Effect of cerebrospinal fluid area mask correction on 123I-FP-CIT SPECT images in idiopathic normal pressure hydrocephalus.

BACKGROUND: Cerebrospinal fluid (CSF) area mask correction reduces the influence of low [123I]-N-fluoropropyl-2b-carbomethoxy-3b-(4-iodophenyl) nortropane (123I-FP-CIT) accumulation in the volume of interest (VOI) by CSF area dilatation on the specific binding ratio (SBR) calculated using the Southampton method. We assessed the effect of CSF area mask correction on the SBR for idiopathic normal pressure hydrocephalus (iNPH) characterized by CSF area dilatation. METHODS: We enrolled 25 patients with iNPH who were assessed using 123I-FP-CIT single-photon emission computed tomography (SPECT) before shunt surgery or the tap test. The SBRs with and without CSF area mask correction were calculated, and changes in quantitative values were verified. Additionally, the number of voxels in the striatal and background (BG) VOI before and after CSF area mask correction were extracted. The number of voxels after correction was subtracted from that before correction, and the volume removed by the CSF area mask correction was calculated. The volumes removed from each VOI were compared to verify their effect on SBR. RESULTS: The images of 20 and 5 patients with SBRs that were decreased and increased, respectively, by CSF area mask correction showed that the volumes removed from the BG region VOI were higher and lower, respectively than those in the striatal region. CONCLUSIONS: The SBR before and after CSF area mask correction was associated with the ratio of the volume removed from the striatal and BG VOIs, and the SBR was high or low according to the ratio. The results suggest that CSF area mask correction is effective in patients with iNPH. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000044826. 11/07/2021.

Syntactic Impairment Associated with Hypoperfusion in the Left Middle and Inferior Frontal Gyri after Right Cerebellar Hemorrhage.

Cerebellar injuries can cause syntax impairments. Cortical dysfunction due to cerebello-cerebral diaschisis is assumed to play a role in this phenomenon. Functional magnetic resonance imaging studies have repeatedly shown the activation of Broca's area in response to syntactic tasks. However, there have been no reports of selective syntax impairment and hypoperfusion restricted to this area after cerebellar injury. We herein report a patient with right cerebellar hemorrhage that led to marked syntax impairment along with severe hypoperfusion confined to the Brodmann area (BA) 45 (anterior part of Broca's area) and BA46.

In vivo [18F]THK-5351 imaging detected reactive astrogliosis in argyrophilic grain disease with comorbid pathology: A clinicopathological study.

Quantification of in vivo reactive astrogliosis, which represents neural inflammation and remodeling in the brain, is an emerging methodology for the evaluation of patients with neurodegenerative diseases. [18F]THK-5351 is a positron emission tomography (PET) tracer for monoamine oxidase B (MAO-B), a molecular marker of reactive astrogliosis. We performed in vivo [18F]THK-5351 PET in a patient who at autopsy was found to have argyrophilic grain disease (AGD) with comorbid pathology to visualize reactive astrogliosis for the first time. We aimed to validate an imaging-pathology correlation using [18F]THK-5351 PET and the autopsy brain. The patient, a 78-year-old man, was pathologically diagnosed with AGD combined with limbic-predominant age-related transactive response DNA-binding protein of 43 kDa encephalopathy and Lewy body disease without Alzheimer disease-related neuropathological changes. Reactive astrogliosis in the postmortem brain was abundant in the inferior temporal gyrus, insular gyrus, entorhinal cortex, and ambient gyrus where premortem [18F]THK-5351 signals were high. We found a proportional correlation between the amount of reactive astrogliosis in the postmortem brain and the in vivo [18F]THK-5351 standardized uptake value ratio (r = 0.8535, p = 0.0004). These results indicated that reactive astrogliosis in AGD with comorbid pathology could be identified and quantified by in vivo MAO-B imaging.

Clinicopathological diversity of semantic dementia: Comparisons of patients with early-onset versus late-onset, left-sided versus right-sided temporal atrophy, and TDP-type A versus type C pathology.

