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Objectives In addition to motor symptoms, patients with Parkinson disease (PD) experience various psychiatric comorbidities, including impulse control disorders (ICDs). Moreover, antiparkinsonian drugs sometimes cause psychiatric symptoms. Antiparkinsonian and antipsychotic drugs are competitive in pharmacodynamics, and psychotropic drugs, including antidepressants, may worsen motor symptoms or induce adverse reactions. Considering this conflicting situation, we examined the effectiveness of electroconvulsive therapy (ECT) on both motor and psychiatric symptoms in PD. Methods We retrospectively examined 12 PD patients with advanced motor symptoms and drug-resistant psychiatric symptoms, including ICDs, who had undergone ECT. Both before and after ECT, the severity of PD motor symptoms were evaluated using Hoehn and Yahr staging, while psychiatric symptoms were evaluated using the Neuropsychiatric Inventory. The patients' doses of antiparkinsonian and antipsychotic drugs were also assessed before and after ECT. Results Both the mean Hoehn and Yahr and Neuropsychiatric Inventory scores were significantly decreased after ECT. The symptoms of ICDs, which were observed in 5 patients, disappeared following ECT. Improvements in motor symptoms and psychiatric symptoms lasted for more than 1 year in 5 cases and 9 cases, respectively. Furthermore, the daily dose of antiparkinsonian drugs was significantly decreased in 6 cases. Conclusions Our results demonstrated that ECT was effective for both severe motor symptoms and psychiatric symptoms in advanced PD patients. ECT might be a solution for the conflicting problem of treating both motor and psychiatric symptoms in PD.

Aim Although dementia with Lewy bodies (DLB) is characterized by a variety of initial symptoms, there are almost no reports of the initial symptoms of DLB assessed in a large number of cases. We retrospectively evaluated the initial symptoms of 234 participants with DLB and DLB-related symptoms at diagnosis and characterized any gender differences in the symptom profiles. Methods This study consisted of 234 participants with probable DLB who met the diagnostic criteria outlined in the Fourth Consensus Report of the DLB Consortium (2017). DLB was confirmed based on several characteristic biomarkers for dopamine transporter imaging with 123 I-N-omega-fluoropropyl-2-beta-carbomethoxy-3-beta (4-iodophenyl) nortropane single-photon emission computed tomography, 123 I-metaiodobenzylguanidine myocardial scintigraphy, and brain perfusion measured with single photon emission computed tomography. In addition, core and supportive clinical features were considered in the diagnosis. Results Initial symptoms included cognitive impairment (41.9%) and psychiatric symptoms (i.e. visual and auditory hallucinations, delusions, and depression) (42.3%). Almost half of the women initially presented with psychiatric symptoms, with significantly more women than men presenting with auditory hallucinations. In contrast, men had a significantly higher rate of rapid eye movement sleep behaviour disorder (RBD) than women did. At diagnosis, DLB-related symptoms differed between men and women, with male patients exhibiting significantly more RBD, parkinsonism, hyposmia, and syncope than female patients. Moreover women presented significantly more often with auditory hallucinations than did men. Conclusions Our results indicate that there are gender differences in the initial symptoms of DLB, as well as in the presentation of subsequent symptoms observed at diagnosis. There was a higher incidence of RBD in men, whereas women had a higher incidence of psychotic symptoms.

Nutritional epidemiology has shown the importance of protein intake for maintaining brain function in the elderly population. Mild cognitive impairment (MCI) may be associated with malnutrition, especially protein intake. We explored blood-based biomarkers linking protein nutritional status with MCI in a multicenter study. In total, 219 individuals with MCI (79.5 ± 5.7 year) from 10 institutions and 220 individuals who were cognitively normal (CN, 76.3 ± 6.6 year) in four different cities in Japan were recruited. They were divided into the training (120 MCI and 120 CN) and validation (99 MCI and 100 CN) groups. A model involving concentrations of PFAAs and albumin to discriminate MCI from CN individuals was constructed by multivariate logistic regression analysis in the training dataset, and the performance was evaluated in the validation dataset. The concentrations of some essential amino acids and albumin were significantly lower in MCI group than CN group. An index incorporating albumin and PFAA discriminated MCI from CN participants with the AUC of 0.705 (95% CI: 0.632–0.778), and the sensitivities at specificities of 90% and 60% were 25.3% and 76.8%, respectively. No significant association with BMI or APOE status was observed. This cross-sectional study suggests that the biomarker changes in MCI group may be associated with protein nutrition.

