Voxel-based Specific Regional Analysis System For Alzheimer's Disease Research Articles

Utility of combining multiple parameters of 123I-IMP SPECT and voxel-based morphometry MRI using a multiparametric scoring system for differentiating dementia with Lewy bodies from Alzheimer's disease.

Brain magnetic resonance imaging voxel-based morphometry (VBM) and perfusion single-photon emission computed tomography (SPECT) are useful for differentiating dementia with Lewy bodies (DLB) from Alzheimer's disease (AD). To determine whether combining multiple parameters of VBM and SPECT using a multiparametric scoring system (MSS) improves diagnostic accuracy in differentiating DLB from AD. In total, 23 patients with DLB and 57 patients with AD underwent imaging using a voxel-based specific regional analysis system for AD (VSRAD), an easy Z-score imaging system, and a Z-Graph using three-dimensional stereotactic surface projection. The cutoff values were determined using the receiver operating characteristic curve to differentiate DLB from AD for all parameters. Patients were scored 1 (DLB) or 0 (AD) for each statistically significant parameter, according to a threshold. The total score was determined for each case to obtain a cutoff value for the MSS. The mean Z-scores in the medial temporal lobes using the VSRAD were significantly lower in patients with DLB than in those with AD. Each Z-score of the summed Z-scores in all four segmented regions of the occipital lobes using the Z-Graph was significantly higher in patients with DLB than in those with AD. Among the five parameters, the highest accuracy was 80% for the Z-score of the summed Z-scores in the left medial occipital lobe. For the MSS, a cutoff value of four improved the diagnostic accuracy to 82%. MSS was more accurate than any single parameter of VBM or SPECT in differentiating DLB from AD.

Alterations in driving ability and their relationship with morphometric magnetic resonance imaging indicators in patients with amnestic mild cognitive impairment and Alzheimer's disease.

Drivers with dementia are at a higher risk of motor vehicle accidents. The characteristics of driving behaviour of patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) have not been fully elucidated. We investigated driving ability and its relationship with cognitive function and magnetic resonance imaging (MRI) morphometry indicators. The driving abilities of 19 patients with AD and 11 with amnestic MCI (aMCI) were evaluated using a driving simulator. The association between each driving ability parameter and the Mini-Mental State Examination (MMSE) score or voxel-based specific regional analysis system for AD (VSRAD) was assessed. Patients with AD made a significantly higher number of operational errors than those with aMCI in attention allocation in the complex task test (P = 0.0008). The number of operational errors in attention allocation in the complex task test significantly and negatively correlated with MMSE scores in all participants (r = -0.4354, P = 0.0162). The decision time in the selective reaction test significantly and positively correlated with the severity and extent of medial temporal structural atrophy (r = 0.4807, P = 0.0372; r = 0.4862, P = 0.0348; respectively). An increase in the operational errors for attention allocation in the complex task test could be a potential indicator of progression from aMCI to AD. Atrophy of the medial temporal structures could be a potential predictor of impaired judgement in driving performance in aMCI and AD. A driving simulator could be useful for evaluating the driving abilities of individuals with aMCI and AD.

Asymmetric Cerebral Peduncle Atrophy: A Simple Diagnostic Clue for Distinguishing Frontotemporal Lobar Degeneration from Alzheimer's Disease.