Semantic dementia (SD) is a unique clinicopathological entity associated with TDP-type C pathology. We present four cases of SD that illustrate the clinicopathological diversity of TDP-43 pathology, including early-onset cases of TDP-type C with corticospinal tract (CST) and motor neuron pathology and late-onset cases of TDP-type A with combined pathology. Case 1 was a 62-year-old man with semantic variant of primary progressive aphasia (svPPA) with left-predominant temporal atrophy and TDP-type C pathology with low Alzheimer's disease neuropathologic changes (ADNC). Case 2 was a 63-year-old woman with right-predominant temporal atrophy and TDP-type C pathology who had prosopagnosia and personality changes. Phosphorylated(p)-TDP-43-positive long dystrophic neurites (DNs) were observed throughout the cerebral cortex; they were more abundant in the relatively spared cortices and less so in the severely degenerated cortices. We observed CST degeneration with TDP-43 pathology in the upper and lower motor neurons, without apparent motor symptoms, in SD with TDP-type C pathology. Case 3 was a 76-year-old man who had svPPA and personality changes, with left-predominant temporal atrophy and TDP-type A pathology with high ADNC and argyrophilic grain (AG) stage 3. Case 4 was an 82-year-old man who had prosopagnosia and later developed symptoms of dementia with Lewy bodies (DLB) with right-predominant temporal atrophy and TDP-type A pathology with high ADNC, DLB of diffuse neocortical type, and AG stage 3. The distribution of p-TDP-43-positive NCIs and short DNs was localized in the anterior and inferior temporal cortices. An inverse relationship between the extent of TDP pathology and neuronal loss was also observed in SD with TDP-type A pathology. In contrast, the extent of AD, DLB, and AG pathology was greater in severely degenerated regions. CST degeneration was either absent or very mild in SD with TDP-type A. Understanding the clinicopathological diversity of SD will help improve its diagnosis and treatment.

Valosin-containing protein Asp395Gly mutation in a patient with frontotemporal dementia: a case report.

BACKGROUND: Variants in the valosin-containing protein (VCP) gene were identified as one of the causes for inclusion body myopathy associated with Paget disease of the bone and frontotemporal dementia (FTD). Previously identified pathogenic variants in VCP are associated with frontotemporal lobar degeneration with TDP-43 inclusions (FTLD-TDP) pathologically, but p.Asp395Gly VCP was recently reported to cause familial FTD with tauopathy characterized by neurofibrillary tau tangles (NFT) and not FTLD-TDP. We describe the clinical and genetic findings of a patient with p.Asp395Gly valosin-containing protein (VCP), who was diagnosed with FTD without a family history and in the absence of muscle or bone disease comorbidity. CASE PRESENTATION: The patient was a 62-year-old man, who developed atypical depression at the age of 37 years. Subsequently, he presented with self-centered behavior at the age of 45 years. The self-centered behavior intensified from around the age of 50 years, which was accompanied by the development of executive dysfunction; therefore, he visited our hospital at 52 years of age. Magnetic resonance imaging revealed bilateral frontal lobe atrophy. Brain perfusion single-photon emission computed tomography revealed bilateral frontal lobe hypoperfusion. The patient fulfilled the diagnostic criteria for behavioral variant of FTD. Ten years after the diagnosis, computed tomography of the trunk and limbs, muscle biopsy, and bone scintigraphy revealed the absence of concomitant muscle and bone disease. The concentrations of cerebrospinal fluid (CSF) total tau and phosphorylated tau proteins were 389 pg/mL and 53.2 pg/mL (cut-off: 50 pg/mL), respectively. Genetic analyses were performed using the whole-exome and Sanger sequencing methods. We identified p.Asp395Gly VCP in this patient with pure FTD. CONCLUSIONS: p.Asp395Gly VCP was identified in a patient with likely sporadic FTD without concomitant muscle and bone disease. The CSF analysis suggested that our patient may have FTD due to NFT accumulation similar to the familial FTD patients with p.Asp395Gly VCP recently reported. Our findings suggest that a genetic search for the pathogenic variants of VCP should be considered not only for familial FTD, but also for patients with sporadic FTD, even in the absence of comorbid muscle or bone disease.

Comparing Medial Temporal Atrophy Between Early-Onset Semantic Dementia and Early-Onset Alzheimer's Disease Using Voxel-Based Morphometry: A Multicenter MRI Study.