Background: Many cases of dementia with Lewy bodies (DLB) present with various psychotic features, including hallucinations, depression, catatonia, and delusions before the onset of cognitive impairment. However, the characteristic features of these psychotic symptoms in prodromal DLB have not been sufficiently described. Objective: To clarify and describe the psychotic features of prodromal DLB before overt cognitive impairment. Methods: The authors analyzed the characteristic psychotic features of prodromal DLB in 21 subjects who developed severe psychotic symptoms without dementia and were diagnosed as DLB after the longitudinal observation period. They were then confirmed to have DLB through indicative and supportive biomarkers of scintigraphy. Results: The psychotic features included a wide variety of symptoms, but convergent to three principal categories: catatonia, delusions-hallucinations, and depression and/or mania. Catatonia was observed in nine cases, five were delusional-hallucinatory, and seven were manic and/or depressive. Seven of the 21 cases exhibited delirium during longitudinal observation. A psychotic state repeatedly appeared without any trigger in 20 of the 21 patients. All subjects developed cognitive impairment at 9.1±4.6 (mean±SD) years after the initial appearance of psychotic symptoms, and subsequently diagnosed with DLB at 71.3±6.1 (mean±SD) years. Conclusion: Elderly patients with psychotic symptoms, such as catatonia, delusion-hallucination, manic and/or depressive features, and delirium without dementia, could indicate symptomatic psychosis or a prodromal stage of any neurocognitive disorder such as DLB. Therefore, further extensive workout (e.g., radioisotope neuroimaging) is required to avoid misdiagnosis.

BACKGROUND Familial idiopathic basal ganglia calcification (FIBGC) is a rare autosomal dominant disorder that causes bilateral calcification of the basal ganglia and/or cerebellar dentate nucleus, among other locations. CASE SUMMARY The aim of this study is to report 10 cases of FIBGC observed in a single family. Seven patients showed calcification on their computed tomography scan, and all of these patients carried the SLC20A2 mutation. However, individuals without the mutation did not show calcification. Three patients among the 7 with calcification were symptomatic, while the remaining 4 patients were asymptomatic. Additionally, we longitudinally observed 10 subjects for ten years. In this paper, we mainly focus on the clinical course and neuroradiological findings in the proband and her son. CONCLUSION The accumulation of more case reports and further studies related to the manifestation of FIBGC are needed.

Aim People living with early-onset dementia (EOD) have specific social needs. Epidemiological studies are needed to obtain current information and provide appropriate service planning. This study aimed to clarify the current prevalence and subtype distribution of EOD, as well as the services frequently used by individuals with EOD. Methods A multisite, population-based, two-step study was conducted. Questionnaires were sent to 26 416 candidate facilities in 12 areas with a target population of 11 630 322 to inquire whether any individuals with EOD had sought services or stayed during the last 12 months (step 1). When "yes" responses were received, additional questionnaires were sent to the facilities both to complete and to distribute to the target individuals with EOD to obtain more detailed information, including the dementia subtype (step 2). Results In step 1, valid responses were obtained from 16 848 facilities (63.8%), and 4077 cases were identified. In step 2, detailed information was obtained for 1614 cases (39.6%) from the facilities and 530 cases (13.0%) from the individuals. The national EOD prevalence rate was estimated to be 50.9/100 000 population at risk (95% confidence interval: 43.9-57.9; age range, 18-64 years). The number of individuals with EOD was estimated to be 35 700 as of 2018. Alzheimer-type dementia (52.6%) was the most frequent subtype, followed by vascular dementia (17.1%), frontotemporal dementia (9.4%), dementia due to traumatic brain injury (4.2%), dementia with Lewy bodies/Parkinson's disease dementia (4.1%), and dementia due to alcohol-related disorders (2.8%). Individuals with EOD were most frequently identified at medical centers for dementia. Conclusion The prevalence rate estimated in this study was comparable to those in previous studies in Japan. However, the subtype distribution differed, with Alzheimer-type dementia being the most prominent. Based on the case identification frequencies, medical centers for dementia are expected to continue to function as the primary special health service by providing quality diagnosis and post-diagnostic support for individuals with EOD.

