ATN Classification and Clinical Progression of the Amyloid-Negative Group in Alzheimer's Disease Neuroimaging Initiative Participants.

Alzheimer's disease has recently been classified using three biological markers (amyloid [A], tau [T], and neurodegeneration [N]) to help elucidate its progression. We aimed to investigate whether there were differences between cognitive function and the clinical dementia symptoms over time relative to the ATN classification in the amyloid-negative group. In the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, 310 participants who underwent all the tests required for ATN classification were enrolled. The cognitive function score differences (Alzheimer's Disease Assessment Scale-Cognitive Subscale 13 [ADAS-Cog 13], Clinical Dementia Rating Sum of Boxes [CDR-SOB], and Mini-Mental State Examination [MMSE]) between the groups were analyzed using the analysis of covariance and score changes over time with a linear mixed-effects model. In the cross-sectional analysis, ADAS-Cog 13 scores were higher for A-T-N+ and A-T+N+ than for A-T-N- (p<0.001) and A-T+N- (p<0.001). In the longitudinal analysis, CDR-SOB scores for A-T+N+ deteriorated faster than A-T-N- (p<0.001), A-T+N- (p<0.001) and A-T-N+ (p<0.001). Hippocampal atrophy progressed faster in A-T-N+ (p<0.001) and A-T+N+ (p=0.02) than in A-T-N-. Through this study, we discovered that even in individuals classified as amyloid negative, neurodegeneration with tau deposition exacerbates cognitive decline and worsens clinical symptoms, underscoring the need for continuous monitoring and observation.

Comparison of automated quantification of amyloid deposition between PMOD and Heuron.

Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p < 0.001), except for the PC/PCC (p = 0.986). However, the Bland-Altman plot analysis indicated that the two quantitative methods may be used interchangeably. Moreover, receiver operating characteristic curve analysis revealed no significant between-method difference in the performance of the SUVRs in evaluating the visual positivity of amyloid deposits (p = 0.948). In conclusion, Heuron and PMOD have comparable performance in quantifying the degree of amyloid deposits in PET images.

Effect of Education on Discriminability of Montreal Cognitive Assessment Compared to Mini-Mental State Examination.

Background and Purpose: The Montreal Cognitive Assessment (MoCA) has been known as a screening test for detecting mild cognitive impairment (MCI) better than Mini-Mental State Examination (MMSE). However, in previous domestic studies, no significant difference was found in the discriminability between MoCA and MMSE. Researchers have suggested that this might be because older Koreans are less educated than older Westerners. This study was conducted to examine the effect of education on the discriminability of MoCA compared to the MMSE. Methods: Participants were 123 cognitively normal elderly, 118 with vascular MCI, 108 with amnestic MCI, 121 with vascular dementia, and 113 with dementia of the Alzheimer's type. The Korean-MoCA (K-MoCA) and Korean-MMSE (K-MMSE) were administered. Multiple regression analyses and receiver operating characteristic (ROC) curve analyses were performed. Results: In all participants, education significantly affected both K-MoCA and K-MMSE scores along with age. The effect of education was re-examined by subgroup analysis after dividing subjects according to the level of education. Effect of education on K-MoCA and K-MMSE was only shown in the group with <9 years of education. ROC curve analyses revealed that the discriminability of K-MoCA to differentiate between vascular MCI and normal elderly was significantly higher than that of K-MMSE. When re-examining subgroups divided by education level, however, this higher discriminability of K-MoCA disappeared in the group with <9 years of education. Conclusions: These results indicate no difference in discriminating cognitive deficits between K-MoCA and K-MMSE in Korean elderly with <9 years of education.

DeepParcellation: A novel deep learning method for robust brain magnetic resonance imaging parcellation in older East Asians.