BACKGROUND: Early-onset Semantic dementia (EOSD) and early-onset Alzheimer's disease (EOAD) are often difficult to clinically differentiate in the early stages of the diseases because of the overlaps of clinical symptoms such as language symptoms. We compared the degree of atrophy in medial temporal structures between the two types of dementia using the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). METHODS: The participants included 29 (age: 61.7±4.5 years) and 39 (age: 60.2±4.9 years) patients with EOSD and EOAD, respectively. The degree of atrophy in medial temporal structures was quantified using the VSRAD for magnetic resonance imaging data. Receiver operating characteristic (ROC) analysis was performed to distinguish patients with EOSD and EOAD using the mean Z score (Z-score) in bilateral medial temporal structures and the absolute value (laterality score) of the laterality of Z-score (| right-left |) for indicating the degree of asymmetrical atrophy in medial temporal structures. RESULTS: The EOSD group had significantly higher Z and laterality scores than the EOAD group (Zscores: mean ± standard deviation: 3.74±1.05 vs. 1.56±0.81, respectively; P<0.001; laterality score: mean ± standard deviation: 2.35±1.23 vs. 0.68±0.51, respectively; P<0.001). In ROC analysis, the sensitivity and specificity to differentiate EOSD from EOAD by a Z-score of 2.29 were 97% and 85%, respectively and by the laterality score of 1.05 were 93% and 85%, respectively. CONCLUSION: EOSD leads to more severe and asymmetrical atrophy in medial temporal structures than EOAD. The VSRAD may be useful to distinguish between these dementias that have several clinically similar symptoms.

Associations of the A118G OPRM1 polymorphism with sociotropy and interpersonal sensitivity.

BACKGROUND: The µ-opioid receptor (MOR) plays an important role in social bonding behaviors, while it is implicated in the pathophysiology of depression. It is shown that the A118G polymorphism (rs1799971) of the MOR gene (OPRM1) causes amino-acid exchange from Asn to Asp, and that this polymorphism is associated with altered mu-opioid receptor function. Meanwhile, sociotropy/autonomy and interpersonal sensitivity are personality vulnerabilities to depression characterized by distinctive interpersonal styles. The present study tested the hypothesis that the functional A118G OPRM1 polymorphism influences these personality traits. METHODS: The subjects were 402 physically and mentally healthy Japanese volunteers. Sociotropy and autonomy were measured by the Sociotropy-Autonomy Scale, and interpersonal sensitivity was evaluated by the Interpersonal Sensitivity Measure. The A118G polymorphism of the OPRM1 was determined by the PCR method. RESULTS: In one factor analysis of covariance, there were differences in scores of sociotropy (uncorrected p < .001, corrected p < .003) and interpersonal sensitivity (uncorrected p = .015, corrected p = .045), but not autonomy, among the A/A, A/G, and G/G genotypes. Post hoc LSD tests showed that sociotropy scores were higher in the A/A group than in the A/G (p = .029) and G/G (p < .001) groups, and higher in the A/G group than in the G/G group (p = .004). Interpersonal sensitivity scores were higher in the A/A group than in the A/G (p = .023) and G/G (p = .009) groups. CONCLUSION: This study suggests that the A118G OPRM1 polymorphism is associated with sociotropy and interpersonal sensitivity, interpersonal vulnerabilities to depression.

Non-pharmacological Approaches to Apathy and Depression: A Scoping Review of Mild Cognitive Impairment and Dementia.

Apathy and depression are frequently observed as behavioral and psychological symptoms of dementia, respectively, and are important for ensuring adequate care. This study aims to explore effective non-pharmacological interventions for apathy and depression with mild cognitive impairment (MCI) and dementia. Five search engines including PubMed, Scopus, CINAHL, PsycInfo, and Web of Science were used to extract relevant studies. Inclusion criteria were studies that involved participants who were diagnosed with MCI or dementia, included quantitative assessments of each symptom, and employed randomized controlled trials. Twenty studies were extracted, with interventions have been conducted in care facilities, the community, and hospitals. Participants in many studies had MCI or mild-to-moderate dementia but were not diagnosed with the subtypes of dementia. Few studies had set apathy and depression as the primary outcomes of non-pharmacological interventions. The findings suggested that emotional and stimulation-oriented approaches to apathy and depression would be useful for people with MCI or mild-to-moderate dementia. It would be helpful for therapists to assess the clinical features of the target symptoms for selecting suitable interventions. Additionally, increasing the number of randomized controlled trials focusing on apathy or depression as primary outcomes would offer a more definite conclusion for future systematic reviews.

Dopamine Transporter Imaging for Frontotemporal Lobar Degeneration With Motor Neuron Disease.

