亀山 征史

Amyloid-beta (Aβ) plays a pivotal role in cognitive decline in Parkinson's disease (PD). The prevalence of amyloid positivity, evaluated using the cerebrospinal fluid (CSF) of patients with PD without dementia in their sixties, is lower than that in individuals with normal cognition without PD diagnosis in the same age range. However, it is unclear whether this is also the case in patients with PD without dementia in their eighties. Eighty-nine patients with PD without dementia were retrospectively classified into two groups with a cut-off age of 73 years at diagnosis: a HIGH group and a LOW group, with mean age at diagnosis of 80.2 and 64.9 years, respectively. The prevalence of amyloid positivity was significantly higher in the HIGH (30.6%) than in the LOW group (10.0%) (p = 0.02). The prevalence of amyloid positivity in both groups was lower than that in participants with normal cognition in the same age range. Our findings may be attributed to the shorter preclinical stage of asymptomatic cerebral Aβ deposition in PD, resulting from Aβ accelerating the transition from the asymptomatic to dementia stage. We believe that our findings will incentivize further studies to identify the best disease-modifying therapy for early PD without dementia.

BACKGROUND: Argyrophilic grain disease (AGD) is a four-repeat tauopathy characterized by the accumulation of argyrophilic grains. Its primary clinical manifestation is late-onset amnestic dementia. While the extension of argyrophilic grains to the substantia nigra may be related to its potential association with parkinsonism, biochemical analyses are lacking. OBJECTIVES: To elucidate the extent of AGD to the midbrain, including the substantia nigra, using histopathological examination and biochemical analysis in a pathologically proven case of AGD presenting with parkinsonism and cognitive impairment. METHODS: We describe the case of a patient suggestive of progressive supranuclear palsy. Neuropathological and biochemical investigations were performed. RESULTS: Neurological examination of an 80-year-old man with a 6-year history of gait disturbance revealed parkinsonism, including gait freezing, postural instability, bradykinesia, and cognitive impairment. The patient was diagnosed with progressive supranuclear palsy with progressive gait freezing. Five years later, the patient reported falling backward repeatedly, became wheelchair-bound, and died of pneumonia. Macroscopic observations revealed marked amygdala atrophy. Microscopic findings revealed argyrophilic grains in the limbic system, compatible with Saito stage III, as well as in the substantia nigra and midbrain tegmentum. Western blotting showed an AGD-specific band pattern, and immunoelectron microscopy analyses showed an AGD-specific tau filament of abnormally phosphorylated tau in both the nucleus accumbens and midbrain. CONCLUSIONS: This report further confirmed that AGD presents with parkinsonism, commensurate with AGD pathology and biochemical findings extending to the midbrain. Therefore, AGD should be considered in the differential diagnosis of cases presenting with parkinsonism and cognitive impairment in the older population.

Argyrophilic grain disease is an age-related disorder characterized by the presence of argyrophilic grains. Argyrophilic grain disease has a sequential distribution pattern that begins in the ambient gyrus (Saito Stage I), spreads to the medial temporal lobe (Saito Stage II) and reaches the basal forebrain and cingulate gyrus (Saito Stage III). A strong association with cognitive decline, especially in cases of Saito Stage III argyrophilic grain disease, has also been reported. The main clinical feature includes cognitive decline characterized by memory disturbance, although conflicting results have been reported. Recent studies suggest an association with parkinsonism. To clarify the association between argyrophilic grain disease, cognitive decline and parkinsonism, we performed a clinicopathological study using the Brain Bank for Aging Research autopsy cohort in Japan. Approximately half (227) of the 452 consecutive autopsy cases had argyrophilic grain disease, and the frequency and stage of argyrophilic grain disease increased with age. Among the argyrophilic grain disease cases, 20 were demented without any comorbid pathology responsible for it, a condition referred to as dementia with grains. Furthermore, 6 of the 20 dementia with grains cases presented with parkinsonism, particularly postural instability, in addition to memory disturbance. Dementia with grains cases with parkinsonism had significantly more argyrophilic grains in the substantia nigra than those without parkinsonism and showed significantly decreased anti-dopamine transporter immunoreactivity in the putamen compared to control cases. Given these findings, argyrophilic grain disease is strongly associated with cognitive decline, especially in Saito Stage III cases, and parkinsonism is a new common clinical presentation. The extension of argyrophilic grain disease pathology to the nigrostriatal system may contribute to the development of parkinsonism.

