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A comparative SPECT study of regional brain perfusion in patients with Alzheimer's disease, progressive supranuclear palsy, and corticobasal degeneration
International Congress Series 1232 (2002) 579 – 582
A comparative SPECT study of regional brain perfusion in patients with Alzheimer’s disease, progressive supranuclear palsy, and corticobasal degeneration Keita Kawabata *, Hisao Tachibana, Shuhei Kasama Division of Neurology, 5th Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Abstract To investigate the underlying mechanism of dementing illnesses that comprise tauopathy, we evaluated the regional cerebral blood flow (rCBF) of patients with Alzheimer’s disease (AD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), and of normal control subjects using single-photon emission computed tomography (SPECT) with 123I-iodoamphetamine as the tracer. rCBF was evaluated semiquantitatively by using the ratio of the RI count to the occipital region count, and the asymmetry index. Compared with the normal controls, AD patients showed significantly decreased rCBF in the inferior and lateral prefrontal, temporal, and posterior parietal cortices, while CBD patients showed significant rCBF reduction in the inferior prefrontal, anterior cingulate, medial premotor, temporal, posterior parietal, and sensorimotor cortices, thalamus, and basal ganglia. PSP patients showed no rCBF reduction in any region. Compared with PSP patients, CBD patients showed significant rCBF reduction in the sensorimotor cortex. Compared with CBD patients, AD patients showed significant rCBF reduction in the posterior parietal cortex, while rCBF in the sensorimotor cortex of the CBD patients was significantly decreased compared to the AD patients. Asymmetry of rCBF was observed in the lateral prefrontal and posterior parietal cortices of the AD patients and in the inferior prefrontal and sensorimotor cortices of the CBD patients. In conclusion, AD patients were characterized by reduced rCBF in the temporoparietal cortex. Although the magnitude of the rCBF reduction was mild in CBD, the decreases extended widely over the subcortical/cortical areas. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Tauopathy; Cerebral blood flow; SPECT;
123
I-iodoamphetamine
*
Corresponding author. Tel.: +81-798-45-6596; fax: +81-798-45-6597. E-mail address: [email protected] (K. Kawabata).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 7 3 9 - 7
580
K. Kawabata et al. / International Congress Series 1232 (2002) 579–582
1. Background Recent developments in molecular neuropathology have shown that Alzheimer’s disease (AD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) are included in the concept of tauopathy. To investigate the underlying mechanism of these diseases from the aspect of brain perfusion, we evaluated regional cerebral blood flow (rCBF) in AD, CBD, and PSP and normal control subjects by single-photon emission computed tomography (SPECT) with 123I-iodoamphetame as the tracer.
2. Subjects The clinical characteristics of the patients are summarized in Table 1. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. PSP was diagnosed by the NINDS-SPSP criteria for probable PSP [1]. The diagnostic criteria for CBD were according to Lang et al. [2]: slowly progressive course, asymmetric akinetic-rigid syndrome, asymmetric limb apraxia, no resting tremor or autonomic disturbance, no beneficial effect of levodopa, and no space occupying or cerebrovascular lesions in the cerebral cortex or basal ganglia on MRI [2].
3. Methods rCBF was measured by SPECT with 123I-iodoamphetamine as the tracer. The SPECT procedure was according to the standard protocol for a single-head rotating gamma-camera (Starcam, General Electric) [3]. rCBF was evaluated semiquantitatively by using ratio of the RI count to the count in the occipital region (rCBF index) and the asymmetry index (= 2L R/(L+R)). Group differences in rCBF and asymmetry indices were tested by ANOVA and Bonferroni’s multiple comparisons. A level of P<0.05 was accepted as statistically significant.
Table 1 Characteristics of the AD, CBD, and PSP patients, and normal control subjects
PSP CBD AD Controls
Number of cases
Age (years)
Duration of illness (years)
MMSE
Motor disability
5 9 16 12
69.8F3.9 70.7F6.6 68.7F9.2 68.2F10.3
3.4F1.1 2.2F0.8 2.8F1.8
18.8F3.8 23.6F5.2 14.3F5.5*
3.8F0.7 3.0F1.3
MMSE: Mini-Mental State examination. Motor disability was evaluated by Hoehn and Yahr’s scale. Values are meansFS.D. * P < 0.05 compared with CBD patients.