Accurate parcellation of cortical regions is crucial for distinguishing morphometric changes in aged brains, particularly in degenerative brain diseases. Normal aging and neurodegeneration precipitate brain structural changes, leading to distinct tissue contrast and shape in people aged >60 years. Manual parcellation by trained radiologists can yield a highly accurate outline of the brain; however, analyzing large datasets is laborious and expensive. Alternatively, newly-developed computational models can quickly and accurately conduct brain parcellation, although thus far only for the brains of Caucasian individuals. To develop a computational model for the brain parcellation of older East Asians, we trained magnetic resonance images of dimensions 256 × 256 × 256 on 5,035 brains of older East Asians (Gwangju Alzheimer's and Related Dementia) and 2,535 brains of Caucasians. The novel N-way strategy combining three memory reduction techniques inception blocks, dilated convolutions, and attention gates was adopted for our model to overcome the intrinsic memory requirement problem. Our method proved to be compatible with the commonly used parcellation model for Caucasians and showed higher similarity and robust reliability in older aged and East Asian groups. In addition, several brain regions showing the superiority of the parcellation suggest that DeepParcellation has a great potential for applications in neurodegenerative diseases such as Alzheimer's disease.

Validity of the Montreal Cognitive Assessment (MoCA) Index Scores: a Comparison with the Cognitive Domain Scores of the Seoul Neuropsychological Screening Battery (SNSB).

BACKGROUND AND PURPOSE: A new approach was proposed to score the Montreal Cognitive Assessment (MoCA) index scores for 6 cognitive domains: orientation (OIS), attention (AIS), language (LIS), visuospatial function (VIS), memory (MIS), and executive function (EIS). This study investigated whether the MoCA index scores represent the functions of each cognitive domain by examining the correlations with the corresponding cognitive domain scores derived from conventional neuropsychological tests included in the Seoul Neuropsychological Screening Battery, 2nd Edition (SNSB-II). METHODS: The participants were 104 amnestic mild cognitive impairment (aMCI), 74 vascular mild cognitive impairment (VaMCI), 73 dementia of the Alzheimer's type (DAT), and 41 vascular dementia (VaD) patients. All participants were administered the Korean-MoCA and SNSB-II. RESULTS: Like the MoCA total score, the MoCA-OIS, MoCA-VIS, and MoCA-MIS showed differences between aMCI and AD groups and between VaMCI and VaD groups. The MoCA-AIS, MoCA-LIS, and MoCA-EIS showed significant differences between VaMCI and VaD groups, but no difference between aMCI and DAT groups. In the aMCI and VaMCI groups, all index scores of the MoCA showed significant correlations with the corresponding cognitive domain scores of the SNSB-II. Except for MoCA-MIS, the MoCA-AIS, MoCA-LIS, MoCA-VIS, and MoCA-EIS also showed significant correlations with the corresponding domain scores of the SNSB-II in the DAT and VaD groups. CONCLUSIONS: These results indicate that all MoCA index scores, except for MoCA-MIS, which does not reflect the severity of memory impairment in dementia patients, provide highly valid information on the function of each cognitive domain in patients with mild cognitive impairment and dementia.

Classification and Graphical Analysis of Alzheimer's Disease and Its Prodromal Stage Using Multimodal Features From Structural, Diffusion, and Functional Neuroimaging Data and the APOE Genotype.

Graphical, voxel, and region-based analysis has become a popular approach to studying neurodegenerative disorders such as Alzheimer's disease (AD) and its prodromal stage [mild cognitive impairment (MCI)]. These methods have been used previously for classification or discrimination of AD in subjects in a prodromal stage called stable MCI (MCIs), which does not convert to AD but remains stable over a period of time, and converting MCI (MCIc), which converts to AD, but the results reported across similar studies are often inconsistent. Furthermore, the classification accuracy for MCIs vs. MCIc is limited. In this study, we propose combining different neuroimaging modalities (sMRI, FDG-PET, AV45-PET, DTI, and rs-fMRI) with the apolipoprotein-E genotype to form a multimodal system for the discrimination of AD, and to increase the classification accuracy. Initially, we used two well-known analyses to extract features from each neuroimage for the discrimination of AD: whole-brain parcelation analysis (or region-based analysis), and voxel-wise analysis (or voxel-based morphometry). We also investigated graphical analysis (nodal and group) for all six binary classification groups (AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs). Data for a total of 129 subjects (33 AD, 30 MCIs, 31 MCIc, and 35 HCs) for each imaging modality were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) homepage. These data also include two APOE genotype data points for the subjects. Moreover, we used the 2-mm AICHA atlas with the NiftyReg registration toolbox to extract 384 brain regions from each PET (FDG and AV45) and sMRI image. For the rs-fMRI images, we used the DPARSF toolbox in MATLAB for the automatic extraction of data and the results for REHO, ALFF, and fALFF. We also used the pyClusterROI script for the automatic parcelation of each rs-fMRI image into 200 brain regions. For the DTI images, we used the FSL (Version 6.0) toolbox for the extraction of fractional anisotropy (FA) images to calculate a tract-based spatial statistic. Moreover, we used the PANDA toolbox to obtain 50 white-matter-region-parcellated FA images on the basis of the 2-mm JHU-ICBM-labeled template atlas. To integrate the different modalities and different complementary information into one form, and to optimize the classifier, we used the multiple kernel learning (MKL) framework. The obtained results indicated that our multimodal approach yields a significant improvement in accuracy over any single modality alone. The areas under the curve obtained by the proposed method were 97.78, 96.94, 95.56, 96.25, 96.67, and 96.59% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIc, AD vs. MCIs, HC vs. MCIc, and HC vs. MCIs binary classification, respectively. Our proposed multimodal method improved the classification result for MCIs vs. MCIc groups compared with the unimodal classification results. Our study found that the (left/right) precentral region was present in all six binary classification groups (this region can be considered the most significant region). Furthermore, using nodal network topology, we found that FDG, AV45-PET, and rs-fMRI were the most important neuroimages, and showed many affected regions relative to other modalities. We also compared our results with recently published results.