Introduction: Frontotemporal lobar degeneration (FTLD) is a clinical syndrome with pathological heterogeneity, including Pick's disease and trans-activating response region (TAR) DNA-binding protein with a molecular mass of 43 kDa (TDP-43) proteinopathy (FTLD-TDP). A previous study reported abnormal findings on dopamine transporter (DAT) imaging in 30% of patients with frontotemporal dementia (FTD) in FTLD. However, the previous study did not consider the pathological heterogeneity of FTD regarding the pathomechanism leading to abnormal DAT findings. Recently, abnormal DAT findings were reported in two patients with FTLD with motor neuron disease (MND), of which FTLD-TDP type B was the most common pathological presentation. This study investigated the DAT findings of patients with a final diagnosis of FTLD-MND to determine the frequency of occurrence of DAT abnormalities in FTLD-MND. Methods: Twenty patients with FTLD who underwent DAT single photon emission computed tomography (DAT-SPECT) were screened, and six patients with a final diagnosis of FTLD-MND were ultimately included. The patients' DAT-SPECT findings were analyzed visually and quantitatively. Neuronal loss and astrogliosis in brain regions (substantia nigra, caudate, and putamen) that could possibly affect DAT findings were evaluated in the three pathologically confirmed cases. Result: All six patients with FTLD-MND showed abnormal visual DAT-SPECT findings. In addition, in a quantitative assessment, the specific binding ratio in the striatum calculated by the Southampton method was below the lower limit of the 95% prediction interval of the healthy controls by age in all the present cases. Interestingly, three of the six patients showed abnormal findings on DAT-SPECT more than half a year before the onset of MND. Neuronal loss and astrogliosis in brain regions that may affect DAT findings were observed in three pathologically confirmed cases. Conclusion: Dopamine transporter single photon emission computed tomography revealed abnormal findings in patients with FTLD-MND, which may manifest even before the onset of MND symptoms. We believe that the possibility of future development of MND should be considered if DAT-SPECT shows abnormal findings in FTLD.

Clinicopathological heterogeneity of Alzheimer's disease with pure Alzheimer's disease pathology: Cases associated with dementia with Lewy bodies, very early-onset dementia, and primary progressive aphasia.

We report four cases depicting the heterogeneity of Alzheimer's disease (AD) associated with pure AD pathology. Case 1 was a 77-year-old man with a false positive diagnosis of dementia with Lewy bodies with reduced dopamine transporter uptake activity of the striatum but no Lewy body pathology. There were tau deposits in the large neurons in the putamen, which may be related to the development of parkinsonism. Case 2 was an AD patient in his early 30s who presented with a psychotic episode and a cognitive decline, and later developed myoclonus and seizures. He demonstrated considerable amyloid-beta deposits in the cerebral cortex, including cotton wool plaques, basal ganglia, and cerebellum. Tau deposits were also abundant in the cerebral neocortex, hippocampus, basal ganglia, and brain stem. Case 3 was a 60-year-old woman who exhibited typical symptoms characteristic of the logopenic variant of primary progressive aphasia (lvPPA). Case 4 was a 68-year-old man who exhibited the semantic variant of primary progressive aphasia (svPPA) plus repetition impairment, a rare case associated with AD pathology. In addition to tau pathology, astrocytic pathology was prominent in the white matter and cortical layers of the left temporoparietal cortices. While the main AD lesion in case 4 was evaluated by tau accumulation and astrogliosis in the left temporal lobe, that in case 3 in was evaluated by the same points in the left parietal lobe. Within the spectrum of lvPPA, case 4 may be regarded as a temporal variant of lvPPA presenting svPPA. The pathology of PPA associated with AD may have broader clinical manifestations than that in previously described cases. Case 4 also showed pathological features characteristic of cerebral amyloid angiopathy throughout the cerebral cortex. The distribution of tau and astrocytic pathologies in the cerebral cortex, basal ganglia, brain stem, and cerebellum may explain the various symptoms of atypical pure AD patients.

Oxytocin receptor polymorphism influences characterization of harm avoidance by moderating susceptibility to affectionless control parenting.

INTRODUCTION: Oxytocin receptor (OXTR) gene polymorphism reportedly moderates effects of negative environments during childhood on mental function and behavior such as depressive symptoms and externalizing problems. This study examined OXTR gene polymorphism effects on personality traits in healthy participants, considering interaction effects of polymorphism with affectionless control (AC) parenting which is one of the dysfunctional and pathogenic parenting styles. METHODS: For 496 Japanese volunteers, personality was evaluated using the Temperament and Character Inventory. The Parental Bonding Instrument, which has subscales of care and protection, was used to assess perceived parental rearing. AC parenting was defined as low care and high protection. A/G polymorphism of the OXTR gene (rs53576) was detected using TaqMan SNP Genotyping Assay. RESULTS: Two-way analysis of covariance revealed significant interaction effects between the genotype and the number of AC parents on scores of harm avoidance, with no significant main effect of genotype on any personality. Post-hoc analysis revealed that the harm avoidance scores were increased in a stepwise manner with respect to the increase of the number of AC parents in the A allele carriers. No similar association was observed in the A allele noncarriers. CONCLUSION: The results of this study suggest that OXTR polymorphism influences characterization of harm avoidance by moderating susceptibility to AC parenting.