K. Kawabata et al. / International Congress Series 1232 (2002) 579–582
581
4. Results For rCBF indices, two-way ANOVA yielded significant main effects for both the groups and cerebral regions ( F = 7.580, P = 0.0004 for the groups and F = 94.86, P < 0.0001 for the regions, respectively) and for interaction between them ( F = 6.199, P < 0.0001), and one-way ANOVA showed significant group differences, except in the cerebellum. The results of Bonferroni’s multiple comparisons are listed in Table 2. Compared with normal control subjects, the AD patients showed significantly decreased rCBF indices in the inferior and lateral prefrontal, temporal, and posterior parietal cortices, while the CBD patients showed significant rCBF reduction in the inferior prefrontal, anterior cingulate, medial premotor, temporal, posterior parietal, and sensorimotor cortices, thalamus, and basal ganglia. The PSP patients showed no rCBF reduction in any regions compared with the normal controls. Compared with PSP, the CBD patients showed a significant reduction in rCBF in the sensorimotor cortex. Compared with CBD, the AD patients showed a significant rCBF reduction in the posterior parietal cortex, while rCBF in the sensorimotor cortex of the CBD patients was significantly decreased compared to the AD patients. For asymmetry indices, two-way ANOVA showed significant main effects for both the groups ( F = 6.266, P = 0.0015) and the cerebral regions ( F = 4.874, P < 0.0001), and for interference ( F = 3.182, P < 0.0001). One-way ANOVA showed significant group differences in the lateral and inferior frontal, medial premotor, posterior parietal, and sensorimotor cortices. The results of Bonferroni’s multiple comparisons are listed in Table 3. Asymmetry of Table 2 Comparison of the rCBF indices of the patients and normal control subjects Regions
Control
PSP
CBD
AD
PSP/CBD
CBD/AD
AD/PSP
Medial prefrontal Lateral prefrontal Inferior prefrontal Anterior cingulate Medial premotor Temporal Occipital Posterior parietal Sensorimotor Thalamus Basal ganglia Cerebellum
0.85F0.08
0.73F0.11
0.77F0.07
0.76F0.10
ns
ns
ns
0.79F0.08
0.77F0.07
0.72F0.09
0.67F0.10*
ns
ns
ns
0.85F0.05
0.82F0.04
0.73F0.07*
0.74F0.09*
ns
ns
ns
0.81F0.06
0.72F0.11
0.67F0.05*
0.74F0.09
ns
ns
ns
0.90F0.04
0.82F0.07
0.77F0.05*
0.85F0.11
ns
ns
ns
0.90F0.04 1.00F0 0.85F0.04
0.84F0.06 1.00F0 0.85F0.07
0.78F0.05* 1.00F0 0.77F0.06*
0.76F0.07* 1.00F0 0.64F0.08*
ns ns ns
ns ns P<0.05**
ns ns P<0.05**
0.83F0.04 0.94F0.07 0.93F0.06 0.95F0.07
0.84F0.06 0.86F0.10 0.87F0.11 1.00F0.05
0.72F0.02* 0.81F0.05* 0.79F0.07* 0.93F0.09
0.84F0.07 0.90F0.08 0.89F0.10 1.00F0.12
P<0.05*** ns ns ns
P<0.05*** ns ns ns
ns ns ns ns
Values are meansFS.D. ns: not significant. * P<0.05 compared with normal controls. ** P<0.05: AD
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K. Kawabata et al. / International Congress Series 1232 (2002) 579–582
Table 3 Comparison of the asymmetry indices of the patients and normal control subjects Regions
Control
Medial prefrontal Lateral prefrontal Inferior prefrontal Anterior cingulate Medial premotor Temporal Occipital Posterior parietal Sensorimotor Thalamus Basal ganglia Cerebellum
PSP
CBD
AD
PSP/CBD
CBD/AD
AD/PSP
0.034F0.022 0.079F0.038 0.056F0.049
0.047F0.037
ns
ns
ns
0.046F0.040 0.048F0.027 0.060F0.047
0.143F0.094* ns
P<0.05**
P<0.05**
0.047F0.031 0.027F0.024 0.135F0.052* 0.071F0.055
P<0.05*** P<0.05*** ns
0.064F0.055 0.055F0.069 0.070F0.052
0.055F0.039
ns
ns
ns
0.083F0.056 0.041F0.042 0.047F0.036
0.031F0.034* ns
ns
ns
0.042F0.037 0.088F0.056 0.070F0.081 0.065F0.06 0.026F0.026 0.054F0.040 0.040F0.038 0.055F0.038 0.112F0.060
0.110F0.092 ns 0.049F0.032 ns 0.157F0.110* ns
ns ns ns
ns ns ns
0.037F0.023 0.046F0.023 0.041F0.038 0.020F0.016
0.054F0.070 0.073F0.061 0.087F0.074 0.042F0.044
P<0.05*** ns ns ns
ns ns ns ns
0.066F0.034 0.049F0.035 0.055F0.033 0.037F0.027
0.135F0.085* 0.077F0.064 0.117F0.095 0.049F0.042
ns ns ns ns
Values are meansFS.D. ns: not significant. * P<0.05 compared with normal controls. ** P<0.05: AD > CBD or PSP. *** P<0.05: CBD>PSP or AD.