MRI-Based Multimodal Approach to the Assessment of Clinical Symptom Severity of Obsessive-Compulsive Disorder.

OBJECTIVE: This study assessed the associations of the abnormal brain activation and functional connectivity (FC) during memory processing and brain volume alteration in conjunction with psychiatric symptom severity in patients with obsessive-compulsive disorder (OCD). METHODS: Twenty-OCD patients and 20-healthy controls (HC) underwent T1-weighted and functional imaging underlying explicit memory task. RESULTS: In memory encoding, OCD patients showed higher activities in right/left (Rt./Lt.) inferior temporal gyrus (ITG), medial prefrontal cortex (MPFC), dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex (ACC), compared with HC. In task-based FC, caudate (Cd) was positively connected with DLPFC and ITG in OCD, while HC showed different connectivities of Cd-ACC and Rt.-Lt. ITG. In memory retrieval, only Cd was activated in OCD patients. Cd was positively connected with DLPFC and vmPFC in OCD, but negatively connected between same brain areas in HC. OCD patients showed increased gray matter (GM) volumes of cerebellum, DLPFC, orbitofrontal cortex (OFC), hippocampus, Cd and ITG, and concurrently, increased white matter volumes of DLPFC. In OCD patients, GM volumes of Cd and OFC were positively correlated with HAMA and Y-BOCS. Functional activity changes of Cd in OCD were positively correlated with Y-BOCS. CONCLUSION: Our findings support to accessing clinical symptom and its severity linked by brain structural deformation and functional abnormality in OCD patients.

A pilot study of brain morphometry following donepezil treatment in mild cognitive impairment: volume changes of cortical/subcortical regions and hippocampal subfields.

The efficacy of donepezil is well known for improving the cognitive performance in patients with mild cognitive impairment (MCI) and Alzheimer's disease (AD). Most of the recent neuroimaging studies focusing on the brain morphometry have dealt with the targeted brain structures, and thus it remains unknown how donepezil treatment influences the volume change over the whole brain areas including the cortical and subcortical regions and hippocampal subfields in particular. This study aimed to evaluate overall gray matter (GM) volume changes after donepezil treatment in MCI, which is a prodromal phase of AD, using voxel-based morphometry. Patients with MCI underwent the magnetic resonance imaging (MRI) before and after 6-month donepezil treatment. The cognitive function for MCI was evaluated using the questionnaires of the Korean version of the mini-mental state examination (K-MMSE) and Alzheimer's disease assessment scale-cognitive subscale (ADAS-Cog). Compared with healthy controls, patients with MCI showed significantly lower GM volumes in the hippocampus and its subfields, specifically in the right subiculum and left cornu ammonis (CA3). The average scores of K-MMSE in patients with MCI improved by 8% after donepezil treatment. Treated patients showed significantly higher GM volumes in the putamen, globus pailldus, and inferior frontal gyrus after donepezil treatment (p < 0.001). However, whole hippocampal volume in the patients decreased by 0.6% after 6-month treatment, and the rate of volume change in the left hippocampus was negatively correlated with the period of treatment. These findings will be useful for screening and tracking MCI, as well as understanding of the pathogenesis of MCI in connection with brain morphometric change.