Due to confusing clinicoradiological features such as amnestic symptoms and hippocampal atrophy in frontotemporal lobar degeneration (FTLD), antemortem differentiation between FTLD and Alzheimer's disease (AD) can be challenging. Although asymmetric atrophy of the cerebral peduncle is regarded as a representative imaging finding in some disorders of the FTLD spectrum, the utility of this finding has not been sufficiently evaluated for differentiating between FTLD and AD. This study aimed to explore the diagnostic performance of asymmetric cerebral peduncle atrophy on axial magnetic resonance imaging as a simple radiological discriminator between FTLD and AD. Seventeen patients with pathologically confirmed FTLD, including six with progressive supranuclear palsy, three with corticobasal degeneration, eight with TAR DNA-binding protein 43 (FTLD-TDP), and 11 with pathologically confirmed AD, were investigated. Quantitative indices representing the difference between the volumes of the bilateral cerebral peduncles (i.e., cerebral peduncular asymmetry index [CPAI]), the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) Z-score representing the degree of hippocampal atrophy, and semiquantitative visual analysis to evaluate the asymmetry of the cerebral peduncle (visual assessment of cerebral peduncular asymmetry: VACPA) were compared between the two groups. Contrary to the VSRAD Z-score, the CPAI and VACPA scores demonstrated higher diagnostic performance in differentiating patients with FTLD from those with AD (areas under the receiver operating characteristic curve of 0.88, 082, and 0.60, respectively). Quantitative and visual analytical techniques can differentiate between FTLD and AD. These simple methods may be useful in daily clinical practice.

Development of an artificial intelligence-based diagnostic model for Alzheimer's disease.

IntroductionThe diagnosis of Alzheimer's disease (AD) is sometimes difficult for nonspecialists, resulting in misdiagnosis. A missed diagnosis can lead to improper management and poor outcomes. Moreover, nonspecialists lack a simple diagnostic model with high accuracy for AD diagnosis.MethodsRandomly assigned data, including training data, of 6000 patients and test data of 1932 from 7932 patients who visited our memory clinic between 2009 and 2021 were introduced into the artificial intelligence (AI)‐based AD diagnostic model, which we had developed.ResultsThe AI‐based AD diagnostic model used age, sex, Hasegawa's Dementia Scale‐Revised, the Mini‐Mental State Examination, the educational level, and the voxel‐based specific regional analysis system for Alzheimer's disease (VSRAD) score. It had a sensitivity, specificity, and c‐static value of 0.954, 0.453, and 0.819, respectively. The other AI‐based model that did not use the VSRAD had a sensitivity, specificity, and c‐static value of 0.940, 0.504, and 0.817, respectively.DiscussionWe created an AD diagnostic model with high sensitivity for AD diagnosis using only data acquired in daily clinical practice. By using these AI‐based models, nonspecialists could reduce missed diagnoses and contribute to the appropriate use of medical resources.

Effect of Probiotic Bifidobacterium breve in Improving Cognitive Function and Preventing Brain Atrophy in Older Patients with Suspected Mild Cognitive Impairment: Results of a 24-Week Randomized, Double-Blind, Placebo-Controlled Trial.

Background:Probiotics have been reported to ameliorate cognitive impairment.Objective:We investigated the effect of the probiotic strain Bifidobacterium breve MCC1274 (A1) in enhancing cognition and preventing brain atrophy of older patients with mild cognitive impairment (MCI).Methods:In this RCT, 130 patients aged from 65 to 88 years old with suspected MCI received once daily either probiotic (B. breve MCC1274, 2×1010 CFU) or placebo for 24 weeks. Cognitive functions were assessed by ADAS-Jcog and MMSE tests. Participants underwent MRI to determine brain atrophy changes using Voxel-based Specific Regional Analysis System for Alzheimer’s disease (VSRAD). Fecal samples were collected for the analysis of gut microbiota composition.Results:Analysis was performed on 115 participants as the full analysis set (probiotic 55, placebo 60). ADAS-Jcog subscale “orientation” was significantly improved compared to placebo at 24 weeks. MMSE subscales “orientation in time” and “writing” were significantly improved compared to placebo in the lower baseline MMSE (< 25) subgroup at 24 weeks. VSRAD scores worsened in the placebo group; probiotic supplementation tended to suppress the progression, in particular among those subjects with progressed brain atrophy (VOI Z-score ≥1.0). There were no marked changes in the overall composition of the gut microbiota by the probiotic supplementation.Conclusion:Improvement of cognitive function was observed on some subscales scores only likely due to the lower sensitiveness of these tests for MCI subjects. Probiotics consumption for 24 weeks suppressed brain atrophy progression, suggesting that B. breve MCC1274 helps prevent cognitive impairment of MCI subjects.

