Effect of Beni-Koji on Blood Pressure and Learning Behavior in Spontaneously Hypertensive Rats

1)紅麹投与群は米粉を投与した対照群と比べ､体重増加に対しては有意な差は認められなかった｡ 2)紅麹投与群は対照群と比べ2週目より有意な血圧下降作用が認められた｡ 3)紅麹投与群は､対照群に比べ総エラー数および参照記憶エラー数の減少､すなわち学習獲得能が高いことが判明した｡ 4)以上の成績より､紅麹の投与により生じた血圧下降が二次的に学習獲得能を上昇させたのではないかと考えられる

Changes of Myelin Organization in Patients with Alzheimer’s Disease Shown by q-Space Myelin Map Imaging

Background: Recent studies detected the aberrant myelination of the central nervous system (CNS) in Alzheimer’s disease (AD). Here, we compared the change of myelination between patients with AD and controls by a novel magnetic resonance imaging modality, “q-space myelin map (MM) imaging.” Methods: Twenty patients with AD and 18 healthy subjects underwent MM imaging. We compared the MM metric between the 2 groups and examined the relationships between the metric and the clinical symptoms of AD. Results: AD patients showed a significant reduction of MM metric in the hippocampus, insula, precuneus, and anterior cingulate regions. There was also a significant negative correlation between the duration of illness and the MM metric in the temporoparietal region. Conclusion: Our findings suggest that MM imaging could be a clinically proper modality to estimate the myelination changes in AD patients

Dissociation of Tau Deposits and Brain Atrophy in Early Alzheimer’s Disease: A Combined Positron Emission Tomography/Magnetic Resonance Imaging Study

The recent advent of tau-specific positron emission tomography (PET) has enabled in vivo assessment of tau pathology in Alzheimer’s disease (AD). However, because PET scanners have limited spatial resolution, the measured signals of small brain structures or atrophied areas are underestimated by partial volume effects (PVEs). The aim of this study was to determine whether partial volume correction (PVC) improves the precision of measures of tau deposits in early AD. We investigated tau deposits in 18 patients with amyloid-positive early AD and in 36 amyloid-negative healthy controls using 18F-THK5351 PET. For PVC, we applied the SPM toolbox PETPVE12. The PET images were then spatially normalized and subjected to voxel-based group analysis using SPM12 for comparison between the early AD patients and healthy controls. We also compared these two groups in terms of brain atrophy using voxel-based morphometry of MRI. We found widespread neocortical tracer retention predominantly in the posterior cingulate and precuneus areas, but also in the inferior temporal lobes, inferior parietal lobes, frontal lobes, and occipital lobes in the AD patients compared with the controls. The pattern of tracer retention was similar between before and after PVC, suggesting that PVC had little effect on the precision of tau load measures. Gray matter atrophy was detected in the medial/lateral temporal lobes and basal frontal lobes in the AD patients. Interestingly, only a few associations were found between atrophy and tau deposits, even after PVC. In conclusion, PVC did not significantly affect 18F-THK5351 PET measures of tau deposits. This discrepancy between tau deposits and atrophy suggests that tau load precedes atrophy

Voxel-based correlation of 18F-THK5351 accumulation and gray matter volume in the brain of cognitively normal older adults

BackgroundsAlthough neurofibrillary tangles (NFTs) mainly accumulate in the medial temporal lobe with human aging, only a few imaging studies have investigated correlations between NFT accumulation and gray matter (GM) volume in cognitively normal older adults. Here, we investigated the correlations between 18F-THK5351 accumulation and GM volume at the voxel level.Material and methodsWe recruited 47 amyloid-negative, cognitively normal, older adults (65.0 ± 7.9 years, 26 women), who underwent structural magnetic resonance imaging, 11C-Pittsburgh compound-B and 18F-THK5351 PET scans, and neuropsychological assessment. The magnetic resonance and 18F-THK5351 PET images were spatially normalized using Statistical Parametric Mapping 12. Voxel-wise correlations between 18F-THK5351 accumulation and GM volume were evaluated using the Biological Parametric Mapping toolbox.ResultsA significant negative correlation (p < 0.001) between 18F-THK5351 accumulation and GM volume was detected in the bilateral medial temporal lobes.ConclusionsVoxel-wise correlation analysis revealed a significant negative correlation between 18F-THK5351 accumulation and GM volume in the medial temporal lobe in individuals without amyloid-β deposits. These results may contribute to a better understanding of the pathophysiology of primary age-related tauopathy in human aging

Age and Sex-Related Effects on Single-Subject Gray Matter Networks in Healthy Participants

Recent developments in image analysis have enabled an individual&rsquo;s brain network to be evaluated and brain age to be predicted from gray matter images. Our study aimed to investigate the effects of age and sex on single-subject gray matter networks using a large sample of healthy participants. We recruited 812 healthy individuals (59.3 &plusmn; 14.0 years, 407 females, and 405 males) who underwent three-dimensional T1-weighted magnetic resonance imaging. Similarity-based gray matter networks were constructed, and the following network properties were calculated: normalized clustering, normalized path length, and small-world coefficients. The predicted brain age was computed using a support-vector regression model. We evaluated the network alterations related to age and sex. Additionally, we examined the correlations between the network properties and predicted brain age and compared them with the correlations between the network properties and chronological age. The brain network retained efficient small-world properties regardless of age; however, reduced small-world properties were observed with advancing age. Although women exhibited higher network properties than men and similar age-related network declines as men in the subjects aged &lt; 70 years, faster age-related network declines were observed in women, leading to no differences in sex among the participants aged &ge; 70 years. Brain age correlated well with network properties compared to chronological age in participants aged &ge; 70 years. Although the brain network retained small-world properties, it moved towards randomized networks with aging. Faster age-related network disruptions in women were observed than in men among the elderly. Our findings provide new insights into network alterations underlying aging

