1000 STROKE VOL 15, N o 6, NOVEMBER-DECEMBER 1984
8. Manuck SB, Kaplan JR, Clarkson TB: Behaviorally induced heart 16. Kuller L, Reisler DM: An explanation for variations in distribution
rate reactivity and atherosclerosis in cynomolgus monkeys. Psy- of stroke and arteriosclerotic heart disease among populations and
chosom Med 45: 95-108, 1983 racial groups. Am J Epidemiol 93: 1-9, 1971
9. Kaplan JR, Manuck SB, Clarkson TB, et al. Social stress and 17. Kuller LH: Epidemiology of stroke. In: Schoenberg BS (ed), Ad-
atherosclerosis in normocholesterolemic monkeys. Science 220: vances in Neurology, Vol. 19. New York, Raven Press, 281-311,
733-735, 1983 1978
10. Lipid Research Clinics Program. Manual of Laboratory Oper- 18. Lavy S: Medical risk factors for stroke. In: Goldstein M et al (eds),
ations: Lipid and lipoprotein analysis. DHEW publication no. Advances in Neurology, Vol. 25. New York, Raven Press, 127—
(NIH) 76-628. Bethesda, Maryland: National Institutes of Health, 133, 1979
1974 19. Wolf PA, Kannel WB, Dawber TR: Prospective investigations:
11. Williams RB: Psychophysical differences between Type A and B The Framingham study and the epidemiology of stroke. In:
individuals that may lead to coronary heart disease. In: Dembroski Schoenberg BS (ed), Advances in Neurology, Vol 19. New York,
TM (ed). Proceedings of the Fonim on Coronary Prone Behavior. Raven Press, 107-120, 1978
DHEW publication no. (NIH) 78-1451:185-191, 1977 20. Corbett WT, Schey HM, Lehner NDM, et al: Standardized method
12. Siegel J: Nonparametric statistics. New York, McGraw Hill, 1956 for recording blood pressure in anesthetized Macaca fascicularis.
13. Castelli WP: High density lipoproteins: An overview. In Gotto AM Lab Anim 15: 37-40, 1981
Jr, Smith LC, Allen B (eds.), Atherosclerosis V. New York, 21. Hollander W, Geer JC, Garcia JH: Aggravation of cerebral athero-
Springer-Verlag, 478-483, 1980 sclerosis by hypertension. Arteriosclerosis 3: 479a, 1983
14. Kirk RE: Experimental design (2nd Edition), Belmont, CA, 22. Glagov S: Low heart rate retards coronary atherosclerosis. Arterio-
Brooks/Cole, 1982 sclerosis 3: 466a, 1983
15. Solberg LA, McGarry PA, Moossy J, et al: Distribution of cerebral 23. Hamm TE, Kaplan JR, Clarkson TB, et al: Gender and social
atherosclerosis by geographic location, race and sex. Lab Invest factors in the atherosclerosis of cynomolgus monkeys. Atheroscle-
18: 604-612, 1968 rosis 48: 221-233, 1983
Downloaded from http://stroke.ahajournals.org/ by guest on October 1, 2016
CT-CBF Correlations of Cognitive Deficits in
Multi-Infarct Dementia
Y A S U H I S A K I T A G A W A , M . D . , P H . D . , JOHN S. MEYER, M . D . , HISAO TACHIBANA, M . D . , P H . D .
K A R L F. MORTEL, P H . D . , AND ROBERT L. ROGERS, M . A .
SUMMARY Fifteen right-handed patients with Multi-Infarct Dementia underwent cognitive testing by
the Jacobs Mini-Mental Scale (MMQ), and xenon contrast CT scanning. Local cerebral blood flow (LCBF)
and local partition coefficient (LX) values were measured by stable xenon contrast CT scanning and
potential methodological errors were discussed. Reduced values were graded: 0 = normal, 1 = mild, 2 =
moderate, 3 = severe. Graded values were pooled and plotted on composite brain maps to display locations
of abnormal LX and LCBF values. Topographic brain maps, showing most frequent locations of reduced L>.
values, confirmed the common anatomical locations of multiple cerebral infarcts to be distributed in both
thalami, temporal lobes, basal ganglia, left internal capsule and right cingulate cortex. Gray matter flow
values were reduced in similar cortical and subcortical regions. There were no correlations between MMQ
scores and reduced LCBF values for caudate and lenticular nuclei. Direct and statistically significant
correlations were found between reduced MMQ scores and mean LCBF values for left or right frontal
cortex, left or right temporal cortex and left or right thalamus. Subgrouping MMQ tests according to
functions assessed, indicated that left mid-temporal ischemia correlated with dyscalculia and memory
disturbances while ischemia of both frontal lobes correlated with disorientation to time and place.