Relationship between neuropsychological test scores and hippocampal atrophy in non-demented Japanese older adults

BackgroundIt is essential to detect morphological changes in the brain prior to the onset of cognitive decline. Although hippocampal volumes have been reported to be correlated with scores on neuropsychological tests, this relationship is still unclear among Japanese non-demented older adults. Thus, this exploratory retrospective study aimed to identify neuropsychological tests that correlate with the degree of hippocampal atrophy in Japanese non-demented older adults. MethodsThirteen non-demented Japanese older adults aged 71.2 ± 5.2 years were included. Hippocampal atrophy was evaluated by assessing the participants’ MRI scans using the voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) software. Spearman’s partial correlation analyses were conducted to reveal relationships between VSRAD scores and neuropsychological test scores, including Raven’s Colored Progressive Matrices test (RCPM), the Standard Verbal Paired Associate Learning test (SP-A), and the Trail Making Test (TMT) scores by controlling for age, sex, and years of education. ResultsThe Spearman’s partial correlation analysis results revealed that there were significant correlations between the degree of hippocampal atrophy and RCPM (rho = -0.691, p = 0.027), TMT part B (rho = 0.823, p = 0.003), and the related SP-A test scores (rho = -0.663, p = 0.027). ConclusionsOur results indicate that neuropsychological tests, particularly the TMT part B, might be used in assessing the degree of hippocampal atrophy in non-demented Japanese elderly individuals and should be studied further in the future to develop screening methods to detect brain atrophy.

Progressive medial temporal degeneration with TDP-43 pathology is associated with upper limb and bulbar onset types of amyotrophic lateral sclerosis

This study aimed to clarify the relationship between progressive medial temporal atrophy and onset subtype in patients with amyotrophic lateral sclerosis (ALS). Medial temporal atrophy, ALS functional rating scale (ALSFRS), and cognitive function were assessed in 119 patients who were grouped into three ALS subtypes: bulbar, upper limb, and lower limb onset. Medial temporal atrophy, represented by a Z-score, was determined using an analysis software of magnetic resonance images known as the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD). Among 119 patients, 60 underwent follow-up VSRAD, ALSFRS, and cognitive testing. The sequential data were compared among onset subtypes. Furthermore, TDP-43 pathology was assessed in 20 autopsied patients (including seven who underwent VSRAD before death) to examine the relationships among medial temporal atrophy, onset subtypes, and severity of the hippocampal TDP-43 pathology. Multiple regression analysis revealed that the Z-score at baseline was associated with the age of onset and duration of illness. A high Z-score at baseline and the bulbar/upper limb subtypes affected the progression rate of Z-score. Pathological examination revealed increased hippocampal TDP-43 pathology score associated with bulbar and upper limb subtypes. Moreover, the Z-score before death correlated with the hippocampal TDP-43 pathology score. Medial temporal atrophy in ALS is associated with bulbar and upper limb onset subtypes. This progression may be related to the extent of TDP-43 pathology.

What is the subtype of dementia in patients with fragility hip fracture?