rCBF was observed in the lateral prefrontal and posterior parietal cortices of the AD patients and in the inferior prefrontal and sensorimotor cortices of the CBD patients.
5. Comment The AD patients showed characteristic rCBF reductions in the temporoparietal cortex, consistent with the findings in our previous study [4]. Although the magnitude of the rCBF reduction was mild in CBD, the decreases extended widely over the subcortical/cortical areas. Our findings suggest that these three types of tauopathy exhibit characteristic rCBF patterns that may be associated with their pathophysiological features.
References [1] I. Litvan, et al., Clinical research criteria for the diagnosis of progressive supranuclear palsy: report of the NINDS-SPSP international workshop, Neurology 47 (1) (1996) 1 – 9. [2] A.E. Lang, et al., Parietal Pick’s disease mimicking cortical – basal ganglionic degeneration, Neurology 44 (1994) 1436 – 1440. [3] B. Okuda, et al., Cerebral blood flow correlates of higher brain dysfunctions in corticobasal degeneration, J. Geriatr. Psychiatry Neurol. 12 (4) (1999) 189 – 193. [4] K. Kawabata, et al., Cerebral blood flow and dementia in Parkinson’s disease, J. Geriatr. Psychiatry Neurol. 4 (1991) 194 – 203.
A comparative SPECT study of regional brain perfusion in patients with Alzheimer’s disease, progressive supranuclear palsy, and corticobasal degeneration Keita Kawabata *, Hisao Tachibana, Shuhei Kasama Division of Neurology, 5th Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Japan
Abstract To investigate the underlying mechanism of dementing illnesses that comprise tauopathy, we evaluated the regional cerebral blood flow (rCBF) of patients with Alzheimer’s disease (AD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP), and of normal control subjects using single-photon emission computed tomography (SPECT) with 123I-iodoamphetamine as the tracer. rCBF was evaluated semiquantitatively by using the ratio of the RI count to the occipital region count, and the asymmetry index. Compared with the normal controls, AD patients showed significantly decreased rCBF in the inferior and lateral prefrontal, temporal, and posterior parietal cortices, while CBD patients showed significant rCBF reduction in the inferior prefrontal, anterior cingulate, medial premotor, temporal, posterior parietal, and sensorimotor cortices, thalamus, and basal ganglia. PSP patients showed no rCBF reduction in any region. Compared with PSP patients, CBD patients showed significant rCBF reduction in the sensorimotor cortex. Compared with CBD patients, AD patients showed significant rCBF reduction in the posterior parietal cortex, while rCBF in the sensorimotor cortex of the CBD patients was significantly decreased compared to the AD patients. Asymmetry of rCBF was observed in the lateral prefrontal and posterior parietal cortices of the AD patients and in the inferior prefrontal and sensorimotor cortices of the CBD patients. In conclusion, AD patients were characterized by reduced rCBF in the temporoparietal cortex. Although the magnitude of the rCBF reduction was mild in CBD, the decreases extended widely over the subcortical/cortical areas. D 2002 Elsevier Science B.V. All rights reserved. Keywords: Tauopathy; Cerebral blood flow; SPECT;
123
I-iodoamphetamine
*
Corresponding author. Tel.: +81-798-45-6596; fax: +81-798-45-6597. E-mail address: [email protected] (K. Kawabata).