Stroke Vol 15, No 6, 1984
DEMENTIA is becoming a serious public health prob- fer from senile dementia of Alzheimer's type (SDAT),
lem in our aging population. Epidemiological studies 20% from multi-infarct dementia (MID) and 10% have
have shown that dementia is present in 4.4-8% of both diseases (MIX).1
populations over age 65 years.'^ Pathological investi- Differentiation between SDAT and MID is a com-
gations have revealed that of the commonest forms of monly encountered diagnostic problem in the clinic.
dementia, about 50% of elderly demented patients suf- Hachinski's ischemic score5 has proven clinically use-
ful in distinguishing between these most common
From the Cerebrovascular Research Laboratories, VA Medical Cen- types of dementia and the validity of this scoring sys-
ter, Department of Neurology, Baylor College of Medicine; and Depart-
ment of Psychology, University of Houston, Houston, Texas. This
tem has been neuropathologically established in a se-
work was supported, in part, by the Veterans Administration Medical ries of autopsied cases by Rosen, et al.6
Center and by a Grant provided by Mr. Harry K. Smith and Mr. Albert The present communication will attempt to correlate
K. Smith, Houston, Texas. cognitive deficits measured in patients with MID with
Address correspondence to: John S. Meyer, M.D., Director, Cere-
brovascular Research Laboratories, VA Medical Center, 2002 Hol-
quantitative measurements of local cerebral blood flow
combe Boulevard, Houston, Texas 77211. measured by xenon contrast CT scanning.
Received October 17, 1983; revision #2 accepted May 11, 1984. In the majority of cases, MID appears to be a cere-
, STABLE XENON, CTCBF IN MID/Kitagawa et al 1001
bral manifestation of long-standing hypertension. At The excellent resolving powers of x-ray transmis-
autopsy hyperplastic cerebral arteriosclerosis is evi- sion tomography, utilizing the CT scanner for measur-
dent with bilateral multiple small lacunar infarcts.7 The ing both LA. and LCBF during inhalation of stable
severity of the dementia is not only proportional to the xenon gas (CTCBF method), overcomes the limita-
cumulative severity of the lacunar state, but also to the tions of the 133Xe clearance method and provides the
locations of the lacunes. 8 From a cognitive point of best resolution of any method presently available for
view, patients with MID may be considered as a useful measuring cerebral blood flow (circa 80 cu mm).24"32
model. They offer an opportunity for studying those The purpose of the present communication is to
regions of the brain, which if damaged by multiple report regional patterns of reduced LA. and LCBF val-
small infarcts, may give rise to dementia. ues measured by the CTCBF method in 15 patients
Cerebral blood flow studies have provided some with well-established MID and to correlate anatomical
insights concerning the pathogenesis and differences zones of regional ischemia with cognitive deficits
between MID and SDAT.9"21 It has been known for 30 measured within a few days of the LCBF and LA.
years that organic dementia is consistently accompa- determinations.
nied by bilateral hemispheric reductions of cerebral
blood flow and oxygen uptake. 9 Case Series
The development of regional methods for measuring Fifteen right-handed and cooperative patients with
cerebral blood flow, such as I33Xe clearance methods, well-defined MID were selected from a larger series
made some regional quantitation possible between with this disease being followed in this laboratory. The
Downloaded from http://stroke.ahajournals.org/ by guest on October 1, 2016
cognitive deficits and the severity and nature of de- diagnosis in all patients was well-established. It was
mentia.10"21 However, these two-dimensional radioiso- confirmed by history of sudden onset and fluctuating
topic methods ignore or underestimate many zones of course, the presence of risk factors for cerebrovascular
zero or reduced flow because clearance of l33Xe from disease and by medical and neurological examinations
bordering zones obscures them (so-called "look showing hypertension, cerebral arteriosclerosis by
through" phenomenon). There are other problems neurovascular examination (bruits, hypertensive ret-
which impair the resolving powers of the 133Xe method inal changes, etc.) and focal neurological signs. The
including Compton scatter and lack of knowledge of cognitive deficits were confirmed by the Mini-Mental
brain-tissue solubility coefficients (IA). Status examination (MMQ) of Jacobs, et al33 modified
With the advent of computerized reconstruction after that described by Folstein, et al.34 Scores in nor-
techniques for transmission and emission tomography mal age-matched volunteers are between 29-31 but the
it is now possible to image the brain in three dimen- patient's scores were between 11-20 (table 1).
