A comparative study: visual rating scores and the voxel-based specific regional analysis system for Alzheimer's disease on magnetic resonance imaging among subjects with Alzheimer's disease, mild cognitive impairment, and normal cognition.

AIM: Hippocampal atrophy shown on magnetic resonance imaging can differentiate Alzheimer's disease (AD) patients from subjects with normal cognition (NC). Simplified automated methods that use volumetric analysis, such as as the voxel-based specific regional analysis system for AD, have become widely used in Japan. However, the diagnostic value of the voxel-based specific regional analysis system compared with visual rating scores for clinical diagnosis is unclear. METHODS: Study participants consisted of 37 AD patients, 29 mild cognitive impairment (MCI) patients, and 21 NC subjects. All participants underwent neuropsychological testing and magnetic resonance imaging. The imaging was scored visually for regional brain atrophy by two raters based on a newly developed visual rating score. The voxel-based specific regional analysis system for AD scores were calculated with the analysis system's advanced software. We analyzed whether these scores aid in discriminating among AD, MCI, and NC. RESULTS: The AD group had significantly different visual rating scores, regional analysis scores, and all neuropsychological test scores than the NC group. The AD group had significantly different visual rating scores than the MCI group, and a significant difference was observed between the MCI and NC groups on regional analysis scores. Both the visual rating and regional analysis scores showed equivalent correlations with the neuropsychological test scores. CONCLUSIONS: Both the visual rating and regional analysis scores are clinically useful tools for differentiating among AD, MCI, and NC.

The Relationship Between Medial Temporal Lobe Atrophy and Cognitive Impairment in Patients With Dementia With Lewy Bodies.

BACKGROUND: The relationship between medial temporal lobe atrophy (MTA) and cognitive impairment in patients with dementia with Lewy bodies (DLB) remains unclear. We examined this relationship using voxel-based specific regional analysis system for Alzheimer disease (VSRAD) advance software, which allowed us to quantify the degree of MTA on images obtained from magnetic resonance imaging (MRI) scans. METHODS: Thirty-seven patients diagnosed with DLB were recruited and scanned with a 1.5 Tesla MRI scanner. All MRI data were analyzed using VSRAD advance. The target volume of interest (VOI) included the entire region of the entorhinal cortex, hippocampus, and amygdala. The degree of MTA was obtained from the averaged positive z-score (Z score) on the target VOI, with higher scores indicating more severe MTA. Mini-Mental State Examination (MMSE) and the Revised Hasegawa Dementia Scale (HDS-R), which strengthened the measures of memory and language more than MMSE, were used to assess the presence of cognitive impairment. RESULTS: A negative correlation was found between the Z score and MMSE total scores or the HDS-R total scores. A stepwise multiple regression analysis performed to adjust the covariate effects of sex, age, the onset age of the disease, duration of DLB, years of education, and donepezil treatment showed that the HDS-R total scores were independently associated with the Z score, whereas MMSE total scores were not. CONCLUSIONS: These results suggest that MTA is related to cognitive impairment in patients with DLB, particularly the regions of orientation, immediate and delayed recall, and word fluency.

The usefulness of combined analysis using CIScore and VSRAD parameters for differentiating between dementia with Lewy body and Alzheimer's disease.

PURPOSE: The Cingulate Island score (CIScore) is useful index for differentiating between dementia with Lewy body (DLB) and Alzheimer's disease (AD) using regional cerebral blood flow (rCBF) SPECT. The Z score standing for medial temporal lobe (MTL) atrophy and the ratio of Z score between dorsal brain stem (DBS) to MTL are useful indices for differentiating between DLB and AD using MRI with VSRAD. The current study investigated the diagnostic ability by the combined use of rCBF SPECT and MRI in the differentiation between AD and DLB. MATERIALS AND METHODS: In cases with 42 AD and 28 DLB undertaken Tc-99m-ECD SPECT and MRI, we analyzed differential diagnostic ability between AD and DLB among following conditions by single or combined settings. Namely, they were (1) the CIScore as a parameter of rCBF SPECT (DLB â‰¦ 0.25), (2) Z score value of MTL atrophy (DLB â‰¦ 2.05), (3) the ratio of Z score of DBS to medial temporal gray matter as a parameter of brain atrophy using VSRAD (DLB â‰§ 0.38). Also, we analyzed them both including and omitting the elderly (over 75 years old). RESULTS: The accuracy of differential diagnosis in this condition was 74% for (1), 69% for (2), and 67% for (3). The accuracy by combination condition was 84% for (1) and (2), 81% for (1) and (3), and 67% for (2) and (3), respectively. The combination method by CIScore and the Z score of MTL showed the best accuracy. When we confined condition to ages younger than 75 years, the accuracy improved to 94% in the combination method. CONCLUSION: The combined use of CIScore and Z score of MTL was suggested to be useful in the differential diagnosis between DLB and AD particularly in younger than 75 years old.