Background and purposeWe previously reported the usefulness of iodine-123 metaiodobenzylguanidine (123I-MIBG) myocardial scintigraphy for differentiation of dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) in a cross-sectional multicentre study. The aim of this study was, by using reassessed diagnosis after 3-year follow-up, to evaluate the diagnostic accuracy of 123I-MIBG scintigraphy in differentiation of probable DLB from probable AD.MethodsWe undertook 3-year follow-up of 133 patients with probable or possible DLB or probable AD who had undergone 123I-MIBG myocardial scintigraphy at baseline. An independent consensus panel made final diagnosis at 3-year follow-up. Based on the final diagnosis, we re-evaluated the diagnostic accuracy of 123I-MIBG scintigraphy performed at baseline.ResultsSixty-five patients completed 3-year follow-up assessment. The final diagnoses were probable DLB (n=30), possible DLB (n=3) and probably AD (n=31), and depression (n=1). With a receiver operating characteristic curve analysis of heart-to-mediastinum (H/M) ratios for differentiating probable DLB from probable AD, the sensitivity/specificity were 0.77/0.94 for early images using 2.51 as the threshold of early H/M ratio, and 0.77/0.97 for delayed images using 2.20 as the threshold of delayed H/M ratio. Five of six patients who were diagnosed with possible DLB at baseline and with probable DLB at follow-up had low H/M ratio at baseline.ConclusionsOur follow-up study confirmed high correlation between abnormal cardiac sympathetic activity evaluated with 123I-MIBG myocardial scintigraphy at baseline and the clinical diagnosis of probable DLB at 3-year follow-up. Its diagnostic usefulness in early stage of DLB was suggested.Trial registration numberUMIN00003419.

Because dementia with Lewy bodies (DLB) has various psychiatric symptoms, early diagnosis in patients without parkinsonism is difficult. To reveal associations between regional brain perfusion and psychiatric symptoms in DLB patients without parkinsonism, we quantified brain perfusion using an automated brain perfusion single-photon emission computed tomography analysis program, FineSRT. We statistically analyzed the differences in brain perfusion between groups, divided by the presence or absence of psychiatric symptoms. In DLB patients with depression, there were significant brain perfusion increases in the left angular gyrus and right upper precuneus. In DLB patients with visual hallucinations, there were significant decreases in the left inferior parietal lobule, left superior temporal gyrus, and right primary visual cortex. In DLB patients with auditory hallucinations, there were significant increases in the right middle occipital and right inferior occipital gyri. Our findings provide clues about the pathomechanisms of psychiatric symptoms and may enable early diagnosis of DLB in the future.

Background Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT), 123 I-metaiodobenzylguanidine myocardial scintigraphy (MIBG scintigraphy), and DAT-SPECT. Taking finances and patient burden into consideration, we compared the tests to determine priority. Methods Thirty-four patients with probable DLB (75.0 ± 8.3 years old; 14 men, 20 women) underwent bp-SPECT, MIBG scintigraphy, and DAT-SPECT. Results Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine-transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp-SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group. Conclusions In terms of stand-alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT-SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp-SPECT, MIBG scintigraphy, and DAT-SPECT increased the accuracy of the clinical diagnosis of DLB.