sions with high resolution. Positron emission tomog- The patient's ages ranged from 57 to 85 years with a
raphy provides considerable advantages of measuring mean age of 71.5 ± 10.1. All patients had a history of
both blood flow and metabolism but has the disadvan- chronic but not malignant or accelerated hypertension,
tages of enormous cost, prolonged time consumption recurrent attacks of cerebral ischemia including tran-
for patients and investigators and relatively poor reso- sient ischemic attacks, reversible ischemic neurologi-
lution compared to computerized x-ray transmission cal deficits and small strokes. Patients with large or
tomography.22-23 aphasic strokes were excluded. All showed evidence
TABLE 1 Case Series
Case Age MABP PECOj Ischemic MMQ
numbers (in years) Gender (mmHg) (mmHg) score value
1 84 F 110 34.6 11 15
2 72 F 104 38.5 7 13
3 54 M 129 34.2 9 17
4 65 M 97 35.6 9 11
5 81 M 98 37.1 8 18
6 72 M 123 34.2 11 20
7 79 M 110 35.7 7 19
8 75 M 97 35.9 12 13
9 85 F 100 28.7 7 16
10 60 F 109 35.9 10 18
11 57 M 99 35.7 9 19
12 74 F 93 33.0 10 14
13 79 F 97 40.2 9 19
14 77 F 93 34.2 7 14
15 59 F 89 35.7 7 16
Mean values 71.5±10.1 7M.8F 103.2± 11.2 35.3±2.6 8.9±1.7 16.1 ±2.7
8. Manuck SB, Kaplan JR, Clarkson TB: Behaviorally induced heart 16. Kuller L, Reisler DM: An explanation for variations in distribution
rate reactivity and atherosclerosis in cynomolgus monkeys. Psy- of stroke and arteriosclerotic heart disease among populations and
chosom Med 45: 95-108, 1983 racial groups. Am J Epidemiol 93: 1-9, 1971
9. Kaplan JR, Manuck SB, Clarkson TB, et al. Social stress and 17. Kuller LH: Epidemiology of stroke. In: Schoenberg BS (ed), Ad-
atherosclerosis in normocholesterolemic monkeys. Science 220: vances in Neurology, Vol. 19. New York, Raven Press, 281-311,
733-735, 1983 1978
10. Lipid Research Clinics Program. Manual of Laboratory Oper- 18. Lavy S: Medical risk factors for stroke. In: Goldstein M et al (eds),
ations: Lipid and lipoprotein analysis. DHEW publication no. Advances in Neurology, Vol. 25. New York, Raven Press, 127—
(NIH) 76-628. Bethesda, Maryland: National Institutes of Health, 133, 1979
1974 19. Wolf PA, Kannel WB, Dawber TR: Prospective investigations:
11. Williams RB: Psychophysical differences between Type A and B The Framingham study and the epidemiology of stroke. In:
individuals that may lead to coronary heart disease. In: Dembroski Schoenberg BS (ed), Advances in Neurology, Vol 19. New York,
TM (ed). Proceedings of the Fonim on Coronary Prone Behavior. Raven Press, 107-120, 1978
DHEW publication no. (NIH) 78-1451:185-191, 1977 20. Corbett WT, Schey HM, Lehner NDM, et al: Standardized method
12. Siegel J: Nonparametric statistics. New York, McGraw Hill, 1956 for recording blood pressure in anesthetized Macaca fascicularis.