Case Report: Changes in Regional Cerebral Blood Flow in Chronic Akathisia of a Depressed Patient Before and After Electroconvulsive Therapy Treatment.

Akathisia, which characterized by subjective restlessness and objective hyperactivity, is induced mostly by antipsychotics and antidepressants. Chronic akathisia is defined as persistence of symptoms for more than 3 months. The pathophysiology of chronic akathisia remains unclear. This report describes a depressed patient, a 66-year-old woman with a diagnosis of major depressive disorder, with chronic akathisia. Her regional cerebral blood flow (rCBF) was measured using single photon emission computed tomography (SPECT) before and after the treatment with electroconvulsive therapy (ECT). She had experienced akathisia-like symptoms three times prior because of risperidone, escitalopram, and clomipramine administration, accompanied by major depression. After levomepromazine was added to quetiapine to treat insomnia, she developed akathisia symptoms such as a sense of restlessness and inability to sit in one place for a few minutes. These antipsychotics were withdrawn. Propranolol was administered, leading to no apparent improvement for 8 months. After she was diagnosed as having major depressive disorder and chronic akathisia, she received 10 sessions of bilateral ECT. Her depressive symptoms improved greatly. Akathisia disappeared completely after ECT. SPECT revealed that rCBF was decreased in the middle frontal gyrus and parietal lobe, that it was increased in the thalamus, fusiform gyrus, and cerebellum before ECT, and that these abnormalities in rCBF were approaching normal levels after ECT. Findings presented in this report suggest ECT as a beneficial treatment for chronic akathisia. Altered rCBF in the middle frontal gyrus, parietal lobe, thalamus, fusiform gyrus, and cerebellum, and especially decreased rCBF in the parietal lobe, may be related to the pathophysiology of chronic akathisia.

Catatonia as the Initial Manifestation of Dementia with Lewy Bodies.

BACKGROUND Catatonia can occur in various neuropsychiatric disorders and is usually treated with benzodiazepines. So far, although 1 case of dementia with Lewy bodies (DLB) with catatonia has been reported, there have been no reports on patients with DLB whose initial symptom was a catatonia. Here, we present a patient who developed benzodiazepine-resistant catatonia and was subsequently diagnosed with DLB based on DLB biomarkers. CASE REPORT The patient was a 92-year-old woman who had not been diagnosed with dementia before. At the age of 91, she experienced catatonia and was initially treated with lorazepam, which did not improve her condition. Later, she transferred to our hospital and was treated with amantadine. Amantadine improved her catatonic symptoms; however, a decline in her cognitive function was observed. We therefore explored the cause of cognitive impairment through imaging studies. We found that the patient did not have the core clinical features of DLB (ie, visual hallucinations, parkinsonism, cognitive fluctuations, and rapid eye movement sleep behavior disorder) but had 2 indicative biomarkers on 123I-metaiodobenzylguanidine myocardial scintigraphy and dopamine transporter imaging. Possible DLB was diagnosed according to the diagnostic criteria. CONCLUSIONS Our case study suggests that catatonia can be an initial symptom of DLB. Moreover, considering the plausible pathophysiology of catatonia in DLB, amantadine treatment may be the most rational choice for the condition when benzodiazepine treatment is ineffective.

Comparison of the decreases in regional cerebral blood flow in the posterior cingulate cortex, precuneus, and parietal lobe between suspected non-Alzheimer's disease pathophysiology and Alzheimer's disease.