IntroductionCognitive function is an important factor that affects functional recovery after hip fracture (HipFx) surgery. The literature on the pathophysiology of dementia in HipFx patients is scarce. We performed a differential diagnosis of dementia in HipFx patients using clinical and brain MRI findings.MethodsThis is a prospective study in which brain MRI was evaluated for patients with HipFx for research purposes. One-hundred-and-five HipFx patients (85 females and 20 males) who underwent surgery and were subsequently able to undergo brain MRI at our hospital were evaluated. The mean age was 84 years. The presence of dementia was determined based on clinical findings and whether the patient meets its diagnostic criteria according to the International Classification of Diseases 10th Edition (ICD-10). The differential diagnosis of dementia was made based on brain MRI findings and the dementia diagnostic flow chart published in the Clinical Practice Guideline for Dementia 2017 (Japanese Society of Neurology). The Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) advance 2 diagnostic software was used to evaluate atrophy of the para-hippocampal gyrus.ResultsFifty-six (53%) patients were clinically diagnosed with dementia according to the ICD-10 criteria. The MRI findings were diverse: Alzheimer’s disease (AD)-type, asymptomatic multiple ischemic cerebral lesions, past symptomatic cerebral infarction or cerebral hemorrhage, Binswanger’s disease (BW)-type, chronic subdural hematoma, disproportionately enlarged subarachnoidal hydrocephalus (DESH), and their combinations thereof. A combination of MRI and clinical findings of dementia patients demonstrated the following distribution of dementia subtypes: AD (n = 20), vascular dementia (n = 33), AD and BW vascular dementia (n = 3).ConclusionThis study revealed that the brain MRI findings of HipFx patients were diverse. Although vascular dementia is found to be common in this particular population, this could be an incidental finding. Further study is warranted to clarify the specificity of our findings by increasing the number of patients, setting the control, and investigating whether dementia subtypes affect postoperative gait acquisition and fall risk.

The Clinical Practice for Hippocampal Neurogenesis by Chronobiological Therapy

The hippocampal neurogenesis in rats has been studied. In addition, when enough activities are provided in daytime, it is suggested that the memory consolidation during sleep will be achieved by hippocampal neurogenesis. We introduce our clinical practice of the chronobiological therapy regarding six dementia cases. Our therapy is based on awakening-sleep rhythm. We performed the medication to promote the changes from sleep to awakening in morning and to stabilize non-REM sleep at night. We also treated the autonomic nervous disorders so that the internal organs became active with Japanese Kampo Medicines, which were integrated with Western medicines. We set our occupational therapy in the daytime. The clinical evaluation was performed by psychological examinations and voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD) of MRI. As for Z-score showing the hippocampal atrophy in VSRAD we accomplished the improvement of 0.55 points from 0.03 about six dementia cases by the chronobiological therapy. These improvements were accompanied by the better changes of the cognitive functions. We speculate that the hippocampal neurogenesis may be derived by reconstructing awakening-sleep rhythm.

671-P: Liraglutide Possibly Prevents Progression of Dementia in Patients with Type 2 Diabetes

Purpose: The purpose of this study is to assess the usefulness of liraglutide in elderly patients with type 2 diabetes to prevent progression of dementia. Methods: We retrospectively reviewed 31 outpatients with 65 years of age or older, who have been treated with liraglutide for 6 years (Group G; 12 males/19 females, 73.1 ± 8.6 years-old, HbA1c 7.5 ± 0.4%, 9 patients with cerebrovascular diseases, 8 patients with cardiovascular diseases, 16 patients with insulin therapy). Daily dose of liraglutide was 0.9 mg except 2 patients (0.6 mg). We examined Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) on MRI, max-IMT measured by carotid artery ultrasonography, visceral fat area, concentrations of HbA1c and FPG, serum levels of CRP, HDL/LDL cholesterol, and TG, both before and after the treatment. Age, HbA1c, and VSRAD values-matched 16 patients who were treated with linagliptin were analyzed as a control (Group D). Results: After 6 years, VSRAD was significantly deteriorated in Group D (1.06±0.98→1.39±1.05 (p&amp;lt;0.01)) but not in Group G (1.28±0.80→1.39±1.1 (NS)). Max IMT and visceral fat are was significantly improved in Group G (2.41±1.50→2.09±0.84 (p&amp;lt;0.05), 141.1±57.2→127.2±52.9 (p&amp;lt;0.01)), but not in group D (2.04±1.01→1.99±0.68 (NS), 102.4±66.5→106.6±62.7cm2 (NS)). CRP was decreased in Group G (0.12±0.11→0.09±0.12mg/dl (p&amp;lt;0.01)). HbA1c (7.5±0.4 → 7.0±0.5 vs. 7.3±0.3 → 6.8±0.4%), FPG (137±19 → 121±11 vs. 129±12→110±15mg/dl), were significantly improved in both groups (p&amp;lt;0.01). No hypoglycemia requiring medical intervention was observed. Only TG in Group G (167±53→147±34mg/dl (p &amp;lt;0.01)) was improved in lipid parameters. During the 6 years, antidementia drugs were prescribed for 2 patients in both groups. A stroke event was found in a patient of Group D. Conclusion: Liraglutide possibly prevent progression of dementia. The reduction of visceral obesity may contribute to this beneficial effect through anti-arteriosclerosis. Disclosure M. Yoshida: None. A. Yoshida: None. E. Oh: None. N. Yamamoto: None. E. Sasaki: None. S. Yoshida: None. N. Ohsawa: None. M. Sugino: None. I. Koyama: None.