13. Castelli WP: High density lipoproteins: An overview. In Gotto AM Lab Anim 15: 37-40, 1981
Jr, Smith LC, Allen B (eds.), Atherosclerosis V. New York, 21. Hollander W, Geer JC, Garcia JH: Aggravation of cerebral athero-
Springer-Verlag, 478-483, 1980 sclerosis by hypertension. Arteriosclerosis 3: 479a, 1983
14. Kirk RE: Experimental design (2nd Edition), Belmont, CA, 22. Glagov S: Low heart rate retards coronary atherosclerosis. Arterio-
Brooks/Cole, 1982 sclerosis 3: 466a, 1983
15. Solberg LA, McGarry PA, Moossy J, et al: Distribution of cerebral 23. Hamm TE, Kaplan JR, Clarkson TB, et al: Gender and social
atherosclerosis by geographic location, race and sex. Lab Invest factors in the atherosclerosis of cynomolgus monkeys. Atheroscle-
18: 604-612, 1968 rosis 48: 221-233, 1983
Downloaded from http://stroke.ahajournals.org/ by guest on October 1, 2016
CT-CBF Correlations of Cognitive Deficits in
Multi-Infarct Dementia
Y A S U H I S A K I T A G A W A , M . D . , P H . D . , JOHN S. MEYER, M . D . , HISAO TACHIBANA, M . D . , P H . D .
K A R L F. MORTEL, P H . D . , AND ROBERT L. ROGERS, M . A .
SUMMARY Fifteen right-handed patients with Multi-Infarct Dementia underwent cognitive testing by
the Jacobs Mini-Mental Scale (MMQ), and xenon contrast CT scanning. Local cerebral blood flow (LCBF)
and local partition coefficient (LX) values were measured by stable xenon contrast CT scanning and
potential methodological errors were discussed. Reduced values were graded: 0 = normal, 1 = mild, 2 =
moderate, 3 = severe. Graded values were pooled and plotted on composite brain maps to display locations
of abnormal LX and LCBF values. Topographic brain maps, showing most frequent locations of reduced L>.
values, confirmed the common anatomical locations of multiple cerebral infarcts to be distributed in both
thalami, temporal lobes, basal ganglia, left internal capsule and right cingulate cortex. Gray matter flow
values were reduced in similar cortical and subcortical regions. There were no correlations between MMQ
scores and reduced LCBF values for caudate and lenticular nuclei. Direct and statistically significant
correlations were found between reduced MMQ scores and mean LCBF values for left or right frontal
cortex, left or right temporal cortex and left or right thalamus. Subgrouping MMQ tests according to
functions assessed, indicated that left mid-temporal ischemia correlated with dyscalculia and memory
disturbances while ischemia of both frontal lobes correlated with disorientation to time and place.
Stroke Vol 15, No 6, 1984
DEMENTIA is becoming a serious public health prob- fer from senile dementia of Alzheimer's type (SDAT),
lem in our aging population. Epidemiological studies 20% from multi-infarct dementia (MID) and 10% have
have shown that dementia is present in 4.4-8% of both diseases (MIX).1
populations over age 65 years.'^ Pathological investi- Differentiation between SDAT and MID is a com-
gations have revealed that of the commonest forms of monly encountered diagnostic problem in the clinic.
dementia, about 50% of elderly demented patients suf- Hachinski's ischemic score5 has proven clinically use-
ful in distinguishing between these most common
From the Cerebrovascular Research Laboratories, VA Medical Cen- types of dementia and the validity of this scoring sys-
ter, Department of Neurology, Baylor College of Medicine; and Depart-
ment of Psychology, University of Houston, Houston, Texas. This
tem has been neuropathologically established in a se-
work was supported, in part, by the Veterans Administration Medical ries of autopsied cases by Rosen, et al.6
Center and by a Grant provided by Mr. Harry K. Smith and Mr. Albert The present communication will attempt to correlate
K. Smith, Houston, Texas. cognitive deficits measured in patients with MID with
Address correspondence to: John S. Meyer, M.D., Director, Cere-
brovascular Research Laboratories, VA Medical Center, 2002 Hol-
quantitative measurements of local cerebral blood flow
combe Boulevard, Houston, Texas 77211. measured by xenon contrast CT scanning.