Influences of Vitamin B12 Supplementation on Cognition and Homocysteine in Patients with Vitamin B12 Deficiency and Cognitive Impairment.

Vitamin B12 deficiency is associated with cognitive impairment, hyperhomocysteinemia, and hippocampal atrophy. However, the recovery of cognition with vitamin B12 supplementation remains controversial. Of the 1716 patients who visited our outpatient clinic for dementia, 83 had vitamin B12 deficiency. Among these, 39 patients (mean age, 80.1 ± 8.2 years) had undergone Mini-Mental State Examination (MMSE) and laboratory tests for vitamin B12, homocysteine (Hcy), and folic acid levels. The hippocampal volume was estimated using the z-score of the MRI-voxel-based specific regional analysis system for Alzheimer's disease. This is multi-center, open-label, single-arm study. All the 39 patients were administered vitamin B12 and underwent reassessment to measure the retested for MMSE and Hcy after 21−133 days (median = 56 days, interquartile range (IQR) = 43−79 days). After vitamin B12 supplementation, the mean MMSE score improved significantly from 20.5 ± 6.4 to 22.9 ± 5.5 (p < 0.001). Hcy level decreased significantly from 22.9 ± 16.9 nmol/mL to 11.5 ± 3.9 nmol/mL (p < 0.001). Significant correlation was detected between the extent of change in MMSE scores and baseline Hcy values. The degree of MMSE score was not correlated with hippocampal atrophy assessed by the z-score. While several other factors should be considered, vitamin B12 supplementation resulted in improved cognitive function, at least in the short term, in patients with vitamin B12 deficiency.

Magnetic resonance imaging changes in Asian people living with HIV.

BACKGROUND: Previous studies have reported a significant increase in age-related magnetic resonance imaging (MRI) changes in relatively younger people living with HIV (PLWH). However, there is little data available for brain changes in Asian PLWH. The data to differentiate HIV specific brain change from usual aging change was also sparse. To clarify them, we assessed the presence of leukoaraiosis and brain atrophic changes on MRI in young and middle-aged Japanese PLWH. METHODS: We reviewed data from well-controlled PLWH (age: 20-64 years) and coeval controls. We evaluated the presence of leukoaraiosis, as well as the extent of whole-brain grey matter (GM) atrophy and parahippocampal atrophy on brain MRI and determined between-group differences. Moreover, we evaluated the severity of parahippocampal atrophy based on the voxel-based specific regional analysis system for Alzheimer's disease. RESULTS: We enrolled 40 PLWH and 33 controls (median age: 40.15 and 48.00 years, respectively, [p = .3585]). Leukoaraiosis was significantly more prevalent among the PLWH (20 cases [50%]) than in the controls (9 cases [27.3%]) (univariate: p = .0483, multivariate: p = .0206). The extent of whole-brain GM atrophy was significantly greater in the PLWH than in the controls (univariate: p < .001, multivariate: p = .0012). Contrastingly, there was no significant between-group difference in the extent and severity of parahippocampal atrophy. CONCLUSIONS: Aging changes in the brain were significantly more prevalent in well-controlled Japanese PLWH. However, the process of atrophic brain changes might differ between HIV and one of age-related diseases, Alzheimer's disease.

[Accuracy of VSRAD Analysis Using Scout Images: Comparison with Conventional 3D-T1WI].

The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD), which targets volume loss in medial temporal lobe, was developed as a sensitive diagnostic tool to detect early stages of Alzheimer's disease. However, conventional three-dimensional T1 -weighted image (3D-T1WI) for VSRAD analysis acquires relatively long acquisition time. Recently, it became possible to acquire Scout images (Scout) for positioning as a 3D image in a short time. The aim of this study was to determine whether Scout was reliable in VSRAD. We measured voxel-based analysis of gray matter volume using VBM and Z-score of medial temporal lobe atrophy using VSRAD advance 2 from conventional 3D-T1WI and Scout. It showed significantly different gray mass between conventional 3D-T1WI and Scout. However, there was no significant difference in Z-score (p=0.41). The Z-scores measured from Scout and conventional 3D-T1WI were significantly correlated (r=0.96, p<0.05). There is a possibility that Scout can be used to detect brain morphometry abnormalities instead of conventional 3D-T1WI in the VSRAD analysis.