The combination of MMSE with VSRAD and eZIS has greater accuracy for discriminating mild cognitive impairment from early Alzheimer's disease than MMSE alone.

Alzheimer's disease (AD) is assessed by carefully examining a patient's cognitive impairment. However, previous studies reported inadequate diagnostic accuracy for dementia in primary care settings. Many hospitals use the automated quantitative evaluation method known as the Voxel-based Specific Regional Analysis System for Alzheimer's Disease (VSRAD), wherein brain MRI data are used to evaluate brain morphological abnormalities associated with AD. Similarly, an automated quantitative evaluation application called the easy Z-score imaging system (eZIS), which uses brain SPECT data to detect regional cerebral blood flow decreases associated with AD, is widely used. These applications have several indicators, each of which is known to correlate with the degree of AD. However, it is not completely known whether these indicators work better when used in combination in real-world clinical practice. We included 112 participants with mild cognitive impairment (MCI) and 128 participants with early AD in this study. All participants underwent MRI, SPECT, and the Mini-Mental State Examination (MMSE). Demographic and clinical characteristics were assessed by univariate analysis, and logistic regression analysis with a combination of MMSE, VSRAD and eZIS indicators was performed to verify whether the diagnostic accuracy in discriminating between MCI and early AD was improved. The area under the receiver operating characteristic curve (AUC) for the MMSE score alone was 0.835. The AUC was significantly improved to 0.870 by combining the MMSE score with two quantitative indicators from the VSRAD and eZIS that assessed the extent of brain abnormalities. Compared with the MMSE score alone, the combination of the MMSE score with the VSRAD and eZIS indicators significantly improves the accuracy of discrimination between patients with MCI and early AD. Implementing VSRAD and eZIS does not require professional clinical experience in the treatment of dementia. Therefore, the accuracy of dementia diagnosis by physicians may easily be improved in real-world primary care settings.

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

PurposeThe 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 MethodsThis 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. ResultsIn 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). ConclusionRight ERC thickness appears to offer a useful predictive biomarker for both MMSE and HDS-R scores.

Correlation between Alzheimer’s Disease and Dementia with Lewy Bodies Scores Using VSRAD Advance

The objective of the study was to explore the relationship between the indicators of Alzheimer’s disease and dementia with Lewy bodies using the voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) advance. Among 36 patients with suspected dementia, patients with Alzheimer’s disease and dementia with Lewy bodies were identified using VSRAD advance from March 1 to October 30, 2019. All patients underwent brain Magnetic Resonance Imaging (MRI). We diagnosed Alzheimer’s disease using Volume of Interest (VOI) in the Medial Temporal Lobe (MTL) atrophy ratio ＞ 2 and dementia with Lewy bodies using both VOI in the MTL atrophy ratio ≤ 2 and gray/white matter atrophy ratio ≥ 0.2. The correlation between the indicators of Alzheimer’s disease and dementia with Lewy bodies was calculated. The number of patients classified as having Alzheimer’s disease and dementia with Lewy bodies was 25 and 11, respectively. In the Alzheimer’s disease group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem gray matter was r = -0.40 (p = 0.045). In dementia with Lewy bodies group, the correlation coefficient between the extent of gray matter atrophy and the severity of atrophy in the dorsal brainstem white matter was r = -0.78 (p < 0.01). Using VSRAD advance, gray matter atrophy and dorsal brainstem grey/white matter atrophy were found to be negatively correlated in Alzheimer’s disease and dementia with Lewy bodies.