Early diagnosis of Alzheimer's disease using combined features from voxel-based morphometry and cortical, subcortical, and hippocampus regions of MRI T1 brain images.

In recent years, several high-dimensional, accurate, and effective classification methods have been proposed for the automatic discrimination of the subject between Alzheimer's disease (AD) or its prodromal phase {i.e., mild cognitive impairment (MCI)} and healthy control (HC) persons based on T1-weighted structural magnetic resonance imaging (sMRI). These methods emphasis only on using the individual feature from sMRI images for the classification of AD, MCI, and HC subjects and their achieved classification accuracy is low. However, latest multimodal studies have shown that combining multiple features from different sMRI analysis techniques can improve the classification accuracy for these types of subjects. In this paper, we propose a novel classification technique that precisely distinguishes individuals with AD, aAD (stable MCI, who had not converted to AD within a 36-month time period), and mAD (MCI caused by AD, who had converted to AD within a 36-month time period) from HC individuals. The proposed method combines three different features extracted from structural MR (sMR) images using voxel-based morphometry (VBM), hippocampal volume (HV), and cortical and subcortical segmented region techniques. Three classification experiments were performed (AD vs. HC, aAD vs. mAD, and HC vs. mAD) with 326 subjects (171 elderly controls and 81 AD, 35 aAD, and 39 mAD patients). For the development and validation of the proposed classification method, we acquired the sMR images from the dataset of the National Research Center for Dementia (NRCD). A five-fold cross-validation technique was applied to find the optimal hyperparameters for the classifier, and the classification performance was compared by using three well-known classifiers: K-nearest neighbor, support vector machine, and random forest. Overall, the proposed model with the SVM classifier achieved the best performance on the NRCD dataset. For the individual feature, the VBM technique provided the best results followed by the HV technique. However, the use of combined features improved the classification accuracy and predictive power for the early classification of AD compared to the use of individual features. The most stable and reliable classification results were achieved when combining all extracted features. Additionally, to analyze the efficiency of the proposed model, we used the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset to compare the classification performance of the proposed model with those of several state-of-the-art methods.

Inner retinal thinning as a biomarker for cognitive impairment in de novo Parkinson's disease.

We investigated the association between retinal changes measured using optical coherence tomography (OCT) and diverse clinical grading scales in patients with Parkinson's disease (PD). Seventy-four eyes of 74 patients with de novo PD and 53 eyes of age-matched control subjects were included. The thickness of the peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) were measured. We analyzed the correlations between the clinical PD grading scales and OCT parameters, and between the OCT parameters and volumetric data in the cerebral cortical and subcortical structures. The area under the receiver operating characteristic curve (AUC) was calculated for diagnosing cognitive impairment in patients with PD. Statistically significant reductions in the thickness of average, temporal, and inferior pRNFL and overall mGCIPL were observed in patients with PD. The Montreal Cognitive Assessment score was significantly associated with mGCIPL thinning. The AUC of the mGCIPL parameters for diagnosing cognitive impairment in patients with PD ranged from 0.651 to 0.760. Moreover, thinning of the mGCIPL was significantly associated with the volumetric parameters of associated brain structures. Our findings highlight the clinical implications of OCT measurements as a potential biomarker for early detection of cognitive impairment in patients with PD.

Alzheimer's Disease Diagnosis Based on Cortical and Subcortical Features.

