Jae Myeong Kang

Stem Cell Therapy for Alzheimer’s Disease: A Review of Recent Clinical Trials

Stem cell therapy has been noted to be a disease-modifying treatment for Alzheimers disease (AD). After the failure to develop new drugs for AD, the number of studies on stem cells, such as mesenchymal stem cells (MSCs) and neural stem cells (NSCs), has increased from the early 2000 s. Issues pertaining to stem cells have been investigated in many animal studies in terms of stem cell origin, differentiation potency, method of culture, tumor formation, injection route, and mobility. Since 2010, mainly in East Asia, researchers began clinical trials investigating the use of stem cells for AD. Two phase I trials on moderate AD have been completed; though they revealed no severe acute or long-term side effects, no significant clinical efficacy was observed. Several studies, which involve more sophisticated study designs using different injection routes, well-established scales, and biomarkers such as amyloid positron emission tomography, are planned for mild to moderate AD patients. Here, we review the concept of stem cell therapy for AD and the progress of recent clinical trials.

Validity of a commercial wearable sleep tracker in adult insomnia disorder patients and good sleepers

OBJECTIVES To compare the accuracy of the commercial Fitbit Flex device (FF) with polysomnography (PSG; the gold-standard method) in insomnia disorder patients and good sleepers. METHODS Participants wore an FF and actigraph while undergoing overnight PSG. Primary outcomes were intraclass correlation coefficients (ICCs) of the total sleep time (TST) and sleep efficiency (SE), and the frequency of clinically acceptable agreement between the FF in normal mode (FFN) and PSG. The sensitivity, specificity, and accuracy of detecting sleep epochs were compared among FFN, actigraphy, and PSG. RESULTS The ICCs of the TST between FFN and PSG in the insomnia (ICC=0.886) and good-sleepers (ICC=0.974) groups were excellent, but the ICC of SE was only fair in both groups. The TST and SE were overestimated for FFN by 6.5min and 1.75%, respectively, in good sleepers, and by 32.9min and 7.9% in the insomnia group with respect to PSG. The frequency of acceptable agreement of FFN and PSG was significantly lower (p=0.006) for the insomnia group (39.4%) than for the good-sleepers group (82.4%). The sensitivity and accuracy of FFN in an epoch-by-epoch comparison with PSG was good and comparable to those of actigraphy, but the specificity was poor in both groups. CONCLUSIONS The ICC of TST in the FFN-PSG comparison was excellent in both groups, and the frequency of agreement was high in good sleepers but significantly lower in insomnia patients. These limitations need to be considered when applying commercial sleep trackers for clinical and research purposes in insomnia.

[18F]-THK5351 PET Imaging in Patients With Semantic Variant Primary Progressive Aphasia.

Background: Semantic variant primary progressive aphasia (svPPA) has been associated with a variety of proteinopathies, mainly transactive response DNA-binding protein, but also with tau and &bgr;-amyloid. Recently selective tau tracers for positron emission tomography (PET) have been developed to determine the presence of cerebral tau deposits in vivo. Here, we investigated the topographical distribution of THK5351 in svPPA patients. Materials and Methods: Five svPPA patients, 14 Alzheimer’s disease patients, and 15 age-matched normal controls underwent [18F]-THK5351 PET scans, magnetic resonance imaging, and detailed neuropsychological tests. [18F]-fluorodeoxyglucose PET was obtained in 3 svPPA patients, whereas the remaining 2 underwent amyloid PET using [18F]-flutemetamol. Tau distribution among the 3 groups was compared using regions of interest–based and voxel-based statistical analyses. Results: In svPPA patients, [18F]-THK5351 retention was elevated in the anteroinferior and lateral temporal cortices compared with the normal controls group (left>right), and in the left inferior and temporal polar region compared with Alzheimer’s disease patients. [18F]-THK5351 retention inversely correlated with glucose metabolism, whereas regional THK retention correlated with clinical severity. [18F]-flutemetamol scans were negative for &bgr;-amyloid. Conclusions: These findings show that [18F]-THK5351 retention may be detected in cortical regions correlating with svPPA pathology.

Cognitive Behavioral Therapy Using a Mobile Application Synchronizable With Wearable Devices for Insomnia Treatment: A Pilot Study.

STUDY OBJECTIVES The use of telemedicine with a mobile application (MA) and a wearable device (WD) for the management of sleep disorders has recently received considerable attention. We designed an MA synchronizable with a WD for insomnia treatment. Our pilot study determined the efficacy of simplified group cognitive behavioral therapy for insomnia (CBT-I) delivered using our MA and assessed participant adherence to and satisfaction with the device. METHODS The efficacy of the CBT-I using MA (CBT-I-MA) was assessed by comparing sleep variables (sleep efficiency [SE], Insomnia Severity Index [ISI], and Pittsburgh Sleep Quality Inventory [PSQI] scores) before and after a 4-week treatment protocol in 19 patients with insomnia disorder patients. SE was assessed using a sleep diary, actigraphy, and the PSQI. RESULTS The intervention significantly improved all three measures of SE (P < .05), and the response rate to treatment was high (94.7%). Total ISI and PSQI scores and sleep latency, as measured by the sleep diary, improved significantly. Participants showed relatively good adherence to our MA, and sleep diary entries were made on 24.3 ± 3.8 of 28 days. Moreover, 94.7% of the participants reported that our MA was effective for treating insomnia. CONCLUSIONS Our pilot study suggested the clinical usefulness of a CBT-I-MA. We expect that our findings will lead to further development and replication studies of CBT-I-MA.