Identification of predictors for mini-mental state examination and revised Hasegawa's Dementia Scale scores using MR-based brain morphometry.

PURPOSE: The early detection of cognitive function decline is crucial to help manage or slow the progression of symptoms. The Mini-Mental State Examination (MMSE) and revised Hasegawa's Dementia Scale (HDS-R) are widely used in screening for cognitive impairment. The purpose of this study was to explore common predictors of the two different cognitive testing systems using MR-based brain morphometry. MATERIALS AND METHODS: This retrospective study included 200 subjects with clinical suspicion of cognitive impairment who underwent 3D T1-weighted MRI at our institution between February 2019 and August 2020. Variables related to the volume of deep gray matter and 70 cortical thicknesses were obtained from the MR images using voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) and FreeSurfer software. The correlation between each variable including age and MMSE/HDS-R scores was evaluated using uni- and multi-variate logistic regression analyses. RESULTS: In univariate analysis, parameters include hippocampal volume and bilateral entorhinal cortex (ERC) thickness showed moderate correlation coefficients with both MMSE and HDS-R scores. Multivariate analysis demonstrated the right ERC thickness was the common parameter which significantly correlates with both MMSE and HDS-R scores (p < 0.05). CONCLUSION: Right ERC thickness appears to offer a useful predictive biomarker for both MMSE and HDS-R scores.

Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) on 3-tesla Normal Database: Diagnostic Accuracy in Two Independent Cohorts with Early Alzheimer's Disease.

Voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) software is widely used in clinical practice in Alzheimer's disease (AD). The existing VSRAD is based on the normal database with 1.5-tesla MRI scans (VSRAD-1.5T), and its utility for patients have undergone 3-tesla MRI is still controversial. We recruited 19 patients with early AD and 28 healthy controls who had undergone 3-tesla MRI scans at our institute (Cohort 1). We also used the 3-tesla MRI data of 30 patients with early AD and 13 healthy controls from the Japanese Alzheimer's Disease Neuroimaging Initiative (Cohort 2). We also created a new VSRAD based on 65 normal subjects' 3-tesla MRI scans (VSRAD-3T), and compared the detectability of AD between VSRAD-1.5T and VSRAD-3T, using receiver operating characteristic curve and area under the curve (AUC) analyses. As a result, there were no significant differences in the detectability of AD between VSRAD-3T and VSRAD-1.5T, except for the whole white matter atrophy score, which showed significantly better AUC in VSRAD-3T than in VSRAD-1.5T in both Cohort 1 (p=0.04) and 2 (p<0.01). Generally, there were better diagnostic values in Cohort 2 than in Cohort 1. The optimal cutoff values varied but were generally lower than in the previously published data. In conclusion, for patients with 3-tesla MRI, the detectability of early AD by the existing VSRAD was not different from that by the new VSRAD based on 3-tesla database. We should exercise caution when using the existing VSRAD for 3-tesla white matter analyses or for setting cutoff values.

Thalamic involvement determined using VSRAD advance on MRI and easy Z-score analysis of 99mTc-ECD-SPECT in Gerstmann-Sträussler-Scheinker syndrome with P102L mutation.

Gerstmann-Sträussler-Scheinker syndrome caused by the P102L mutation in the prion protein gene (GSS102) is usually characterized by the onset of slowly progressive cerebellar ataxia, with dementia occurring much later. Because of the relatively long disease course and the prominence of progressive cerebellar ataxia in the early stage, GSS102 is often misdiagnosed as other neurodegenerative disorders. We present two cases of genetically proven GSS102L, both of which present with atrophy and decreased blood flow of the thalamus as determined by voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) advance software and easy Z-score analysis for 99mTc-ethyl cysteinate dimer-SPECT, respectively. These thalamic abnormalities have not been fully evaluated to date, and detecting them might be useful for differentiating GSS102 from other neurodegenerative disorders.

MRI morphometry in Alzheimer's disease.

MRI based evaluation of brain atrophy is regarded as a valid method to stage the disease and to assess progression in Alzheimer's disease (AD). Volumetric software programs have made it possible to quantify gray matter in the human brain in an automated fashion. At present, voxel based morphometry (VBM) is easily applicable to the routine clinical procedure with a short execution time. The importance of the VBM approach is that it is not biased to one particular structure and is able to assess anatomical differences throughout the brain. Stand-alone VBM software running on Windows, Voxel-based Specific Regional analysis system for AD (VSRAD), has been widely used in the clinical diagnosis of AD in Japan. On the other hand, recent application of graph theory to MRI has made it possible to analyze changes in structural connectivity in AD.