Received October 17, 1983; revision #2 accepted May 11, 1984. In the majority of cases, MID appears to be a cere-
, STABLE XENON, CTCBF IN MID/Kitagawa et al 1001
bral manifestation of long-standing hypertension. At The excellent resolving powers of x-ray transmis-
autopsy hyperplastic cerebral arteriosclerosis is evi- sion tomography, utilizing the CT scanner for measur-
dent with bilateral multiple small lacunar infarcts.7 The ing both LA. and LCBF during inhalation of stable
severity of the dementia is not only proportional to the xenon gas (CTCBF method), overcomes the limita-
cumulative severity of the lacunar state, but also to the tions of the 133Xe clearance method and provides the
locations of the lacunes. 8 From a cognitive point of best resolution of any method presently available for
view, patients with MID may be considered as a useful measuring cerebral blood flow (circa 80 cu mm).24"32
model. They offer an opportunity for studying those The purpose of the present communication is to
regions of the brain, which if damaged by multiple report regional patterns of reduced LA. and LCBF val-
small infarcts, may give rise to dementia. ues measured by the CTCBF method in 15 patients
Cerebral blood flow studies have provided some with well-established MID and to correlate anatomical
insights concerning the pathogenesis and differences zones of regional ischemia with cognitive deficits
between MID and SDAT.9"21 It has been known for 30 measured within a few days of the LCBF and LA.
years that organic dementia is consistently accompa- determinations.
nied by bilateral hemispheric reductions of cerebral
blood flow and oxygen uptake. 9 Case Series
The development of regional methods for measuring Fifteen right-handed and cooperative patients with
cerebral blood flow, such as I33Xe clearance methods, well-defined MID were selected from a larger series
made some regional quantitation possible between with this disease being followed in this laboratory. The
Downloaded from http://stroke.ahajournals.org/ by guest on October 1, 2016
cognitive deficits and the severity and nature of de- diagnosis in all patients was well-established. It was
mentia.10"21 However, these two-dimensional radioiso- confirmed by history of sudden onset and fluctuating
topic methods ignore or underestimate many zones of course, the presence of risk factors for cerebrovascular
zero or reduced flow because clearance of l33Xe from disease and by medical and neurological examinations
bordering zones obscures them (so-called "look showing hypertension, cerebral arteriosclerosis by
through" phenomenon). There are other problems neurovascular examination (bruits, hypertensive ret-
which impair the resolving powers of the 133Xe method inal changes, etc.) and focal neurological signs. The
including Compton scatter and lack of knowledge of cognitive deficits were confirmed by the Mini-Mental
brain-tissue solubility coefficients (IA). Status examination (MMQ) of Jacobs, et al33 modified
With the advent of computerized reconstruction after that described by Folstein, et al.34 Scores in nor-
techniques for transmission and emission tomography mal age-matched volunteers are between 29-31 but the
it is now possible to image the brain in three dimen- patient's scores were between 11-20 (table 1).
sions with high resolution. Positron emission tomog- The patient's ages ranged from 57 to 85 years with a
raphy provides considerable advantages of measuring mean age of 71.5 ± 10.1. All patients had a history of
both blood flow and metabolism but has the disadvan- chronic but not malignant or accelerated hypertension,
tages of enormous cost, prolonged time consumption recurrent attacks of cerebral ischemia including tran-
for patients and investigators and relatively poor reso- sient ischemic attacks, reversible ischemic neurologi-
lution compared to computerized x-ray transmission cal deficits and small strokes. Patients with large or
tomography.22-23 aphasic strokes were excluded. All showed evidence
TABLE 1 Case Series
Case Age MABP PECOj Ischemic MMQ
numbers (in years) Gender (mmHg) (mmHg) score value
1 84 F 110 34.6 11 15
2 72 F 104 38.5 7 13
3 54 M 129 34.2 9 17
4 65 M 97 35.6 9 11
5 81 M 98 37.1 8 18
6 72 M 123 34.2 11 20
7 79 M 110 35.7 7 19
8 75 M 97 35.9 12 13
9 85 F 100 28.7 7 16
10 60 F 109 35.9 10 18
11 57 M 99 35.7 9 19
12 74 F 93 33.0 10 14
13 79 F 97 40.2 9 19
14 77 F 93 34.2 7 14
15 59 F 89 35.7 7 16
Mean values 71.5±10.1 7M.8F 103.2± 11.2 35.3±2.6 8.9±1.7 16.1 ±2.7