PTSD correlates with somatization in sexually abused children: Type of abuse moderates the effect of PTSD on somatization

Purpose Somatization is a major post-traumatic symptom in sexually abused children. Thus, the present study aimed to determine the relationship between post-traumatic stress disorder (PTSD) symptoms and somatization, and between intelligence and somatization in child sexual abuse victims and to elucidate whether type of abuse had an effect on the relationship between PTSD symptoms and somatization. Methods This study evaluated the somatizations (Child Behavioral Checklist/6–18 [CBCL]), PTSD symptoms (Trauma Symptom Checklist for Children [TSCC]), and intelligence levels of 63 sexually abused children. Correlation and regression analyses were performed to predict somatization based on PTSD symptoms, intelligence, age, and type of sexual abuse, and to find moderating effect of type of abuse on the effect of PTSD symptom on somatization. Results PTSD symptoms (β = 0.471, p = 0.001) and intelligence (β = 0.327, p = 0.021) were associated with somatization. Type of abuse was not, by itself, correlated with somatization (β = 0.158, p = 0.281), but it did have a moderating effect on the effect of PTSD symptoms on somatization (Type of abuse*PTSD symptoms, β = -0.299, p = 0.047). PTSD symptoms were associated with somatization only among those who experienced the molestation type of abuse. Conclusions Somatization in sexually abused children was influenced by the severity of PTSD symptoms and intelligence, and the effect of the PTSD symptoms on somatization was moderated by type of abuse. Specifically, the rape type of abuse may attenuate the effect of post-traumatic symptoms on somatization.

IMPROVEMENTS IN BRAIN CONNECTIVITY IN PATIENTS WITH COGNITIVE IMPAIRMENTS AFTER SMARTPHONE-BASED COGNITIVE TRAINING: A PRELIMINARY STUDY

GDS: Geriatric Depression Scale, CDR: Clinical Dementia Rating, CDR SOB: Clinical Dementia Rating Sum of Box, K-IADL: Korean version of Instrumental Activities of Daily Livint, K-MMSE: Korean version of Mini-Mental State Examination,M:Male, F: Female, AD: Alzheimer’s Disease, MCI: Mild Cognitive Impairment, SD: Standard Deviation K-MMSE, Korean version of the Mini-Mental Status Examination; RLA, Rancho Los Amigos; GSI, Global synchronization index; tDCS 10, 10 days after Transcranial direct current stimulation; tDCS 20, 20 days after Trancranial direct current stimulation

Dementia Care by Healthy Elderly Caregivers Is Associated with Improvement of Patients' Memory and the Caregivers' Quality of Life: A Before and After Study

Objective The provision of care for elderly people with dementia by healthy elderly caregivers is one of the new health-care paradigms in South Korea. The aim of this study was to determine whether this type of care, which includes cognitive stimulation, would improve the cognitive function of dementia patients and the quality of life of the healthy elderly caregiver. Methods Totals of 132 dementia patients and 197 healthy elderly caregivers participated in this study. We evaluated the cognitive function of the dementia patients at baseline and after providing the program for 6 months using the Korean version of the Consortium to Establish a Registry for Alzheimers disease, 1st Edition (CERAD-K). We also evaluated the quality of life of the healthy elderly caregivers using the World Health Organization Quality of Life-Short Version (WHOQOL-BREF) at baseline and after 6 months. Results The word-list memory results of CERAD-K for the included dementia patients improved after 6 months (Z=-2.855, p=0.004). The WHOQOL-BREF score among the elderly caregiver also improved significantly (Z=-2.354, p=0.019). Conclusion These data suggest that dementia care is associated with improvements in both the cognitive function of dementia patients and the quality of life of the healthy elderly caregivers.