Relationship between cerebral atrophy and number of present teeth in elderly individuals with cognitive decline.

Recent shifts in the distribution of Japan's population towards older ages, have meant that the chance of encountering patients with dementia in dental clinics is increasing. Many studies have shown that the brain volume decreases along with the progression of dementia. Although previous studies have reported a relationship between tooth loss or periodontitis and the onset of dementia, the pathological mechanisms underlying this association have not been elucidated. In this study, we aimed to examine the relationship between the oral condition and brain atrophy and to discuss how to adequately deal with patients with dementia. This cross-sectional study included 15 participants who underwent brain magnetic resonance imaging (MRI). The participants were 60years or older and presented with cognitive decline, including Alzheimer's disease (AD) and mild cognitive impairment (MCI), diagnosed by a neurologist. We obtained information on the oral condition, lifestyle, cognitive function, and brain atrophy. Cognitive function was assessed using the Mini-Mental State Examination (MMSE). MR images of each patient were analyzed using the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) to provide a quantitative measure of the degree of brain atrophy. The study population included 4 male and 11 female patients. The mean age and mean number of present teeth were 75.9years (SD 6.7) and 15.0 (SD 11.1), respectively. The median MMSE score was 25.6 (SD 3.7). The degree of atrophy of the whole brain was significantly correlated with the number of present teeth (ρ=-0.72, p<0.05) and the presence of a daily exercise habit (ρ=-0.66, p<0.05). This study demonstrated that the number of present teeth could be an indicator of the progress of dementia. Preserving the teeth as well as the acquisition of a regular exercise habit might be important for preventing progression of dementia. Further research examining a larger study population and analyzing a greater number of factors is warranted.

Relationship between cerebral microbleeds, ventricular enlargement and white matter hyperintensities in Alzheimer’s disease

AbstractBackgroundTo investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.MethodForty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non‐multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB were defined in axial gradient recalled echo (GRE) T2*‐weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel‐based Specific Regional Analysis System for Alzheimer's Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).ResultEI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.ConclusionThe difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

The Effects of a 5-Year Physical Exercise Intervention with Music in Community- Dwelling Normal Elderly People: The Mihama-Kiho Follow-Up Project.

We previously reported the enhanced effects of physical exercise when combined with music (ExM) on cognitive function in community-dwelling normal elderly people compared to exercise alone. Following that study, participants voluntarily continued the ExM classes for 5 years. To identify the effects of a 5-year ExM intervention on cognitive function in normal elderly people. Fifty-four subjects continued the ExM classes once a week for 5 years (ExM group). Thirty-three subjects retired from the ExM class during the 5 years (Retired group). Twenty-one subjects never participated in any intervention over the 5 years (No-exercise group). Cognitive function and ADLs were assessed using neuropsychological batteries and the functional independence measure (FIM), respectively. The voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) was used to investigate medial temporal lobe atrophy. Analyses of the raw scores after the 5-year intervention showed significant differences between the ExM and No-exercise groups in their MMSE scores, Raven's colored progressive matrices (RCPM) time, logical memory (LM)-I, as well as the total and physical exercise sub-scores of the FIM. Analysis of subjects aged 70- 79 years at the beginning of this project showed significantly quicker performance on the RCPM in the ExM compared to No-exercise groups. The correlation coefficients between the total number of ExM sessions attended and the degree of changes in physical, neuropsychological, and VSRAD scores were significant for RCPM performance time and LM-I scores. Long-term ExM intervention reinforces multifaceted cognitive function in normal elderly people, and is especially beneficial for psychomotor speed.