Harmonized Z-Scores Calculated from a Large-Scale Normal MRI Database to Evaluate Brain Atrophy in Neurodegenerative Disorders

Alzheimer’s disease (AD), the most common type of dementia in elderly individuals, slowly and progressively diminishes the cognitive function. Mild cognitive impairment (MCI) is also a significant risk factor for the onset of AD. Magnetic resonance imaging (MRI) is widely used for the detection and understanding of the natural progression of AD and other neurodegenerative disorders. For proper assessment of these diseases, a reliable database of images from cognitively healthy participants is important. However, differences in magnetic field strength or the sex and age of participants between a normal database and an evaluation data set can affect the accuracy of the detection and evaluation of neurodegenerative disorders. We developed a brain segmentation procedure, based on 30 Japanese brain atlases, and suggest a harmonized Z-score to correct the differences in field strength and sex and age from a large data set (1235 cognitively healthy participants), including 1.5 T and 3 T T1-weighted brain images. We evaluated our harmonized Z-score for AD discriminative power and classification accuracy between stable MCI and progressive MCI. Our procedure can perform brain segmentation in approximately 30 min. The harmonized Z-score of the hippocampus achieved high accuracy (AUC = 0.96) for AD detection and moderate accuracy (AUC = 0.70) to classify stable or progressive MCI. These results show that our method can detect AD with high accuracy and high generalization capability. Moreover, it may discriminate between stable and progressive MCI. Our study has some limitations: the age groups in the 1.5 T data set and 3 T data set are significantly different. In this study, we focused on AD, which is primarily a disease of elderly patients. For other diseases in different age groups, the harmonized Z-score needs to be recalculated using different data sets

Centiloid scale analysis for 18F-THK5351 PET imaging in Alzheimer\u27s disease

Purpose: A standardized method for quantification is required for analyzing PET data, but such standards have not been established for tau PET imaging. The Centiloid scale has recently been proposed as a standard method for quantifying amyloid deposition on PET imaging. Therefore, the present study aimed to apply the Centiloid scale to 18F-THK5351 PET imaging in Alzheimer’s disease (AD). Methods: We acquired 18F-THK5351 PET, 11C-PiB PET, and MR images from 47 cognitively normal (CN) individuals and 28 patients with AD with mild to moderate dementia. PET images were spatially normalized to Montreal Neurological Institute space. The PET signals were then normalized using the signal in the reference volume of interest (VOI). Target VOI for specific 18F-THK5351 retention in AD was extracted by voxel-wise comparison of PET images between the 47 CN individuals and 16 AD patients with moderate dementia. Scale anchor points were defined by the CN individuals as 0-anchor points and by that of the average of the typical AD patients as 100-anchor points.Results: Specific retention of 18F-THK5351 was predominant in the angular gyrus, inferior temporal cortex, and parieto-occipital regions in patients with AD. Standardized uptake value ratio (SUVR) of 1.227 and 1.797 were defined as 0- and 100-anchor points, respectively. 18F-THK5351 PET data could be expressed using the Centiloid scale, with the SUVR of the 18F-THK5351 PET images converted to Centiloid using our VOI, the standard Centiloid reference VOI, and the following equation: Centiloid = 169.0 × SUVR–204.6. Conclusion: Centiloid methods can be applied to tau PET imaging using 18F-THK5351

In vivo evaluation of gray and white matter volume loss in the parkinsonian variant of multiple system atrophy using SPM8 plus DARTEL for VBM

AbstractIn multiple system atrophy with predominant parkinsonism (MSA-P), several voxel-based morphometry (VBM) studies have revealed gray matter loss; however, the white matter volume changes have been rarely reported. We investigated the volume changes of white matter as well as gray matter by VBM. A retrospective MRI study was performed in 20 patients with MSA-P and 30 age-matched healthy controls. We applied VBM with statistical parametric mapping (SPM8) plus diffeomorphic anatomical registration through exponentiated Lie algebra (DARTEL) to explore the regional atrophy of gray and white matter in all of the MSA-P patients, 14 patients with left-side dominant and 6 patients with right-side dominant onset as compared to controls. In all of the MSA-P patients, VBM revealed a significant volume reduction of gray matter in the bilateral putamina, cerebellums and dorsal midbrain. White matter loss was located in bilateral globus pallidi, external capsules extending to the midbrain, right subcortical to precentral area through internal capsule, the pons, bilateral middle cerebellar peduncles and left cerebellum. In left-side dominant MSA-P patients, the gray and white matter volume loss was detected predominantly on the right side and vice versa in right-side dominant MSA-P patients. A correlation with disease duration and severity was not detected. VBM using SPM8 plus DARTEL detected significant volume loss not only in the gray but also in the white matter of the area affected by MSA-P