Objective: Memantine is a noncompetitive N-methyl-D-aspartate receptor (NMDAR)ant agoni st that im proves or stabilizes cognitive impairment in moderate to severeAlzheimer’s disease (AD). However, the effects of memantine on regional brain metabolic activity and perfusion are not fully known. To clarify these effects, we investigated the efficacyof memantine monotherapy using multimodal neuroimaging in drug-naive patients withmoderate AD. Methods: This was a prospective open-labeled study of patients with drug- naive modera teAD ( Mini-Mental State Examination scores of 14-19) before and after 12 weeks of treatmentwith memantine, conducted between April 2015 and December 2016. Imaging was performedusing 18F-fluorodeoxyglucose-positron emission tomography (18F-FDG-PET) and 99mTcethylcysteinate dimer-single photon emission computed tomography (99mTc-ECD-SPECT),to assess brain metabolic activity and perfusion, respectively. The imaging data, registered toa probabilistic anatomical atlas, were evaluated by voxel-based analysis. Results: A total of 20 patients were enrolled and 17 patients’ datasets were a nalyzed. T heaver age Mini-Mental State Examination was 16.6 (1.8) at baseline and 16.9 (4.1) posttreatment.The average Neuropsychiatric Inventory score was 2.8 (7.6) at baseline and 3.9(9.2) post-treatment. Brain regions with increased metabolic activity following memantinetreatment in previously drug-naive AD patients included a wide range of cerebral cortexes, particularly the right inferior pari etal lobule, right supramarginal gyrus, right angular gyru s,and right paracentral lobule (p < 0.01, paired t-test). Only small regions had increased brainperfusion (p < 0.01, paired t-test). Conclusion: We believe this is the first stu dy focusing on brain metabolic activity and perfusioni n the same drug-naive moderate AD patients before and after memantine treatment. Therewere inconsistencies between the regions with increased metabolic activity and perfusionafter memantine treatment in drug-naive AD patients, suggesting that brain metabolism mayincrease without a concurrent increase in blood perfusion. This study may help elucidate themechanism of action of memantine.

Current diagnostic criteria recommend neuroimaging as a diagnostic support tool for the clinical diagnosis of dementia with Lewy bodies (DLB). Because DLB causes characteristic impairments and disabilities, such as neuroleptic hypersensitivity, which may significantly increase morbidity and mortality, its prompt and correct diagnosis is very important. The aim of this study was to evaluate the extent to which diagnostic accuracy can be increased by using different combinations of brain perfusion single-photon emission computed tomography (bp-SPECT),Thirty-four patients with probable DLB (75.0 ± 8.3 years old; 14 men, 20 women) underwent bp-SPECT, MIBG scintigraphy, and DAT-SPECT.Our comparison of three functional imaging techniques indicated that MIBG scintigraphy (79%) and Dopamine-transporter (DAT) SPECT (79%) had better sensitivity for characteristic abnormalities in DLB than bp-SPECT (53%). The combination of the three modalities could increase sensitivity for diagnosis of DLB to 100%. Additionally, the ratio of patients with rapid eye movement sleep behaviour disorder was significantly higher in the positive finding group on MIBG scintigraphy than in the negative finding group.In terms of stand-alone diagnostic means, priority should be placed on MIBG scintigraphy or DAT-SPECT for the diagnosis of DLB. However, our results suggest that the combination of bp-SPECT, MIBG scintigraphy, and DAT-SPECT increased the accuracy of the clinical diagnosis of DLB.

In the latest criteria for the clinical diagnosis of dementia with Lewy bodies (DLB), supportive features include generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity. In this study, we investigated the usefulness of a cerebral blood flow (CBF) quantification program '3DSRT' in detecting occipital hypoperfusion in DLB. Twenty two patients with probable DLB, 38 patients with probable Alzheimer's disease (AD) and 16 normal controls underwent brain perfusion SPECT. Compared with AD, DLB patients had a bilateral lower CBF in the posterior cerebral segments. The correlation of clinical symptoms and brain blood perfusion was examined by dividing the subjects into subgroups. DLB patients with Parkinsonism, when compared to non-Parkinsonism subgroup, had a lower CBF throughout the cerebrum with statistical significance in the posterior cerebral segments. The quantitative analysis of brain perfusion SPECT by 3DSRT could be a useful supportive measurement in the diagnosis of DLB.