Alzheimer's disease (AD) is a common neurodegenerative disease with an often seen prodromal mild cognitive impairment (MCI) phase, where memory loss is the main complaint progressively worsening with behavior issues and poor self-care. However, not all patients clinically diagnosed with MCI progress to the AD. Currently, several high-dimensional classification techniques have been developed to automatically distinguish among AD, MCI, and healthy control (HC) patients based on T1-weighted MRI. However, these method features are based on wavelets, contourlets, gray-level co-occurrence matrix, etc., rather than using clinical features which helps doctors to understand the pathological mechanism of the AD. In this study, a new approach is proposed using cortical thickness and subcortical volume for distinguishing binary and tertiary classification of the National Research Center for Dementia dataset (NRCD), which consists of 326 subjects. Five classification experiments are performed: binary classification, i.e., AD vs HC, HC vs mAD (MCI due to the AD), and mAD vs aAD (asymptomatic AD), and tertiary classification, i.e., AD vs HC vs mAD and AD vs HC vs aAD using cortical and subcortical features. Datasets were divided in a 70/30 ratio, and later, 70% were used for training and the remaining 30% were used to get an unbiased estimation performance of the suggested methods. For dimensionality reduction purpose, principal component analysis (PCA) was used. After that, the output of PCA was passed to various types of classifiers, namely, softmax, support vector machine (SVM), k-nearest neighbors, and naïve Bayes (NB) to check the performance of the model. Experiments on the NRCD dataset demonstrated that the softmax classifier is best suited for the AD vs HC classification with an F1 score of 99.06, whereas for other groups, the SVM classifier is best suited for the HC vs mAD, mAD vs aAD, and AD vs HC vs mAD classifications with the F1 scores being 99.51, 97.5, and 99.99, respectively. In addition, for the AD vs HC vs aAD classification, NB performed well with an F1 score of 95.88. In addition, to check our proposed model efficiency, we have also used the OASIS dataset for comparing with 9 state-of-the-art methods.

HbA1c (Glycated Hemoglobin) Levels and Clinical Outcome Post-Mechanical Thrombectomy in Patients With Large Vessel Occlusion.

Background and Purpose- We analyzed the relationship between HbA1c (glycated hemoglobin) levels and clinical outcomes in patients with large vessel occlusion treated with mechanical thrombectomy (MT). Methods- A total of 534 patients with acute ischemic stroke (AIS) treated with MT were enrolled in this prospective cohort study. The primary outcome measured was the modified Rankin Scale score at 3 months, according to HbA1c level. High HbA1c levels were defined as a plasma level of HbA1c >6.5%. Favorable outcomes were defined as functional independence, with modified Rankin Scale scores of 0 to 2. Secondary functional outcomes included mortality, early clinical outcomes, and intracranial hemorrhage. Results- The number of patients with a favorable outcome was significantly lower in patients with HbA1c >6.5% than in those with HbA1c ≤6.5% (28.8% versus 42.1%; P=0.006). In multivariate analysis, high HbA1c levels (especially >7.0% HbA1c) were significantly associated with poor functional outcomes 3 months after AIS in patients with large vessel occlusion treated with MT. High HbA1c was also significantly associated with increased mortality and worse early clinical outcomes after AIS in patients treated with MT. Subgroup analyses showed that HbA1c >6.5% was associated with significantly lower odds of functional independence at 3 months after AIS, when comparing the recanalized group with nonrecanalized patients. Conclusions- These results suggest that high HbA1c level is an independent predictor of a poor outcome at 3 months after AIS in patients with large vessel occlusion treated with MT, particularly in those with recanalization, and may augment the risk of mortality and early clinical worsening after AIS.

Impact of Microbleeds on Outcome Following Recanalization in Patients With Acute Ischemic Stroke.

Background and Purpose- We analyzed the association between cerebral microbleeds (CMBs) and clinical outcome in acute ischemic stroke patients and especially in a subgroup of patients with successful recanalization. Methods- A total of 1532 acute ischemic stroke patients treated with intravenous thrombolysis or mechanical thrombectomy were enrolled in this prospective cohort study. The primary outcome was measured using the modified Rankin Scale at 3 months, according to the CMB status based on magnetic resonance imaging at admission. Favorable outcome was defined as functional independence with modified Rankin Scale scores of 0 to 2. Secondary outcomes included the occurrence of symptomatic intracranial hemorrhage. Results- There was no statistically significant association between the presence of CMB and favorable outcome at 3 months when considering all patients (44.3% versus 37.6%; P=0.121). In patients with recanalization, the number of patients with favorable outcomes was significantly higher in the CMB-negative than in the CMB-positive group (57.0% versus 36.0%; P<0.001). In the final multivariate analysis, the presence of CMB, and in particular high CMB burden (≥5), and lobar location, were significantly associated with less favorable 3-month outcomes (odds ratio=0.57; 95% CI, 0.33-0.97; P=0.038) and symptomatic intracranial hemorrhage (odds ratio=3.21; 95% CI, 1.37-7.49; P=0.007) in patients with recanalization. In the analysis of subgroups, a statistically significant interaction was found between CMB presence and recanalization in predicting functional outcomes at 3 months. Conclusions- These results indicate that the presence of CMBs, and especially high burden and lobar location, are independent predictors of poor 3-month clinical outcomes and may increase symptomatic intracranial hemorrhage risk in acute ischemic stroke patients with recanalization. Our findings suggest that CMBs lead to more unfavorable effects in patients with recanalization after large vessel occlusion than in those without recanalization.