<jats:title>Abstract</jats:title><jats:p>Although α-synuclein seed amplification assays (α-syn SAA) are promising, its sensitivity may be affected by heterogeneity among patients with Lewy body disease (LBD). We evaluated whether α-syn SAA sensitivity is affected by patient heterogeneity, using <jats:sup>123</jats:sup>I-meta-iodobenzylguanidine (MIBG) cardiac scintigraphy in early drug-naïve patients. Thirty-four patients with clinically established or probable Parkinson’s disease (PD) and seven with dementia with Lewy bodies (DLB) or prodromal DLB were included. While 85.2% of patients with abnormal cardiac MIBG were α-syn SAA positive, only 14.3% were positive among those with normal scans. Logistic regression analysis showed that MIBG positivity was the only significant variable associated with α-syn SAA positivity (odds ratio 74.2 [95% confidence interval 6.1–909]). Although α-syn SAA is sensitive for LBD in patients with abnormal MIBG, the sensitivity may be lower in those with normal MIBG. Further studies are necessary to evaluate the association between patient heterogeneity and α-syn SAA sensitivity.</jats:p>

Currently, monoamine oxidase B is recognized as the primary target of 18F-THK5351, although 18F-THK5351 was initially developed to target neurofibrillary tangles (NFTs) in Alzheimer disease. When clinically applying 18F-THK5351 PET to visualize ongoing astrogliosis via estimating monoamine oxidase B levels, a crucial concern is how much degree 18F-THK5351 uptake reflects NFTs in in vivo images. To unravel this concern, a head-to-head comparison between 18F-THK5351 and 18F-MK-6240 (estimating NFT) images in the NFT lesion ideally without accompanying astrogliosis is essential. Here, we present such a case suggesting that 18F-THK5351 uptake may not estimate NFTs in in vivo images.

Argyrophilic grain disease (AGD) is one of the major pathological backgrounds of senile dementia. Dementia with grains refers to cases of dementia for which AGD is the sole background pathology responsible for dementia. Recent studies have suggested an association between dementia with grains and parkinsonism. In this study, we aimed to present two autopsy cases of dementia with grains. Case 1 was an 85-year-old man who exhibited amnestic dementia and parkinsonism, including postural instability, upward gaze palsy, and neck and trunk rigidity. The patient was clinically diagnosed with progressive supranuclear palsy and Alzheimer's disease. Case 2 was a 90-year-old man with pure amnestic dementia, clinically diagnosed as Alzheimer's disease. Recently, we used cryo-electron microscopy to confirm that the tau accumulated in both cases had the same three-dimensional structure. In this study, we compared the detailed clinical picture and neuropathological findings using classical staining and immunostaining methods. Both cases exhibited argyrophilic grains and tau-immunoreactive structures in the brainstem and basal ganglia, especially in the nigrostriatal and limbic systems. However, Case 1 had more tau immunoreactive structures. Considering the absence of other disease-specific structures such as tufted astrocytes, astrocytic plaques and globular glial inclusions, lack of conspicuous cerebrovascular disease, and no history of medications that could cause parkinsonism, our findings suggest an association between AGD in the nigrostriatal system and parkinsonism.