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

Although folate deficiency was reported to be associated with hyperhomocysteinemia, influence of folate supplementation on cognition remains controversial. Therefore, we explored the effects of folate supplementation on the cognition and Homocysteine (Hcy) level in relatively short periods in patients with folate deficiency and cognitive impairment. Enrolled 45 patients (mean age of 79.7 ± 7.9 years old) with folate deficiency (<3.6 ng/mL) with cognitive impairment underwent Mini-Mental State Examination (MMSE), and laboratory examinations, including folate, vitamin B12, and Hcy. The degree of hippocampal atrophy in MRI was estimated using a voxel-based specific regional analysis system for Alzheimer’s disease (VSRAD). Patients were administrated folate (5 mg/day), then Hcy, and MMSE score were re-examined after 28 to 63 days. Mean Hcy significantly decreased from 25.0 ± 18.0 to 11.0 ± 4.3 nmol/mL (p < 0.001). Average MMSE scores also significantly changed from 20.1 ± 4.7 to 22.2 ± 4.3 (p < 0.001). The degree of change in the MMSE score and basic Hcy or Hcy change was significantly positively correlated, while degree of hippocampal atrophy in MRI did not. Although several factors should be taken into account, folate supplementation ameliorated cognitive impairment, at least for a short period, in patients with folate deficiency.

Increased Presence of Cerebral Microbleeds Correlates With Ventricular Enlargement and Increased White Matter Hyperintensities in Alzheimer's Disease.

Objective: To investigate whether the number of cerebral microbleeds (CMB) could be a useful indicator to predict glymphatic system dysfunction in Alzheimer’s disease (AD) patients, by comparing the degree of cerebral spinal fluid (CSF) and interstitial fluid (ISF) stasis.Methods: Forty probable AD patients were included, with those exhibiting two or more CMB were included in the multiple CMB group (mCMB, n = 21, mean = 11.1), and none or one CMB included in the non-multiple CMB group (nmCMB, n = 19, mean = 0.84). CMB was defined in axial gradient recalled echo (GRE) T2*-weighted images. Evans index (EI) was calculated to measure lateral ventricle enlargement, Voxel-based Specific Regional Analysis System for Alzheimer’s Disease (VSRAD) software was used to determine the extent of gray and white matter atrophy, and Fazekas scale (FS) was used to determine white matter hyperintensities (WMH).Results: EI was significantly larger in mCMB than in nmCMB, while the gray and white matter volume was not different between groups. Thus, the difference in lateral ventricle enlargement between AD with and without multiple CMB reflects a combination of the degree of brain atrophy and the extent of CSF stasis. FS was higher in mCMB than in the nmCMB, suggesting the failure of ISF elimination was more severe in mCMB cases.Conclusion: The difference in lateral ventricle enlargement and WMH between AD with or without multiple CMB may reflect a difference in the degree of CSF/ISF stagnation.

The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: A cross-sectional study conducted in Japan

Recent studies have revealed an association between the dysregulation of the gut microbiome and dementia. However, whether this dysregulation is associated with mild cognitive impairment (MCI), an early stage of cognitive decline, in patients without dementia remains unclear. We performed a cross-sectional analysis to determine the association between the gut microbiome and MCI. Data, including patient demographics, risk factors, cognitive function, and brain imaging, were collected. The gut microbiome was assessed through terminal restriction fragment length polymorphism analysis. Multivariable logistic regression models were used to identify factors independently associated with MCI. Graphical modelling was used to illustrate mutual associations between MCI and identified factors. We analysed 82 patients, 61 of whom exhibited MCI. Patients with MCI had a higher prevalence of Bacteroides. Furthermore, patients with more Bacteroides were more likely to present with white matter hyperintensity and high voxel-based specific regional analysis system for Alzheimer’s Disease (VSRAD) scores, indicating cortical and hippocampal atrophy. A multivariable logistic regression analysis revealed that a greater prevalence of Bacteroides was independently associated with MCI. Graphical modelling also showed a close association between Bacteroides and MCI. In conclusion, an increased prevalence of Bacteroides is independently associated with the presence of MCI in patients without dementia.