BACKGROUND: Suspected non-Alzheimer's disease pathophysiology (SNAP) shows Alzheimer's disease (AD)-like neurodegeneration; however, amyloid ß, which is a biological marker in AD, remains within normal levels. Since the effectiveness of anti-dementia drugs for AD on SNAP is unknown, it is important to distinguish between patients with SNAP and AD. We aimed to compare decreases in regional cerebral blood flow (rCBF) of the posterior cingulate cortex (PCC), precuneus, and parietal lobe critical to AD between SNAP and AD groups using the easy Z-score imaging system in single-photon emission computed tomography (eZIS-SPECT). METHODS: We retrospectively analysed eZIS-SPECT data of 13 SNAP and 24 AD patients. The three indicators (severity, extent, and ratio) that distinguished AD patients from healthy controls in previous studies were automatically calculated and were compared between the SNAP and AD groups. Receiver operating characteristic curve analysis and the area under the curve (AUC) were used to evaluate the diagnostic performance of the three indicators of eZIS in discriminating between the two groups. RESULTS: The mean values of severity, extent, and ratio were significantly lower in the SNAP group than in the AD group (P = 0.024, P = 0.044, and P = 0.045, respectively). The AUC values for severity, extent, and ratio were 0.668, 0.683, and 0.692, respectively. CONCLUSIONS: The present study suggests that SNAP shows milder reduction of rCBF in the PCC, precuneus, and parietal lobe as compared to AD. However, it may be difficult to distinguish between SNAP and AD with the degrees of decrease in rCBF in these regions.

Improvement of Somatic Delusions with Altered Regional Cerebral Blood Flow Following Electroconvulsive Therapy in a Patient with Schizoaffective Disorder.

BACKGROUND Somatic delusions are false and fixed beliefs about health and organ function, which are observed in various psychiatric disorders. Psychotropic drugs such as antipsychotics and antidepressants are effective for some patients, while the efficacy of electroconvulsive therapy (ECT) for pharmacotherapy-resistant cases has been reported. Previous reports suggest that somatic delusions in delusional disorder somatic type are associated with reduced regional cerebral blood flow (rCBF), but it remains unclear whether this association is also observed in other psychiatric disorders. We report the case of a patient with schizoaffective disorder whose drug-resistant somatic delusions showed remarkable improvement accompanied by altered rCBF after successful ECT. CASE REPORT The patient was a Japanese man aged 52 years with a diagnosis of schizoaffective disorder. He was suffering from severe and persistent somatic delusions such as "There is a thick stick or bowl in my head" and "Something like a film stretches over my head and face", which were resistant to several antipsychotics and antidepressants. In our hospital, he received bitemporal ECT 8 times. His somatic delusions started to improve from the third administration, and they disappeared by the eighth administration. In parallel with this clinical improvement, reduction of rCBF in the bilateral parietal and occipital lobes observed before ECT disappeared. CONCLUSIONS The present study suggests that ECT is a useful choice for drug-resistant somatic delusions. Reduction of rCBF in the bilateral parietal and occipital lobes may be associated with manifestation of somatic delusions in schizoaffective disorder.

Comparison of Alzheimer's disease patients and healthy controls in the easy Z-score imaging system with differential image reconstruction methods using SPECT/CT: verification using normal database of our institution.

OBJECTIVE: The easy Z-score imaging system (eZIS) analysis is used for the diagnosis of dementia by cerebral blood flow on single photon emission computed tomography (SPECT). Differences in the acquisition and reconstruction conditions in SPECT may affect the eZIS analysis results. The present study aimed to construct our institutional normal database (NDB) and Alzheimer's disease (AD)-specific volumes of interest (VOIs) in eZIS analysis, and to compare the differential diagnostic ability between healthy controls (HC) and patients with AD in the image reconstruction filtered back projection (FBP) and ordered subset expectation maximization (OSEM) methods. METHODS: An NDB was constructed at our institution from 30 healthy individual using the FBP and OSEM reconstruction methods. We divided 51 HC and 51 AD patients into two groups, one for AD disease-specific VOI construction (HC, AD) and the other for NDB verification (HC, AD); image reconstruction was performed using FBP and OSEM. The areas of reduced blood flow in AD patients were compared with those of HC using the two types of image reconstruction methods. We used AD disease-specific VOI and NDB from each reconstruction method in eZIS analysis and compared the differential diagnostic ability for HC and AD with the different reconstruction methods. RESULTS: Comparing the areas of reduced blood flow in AD patients using the different image reconstruction methods, OSEM showed decreased blood flow in the medial region of the temporal lobes compared to FBP. Comparing the differential diagnostic ability for HC and AD using eZIS, the Severity, Extent, and Ratio showed higher values in the analysis performed using OSEM image reconstruction compared to FBP. CONCLUSION: With the 99mTc-ECD SPECT, the eZIS analysis equipped with our institutional AD-specific VOI and NDB using OSEM image reconstruction could distinguish HC from AD better than eZIS analysis using FBP image reconstruction. This study is registered in UMIN Clinical Trials Registry (UMIN-CTR) as UMIN study ID: UMIN000042362.