Hoowon Kim

Marital status of people with epilepsy in Korea

A multicentre face-to-face interview was conducted to identify factors contributing to the marital status of people with epilepsy (PWE) in Korea. The marriage rate of PWEs was only 80% and the divorce rate was more than double that in the general population. Among the single subjects, 34% replied that they were unmarried because of epilepsy, and 76% of divorced PWEs replied that epilepsy was the cause of the divorce. The factors affecting the single and divorced status in PWEs included gender, an earlier onset of seizure and seizure onset before marriage. Not informing the spouse of the disease before marriage for fear of discrimination was not related to disadvantage in marriage negotiation or to divorce. Social stigmatization of epilepsy continues and impacts on the marital status of PWEs in Korea. However, there is no correlation between the perceived and the enacted stigmas of epilepsy.

Altered Executive Function in Pre-Mild Cognitive Impairment

BACKGROUND For the early detection of Alzheimers disease (AD), there is increasing interest in pre-mild cognitive impairment (pre-MCI). OBJECTIVE We explored the neuropsychological characteristics in a group of pre-MCI and cognitively normal (CN) elderly individuals, with the aim of providing measures sensitive to cognitive change in pre-MCI. METHODS We included 188 CN elderly and 77 individuals with pre-MCI. All participants underwent comprehensive clinical and neuropsychological assessment. We compared 17 cognitive tests between the CN and pre-MCI groups by using one-way ANOVAs with false discovery rate correction for multiple comparisons. Pearsons correlations were also obtained between episodic memory and executive function tests in the pre-MCI group. RESULTS The pre-MCI group showed significantly lower scores for visual immediate recall, fluency tests, and Stroop color naming in the color-word incongruent condition than the CN group (p < 0.05). Most of these executive function measures were significantly correlated with episodic memory (p < 0.05). There were no significant group-differences in other tests assessing attention, verbal memory, visuospatial ability, and language. CONCLUSION Our findings indicate that poor executive function especially demanding inhibition and goal-directed behaviors within time limit could be the characteristics of the very early cognitive sign in the course of AD.

Association of subjective memory complaint and depressive symptoms with objective cognitive functions in prodromal Alzheimer's disease including pre-mild cognitive impairment

BACKGROUND Subjective memory complaints (SMC) and depressive symptoms (SDS) are common in the elderly population. However, the relationship among SMC, SDS, and cognitive function remains unclear. We investigated these associations in the elderly from cognitively normal (CN), pre-mild cognitive impairment (MCI), and amnestic MCI (aMCI) groups. METHODS Participants (CN, 299; pre-MCI, 106; aMCI, 267) underwent comprehensive clinical and neuropsychological assessment. and self-report SMC and SDS questionnaires. SMC and SDS were administered in a self-report format. For each neuropsychological test z-score, stepwise multiple linear regressions were performed to assess the relative contribution of SMC, SDS, and their interactions. RESULTS SMC are associated with lower objective memory, while SDS are associated with lower psychomotor speed. Interactions between SMC and SDS were significant for tests of memory, executive function, psychomotor speed, and global cognition. Additional analyses revealed that SDS moderated the SMC-cognition relationship such that only individuals with higher SDS showed significant SMC-cognition associations. LIMITATIONS Due to the cross-sectional design, associations among SMC, SDS, and cognitive function was rather weak, albeit significant. Additionally, future biomarker studies, such as those assessing amyloid burden, are needed to explore the mechanisms underlying the relationship among SMC, SDS, and cognitive function. CONCLUSION Early identification of individuals at risk for developing abnormal cognitive changes is critical. Our findings from the study involving a large sample of carefully selected participants suggest that SMC and SDS could be used as early detection markers of Alzheimers disease.

Pre-Mild Cognitive Impairment: Can Visual Memory Predict Who Rapidly Convert to Mild Cognitive Impairment?