Comparison of regional gray matter volume abnormalities in Alzheimer׳s disease and late life depression with hippocampal atrophy using VSRAD analysis: a voxel-based morphometry study.

Previous voxel-based morphometry (VBM) studies revealed that hippocampal volume loss in patients with late life depression (LLD) is associated with cognitive impairment and a higher risk for dementia. However, LLD patients can experience hippocampal atrophy without cognitive impairment. Thus, while LLD and AD can show comparable hippocampal atrophy, they may encompass different neuropathological changes. Using VBM, we therefore investigated differences in regional gray matter changes in 17 late-onset LLD patients and 21 AD patients (without a history of LLD) who exhibited comparably severe atrophy of the entorhinal cortex and the parahippocampal gyrus on MRI scans for voxel-based specific regional analysis system for AD (VSRAD). Relative to the VSRAD database for healthy individuals, significant atrophy was observed in mesial temporal lobe structures and the anterior cingulate cortex in both groups. Atrophy of the posterior cingulate cortex and precuneus was observed only in the AD group. Comparisons of gray matter volume by multivariate analysis of variance revealed significantly reduced volume of the right middle and inferior temporal gyrus, uncus, posterior cingulate cortex, and precuneus in the AD group only, suggesting impairment of different networks in AD and LLD. Indeed, structural changes in the posterior part of the default-mode network are believed to be associated with cognitive impairments specific to AD.

The feasibility of white matter volume reduction analysis using SPM8 plus DARTEL for the diagnosis of patients with clinically diagnosed corticobasal syndrome and Richardson's syndrome.

PURPOSE: Diagnosing corticobasal degeneration (CBD) and progressive supranuclear palsy (PSP) is often difficult due to the wide variety of symptoms and overlaps in the similar clinical courses and neurological findings. The purpose of this study was to evaluate the utility of white matter (WM) atrophy for the diagnosis of patients with clinically diagnosed CBD (corticobasal syndrome, CBS) and PSP (Richardson's syndrome, RS). METHODS: We randomly divided the 3D T1-weighted MR images of 18 CBS patients, 33 RS patients, and 32 age-matched controls into two groups. We obtained segmented WM images in the first group using Voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping (SPM) 8 plus diffeomorphic anatomical registration through exponentiated Lie algebra. A target volume of interest (VOI) for disease-specific atrophy was subsequently determined in this group using SPM8 group analyses of WM atrophy between patients groups and controls. We then evaluated the utility of these VOIs for diagnosing CBS and RS patients in the second group. Z score values in these VOIs were used as the determinant in receiver operating characteristic (ROC) analyses. RESULTS: Specific target VOIs were determined in the bilateral frontal subcortical WM for CBS and in the midbrain tegmentum for RS. In ROC analyses, the target VOIs of CBS and RS compared to those of controls exhibited an area under curve (AUC) of 0.99 and 0.84, respectively, which indicated an adequate diagnostic power. The VOI of CBS revealed a higher AUC than that of RS for differentiating between CBS and RS (AUC, 0.75 vs 0.53). CONCLUSIONS: Bilateral frontal WM volume reduction demonstrated a higher power for differentiating CBS from RS. This VOI analysis is useful for clinically diagnosing CBS and RS.

Utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy as adjunct techniques for screening and predicting dementia due to Alzheimer's disease in clinical practice.

We validated the utility of SPM8 plus DARTEL (VSRAD) combined with magnetic resonance spectroscopy (1H MRS) as an adjunct screening technique for dementia due to Alzheimer's disease (AD). We examined the posterior cingulate gyri of 228 subjects using VSRAD and 1H MRS in addition to conventional cerebrospinal fluid biomarkers at baseline. At the 3-year follow-up, the 228 subject were classified as follows: 93 healthy subjects, 42 MCI-non-converters (MCI-NC), 25 MCI-converters to AD (MCI-C), 44 AD, 8 dementia with Lewy bodies (DLB), 5 normal pressure hydrocephalus, and 11 patients with other neurological diseases. Our results demonstrated that subjects with increased medial temporal atrophy (MTA) severity on VSRAD, increased Cho/Cr, MI/Cr ratio, and decreased NAA/Cr and NAA/MI ratio on 1H MRS at baseline were at risk of dementia due to AD. Receiver operating characteristic analysis showed that severity of MTA and the NAA/MI ratio distinguished patients with AD and MCI-C from controls. Furthermore, the 118 subjects without dementia and MTA showing only a decreased NAA/MI ratio at baseline developed to MCI-C, AD, and DLB 3 years later. 1H MRS detected biochemical abnormalities preceding brain atrophy and cognitive decline. VSRAD combined with 1H MRS may be routinely applied to screen for MCI/AD and prodromal AD in clinical practice.

