10^th World Congress on Alzheimers Disease & Dementia May 30-31, 2018 Osaka, Japan

Joon Hyuk Park had completed PhD from Seoul National University. He is an assoicate professor at Jeju National University School of Medicine and a director of Jeju Province Dementia Center. His recearch interests include epidemiology of dementia, BPSD, and vascular depression. He had published more than 50 papers in reputed journals.

The purpose of this study is to investigate the effects of three major neuroimaging markers of Cerebral Autosomal Dominant Arteriopathy with Subcortical infarcts and Leukoencephalophathy (CADASIL) on cognition and quality of life (QoL). Eighty four participants with CADASIL completed the comprehensive clinical evaluation including 3T MRI and genotyping of NOTCH3. WMH volume was calculated using volumes were measure by a fully automated monospectral segmentation method using FLAIR MRIs. Neurocognitive function was evaluated using CERAD-K neuropsychological assessment battery (CERAD-NP) and quality of life was measured using the Short Form 36 Health Survey Questionnaire (SF-36). Greater WMH volume had a negative impact on 8 neurocognitive tests (p<0.05, t-test) in CERAD-NP except constructional praxis. The number of lacunar infarctions was associated with poor performance of MMSE-KC (p<0.05, t-test) only, and the number of CMBs was not related to any neurocognitive test scores. WMH volume was negatively associated with physical function (PF), role limitations, vitality (VT), mental health (MH), physical component score (PCS), and the mental component score. The number of lacunar infarction was only related to poor PF (p<0.05, t-test). The number of CMB was associated with the lower scores of quality of life, especially in general health, VT, MH, and PCS. WMH volume (odds ratio [OR]: 1.03, 95% confidence interval [CI]: 1.007-1.060) in patients with CADASIL was associated with dementia, indicating that for every 1ml of WMH volume, the risk of depressive disorder increased by 3%. WMH volume has the most significant effect on both cognitive function and quality of life.

Jae-Kyung Lee has completed her PhD in UNT Health Science Center and Postdoctoral studies from UT Southwestern Medical Center at Dallas. She had worked as an Assiatant Professor at Emory University until 2015. Currently, she is an Assistant Professor in University of Georgia, USA. She has published more than 24 papers in reputed journals. Her research focused on understanding how inflammation influences neurodegenerative diseases.

Insulin resistance and aging-related metabolic disorders constitute serious threats to human health as risk factors for Alzheimer’s Disease (AD); especially impaired brain glucose homeostasis was related to the severity of the AD pathology. Regulator of G-protein Signaling proteins (RGSs) are a family of proteins that negatively regulate G-Protein Coupled Receptors (GPCR) through their GTPase Accelerating Protein (GAP) activity. RGS10 is one of the smallest RGS family proteins which we have shown to negatively regulate microglia activation and the level of RGS10 in microglia significantly decreased within the microglia by age. RGS10-deficient microglia displayed impaired phagocytic activity to amyloid-beta fibrils (fA). Interestingly, RGS10-deficient mice spontaneously gained weight with age (>15 months) and the level of RGS10 protein was decreased in postmortem brains of the AD and Frontal Temporal Dementia (FTD). Our data demonstrate that RGS10-deficient mice display impaired glucose tolerance, the high level of triglycerides (TG) in plasma. RGS10-deficient mice spontaneously gained weight with age (>15 months). We also tested whether RGS10 plays a role in high-fat-induced chronic inflammation and glucose metabolism as a risk factor for metabolic disorder in the periphery and the CNS. Indeed, HFD-fed RGS10-deficient mice gained significantly more weight compared to HFD-fed wild-type (WT) mice. Importantly, HFD-fed RGS10-deficient mice displayed an insulin resistance phenotype and impaired Long-Term Potentiation (LTP). These data implicate RGS10 may play a critical role of in insulin sensitivity during metabolic disorders in the periphery and the CNS. Importantly, peripheral metabolic disorders, including obesity and insulin resistance along with chronic inflammation have been shown to contribute to development and progression of cognitive impairment and Alzheimer’s disease through multiple mechanisms. Our data strongly implicate the role of RGS10 in modulating metabolic homeostatsis related to its role in neuroinflammation. Elucidating RGS10 function in maintaining metabolic homeostasis in the CNS and periphery may provide the mechanism to link aging associated chronic inflammation and metabolic disorders, which could be a potential therapeutic target for Alzheimer’s diseases with dual effects on both inflammation and metabolic disruption. Overall, our study produced highly novel data delineating potential mechanisms of RGS10 function in metabolic homeostasis in the brain.

