndrome associated with senile or presenile brain disease, although it is sometimes erroneously attributed to cerebral arteriosclerosis. Procedures All patients in the study were admitted to the Neurology Service of Duke Hospital or the Durham VA Hospital for careful diagnostic screening, following which pre-treatment evaluations were carried out. Eight consecutive patients were randomly assigned to the control or treatment group (4 each). The remaining 13 were assigned only to the treatment group (Fig. 1). Table 1. Mean Age, IQ, and Educational Level for the Two Patient Groups. Cortical Atrophy
Cerebrovascular Disease
13(3)-
8(1)-
59 (50-67)
64(51-80)
9 4
7
Lowest education
6th grade
6th grade
Highest education
No. cases Mean age (range) Male Female
1
Graduate degree
Graduate degree
Mean full scale IQ (range)
70(45-91)
Mean verbal IQ (range)
76(45-96)
83(55-125) 89(60-140)
Mean performance IQ (range)
67(53-85)
77(55-100)
"Parentheses indicate number of control patients.
RESEARCH PLAN Screening Evaluation Pre-Treatment Evaluation CONTROL
TREATMENT Treatment- 15 days
Control-15 days
I
I
Post-Treatment Evaluation
Post-Control Evaluation T Treatment -15 days
Post-Treotment Evaluation
Hospital Discharge Follow-Up Evaluation (2wks,4wks,8wks)
Fig. 1. General outline of the research plan.
Hyperbaric therapy consisted of the same procedures used by Jacobs and her coworkers, i.e., exposure to 100% oxygen at 2.5 atmospheres absolute pressure for 90 min. twice daily over a 15-day period. The controls received identical treatment, except that they were given room air instead of 100% oxygen. In order to simulate pressure conditions, the controls were initially pressurized to a depth of 20 feet. The pressure was then slowly reduced to a minimal level sufficient to keep the doors of the chamber closed. Following 15 days of sham treatment, the 4 control patients were "crossed over" into the treatment group. With one exception, none of the patients or the staff was aware of the form of therapy at the time of the post-treatment evaluation. Although the procedure was generally well tolerated, one patient with cerebrovascular disease developed acute hemiparesis 4 weeks after hospital discharge, while another sustained a stroke during the treatment period which necessitated his removal from the study. Two patients (one with cerebrovascular disease and one with cortical atrophy) manifested transient mild paranoid reactions that required the attention of a psychiatrist. Oxygen was administered via a semi-closed respiratory assembly and plastic hood, tightly affixed to the upper thorax. The gaseous environment within the hood was monitored continuously. A high internal circulation rate, an effective CO2 removal system, and continuous replenishment of oxygen resulted in measured O2 concentrations of 96-99% and CO2 concentrations below 0.2%. Measurements of arterial blood revealed comparable or higher pO2 values than those obtained by other delivery systems under similar circumstances. Behavioral and physiological evaluations were performed over a 2-day period immediately before and immediately after the treatment and control conditions. These included a battery of psychological tests, measurements of regional cerebral blood flow, and both routine and special electroencephalographic examinations. Two rating scales were employed to evaluate behavior on the ward and at home, i.e., the Stockton Geriatric Scale used by nurses on the ward and an Activities of Daily Living Scale used by both nurses and the patient's family. Portions of the psychological battery, as well as the behavioral ratings, were repeated at 2,4 and 8 weeks post-treatment.