The Brain Donation Program in South Korea.

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Proposal Guidelines for Standardized Operating Procedures of Brain Autopsy: Brain Bank in South Korea.

To obtain an in-depth understanding of brain diseases, including neurodegenerative diseases, psychiatric illnesses, and neoplasms, scientific approach and verification using postmortem human brain tissue with or without disease are essential. Compared to other countries that have run brain banks for decades, South Korea has limited experience with brain banking; nationwide brain banks started only recently. The goal of this study is to provide provisional guidelines for brain autopsy for hospitals and institutes that have not accumulated sufficient expertise. We hope that these provisional guidelines will serve as a useful reference for pathologists and clinicians who are involved and interested in the brain bank system. Also, we anticipate updating the provisional guidelines in the future based on collected data and further experience with the practice of brain autopsy in South Korea.

Caregiver Preference and Treatment Compliance in Patients with Mild-to-Moderate Alzheimer's Disease in South Korea: RECAP Study Results.

INTRODUCTION: The aim of this study was to assess caregiver preference and treatment compliance with oral and transdermal medications in a "real-world" setting in patients with mild-to-moderate Alzheimer's disease (AD) in South Korea. METHODS: Real-world evaluation of compliance and preference in Alzheimer's disease treatment (RECAP) was a 24-week, multicenter, prospective, non-interventional study in patients with AD treated with oral or transdermal therapy. Here, we report data from patients living in South Korea. Eligible patients were grouped into one of two treatment cohorts: oral (donepezil, galantamine, rivastigmine, or memantine) or transdermal (rivastigmine patch). Caregiver preference, patient compliance, and physician preference were assessed at week 24 (end of the study). Safety was assessed by reported adverse events (AEs). RESULTS: A total of 398 patients were enrolled (oral 51.8%; transdermal 48.2%) and 79.4% completed the study. Caregivers of patients that were exposed to either the oral or transdermal monotherapy showed a preference for the treatment to which the patients were exposed (both p < 0.0001). However, caregivers of patients that were exposed to both forms of treatments reported a higher preference for transdermal monotherapy (65.9%; p < 0.0041). Patients in both treatment cohorts showed good compliance, with an overall mean (SD) score of 8.84 (1.514) (a median of 9). Of the 15 participating physicians, eight indicated their preference for transdermal therapy and seven preferred oral therapy at week 24. A total of 133 (33.4%) patients reported at least one AE during the study period (oral: 60 patients; transdermal: 73 patients). CONCLUSION: The study showed higher caregiver preference for transdermal monotherapy over oral monotherapy when patients with AD were exposed to both forms of treatment and good patient compliance for both oral and transdermal treatments.

Usefulness of 3-dimensional stereotactic surface projection FDG PET images for the diagnosis of dementia.

To compare diagnostic performance and confidence of a standard visual reading and combined 3-dimensional stereotactic surface projection (3D-SSP) results to discriminate between Alzheimer disease (AD)/mild cognitive impairment (MCI), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD).[F]fluorodeoxyglucose (FDG) PET brain images were obtained from 120 patients (64 AD/MCI, 38 DLB, and 18 FTD) who were clinically confirmed over 2 years follow-up. Three nuclear medicine physicians performed the diagnosis and rated diagnostic confidence twice; once by standard visual methods, and once by adding of 3D-SSP. Diagnostic performance and confidence were compared between the 2 methods.3D-SSP showed higher sensitivity, specificity, accuracy, positive, and negative predictive values to discriminate different types of dementia compared with the visual method alone, except for AD/MCI specificity and FTD sensitivity. Correction of misdiagnosis after adding 3D-SSP images was greatest for AD/MCI (56%), followed by DLB (13%) and FTD (11%). Diagnostic confidence also increased in DLB (visual: 3.2; 3D-SSP: 4.1; P < 0.001), followed by AD/MCI (visual: 3.1; 3D-SSP: 3.8; P = 0.002) and FTD (visual: 3.5; 3D-SSP: 4.2; P = 0.022). Overall, 154/360 (43%) cases had a corrected misdiagnosis or improved diagnostic confidence for the correct diagnosis.The addition of 3D-SSP images to visual analysis helped to discriminate different types of dementia in FDG PET scans, by correcting misdiagnoses and enhancing diagnostic confidence in the correct diagnosis. Improvement of diagnostic accuracy and confidence by 3D-SSP images might help to determine the cause of dementia and appropriate treatment.