Jun-Ah Song has completed her PhD from University of Michigan, School of Nursing and Postdoctoral studies from Oregon Health and Sciences University. She is a Professor of Korea University College of Nursing and an Expert Committee of the National Institute of Dementia in Korea. She has been serving as a Chief Editor of the Journal of Korean Gerontological Nursing and an Editorial Board Member of other professional journals. She has published more than 30 papers about caregiving issues related to dementia in reputed national and international journals.

It is important for health professionals to teach family caregivers of persons with dementia about how to deal with Behavioral Psychological Symptoms of Dementia (BPSD) well. However, little information is available about what aspects exactly they need to learn to be competent in managing BPSD. The purpose of this study was to explore attributes of the concept of family caregiver’s competence for managing BPSD (CM-BPSD). A rapid realist review was conducted to synthesize the complex range of concepts and define attributes of the family caregiver’s CM-BPSD from the comprehensive literature. Three databases were used including MEDLINE, Embase and CINAHL. The search terms used were dementia, caregiver, coping (managing) and competence. The selection criteria were articles being published in English between 1990 and 2017 and considered appropriate for the topic. Among the 235 articles, 89 were excluded for duplication and six for not being written in English. From the concept synthesis of competence for managing, four dimensions were defined: Judging, setting the direction, adjusting and reflecting. For the concept of family caregiver’s CM-BPSD, eleven attributes were derived. Findings of this study suggest that the concept of family caregiver’s CM-BPSD should reflect the procedural aspect. Reflecting can be considered as a meta-competence because it may influence the other three phases of managing BPSD. A field study would be of great value to clarify the attributes of the concept.

Hyunji Jo has graduated from Konyang University in 2016. She is currently pursuing Doctoral studies in Pharmacy at Ewha Womans University. Her research focuses on studying the role of AMPK as a novel therapeutic target for Alzheimer’s disease.

Alzheimer ’s Disease (AD) is an aging-associated neurodegenerative disease. AD patients suffer from behavioral deficits, mental distress and progressive memory impairments. Currently existing AD drugs are merely symptomatic treatments. Therefore, we need to find a novel therapeutic strategy for AD. Amyloid beta (Aβ), known as a marker of AD, is generated by cleaving Amyloid-Precursor Protein (APP) with β-secretase (BACE1) and γ-secretase. Identifying effective methods to suppress the Aβ accumulation has long been of great interest. Recently, AMP-Activated Protein Kinase (AMPK), a serine/threonine protein kinase, began to be focused as a novel therapeutic target since it has been reported to regulate formation of Aβ. Thus, in this study, 100 compounds were selected from screening a chemical library containing one million compounds by in silico study. We finally found YE-06 through chemical modifications and various bioassays. In accordance with the docking study, YE-06 potentially bound to the AMP binding site of AMPK. Compared to Metformin, which is a well-known AMPK activator, YE-06 significantly activated AMPK and consequently down-regulated the protein level of BACE1. The mRNA level of BACE1 was significantly reduced. We showed improvements in the cognition and movement coordination of AD rat model in YE-06 treated group through water maze test, probe test, passive avoidance test, rotarod test and vertical pole test. YE-06 efficiently increased ACh and decreased the AChE activity. Also, YE-06 significantly reduced neuronal cell death of AD rat models. Therefore, our results suggest that YE-06 is a potential compound for AD treatment.