<jats:p>Background. Although patients can present with progressive pseudobulbar palsy due to neurodegenerative diseases, detection of the precise location of radiological abnormalities can be difficult. 18F-THK5351 was initially developed as a tau positron emission tomography (PET) tracer. Later, it was found to sensitively detect astrogliosis associated with neurodegeneration. Therefore, it has been used in diagnosis of various diseases. However, its utility in progressive pseudobulbar palsy was unknown. Methods. 18F-THK5351 PET results of two patients presenting with progressive pseudobulbar palsy are reported. Results. Patient 1 was a 77-year-old man with a two-year history, and Patient 2 was a 61-year-old woman with a 1-year history. Both patients presented with gradually progressive spastic dysarthria, suggesting pseudobulbar palsy without clinical lower motor neuron signs. Facial asymmetry was detected in both patients, while left-dominant pyramidal signs in the extremities were detected only in Patient 2. Brain magnetic resonance imaging did not show signal abnormality explaining pseudobulbar palsy. However, 18F-THK5351 PET clearly visualized bilateral increased uptake in limited areas of the posterior portion of the precentral gyrus, corresponding to the midportion of the primary motor cortex. Laterality of increased 18F-THK5351 uptake corresponded to the symptom laterality and was higher on the left and right side in patients 1 and 2, respectively. After one year, Patient 1 was unable to vocalize and could only produce grunts; concomitant apraxia of speech was suspected. Conclusions. 18F-THK5351 PET is a useful method to detect bilateral primary motor cortex involvement in patients presenting with progressive pseudobulbar palsy, likely by imaging astrogliosis.</jats:p>

BACKGROUND: The cingulate island sign (CIS) ratio is a diagnostic adjunct for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). A recent study showed that the CIS ratio in DLB changed depending on the Mini-Mental State Examination (MMSE) score. We aimed to evaluate whether the diagnostic performance (sensitivity and specificity) of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score. METHODS: Twenty-two patients with DLB and 26 amyloid-positive patients with AD, who underwent 18F-FDG PET and completed an MMSE examination, were classified into three groups according to MMSE scores: Group A (MMSE >24), Group B (20 ≤ MMSE ≤24), and Group C (MMSE <20). In each group, we compared the CIS ratio between patients with DLB and AD and conducted receiver operating characteristic (ROC) curve analysis to calculate the sensitivity and specificity. RESULTS: Within Group B, the CIS ratio in DLB was significantly higher than that in AD (p = 0.0005), but not within Groups A (p = 0.5117) and C (p = 0.8671). ROC curve analyses showed that the sensitivities and specificities of the CIS ratio for differentiating DLB from AD were 66.7% and 77.8% in Group A, 91.7% and 100.0% in Group B, and 75.0% and 66.7% in Group C, respectively. CONCLUSIONS: The present study suggests that the diagnostic performance of the CIS ratio for differentiating DLB from AD changes depending on the MMSE score, with higher sensitivity and specificity at MMSE scores of 20-24.

The recent evolution of artificial intelligence (AI) can be considered life-changing. In particular, there is great interest in emerging hot topics in AI such as image classification and natural language processing. Our world has been revolutionized by convolutional neural networks and transformer for image classification and natural language processing, respectively. Moreover, these techniques can be used in the field of dementia. We introduce some applications of AI systems for treating and diagnosing dementia, including image-classification AI for recognizing facial features associated with dementia, image-classification AI for classifying leukoaraiosis in MRI images, object-detection AI for detecting microbleeding in MRI images, object-detection AI for support care, natural language-processing AI for detecting dementia within conversations, and natural language-processing AI for chatbots. Such AI technologies can significantly transform the future of dementia diagnosis and treatment. Geriatr Gerontol Int 2023; ••: ••-••.

BACKGROUND: Hemoglobin A1c (HbA1c) levels are low in patients with hemolytic anemia, as HbA1c reflects mean erythrocyte age (MRBC ). Erythrocyte creatine (EC) is a hemolytic indicator that also reflects MRBC . We previously reported an equation for estimating MRBC using EC (EC-MRBC ). AIMS: In this study, EC-MRBC was compared to the HbA1c level expressed in the International Federation of Clinical Chemistry and Laboratory Medicine units (iA1c) and to the iA1c/glycated albumin (GA) ratio to estimate MRBC . METHODS: This study included 238 subjects, including patients with hemolytic anemia and/or type 2 diabetes mellitus (T2DM). RESULTS: In non-diabetic individuals, both iA1c and iA1c/GA showed a strong positive correlation with EC-MRBC (p < 0.0001). The equations to estimate iA1c-MRBC and iA1c/GA-MRBC derived from the regression equations between EC-MRBC and iA1c, and EC-MRBC and iA1c/GA in nondiabetic individuals were 1.45 × iA1c and 20.0 × iA1c/GA, respectively. iA1c-MRBC and iA1c/GA-MRBC in non-diabetic individuals without hemolytic anemia were 57.6 ± 4.0 and 57.1 ± 6.4 days, respectively, and iA1c/GA-MRBC in T2DM patients without hemolytic anemia was 56.0 ± 8.8 days.; no significant difference was seen in the comparisons. CONCLUSIONS: The MRBC can be estimated using iA1c or iA1c/GA in non-diabetic individuals, and iA1c/GA in T2DM patients.