0531-5131/02 D 2002 Elsevier Science B.V. All rights reserved. PII: S 0 5 3 1 - 5 1 3 1 ( 0 1 ) 0 0 7 3 9 - 7
580
K. Kawabata et al. / International Congress Series 1232 (2002) 579–582
1. Background Recent developments in molecular neuropathology have shown that Alzheimer’s disease (AD), corticobasal degeneration (CBD), and progressive supranuclear palsy (PSP) are included in the concept of tauopathy. To investigate the underlying mechanism of these diseases from the aspect of brain perfusion, we evaluated regional cerebral blood flow (rCBF) in AD, CBD, and PSP and normal control subjects by single-photon emission computed tomography (SPECT) with 123I-iodoamphetame as the tracer.
2. Subjects The clinical characteristics of the patients are summarized in Table 1. AD was diagnosed by the NINCDS-ADRDA criteria for probable AD. PSP was diagnosed by the NINDS-SPSP criteria for probable PSP [1]. The diagnostic criteria for CBD were according to Lang et al. [2]: slowly progressive course, asymmetric akinetic-rigid syndrome, asymmetric limb apraxia, no resting tremor or autonomic disturbance, no beneficial effect of levodopa, and no space occupying or cerebrovascular lesions in the cerebral cortex or basal ganglia on MRI [2].
3. Methods rCBF was measured by SPECT with 123I-iodoamphetamine as the tracer. The SPECT procedure was according to the standard protocol for a single-head rotating gamma-camera (Starcam, General Electric) [3]. rCBF was evaluated semiquantitatively by using ratio of the RI count to the count in the occipital region (rCBF index) and the asymmetry index (= 2L R/(L+R)). Group differences in rCBF and asymmetry indices were tested by ANOVA and Bonferroni’s multiple comparisons. A level of P<0.05 was accepted as statistically significant.
Table 1 Characteristics of the AD, CBD, and PSP patients, and normal control subjects
PSP CBD AD Controls
Number of cases
Age (years)
Duration of illness (years)
MMSE
Motor disability
5 9 16 12
69.8F3.9 70.7F6.6 68.7F9.2 68.2F10.3
3.4F1.1 2.2F0.8 2.8F1.8
18.8F3.8 23.6F5.2 14.3F5.5*
3.8F0.7 3.0F1.3
MMSE: Mini-Mental State examination. Motor disability was evaluated by Hoehn and Yahr’s scale. Values are meansFS.D. * P < 0.05 compared with CBD patients.
K. Kawabata et al. / International Congress Series 1232 (2002) 579–582
581
4. Results For rCBF indices, two-way ANOVA yielded significant main effects for both the groups and cerebral regions ( F = 7.580, P = 0.0004 for the groups and F = 94.86, P < 0.0001 for the regions, respectively) and for interaction between them ( F = 6.199, P < 0.0001), and one-way ANOVA showed significant group differences, except in the cerebellum. The results of Bonferroni’s multiple comparisons are listed in Table 2. Compared with normal control subjects, the AD patients showed significantly decreased rCBF indices in the inferior and lateral prefrontal, temporal, and posterior parietal cortices, while the CBD patients showed significant rCBF reduction in the inferior prefrontal, anterior cingulate, medial premotor, temporal, posterior parietal, and sensorimotor cortices, thalamus, and basal ganglia. The PSP patients showed no rCBF reduction in any regions compared with the normal controls. Compared with PSP, the CBD patients showed a significant reduction in rCBF in the sensorimotor cortex. Compared with CBD, the AD patients showed a significant rCBF reduction in the posterior parietal cortex, while rCBF in the sensorimotor cortex of the CBD patients was significantly decreased compared to the AD patients. For asymmetry indices, two-way ANOVA showed significant main effects for both the groups ( F = 6.266, P = 0.0015) and the cerebral regions ( F = 4.874, P < 0.0001), and for interference ( F = 3.182, P < 0.0001). One-way ANOVA showed significant group differences in the lateral and inferior frontal, medial premotor, posterior parietal, and sensorimotor cortices. The results of Bonferroni’s multiple comparisons are listed in Table 3. Asymmetry of Table 2 Comparison of the rCBF indices of the patients and normal control subjects Regions