Objective Little is known about the natural course of pre-mild cognitive impairment (pre-MCI) and predictors to MCI. We followed-up individuals with pre-MCI and cognitively normal (CN) elders to identify neuropsychological predictors for rapid conversion to MCI. Methods Seventy-seven individuals with pre-MCI and 180 CN elders were recruited from the pool of individuals registered at the National Research Center for Dementia in Gwangju, Korea. We followed-up with them after a mean of 14±2.29 months. All participants underwent comprehensive clinical and neuropsychological assessment. Logistic regression analysis examined the ability of neuropsychological tests to predict conversions to MCI. Results Of 257 participants, 142 (55.3%) were eligible for the follow-up study (102 CN, 40 pre-MCI). Logistic regression revealed that spatial delayed recall significantly predicted the conversion from pre-MCI to MCI. In CN, copy for a complex figure significantly predicted the conversion to pre-MCI or MCI. Conclusion Our findings indicated that spatial delayed recall was associated with rapid conversion from pre-MCI to MCI. Spatial organization and planning, measured by complex figure reproduction, were associated with rapid conversion from CN to pre-MCI or MCI. Our study suggests that inclusion of visuospatial reproduction and memory using a complex figure further facilitates early detection of MCI.

Differences Between APOE Carriers and Non-APOE Carriers on Neurocognitive Tests: Jensen Effects?:

Background: Being a carrier of the apolipoprotein E (APOE) ε4 allele is a clear risk factor for development of Alzheimer’s disease (AD). On some neurocognitive tests, there are smaller differences between carriers and noncarriers, while other tests show larger differences. Aims: We explore whether the size of the difference between carriers and noncarriers is a function of how well the tests measure general intelligence, so whether there are Jensen effects. Methods: We used the method of correlated vectors on 441 Korean older adults at risk for AD and 44 with AD. Results: Correlations between APOE carriership and test scores ranged from −.05 to .11 (normal), and −.23 to .54 (AD). The differences between carriers and noncarriers were Jensen effects: r = .31 and r = .54, respectively. Conclusion: A composite neurocognitive score may show a clearer contrast between APOE carriers and noncarriers than a large number of scores of single neurocognitive tests.

APOE PROMOTER POLYMORPHISM ACTS AS AN EFFECT MODIFIER FOR APOE ε4 ON ALZHEIMER’S DISEASE

Zbigniew Wszolek, John C. van Swieten, Suzee E. Lee, University of California San Francisco, San Francisco, CA, USA; Erasmus Medical Center, Rotterdam, Netherlands; Alzheimer Center and Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands; Mayo Clinic, Rochester, MN, USA; Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; University of California, Los Angeles School of Medicine, Los Angeles, CA, USA; Massachusetts General Hospital, Boston, MA, USA; University of California Los Angeles, Los Angeles, CA, USA; Indiana University School of Medicine, Indianapolis, IN, USA; University of California San Diego, La Jolla, CA, USA; Washington University School of Medicine, St. Louis, MO, USA; Mayo Clinic, Jacksonville, FL, USA; University of British Columbia, Vancouver, BC, Canada; Gertrude H. Sergievsky Center at Columbia University, New York, NY, USA; Univ of Penn, Philadelphia, PA, USA; University of North Carolina, Chapel Hill, NC, USA; CurePSP, New York, NY, USA; National Alzheimer’s Coordinating Center, University of Washington, Seattle, WA, USA; University of California San Diego, San Diego, CA, USA; Greater Los Angeles VA Healthcare System, Los Angeles, CA, USA; Memory and Aging Center, UCSF Weill Institute for Neurosciences, University of California, San Francisco, San Francisco, CA, USA; Johns Hopkins University, Baltimore, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA; University of Alabama at Birmingham, Birmingham, AL, USA; Tanz Centre for Research in Neurodegenerative Diseases, University of Toronto, Toronto, ON, Canada; The AFTD, Radnor, PA, USA; Stevens Neuroimaging and Informatics Institute, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA; Northwestern University, Chicago, IL, USA; Department of Neurology, Erasmus University Medical Center, Rotterdam, Netherlands. Contact e-mail: Suzee.Lee@ucsf.edu

PURE WHITE MATTER HYPERINTENSITY DOES NOT EVOKE CORTICAL SHRINKAGE AND COGNITIVE DYSFUNCTION

P2-444 PURE WHITE MATTER HYPERINTENSITY DOES NOT EVOKE CORTICAL SHRINKAGE AND COGNITIVE DYSFUNCTION Hoowon Kim, Ilhan Choo, Kun Ho Lee, Yu Yong Choi, Jang Jae Lee, Ji Yeon Chung, Kyu Yeong Choi, Department of Neurology, Chosun University School of Medicine, Gwangju, South Korea; Chosun University/Chosun University Hospital, Gwangju, South Korea; Department of Life Science, Chosun University, Gwangju, South Korea; National Research Center for Dementia, Chosun University, Gwangju, South Korea; Department of Premedics, Chosun University, Gwangju, South Korea. Contact e-mail: hoowon@chosun.ac.kr