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59-86 years) and a disease duration of 2 years (0.5-7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

Abstract Both cerebrospinal fluid (CSF) homovanillic acid (HVA) and striatal dopamine transporter (DAT) binding on single-photon emission computed tomography (SPECT) reflect nigrostriatal dopaminergic function, but studies on the relationship between the two have been limited. It is also unknown whether the reported variance in striatal DAT binding among diseases reflects the pathophysiology or characteristics of the subjects. We included 70 patients with Parkinson’s disease (PD), 12 with progressive supranuclear palsy (PSP), 12 with multiple system atrophy, six with corticobasal syndrome, and nine with Alzheimer’s disease as disease control, who underwent both CSF analysis and ¹²³I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl)nortropane (¹²³I-ioflupane) SPECT. We evaluated the correlation between CSF HVA concentration and the specific binding ratio (SBR) of striatal DAT binding. We also compared the SBR for each diagnosis, controlling for CSF HVA concentration. The correlations between the two were significant in patients with PD (r = 0.34, p = 0.004) and PSP (r = 0.77, p = 0.004). The mean SBR value was the lowest in patients with PSP and was significantly lower in patients with PSP than in those with PD (p = 0.037) after adjusting for CSF HVA concentration. Our study demonstrates that striatal DAT binding correlates with CSF HVA concentration in both PD and PSP, and striatal DAT reduction would be more advanced in PSP than in PD at an equivalent dopamine level. Striatal DAT binding may correlate with dopamine levels in the brain. The pathophysiology of each diagnosis may explain this difference.

PURPOSE: In Lewy body diseases (LBD), various symptoms occur depending on the distribution of Lewy body in the brain, and the findings of brain perfusion and dopamine transporter single-photon emission computed tomography (DAT-SPECT) also change accordingly. We aimed to evaluate the correlation between brain perfusion SPECT and quantitative indices calculated from DAT-SPECT in patients with LBD. PROCEDURES: We retrospectively enrolled 35 patients with LBD who underwent brain perfusion SPECT with N-isopropyl-p-[123I] iodoamphetamine and DAT-SPECT with 123I-ioflupane. Mini-mental state examination (MMSE) data were also collected from 19 patients. Quantitative indices (specific binding ratio [SBR], putamen-to-caudate ratio [PCR], and caudate-to-putamen ratio [CPR]) were calculated using DAT-SPECT. These data were analysed by the statistical parametric mapping procedure. RESULTS: In patients with LBD, decreased PCR index correlated with hypoperfusion in the brainstem (medulla oblongata and midbrain) (uncorrected p < 0.001, k > 100), while decreased CPR index correlated with hypoperfusion in the right temporoparietal cortex (family-wise error corrected p < 0.05), right precuneus (uncorrected p < 0.001, k > 100), and bilateral temporal cortex (uncorrected p < 0.001, k > 100). However, there was no significant correlation between decreased SBR index and brain perfusion. Additionally, the MMSE score was correlated with hypoperfusion in the left temporoparietal cortex (uncorrected p < 0.001). CONCLUSIONS: This study suggests that regional changes in striatal 123I-ioflupane accumulation on DAT-SPECT are related to brain perfusion changes in patients with LBD.