Donepezil, an acetylcholinesterase inhibitor, has been reported to have an effect that improves cerebral blood flow (CBF) alongside its primary effect on memory function. The aim of this study was to investigate the effects of long-term, low-dose donepezil therapy on blood perfusion in Alzheimer's disease (AD) by using a fully automated regional CBF quantification program named 3DSRT.Fifteen subjects with mild to moderate AD according to NINCDS/ADRDA criteria underwent 99mTc-ethylcysteinate dimer (ECD) brain perfusion single photon emission computed tomography (SPECT) twice with an interval of 55.1 +/- 11.0 weeks. The dose of donepezil was fixed at 5 mg/day following the induction period (3 mg/day) of 2 weeks. Clinical efficacy of donepezil was assessed by using the Mini-Mental State Examination (MMSE). The results of SPECT imaging under exactly identical conditions were analyzed by 3DSRT, which enables us to perform a very objective assessment.Despite a decrease of the MMSE score from 20.9 +/- 4.7 to 18.7 +/- 5.7, CBF was increased in almost all cerebral areas except the left temporal segment. The increase was statistically significant in the left callosomarginal, right central, and bilateral pericallosal and lenticular nucleus segments.Thus far, no direct cerebrovascular effects have been reported for donepezil. We hypothesize that these CBF-promoting effects of donepezil might be related to increased neuronal activity and enhanced connection of neurons.

Aim: The Apolipoprotein E (APOE) e4 allele is a risk factor for developing Alzheimer’s disease (AD), however its impact on cerebral functional changes in AD remains controversial. Previous studies reported conflicting results or failed to confirm any association, possibly because they failed to consider either the effect of patient age at onset or that of clinical stage. We performed functional neuroimaging studies using current improved techniques to re-examine the effect of APOE e4 allele, taking both the age at onset and clinical stage into account. Methods: 111 late onset AD (LOAD) subjects were divided into 3 subgroups based on Clinical Dementia Rating (CDR). We investigated the influence of e4 allele on functional cerebral changes in each group of LOAD by using cutting-edge analysis software, 3DSRT. Results: The APOE e4 allele was significantly associated with relatively preserved cerebral blood flow in the cerebral cortices. The influence of APOE e4 allele is not apparent in the mild stage, but is significantly demonstrable in the moderate stage. Conclusion: Dividing AD subjects into subgroups based on the severity as well as the age at onset is important for precise outcomes. This study may help resolve the uncertainties of previous studies which reported conflicting results or failed to confirm any association. We believe this is the first study focused on the effect of APOE e4 allele on functional cerebral changes at each stage of AD.

Background The apolipoprotein E (APOE) e4 allele has been reported to be a risk factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). Previous neuropathological studies have demonstrated similar frequencies of the APOE e4 allele in AD and DLB. However, the few ante-mortem studies on APOE allele frequencies in DLB have shown lower frequencies than post-mortem studies. One reason for this may be inaccuracy of diagnosis. We examined APOE genotypes in subjects with AD, DLB, and a control group using the latest diagnostic criteria and MRI, SPECT, and MIBG myocardial scintigraphy. Methods The subjects of this study consisted of 145 patients with probable AD, 50 subjects with probable DLB, and a control group. AD subjects were divided into two groups based on age of onset: early onset AD (EOAD) and late onset AD (LOAD). All subjects had characteristic features on MRI, SPECT, and/or myocardial scintigraphy. Results The rate of APOE4 carrier status was 18.3% and the frequency of the e4 allele was 9.7% in controls. The rate of APOE4 carrier status and the frequency of the e4 allele were 47% and 27% for LOAD, 50% and 31% for EOAD, and 42% and 31% for DLB, respectively. Conclusion The APOE4 genotypes in this study are consistent with previous neuropathological studies suggesting accurate diagnosis of AD and DLB. APOE4 genotypes were similar in AD and DLB, giving further evidence that the e4 allele is a risk factor for both disorders.

Alzheimer's disease (AD) differs from other forms of dementia in its relation to amyloid β peptide (Aβ). Aβ, a proteolytic product of amyloid precursor proteins (APP), has a toxic effect on neuronal cells, which involves perturbation of their Ca2+ homeostasis. This effect implies that changes of protein expression in neuronal cells with calcium stress should provide a molecular marker for this disease. In the present study, we used the supernatant from a neuronal cell culture after incubation with or without Aβ and isolated a Ca2+-dependent acidic phospholipid binding fraction to perform a proteomic study. Several unique proteins were identified after incubation with Aβ. We focused on annexin A5, among these proteins, because it binds both Ca2+ and lipids likely to be involved in calcium homeostasis. Tg2576 transgenic mice (AD model) overexpressing mutant human APP showed a significant increase of annexin A5 in the brain cortex but not in other organs, including liver, kidney, lung, and intestine. In human plasma samples, the level of annexin A5 was significantly increased in a proportion of AD patients compared with a control group (P < 0.0001 in the logistic regression analysis). From the receiver operating characteristic (ROC) curve with plasma annexin A5 concentrations, the mean area under the curve (AUC 0.898) suggests that annexin A5 is a favorable marker for AD. © 2010 Wiley-Liss, Inc.