Lipoic Acid Use and Functional Outcomes after Thrombolysis in Patients with Acute Ischemic Stroke and Diabetes.

BACKGROUND: Alpha-lipoic acid (aLA) is a strong antioxidant commonly used for treating diabetic polyneuropathy. Previously, we demonstrated the neurorestorative effects of aLA after cerebral ischemia in rats. However, its effects on patients with stroke remain unknown. We investigated whether patients treated with aLA have better functional outcomes after acute ischemic stroke (AIS) and reperfusion therapy than patients not receiving aLA. METHODS: In this retrospective study of 172 prospectively registered patients with diabetes and AIS treated with tissue plasminogen activator (tPA), we investigated the relationship between aLA use and functional outcome both after 3 months and after 1 year. The functional outcomes included occurrence of hemorrhagic transformation (HT), early neurological deterioration (END), and early clinical improvement (ECI). Favorable outcomes were defined as modified Rankin Scale (mRS) scores of 0-2. RESULTS: Of the 172 patients with AIS and diabetes, 47 (27.3%) used aLA. In the entire cohort, favorable outcomes occurred at significantly higher rates both at 3 months and at 1 year in those treated with aLA. The risks for END and HT were lower and the occurrence of ECI was higher in patients treated with aLA. In multivariable analysis, aLA use was associated with favorable outcomes both at 3 months and at 1 year. Age, HT, and increased National Institutes of Health Stroke Scale scores were negative predictors of a favorable outcome. CONCLUSIONS: The use of aLA in patients with AIS and diabetes who are treated with tPA is associated with favorable outcomes. These results indicate that aLA could be a useful intervention for the treatment of AIS after reperfusion therapy.

Effects of donepezil on brain morphometric and metabolic changes in patients with Alzheimer's disease: A DARTEL-based VBM and (1)H-MRS.

A few studies have performed on the brain morphometric changes over the whole brain structure following donepezil treatment in patients with Alzheimer's disease (AD). We evaluated the gray matter (GM) and white matter (WM) volume alterations and cellular metabolic changes in patients with AD before and after donepezil treatment, and further to reveal the correlations of the scores of various neuropsychological scales with the volumetric and metabolic changes. Twenty-one subjects comprising of 11 patients with AD and 10 age-matched healthy controls participated in this study. All of the patients participated in the follow-up study 24weeks following donepezil treatment. In this study, a combination of voxel-based morphometry (VBM) and proton magnetic resonance spectroscopy ((1)H-MRS) was used to assess the brain morphometric and metabolic alterations in AD. In the GM volumetric analysis, both of the untreated and treated patients with donepezil showed significantly reduced volumes in the hippocampus (Hip), parahippocampal gyrus (PHG), precuneus (PCu) and middle frontal gyrus compared with healthy controls. However, donepezil-treated patients showed significantly increased volumes in the Hip, PCu, fusiform gyrus and caudate nucleus compared to untreated patients. In the WM volumetric analysis, untreated and treated patients showed significant volume reductions in the posterior limb of internal capsule (PLIC), cerebral peduncle of the midbrain and PHG compared to healthy controls. However, there was no significant WM morphological change after donepezil treatment in patients with AD. In MRS study, untreated patients with AD showed decreased N-acetylaspartate/creatine (NAA/Cr) and increased myo-inositol (mI)/Cr compared to healthy controls, while treated patients showed only decreased NAA/Cr in the same comparison. However, the treated patients showed simultaneously increased NAA/Cr and decreased mI/Cr and choline (Cho)/Cr ratios compared to untreated patients. This study shows the regional GM and WM volume changes in combination with metabolic changes following donepezil treatment in AD. These findings would be helpful to aid our understanding of the neuroanatomical mechanisms associated with effects of donepezil on the cognitive function in AD.