OBJECTIVES: Whereas HbA1c values are low relative to glycemia in patients with hemolytic anemia, including compensatory anemia, low HbA1c levels along with negative results for conventional hemolysis indicators have been reported in patients with latent hemolysis. Conversely, glycated albumin (GA) is a glycemic control indicator unaffected by hemolysis. Erythrocyte creatine (EC) is a hemolysis indicator that reflects the mean age of red blood cells (MRBC). We recently reported a formula for obtaining MRBC based on EC. The present study examined the usefulness of EC measurements and MRBC calculated with EC for diagnosing latent hemolysis. MATERIALS AND METHODS: Two patients with latent hemolysis and low HbA1c values relative to glycemia were investigated, while controls comprised 214 patients (including patients with hemolysis and/or type 2 diabetes mellitus). HbA1c was expressed in International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) units (iA1c). GA/iA1c ratios, reticulocyte counts, EC, and MRBC in patients with latent hemolysis were compared to non-hemolysis, compensatory hemolysis, and hemolytic anemia patients. RESULTS: Both reticulocyte counts and haptoglobin levels were within reference ranges in patients with latent hemolysis. GA/iA1c ratios and EC were higher than reference values in patients with latent hemolysis, and MRBC values were 41.6 and 48.4 days, respectively, shorter than the reference range (49.1-66.8 days). CONCLUSIONS: EC measurement and MRBC values calculated on the basis of EC might be useful for diagnosing latent hemolysis.

BACKGROUND AND OBJECTIVES: 123I-meta-iodobenzyl-guanidine (123I-MIBG) myocardial scintigraphy is employed as a diagnostic imaging test to differentiate Lewy body diseases (LBDs), including Parkinson's disease and dementia with Lewy bodies, from other similar diseases. However, its diagnostic accuracy lacks validation compared with that of the gold standard. We aimed to validate the diagnostic accuracy of 123I-MIBG myocardial scintigraphy for LBD against autopsy, the gold standard. METHODS: This retrospective, cross-sectional study included consecutive autopsy patients from the Brain Bank for Aging Research who had undergone 123I-MIBG myocardial scintigraphy. We compared the 123I-MIBG myocardial scintigraphy findings with autopsy findings. Furthermore, the proportion of residual tyrosine hydroxylase (TH)-immunoreactive sympathetic fibers in the anterior wall of the left ventricle was investigated to assess the condition of the cardiac sympathetic nerves assumed to cause reduced 123I-MIBG uptake in LBDs. RESULTS: We analyzed the data of 56 patients (30 with pathologically confirmed LBDs and 26 without LBD pathology). Compared with the neuropathological diagnosis, the early heart-to-mediastinum (H/M) ratio had a sensitivity and specificity of 70.0% (95% confidence interval [CI]: 50.6-85.3%) and 96.2% (95% CI: 80.4-99.9%), respectively. The delayed H/M ratio had a sensitivity and specificity of 80.0% (95% CI: 61.4-92.3%) and 92.3% (95% CI: 74.9-99.1%), respectively. The washout rate had a sensitivity and specificity of 80.0% (95% CI: 61.4-92.3%) and 84.6% (95% CI: 65.1-95.6%), respectively. The proportion of residual TH-immunoreactive cardiac sympathetic fibers strongly correlated with the amount of cardiac 123I-MIBG uptake when assessed with early and delayed H/M ratio values (correlation coefficient: 0.75 and 0.81, respectively; p < 0.001). DISCUSSION: This clinicopathological validation study revealed that 123I-MIBG myocardial scintigraphy could robustly differentiate LBDs from similar diseases. Abnormal 123I-MIBG myocardial scintigraphy findings strongly support the presence of LBD and cardiac sympathetic denervation. However, LBD pathology should not necessarily be excluded by normal myocardial scintigraphy results, especially when other biomarkers suggest the presence of comorbid Alzheimer's disease pathology. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that 123I-MIBG myocardial scintigraphy accurately identifies patients with LBD.

Shortening the amount of time required to acquire amyloid positron emission tomography (PET) brain images while maintaining the accuracy of quantitative evaluation would help to overcome motion artifacts associated with Alzheimer's disease patients. The present study aimed to validate the quantitative accuracy of [18F]florbetapir ([18F]FBP) imaging over a shorter acquisition duration. Forty participants were injected with [18F]FBP, and PET images were acquired for 50-55, 50-60, and 50-70 min after injection. Three physicians visually assessed the reprocessed [18F]FBP images using a binary scale to classify them as amyloid β (Aβ) negative or positive. A mean composite standard uptake value ratio (cSUVR) > 1.075 was defined as Aβ-positive based on receiver operating characteristic curves. Inter-reader and inter-acquisition duration agreements with visual assessment were evaluated using Cohen's kappa (κ). Binary visual discrimination of 102 for the 120 [18F]FBP images, was consistent among the three readers. Sixteen, sixteen, and fourteen of the 40 [18F]FBP images acquired for 50-55, 50-60, and 50-70 min after injection, respectively, were deemed Aβ-positive by visual assessment. The inter-rater agreement was high, and the inter-acquisition duration agreement was almost perfect. The cSUVR did not change significantly among the acquisition durations, and the acquisition duration did not affect the outcome of discrimination based on the cSUVR cutoff. A shorter acquisition duration changed the visual assessment outcomes. Stable quantitative values were derived from [18F]FBP images acquired within 5 min. cSUVR helped to improve the performance and confidence in the outcomes of visual assessment.