Control
PSP
CBD
AD
PSP/CBD
CBD/AD
AD/PSP
Medial prefrontal Lateral prefrontal Inferior prefrontal Anterior cingulate Medial premotor Temporal Occipital Posterior parietal Sensorimotor Thalamus Basal ganglia Cerebellum
0.85F0.08
0.73F0.11
0.77F0.07
0.76F0.10
ns
ns
ns
0.79F0.08
0.77F0.07
0.72F0.09
0.67F0.10*
ns
ns
ns
0.85F0.05
0.82F0.04
0.73F0.07*
0.74F0.09*
ns
ns
ns
0.81F0.06
0.72F0.11
0.67F0.05*
0.74F0.09
ns
ns
ns
0.90F0.04
0.82F0.07
0.77F0.05*
0.85F0.11
ns
ns
ns
0.90F0.04 1.00F0 0.85F0.04
0.84F0.06 1.00F0 0.85F0.07
0.78F0.05* 1.00F0 0.77F0.06*
0.76F0.07* 1.00F0 0.64F0.08*
ns ns ns
ns ns P<0.05**
ns ns P<0.05**
0.83F0.04 0.94F0.07 0.93F0.06 0.95F0.07
0.84F0.06 0.86F0.10 0.87F0.11 1.00F0.05
0.72F0.02* 0.81F0.05* 0.79F0.07* 0.93F0.09
0.84F0.07 0.90F0.08 0.89F0.10 1.00F0.12
P<0.05*** ns ns ns
P<0.05*** ns ns ns
ns ns ns ns
Values are meansFS.D. ns: not significant. * P<0.05 compared with normal controls. ** P<0.05: AD
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K. Kawabata et al. / International Congress Series 1232 (2002) 579–582
Table 3 Comparison of the asymmetry indices of the patients and normal control subjects Regions
Control
Medial prefrontal Lateral prefrontal Inferior prefrontal Anterior cingulate Medial premotor Temporal Occipital Posterior parietal Sensorimotor Thalamus Basal ganglia Cerebellum
PSP
CBD
AD
PSP/CBD
CBD/AD
AD/PSP
0.034F0.022 0.079F0.038 0.056F0.049
0.047F0.037
ns
ns
ns
0.046F0.040 0.048F0.027 0.060F0.047
0.143F0.094* ns
P<0.05**
P<0.05**
0.047F0.031 0.027F0.024 0.135F0.052* 0.071F0.055
P<0.05*** P<0.05*** ns
0.064F0.055 0.055F0.069 0.070F0.052
0.055F0.039
ns
ns
ns
0.083F0.056 0.041F0.042 0.047F0.036
0.031F0.034* ns
ns
ns
0.042F0.037 0.088F0.056 0.070F0.081 0.065F0.06 0.026F0.026 0.054F0.040 0.040F0.038 0.055F0.038 0.112F0.060
0.110F0.092 ns 0.049F0.032 ns 0.157F0.110* ns
ns ns ns
ns ns ns
0.037F0.023 0.046F0.023 0.041F0.038 0.020F0.016
0.054F0.070 0.073F0.061 0.087F0.074 0.042F0.044
P<0.05*** ns ns ns
ns ns ns ns
0.066F0.034 0.049F0.035 0.055F0.033 0.037F0.027
0.135F0.085* 0.077F0.064 0.117F0.095 0.049F0.042
ns ns ns ns
Values are meansFS.D. ns: not significant. * P<0.05 compared with normal controls. ** P<0.05: AD > CBD or PSP. *** P<0.05: CBD>PSP or AD.
rCBF was observed in the lateral prefrontal and posterior parietal cortices of the AD patients and in the inferior prefrontal and sensorimotor cortices of the CBD patients.
5. Comment The AD patients showed characteristic rCBF reductions in the temporoparietal cortex, consistent with the findings in our previous study [4]. Although the magnitude of the rCBF reduction was mild in CBD, the decreases extended widely over the subcortical/cortical areas. Our findings suggest that these three types of tauopathy exhibit characteristic rCBF patterns that may be associated with their pathophysiological features.
References [1] I. Litvan, et al., Clinical research criteria for the diagnosis of progressive supranuclear palsy: report of the NINDS-SPSP international workshop, Neurology 47 (1) (1996) 1 – 9. [2] A.E. Lang, et al., Parietal Pick’s disease mimicking cortical – basal ganglionic degeneration, Neurology 44 (1994) 1436 – 1440. [3] B. Okuda, et al., Cerebral blood flow correlates of higher brain dysfunctions in corticobasal degeneration, J. Geriatr. Psychiatry Neurol. 12 (4) (1999) 189 – 193. [4] K. Kawabata, et al., Cerebral blood flow and dementia in Parkinson’s disease, J. Geriatr. Psychiatry Neurol. 4 (1991) 194 – 203.