Identification of atrophy of the subgenual anterior cingulate cortex, in particular the subcallosal area, as an effective auxiliary means of diagnosis for major depressive disorder.

BACKGROUND: Despite being a very common psychiatric disorder, physicians often have difficulty making a diagnosis of major depressive disorder (MDD) because, without established diagnostic criteria, they have to depend on interviews with patients and observation to assess psychiatric symptoms. However, previous researchers have reported that magnetic resonance imaging (MRI) scans identify morphological changes in the brains of patients with MDD, which inspired us to hypothesize that assessment of local changes in the brain using voxel-based morphometry would serve as an auxiliary diagnostic method for MDD. Therefore, we focused on the VSRAD(®) plus (voxel-based specific regional analysis system for Alzheimer's disease), a diagnostic support system for use in early Alzheimer's disease, which allowed us to identify regional atrophy in the brain easily based on images obtained from MRI scans. METHODS: The subjects were 75 patients with MDD, 15 with bipolar disorder, and 30 healthy subjects, aged 54-82 years. First, 1.5 T MRI equipment was used to scan three-dimensional T(1)-weighted images for the individual subjects, and the imaged data were analyzed by VSRAD advance (voxel-based morphometric software developed for diagnosis of early Alzheimer's disease). The efficacy of the equipment for diagnosis of MDD was evaluated based on the distribution of atrophy in the subgenual anterior cingulate cortex (sACC) on the z-score map obtained. RESULTS: No significant difference in atrophy was noted between the left and right sACCs. The VSRAD advance used in the present study was more effective than the VSRAD plus for diagnosis of MDD, with a sensitivity of 90.7%, specificity of 86.7%, accuracy of 89.5%, a positive predictive value of 94.4%, and a negative predictive value of 78.8%. In particular, atrophy was observed in the subcallosal area of the sACC. CONCLUSION: The identification of atrophy in the sACC, in particular of the subcallosal area, with the use of updated voxel-based morphometric software proved to be effective as an auxiliary diagnostic method for MDD.

Diagnosis of depression by MRI scans with the use of VSRAD - a promising auxiliary means of diagnosis: a report of 10 years research.

OBJECTIVES: This study was designed to evaluate the usefulness of assessing subgenual anterior cingulate cortex (sACC) volume reduction by magnetic resonance imaging (MRI) as an objective auxiliary means of diagnosis of depression. The study was additionally designed to analyze the association of sACC volume reduction with the effectiveness of treatments for depression and other diseases presenting with similar symptoms, and to examine the possibility of using sACC volume reduction in the distinction between depression and bipolar disorder and determining optimum medication for these conditions. METHODS: Three-dimensional T1-weighted sagittal images, taken with Achieva 1.5T NOVA (Philips), were analyzed with VSRAD plus(®) to evaluate a reduction in sACC volume. The finding from this analysis was compared with the clinical data, including the longitudinal course follow-up data based on the treatment algorithm. SUBJECTS: The study involved 88 patients aged over 54 who received MRI during 2010, ie, 71 patients with major depressive disorder (MDD), 11 patients bipolar disorder, and 6 patients in whom the initial diagnosis (MDD) was later modified. Thirty-three normal individuals served as controls. RESULTS: sACC volume reduction was noted in 66 of the 71 patients receiving treatment of MDD, with sensitivity of 93%, specificity of 85%, and accuracy of 90%. In the 66 patients diagnosed as having MDD and exhibiting sACC volume reduction, the disease showed remission in response to treatment with antidepressants, but medication needed to be continued after achievement of remission. In cases initially diagnosed as having MDD but not exhibiting sACC volume reduction, the necessity of modifying the diagnosis was considered. Typical cases of bipolar disorder did not exhibit sACC volume reduction. CONCLUSION: That patients receiving treatment of MDD often showed reduction in sACC volume suggests the usefulness of this parameter as an objective auxiliary means of diagnosis for MDD.