Soo Hyun Joo

Three Large-Scale Functional Brain Networks from Resting-State Functional MRI in Subjects with Different Levels of Cognitive Impairment

Normal aging and to a greater degree degenerative brain diseases such as Alzheimers disease (AD), cause changes in the brains structure and function. Degenerative changes in brain structure and decline in its function are associated with declines in cognitive ability. Early detection of AD is a key priority in dementia services and research. However, depending on the disease progression, neurodegenerative manifestations, such as cerebral atrophy, are detected late in course of AD. Functional changes in the brain may be an indirect indicator of trans-synaptic activity and they usually appear prior to structural changes in AD. Resting-state functional magnetic resonance imaging (RS-fMRI) has recently been highlighted as a new technique for interrogating intrinsic functional connectivity networks. Among the majority of RS-fMRI studies, the default mode network (DMN), salience network (SN), and central executive network (CEN) gained particular focus because alterations to their functional connectivity were observed in subjects who had AD, who had mild cognitive impairment (MCI), or who were at high risk for AD. Herein, we present a review of the current research on changes in functional connectivity, as measured by RS-fMRI. We focus on the DMN, SN, and CEN to describe RS-fMRI results from three groups: normal healthy aging, MCI and AD.

The association between hippocampal subfield volumes and education in cognitively normal older adults and amnestic mild cognitive impairment patients

Objective Previous research has indicated that there are potential associations between education and total hippocampal volume in the trajectory of Alzheimer’s disease (AD). However, the correlation between education and hippocampal subfield volumes in the progression of AD has yet to be understood. This study examined the relationship between education, which is a standard proxy for cognitive reserve, and hippocampal subfield volumes in healthy and amnestic mild cognitive impairment (aMCI) groups. Subjects and methods Thirty-eight subjects with aMCI and 39 healthy control subjects underwent 3 T magnetic resonance imaging, and hippocampal subfield volumes were measured by automated segmentation. Multiple linear regression analysis was used to determine the association between education and hippocampal subfield volumes. Results Education had a significant negative correlation with the left parasubiculum, presubiculum, and subiculum volumes in the aMCI group. In addition, multiple subfield volumes including left parasubiculum, left/right presubiculum, left cornus ammonis (CA)3, and left CA4 showed a significant correlation with the neuropsychological test scores in the control group and aMCI group. Conclusion These findings contribute to a better understanding of the association between education, hippocampal subfield volumes, and amnestic cognitive functions in the early phase of AD.

Thalamic Shape and Cognitive Performance in Amnestic Mild Cognitive Impairment.

Objective This study aimed to investigate thalamic shape alterations and their relationships with various episodic memory impairments in subjects with amnestic mild cognitive impairment (aMCI). Methods We compared volumes and morphological alterations of the thalamus between aMCI subjects and healthy controls. In addition, we investigated the correlation between thalamic deformations and various memory impairments in aMCI subjects using a comprehensive neuropsychological battery. Results The normalized left thalamic volumes of the aMCI group were significantly smaller than those of the healthy control group (p<0.0001). aMCI subjects exhibited significant thalamic deformations in the left thalamic dorso-medial and antero-medial areas compared with healthy individuals. CERAD-K Word List Memory scores were significantly correlated with the left dorso-medial areas in aMCI subjects. There were no significant correlations between verbal fluency, Boston naming test, constructional praxis, Word List Recognition, and Visuospatial Recall scores and thalamic shape in aMCI subjects. Verbal delayed recall scores were also significantly correlated with the left dorso-medial areas in the aMCI group. Conclusion Structural alterations in the thalamic deformations in the left dorso-medial and antero-medial areas might be core underlying neurobiological mechanisms of thalamic dysfunction related to Word List Memory and delayed verbal recall in individuals with aMCI.

Apathy and intrinsic functional connectivity networks in amnestic mild cognitive impairment

Background Although several prior works reported that apathy is associated with conversion to Alzheimer’s disease in individuals with amnestic mild cognitive impairment (aMCI), effects of apathy on the functional connectivity (FC) of the brain remain unclear. In this study, we assessed the pattern of association between apathy and default mode network (DMN), salience network and central executive network (CEN) in aMCI subjects. Methods Fifty subjects with aMCI and 50 controls (CONs) participated in this study. They underwent clinical assessments and magnetic resonance imaging for the structural and resting-state scan. We explored the patterns of association between apathy inventory (IA) total score and the whole-brain voxel-wise FCs of the DMN, salience network and CEN in aMCI subjects. Results We observed that the FCs of the DMN were less and those of CEN were more in the aMCI group than the CON group. Total IA score was negatively correlated with FCs of the anterior cingulate within the DMN, and positively correlated with FCs of the middle frontal, inferior frontal, and supramarginal gyrus within the CEN in the aMCI group. Conclusion Our findings suggest that distinctive patterns of association between apathy and FCs in the DMN and CEN in the aMCI group might reflect the putative role of functional network change in the development of apathy in aMCI.