AGE-WEIGHTED POLYGENIC RISK MODEL EFFECTIVELY PREDICTS THE ONSET OF ALZHEIMER DISEASE

addressed this problem by developing a technology to reproducibly generate stable soluble Aß1-42 oligomers that are devoid of monomeric or fibrillar Aß and show biophysical properties indistinguishable from the native species. Furthermore, Crossbeta oligomers demonstrate typical functionality of pathological Ab species such as neurotoxicity, in vivo LTP depression and induction of inflammatory response. The availability of the stable oligomers opens previously inaccessible avenues for R&D. For example, it enabled high throughput screening of drug-like compound libraries. Derived from a 100k compound screening effort, small molecule CBB68 was identified and shown to neutralize oligomer-induced neurotoxicity in rat primary neurons and to rescue the synaptic deficit induced by Ab oligomers in vivo as well as in vitro. In particular, the in vivo LTP assay demonstrated the efficacy and brain penetration of CBB68 after intravenous administration. In another application, Crossbeta’s oligomers have also been used to select shark antibodies that specifically recognize a conformational oligomeric epitope and bind to Aß142 oligomers with high affinity (sub-nM), but not to the monomers or fibrils. This antibody provides potential to selectively quantify Aß1-42 oligomers in patient material as part of a high sensitivity biomarker assay together with the stable Crossbeta oligomers as calibrator. Furthermore, the oligomers are excellent research tools, e.g. in disease-relevant bioassays. We show and conclude that the stable oligomers enable multiple applications and constitute optimum drug targets.

PRE-MILD COGNITIVE IMPAIRMENT: CAN MEMORY PREDICT WHO RAPIDLY CONVERTS TO MILD COGNITIVE IMPAIRMENT?

-2 standard deviation) for cognitive impairment ranged from <23 to <26 depending on age group and education level. Significant predictors for MoCA score were age, sex and level of education. Conclusions: We present detailed normative MoCA data and cut-offs according to the DSM-5 criteria for cognitive impairment based on a large population-based cohort of elderly individuals, screened and thoroughly investigated to rule out cognitive impairment. Level of education, sex and age should be taken in account when evaluating MoCA score, which is facilitated by our online regression-based calculator that provide percentile and z-score for a subject’s MoCA score.

SUBJECTIVE DEPRESSIVE SYMPTOMS ARE ASSOCIATED WITH OBJECTIVE MEMORY DECLINE IN PRECLINICAL ALZHEIMER’S DISEASE

nance or retrieval of information. However, evidence for a retention or retrieval deficit remains equivocal. It is also unclear what cognitive mechanism in working memory is impaired in MCI or early AD. Methods: We enrolled forty-six subjects from our Memory Clinics and community, with 24 amnesic MCI patients and 22 normal subjects. After neurological and cognitive assessments, they performed a classic delayed match to sample task with simultaneous event-related potential (ERP) recorded. The ERP in encoding and retrieval epoch during WM were analyzed separately. The latency and amplitude of every ERP component found in the study were compared between two groups. The ERP parameters were further analyzed to explore their relationship with neuropsychological performance. Finally, the locations of maximal difference in cortex were calculated by standard low-resolution tomographic analysis during specific time range. Results: Five components were found: P1, N1, P2, N2 and P300. The amplitude of P2 and P300 was larger in normal subjects than in MCI patients only during retrieval, not encoding epoch, while the latency of them did not show statistical difference. The latency and amplitude of P1 and N1 were similar in two groups. P2 amplitude in the retrieval epoch positively correlated with memory test (auditory verbal learning test) and visual spatial score of Chinese Addenbrooke’s Cognitive Examination-Revised, while P300 amplitude correlated with ACE-R score. The activation difference in P2 time range was maximal at medial frontal gyrus and also significant at superior frontal gyrus. However, the difference in cortex activation during P300 time range did not show significance. Conclusions: The amplitude of P2 indicated deficiency in memory retrieval process, potentially due to dysfunction of central executive in WM model. Regarding the location of P2, medial frontal plays important role in memory retrieval. The findings in the present study suggested that MCI patients have retrieval deficit, probably due to central executive (attention allocation) based on medial and superior frontal gyrus. Thus, it may provide new biomarker for early detection and intervention for aMCI.