OBJECTIVE: The γ-Ray Evaluation with iodoamphetamine for Cerebral Blood Flow Assessment (REICA) is a new method for quantifying cerebral blood flow (CBF) using single-photon emission computed tomography (SPECT) and [123I]N-isopropyl-p-iodoamphetamine (123I-IMP). The present study aimed to validate the REICA method using data including acetazolamide challenge test. METHODS: The REICA and Graph-Plot (GP) methods were used to calculate mean CBF (mCBF) for 92 acquisitions (rest: 57, stress: 35) and cerebrovascular reactivity (CVR) in 33 patients. To obtain stress data, 15 mg/kg of acetazolamide was injected intravenously 10 min before the administration of 123I-IMP, and blood samples were collected under the same conditions as rest data. The reference standard was the Autoradiograph (ARG) method using arterial blood sampling, and the accuracy of the REICA method was analyzed by comparing it with each method. RESULTS: For mCBF, the correlation coefficients (r) were 0.792 for the REICA method and 0.636 for the GP method. For CVR, r values were 0.660 for the REICA method and 0.578 for the GP method. In both acquisitions, the REICA method had a stronger correlation with the ARG method than the GP method. For mCBF, there was a significant difference in the correlation coefficient between the two correlation coefficients (p < 0.01). CONCLUSIONS: The REICA method was more accurate than the GP method in quantifying CBF and closer to the ARG method. The REICA method, which is a noninvasive method of cerebral blood flow quantification using 123I-IMP, has great medical usefulness.

BACKGROUND AND PURPOSE: Little evidence exists on the role of type 1 metabotropic glutamate receptor (mGluR1) in the pathophysiology of Alzheimer's disease (AD), although mGluR1 may be involved in the regulation of neuronal excitability and synaptic plasticity. We have recently reported that mGluR1 availability in the early stage of AD is equivalent to that in healthy subjects. This study aimed to address whether mGluR1 availability changes with the progression of AD. METHODS: Eight patients with AD (79.1 ± 4.6 years) underwent a total of two positron emission tomography (PET) examinations using the mGluR1 radioligand during the early-to-middle stages of AD. The mean interval was 2.8 years. Volumes-of-interest were placed on the frontal, parietal, and temporal cortices, hippocampus, anterior and posterior lobes, and vermis in the cerebellum. The binding potential (BPND ) was calculated to estimate mGluR1 availability, applying partial volume correction to the BPND values. RESULTS: No significant difference was observed in BPND values between the first and second PET examinations in the frontal cortex (p = 0.94), parietal cortex (p = 0.67), temporal cortex (p = 0.20), hippocampus (p = 0.17), anterior lobe (p = 0.73), posterior lobe (p = 0.21), and vermis (p = 0.22). CONCLUSION: This study suggests that mGluR1 availability is unchanged in the follow-up period of a few years during the early-to-middle stages of AD.

Cerebral blood flow (CBF) / cerebral blood volume (CBV) ratio derived by [15O] H2O/ CO2 and CO positron emission tomography (PET) examination has been used as an index for cerebral perfusion pressure (CPP). CBF/CBV was demonstrated to be related mean arterial pressure (MAP) in baboons. However, this formula has not been confirmed to be proportionate to CPP. We have developed a new index for CPP using the Poiseuille equation based on a simple model. Our model suggests that CBF/CBV2 is proportionate to CPP and that it is mathematically a more accurate index than CBF/CBV. This new index needs experimental validation in the future.