Body Mass Index in Mild Cognitive Impairment According to Age, Sex, Cognitive Intervention, and Hypertension and Risk of Progression to Alzheimer's Disease

Introduction: Mild cognitive impairment (MCI) is a prodromal stage of dementia. The association of body mass index (BMI) and progression to Alzheimers disease (AD) in MCI subjects according to age, sex, and cognitive intervention remains unknown. We investigated the relationship between BMI and the risk of progression to AD in subjects with MCI, as well as the effect of BMI on progression to AD depending on age, sex, cognitive intervention, and chronic diseases. Methods: Three hundred and eighty-eight MCI subjects were followed for 36.3 ± 18.4 months, prospectively. They underwent neuropsychological testing more than twice during the follow-up period. The MCI subjects were categorized into underweight, normal weight, overweight, and obese subgroups. The associations between baseline BMI and progression to AD over the follow-up period were estimated using Cox proportional hazard regression models. Data were analyzed after stratification by age, sex, cognitive intervention, and chronic diseases. Results: After adjustment for the covariates, the underweight MCI group had a higher risk of progression to AD [hazard ratio (HR): 2.38, 95% confidence interval (CI): 1.17–4.82] relative to the normal weight group. After stratifying by age, sex, cognitive intervention, and chronic diseases, this effect remained significant among females (HR: 3.15, 95% CI: 1.40–7.10), the older elderly ≥75 years old (HR: 3.52, 95% CI: 1.42–8.72), the non-intervention group (HR: 3.06, 95%CI: 1.18–7.91), and the hypertensive group (HR: 4.71, 95% CI: 1.17–18.99). Conclusion: These data indicate that underweight could be a useful marker for identifying individuals at increased risk for AD in MCI subjects. This association is even stronger in females, older elderly subjects, the non-cognitive intervention group, and the hypertensive group.

CYANIDIN-3-GLUCOSIDE RICH BLACK RICE EXTRACT AND COGNITIVE FUNCTION IN SUBJECTIVE COGNITIVE IMPAIRMENT OLDER ADULTS: A DOUBLE-BLIND, PLACEBO-CONTROLLED, RANDOMIZED CLINICAL TRIAL

Background: The memory clinic at the Danish Dementia Research Centre has been reporting data to a quality registry since 2006. During that time period some of the cholinesterase-inhibitors (ChEI) and memantine have become generic. Generic donepezil was introduced in Demark Q1 of 2012. The aim of this abstract is to assess the prescription pattern of anti-dementia drugs over this time period in a tertiary referral center.Methods: Data from 2006 to 2017 on the use of anti-dementia drugs at the time of evaluation/diagnosis for patients diagnosed with Alzheimer’s disease, Mixed dementia (Alzheimer + Vascular), Dementia with Lewy Bodies, and Parkinson’s disease dementia was drawn from the clinical quality registry at the memory clinic at the Danish Dementia Research Centre. The 2017 data cleaning cutoff is Feb/18/2018, thus 2017-data may change. Persons referred for genetic counselling are excluded. Results: Of 8473 new referrals, 2619 patients (31% of all new referrals) were diagnosed with the relevant diagnosis (AD, Mixed dementia, DLB, PDD) (Table 1). Around the year 2012, the percentage of non-treated subjects dropped from approximately 25% to around 12%. At the same time the donepezil percentage of ChEI’s increased from 50-60% to approximately 95%. Conclusions: The data indicates that it had a major impact on the prescription practice, when donepezil became generic in 2012. The data only includes newly diagnosed patients with primarily mild dementia where memantine is off-label and only rarely used in Denmark.

LONGITUDINAL INTRINSIC FUNCTIONAL CONNECTIVITY CHANGES IN PRECLINICAL ALZHEIMER’S DISEASE: A TWO-YEAR FOLLOW UP STUDY

IC-P-033 LONGITUDINAL INTRINSIC FUNCTIONAL CONNECTIVITY CHANGES IN PRECLINICAL ALZHEIMER’S DISEASE: A TWO-YEAR FOLLOW UP STUDY Hyun Kook Lim, Chang Uk Lee, Dong Woo Kang, Yoo Hyun Um, Changtae Hahn, Soo hyun Joo, The Catholic University of Korea, Seoul, Republic of South Korea; Seoul St. Mary’s Hospital, Catholic Medical College, The Catholic University of Korea, Seoul, Republic of South Korea; Seoul Saint Mary’s Hospital, Seoul, Republic of South Korea; St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Suwon, Republic of South Korea; College of Medicine, The Catholic University of Korea, Seoul, Republic of South Korea. Contact e-mail: drblues@catholic.ac.kr

Association between degenerative changes in brain and cognitive functions in Alzheimer’s disease

Soo Hyun Joo, Chang Uk Lee, Seoul St. Mary’s Hospital, Medical College, The Catholic University of Korea, Seoul, South Korea. Contact e-mail: purple-sh@hanmail.net Background:The aim of this study is to investigate the correlation between degenerative changes in brain (i.e. global cortical atrophy, medial temporal atrophy, white matter hyperintensities) and neurocognitive dysfunction in Korean patients with Alzheimer’s disease. Methods: A total of 62 elderly subjects diagnosed with Alzheimer’s disease were included in this study. The degenerative changes in brain MRI were rated with standardized visual rating scales (GCA, MTA, Fazekas scale) and the subjects were divided into two groups according to the degree of degeneration for each scale. Cognitive function was evaluated with CERAD-K (Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease) and several clinical features, including apolipoprotein E ε4 status, lipid profile and thyroid hormones, were also examined. Chi-square test was performed to

Apathy and intrinsic connectivity networks in amnestic mild cognitive impairment

Figure. A) Co the DMN, SN between apath lation between the inter-ICN significant pos DMN-CEN in the aMCI grou and the CEN CEN as eviden roni corrected NETWORKS IN AMNESTIC MILD COGNITIVE IMPAIRMENT Chang Uk Lee, Soo Hyun Joo, Hyun Kook Lim, Seoul St. Mary’s Hospital, Medical College, The Catholic University of Korea, Seoul, South Korea; Medical College, the Catholic University of Korea, Seoul, South Korea. Contact e-mail: jihan@catholic.ac.kr