HYPERBARIC OXYGEN IN ELDERL Y PA TIENTS
25
The specific psychological procedures were:
aminations were performed on 16 subjects in which a special effort was made to prevent 1. Wechsler Memory Scale. This is a test of recent drowsiness and reduce muscle tension by enlearning and memory. Subscales include personal and curvironmental manipulation. This was conrent information, orientation, mental control, logical memory, digits forward and backward, paired associate sidered necessary, since interpretation of testlearning, and visual retention. retest changes assumes comparable levels of 2. Benton Visual Retention Test. This test requires that arousal, not easily achieved by routine clinical the patient draw from memory outlines of familiar shapes methods. The EEGs were read independently presented for 10 sec. 3. Raven's Progressive Matrices (children's form). This by two electroencephalographers. Agreement between observers was high; the few instances test requires the patient to find the missing part of a design from an array of six possible selections. It reflects spatial of disagreement were resolved by consultation.
reasoning and is thought by some psychologists to be a measure of "g" factor intelligence. RESULTS 4. Hooper Visual Organization Test. This is a complex Psychological Tests visual perception task in which the patient has to identify an Fig. 2 presents the results of the object by looking at disassembled parts. 5. Tiens Organic Integrity Test. This is a test of psychological tests administered before and abstracting ability which involves matching objects ac- after treatment. The values shown in these bar cordingjo color or structure. graphs are mean scores. None of the eight tests 6. Word Naming. This procedure requires that the pawas statistically significant by the Wilcoxon tient name as many words as he can beginning with " C " or matched pairs signed-ranks test. "S" in successive two-min. periods. 7. Tapping Test. This is a simple motor task adapted There were no discernible trends either befrom the Halstead Reitan battery in which the patient taps a tween or within subjects. Intercorrelations of key as fast as possible. Five 10-sec. samples with left and pre- and post-treatment changes in the psychoright index fingers were obtained.
Regional cerebral blood flow was determined by the noninvasive xenon-133 inhalation method developed by Obrist, Thompson, Wang, and Wilkinson (1975). Studies were carried out on 13 of the patients (4 with cerebrovascular disease and 9 with cortical atrophy) within 48 hours of the onset and termination of treatment. Blood flow measurements were not obtained on the remaining subjects for technical reasons, lack of cooperation, or marked hyperventilation during the procedures. Radioactivity was monitored for 10 min. from 4 extracranial detectors (15 mm diameter), following a one-min. inhalation of air containing tracer amounts of xenon-133. Computer analysis of the resulting clearance curves yielded grey matter blood flow in ml/100 gm/min for the frontal and parietal regions, bilaterally. Additional measurements were available for the temporal areas in 6 of the patients. Appropriate blood flow corrections were made in 5 subjects who showed inter-test differences in arterial pCO2, estimated capnographically. Pre- and post-treatment clinical EEGs were recorded on 18 patients (7 with cerebrovascular disease and 11 with cortical atrophy). Standard monopolar and bipolar techniques were employed, with electrodes placed according to the International System. Additional EEG ex-
logical measures were small and variable, with no consistent pattern in evidence. Thus, a patient who showed a positive change on a given test did not necessarily have a positive change on another test. Table 2 presents the Pearson productmoment correlations between initial WAIS full PSYCHOLOGICAL TESTS BEFORE ANO AFTER HYPERBARIC EXPOSURE 80 60
I I Pre-Exposure • • Post-Exposure
Corticol Atrophy-13
40 20
Irin
80
Cerebrovascular-8
60 > 40
20 80 60 40 20
nnn
1
Wch.M S. Benton Raven's Hooper
Controls-4
Tien's
Word Noming
Finger Tapping Right Left
Fig. 2. Mean values for the 8 behavioral tests administered before and after exposure to hyperbaric oxygenation.
THOMPSON, DA VIS, OBRIST, AND HEYMAN
26
Table 2. Product-moment Correlations" Between WAIS Full Scale IQ and Changes in Psychological Test Scores with Hyperbaric Treatment (N = 21). Test
r
Test
r
Wechsler Memory Scale
-.128
Tien's Organic Int.
Benton Visual Retention
-.491*
Word Naming
-.019
Raven's Progressive Matrices
-.079
Finger Tap., Right
-.186
Hooper Visual Organization
+ .451*
Finger Tap., Left
-.284
+ .003
'A positive correlation indicates an association between high initial IQ and improvement in test performance. •p