Background/Aims: It is often difficult to distinguish idiopathic normal pressure hydrocephalus (iNPH) from other neurodegenerative disorders such as Alzheimer’s disease (AD). To understand the characteristic pattern of blood flow in iNPH, we performed brain perfusion SPECT and analyzed the results by using the easy Z-score imaging system (eZIS). Methods: Subjects were 12 patients with probable iNPH and 10 probable AD patients with prominent ventriculomegaly. They underwent brain perfusion SPECT using 99mTc-ethylcysteinate dimer as a tracer. Results: The two-tailed view display in eZIS demonstrated an obvious two-layer structure consisting of decreased blood flow around the corpus callosum and, in iNPH, enhanced perfusion in areas surrounding the cingulate gyrus in the sagittal view, while no AD cases showed these findings. Conclusion: Hypoperfusion around the corpus callosum in iNPH could be, at least partially, a false-positive finding due to an insufficient anatomical standardization of SPECT images caused by an abnormally enlarged ventricle. Increased blood perfusion in the external layer adjacent to the hypoperfused area might be caused by increased radioisotope count per volume resulting from exclusion of cerebral cortex by a dilated ventricle. Our results demonstrate that a two-layer appearance revealed by the two-tailed view analysis of brain perfusion SPECT using eZIS could be a means to detect iNPH.

Background: Supportive features in the diagnostic criteria for dementia with Lewy bodies (DLB) include occipital hypoperfusion and decreased cardiac uptake of 123I-metaiodobenzylguanidine (MIBG). In this study, we performed both brain perfusion single photon emission computed tomography (SPECT) and MIBG myocardial scintigraphy in the same subjects and evaluated their sensitivity to detect the characteristic features of DLB. Methods: Twenty-five patients with probable DLB (76.8 ± 5.1 years old, 10 male) underwent 99mTc-ethylcysteinate dimer brain perfusion SPECT and 123I-MIBG myocardial scintigraphy. The results of SPECT were analyzed using a qualitative analysis program, easy Z score imaging system (eZIS), and an automated quantitative analysis program, 3DSRT. Results: Qualitative analysis using eZIS demonstrated occipital hypoperfusion in 17 subjects (68%). The quantified mean blood perfusion in the occipital segment on the 3DSRT template was 40.7 ± 5.03 ml/100 g/min (right) and 40.5 ± 5.38 ml/100 g/min (left), and in 19 DLB patients these values were below the normal limit. Twenty-four of 25 subjects (96%) had decreased cardiac MIBG uptake in the delayed image. Conclusion: MIBG myocardial scintigraphy was superior to brain perfusion SPECT in detecting a characteristic feature of DLB. Our results suggest that combining SPECT and MIBG scintigraphy could increase the accuracy of clinical diagnosis of DLB.

Purpose The clinical symptoms of Alzheimer's disease (AD) show great diversity depending on the clinical stage. We investigated the correlation of regional cerebral blood flow (rCBF) changes and the clinical severity of AD patients. Methods Thirty-nine AD patients and 16 normal subjects participated in this study. AD patients were divided into three subgroups by clinical severity. Quantitative brain perfusion SPECT analyses were performed using a rCBF quantification software, 3DSRT. Results In mild AD, significant decreases of rCBF were detected in the bilateral parietal, angular gyrus, pericallosal, thalamus, right temporal and left hippocampal regions. Moderate AD patients showed significantly lower blood flow than those with mild AD only to the right hippocampus. Analysis of the severe AD group revealed a nearly diffuse decrease of rCBF throughout the cerebral cortex except for part of the frontal lobe compared with moderate patients. Conclusions These results were consistent with previous findings demonstrated by qualitative analysis of CBF. The decreased thalamic blood flow was noteworthy as this finding has rarely been reported. In consideration of the structure and function of the Papez circuit, which connects the medial temporal lobe and thalamus, a remote metabolic effect might be the cause of lower rCBF in the thalamus.