Hae Won Kim is a Specialist in the Department of Nuclear Medicine at Keimyung University Dongsan Medical Center, Republic of Korea.

Background & Purpose: White Matter Lesions (WML), detected as hyperintensities on T2-weighted magnetic resonance imaging, represent chronic microvascular ischemia in the brain and are considered potential risk factors for memory and cognitive impairment in the elderly. The purpose of this study is to evaluate the association between WML and the cerebral β-Amyloid (Aβ) burden in patients with cognitive impairment. Method: 19, 30 and 34 patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer’s disease, respectively, who underwent brain MRI and F-18 florbetaben PET, were included. The Fazekas scale was used to quantify WML on brain T2-weighted images. The cerebral Aβ burden was quantitatively estimated using volume-of-interest analysis. The difference in Fazekas scale was evaluated between the Aβ positive and negative groups. The relationship between the Fazekas scale and the cerebral Aβ burden was evaluated using linear regression analysis after adjustment for age and sex. Result: There were no differences in age and sex among the patients with subjective cognitive impairment, mild cognitive impairment and Alzheimer’s disease. In the overall cohort and mild cognitive impairment group, Aβ positive patients exhibited significantly higher Fazekas scale compared with Aβ negative patients (0.8 vs. 1.3; P=0.024 and 0.5 vs. 1.4; P=0.022). In addition, the cerebral Aβ burden was positively correlated with the Fazekas scale (β=0.299; P=0.006 and β=0.517; P=0.003). Conclusion: WML are associated with the cerebral Aβ burden in patients with cognitive impairment. This suggests that chronic microvascular ischemia contributes to the development of Alzheimer’s disease.

Yung-Chih Kuo is a Professor at National Chung Cheng University, Taiwan. His research interests are focused on biomaterials, nanomedicine, tissue engineering, blood-brain barrier, cancer therapy, nerve regeneration, spinal cord injury and stroke treatment and Alzheimer’s and Parkinson’s disease therapy. He has authored over 140 SCI journal papers. He is a Fellow of Royal Society of Chemistry, UK and an Honor Member of Phi Tau Phi Society. He has also won Prof. Yen-Ping Shih Award in 2017; Best Paper Award in 2016 and 2008; Prof. Tsai-Teh Lai Award in 2015; Special and Talented Scholar Award in 2013 and Outstanding Research Award in 2013.

Polymeric nanoparticles (NPs) combined with lipids can have profound effects on treatment efficacy in patients with neurological disorders such as Alzheimer’s Disease (AD). We developed polyacrylamide (PAAM)-cardiolipin (CL)-poly(lactide-co-glycolide) (PLGA) NPs grafted with surface 83-14 Monoclonal Antibody (MAb) to carry Rosmarinic Acid (RA) and Curcumin (CUR). This drug delivery system was used to cross the Blood-Brain Barrier (BBB) and enhance the viability of SK-N-MC cells insulted with β-Amyloid (Aβ) deposits. Experimental evidence revealed that an increase in the concentration of 83-14 MAb enhanced the permeability coefficient of RA and CUR using the nanocarriers. The levels of phosphorylated p38 and phosphorylated τ-protein at serine 202 in degenerated SK-N-MC cells were in the order: Aβ>(Aβ+RA-CUR)>(Aβ+83-14 MAb-RA-CUR-PAAM-PLGA NPs)>(Aβ+83-14 MAb-RA-CUR-PAAM-CL-PLGA NPs)≈control. The viability of SK-N-MC cells reduced with time and CL in 83-14 MAb-RA-CUR-PAAM-CL-PLGA NPs advantaged Aβ-targeted delivery of RA-CUR. These results evidenced that the current 83-14 MAb-RA-CUR-PAAM-CL-PLGA NPs can be a promising pharmacotherapy to permeate the BBB and reduce the fibrillar Aβ-induced neurotoxicity.