DIFFERENCES BETWEEN MONTREAL COGNITIVE ASSESSMENT AND MINI-MENTAL STATE EXAMINATION IN REFLECTING COGNITIVE RESERVE

Background:Apathy is one of the most common behavioural and psychological symptoms of dementia. Prevalence of apathy in Alzheimer’s Disease (AD) is estimated to be 36% (range – 17%-82%) for individuals in nursing homes. When measured by the NPI, prevalence is 32% (range – 23%-48%). Although common, apathy continues to be under-diagnosed and under-researched. While thought to be co-morbid with depression, the literature supports apathy as a distinct clinical entity although the exact biological cause is unknown. As part of a larger ongoing international collaboration between King’s College London and University of Exeter in the UK and Innlandet Hospital Trust, Norwegian University of Science and Technology and the Norwegian National Advisory Unit on Ageing and Health in Norway, we present the apathy and depression data in a cohort of nursing home and community-based participants. Methods: Nursing home and community-based participants (n1⁄42313) with AD were assessed with the 12-item Neuropsychiatric Inventory (NPI). An NPI score of 0 represented no symptoms present. Score of each NPI subscale was calculated by multiplying severity by frequency. Participants’ characteristics, means, standard deviations (SD), Mini-Mental State Exam (MMSE), Clinical Dementia Rating (CDR) scale, NPI apathy and depression scores were analysed by descriptive statistics in SPSS. Results: For the whole cohort, mean age 6 SD was 81.6 6 7.38. 32.6% were male and 67.4% were female. The mean MMSE 6 SD was 15.6 6 7.99 and median CDR was 2. 49.3% had apathy and 46.7% had depression as measured by the NPI. Apathy occurred in 20.5% in isolation while 17.8% had depression alone. 28.0% of participants had both symptoms. Conclusions:There is a subset of people with AD that can have apathy without depression and vice versa, therefore supporting apathy as a separate clinical entity. Future work should be done to ascertain the extent of shared and unique biological correlates between the two symptoms.

TAU PET IMAGING IN SEMANTIC VARIANT PRIMARY PROGRESSIVE APHASIA USING 18F-THK5351 PET

resonance imaging and detailed neuropsychological tests. To compare the distribution of tau deposition among the three groups (AD, aMCI and normal controls), regional of interest (ROI)-based statistical analyses and voxel-based statistical analyses were performed. Correlation analyses between THK5351 retention and glucose metabolism were performed in the 82 ROI of the cerebral cortices. Results:Global tau retention was significantly greater in AD compared to NC. The regions with higher tau uptake in AD compared to NC were frontal, inferior temporal, superior and inferior parietal, occipital, anterior cingulate cortex, posteior cingulate cortex, and striatum. The patients with aMCI showed higher uptake in the inferior temporal lobe compared to NC. In the correlation analyses, THK5351 retention showed negative correlation with glucose metabolism, in the patients with AD dementia. Meanwhile, in the amnestic MCI patients, there were a few regions with positive correlation between THK5351 retention and glucose metabolism, which is known as regions where NFT deposit at the early stage. Conclusions:THK5351 PET reflects symptoms and disease severity. THK5351 retention in inferior temporal cortex may indicate the increase risk ofAD. These study suggests synaptic lossmay follow tau uptake in the AD spectrum disease. In addition, positive correlation between THK5351 retention and glucosemetabolism in the patients with aMCImay suggest that it may be related to secondary compensation mechanism of synaptic changes following tau uptake.

POSITIVE EFFECTS OF AN INTEGRATED SUPPORT AND TRAINING PROGRAM FOR FAMILY CAREGIVERS OF ELDERLY WITH DEMENTIA: A BEFORE AND AFTER STUDY

Objects:Patients with dementia are increasing in the aging society and over 60 percent of caregivers are family members in South Korea. An integrated support and training program for family caregivers is greatly required to relieve the care burden and prevent serious conflicts in families. This study aimed to determine effects of the integrated support program on the caregivers of the elderly with dementia. Methods: Total of 28 dementia family caregivers visited dementia counseling centers participated in this study. A 6 weeks of comprehensive caregiver support and training program, Hyu-Sig-Gong-Gan, developed by IncheonMetropolitan Dementia Center was provided to the participants. Hyu-Sig-Gong-Gan means resting place and it consists of education on dementia, stress coping strategy, cognitive behavior therapy, psychological counselling, linkage to social support service and self-help group. Effects of the program on caregivers were evaluated with Zarit Burden Interview-Korean version (ZBI-K), Center for Epidemiologic Studies Depression (CES-D), EuroQOL 5 Dimensions questionnaire, Medical Outcome Scale Social Support Survey, Brief Resilience Scale (BRS), Coping Self-Efficacy scale, and time spent on caregiving before and after 6 weeks of the program. Results: The evaluated levels of care burden (ZBI-K, Z1⁄4–3.069, p1⁄40.002), depression (CES-D, Z1⁄4–3.751, p<0.001), resilience (BRS, Z1⁄4–3.597, p<0.001) in caregivers who participated the integrated support program were improved. Also, the time spent for giving medication to their patients were decreased significantly (Z1⁄4–1.972, p<0.049) after the program. Conclusions:The integrated support and training program for family caregivers of the elderly with dementia is associated with improvement of the care burden, depression level, resilience, and reduction of time spent on caregiving by improving the efficacy. P3-358 PSYCHOSOCIAL INTERVENTION FOR DEMENTIA CAREGIVER: PILOT STUDY