Kyu Yeong Choi

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.

TOWARD PERCEPTUAL DEEP LEARNING–BASED ABNORMAL BEHAVIOR PATTERN ANALYSIS FOR PATIENTS WITH ALZHEIMER’S DISEASE

the dementia prevention campaign was started in 2011. As the tool of easy screening of dementia, short questionnaire was selected by the Dementia Prevention Team in Fukui. The questionnaires were sent via mail to the people aged 65 years and older without nursing certification living in Fukui prefecture, Japan. The people who have at least one positive item of questions were advised to be seen by the doctors. However, the number of specialists of dementia, neurologists or psychiatrists is not enough to handle such people, in Fukui, Japan. So, training course of evaluation and management of dementia for primary care physicians was planned. Methods: Several lectures about dementia, including differential diagnosis, radiological findings, treatment, or management were performed in the morning. Management of the behavioral and psychological symptoms of dementia (BPSD) is also included. In the afternoon, the practice how to take the interview, or how to do Mini-Mental State Examination (MMSE), or how to do core neurological examination to the simulated patients of AD and dementia with lewy bodies (DLB) was performed. Simulated patients are Certified nurse of dementia. After finishing the training course, questionnaires were collected by the attendee. Results:The attending primary care physicians are generally satisfied by the training course. Many of the attendee are interested in the evaluation and management of dementia. They started to do MMSE or core neurological examination by themselves. After the training course, many of patients who advised to be seen by the primary care physicians first by the results of short questionnaire were tentatively diagnosed as AD, DLB, vascular dementia, or frontotemporal dementia. If necessary, such patients were referred to specialists. Such patients were treated by primary care physicians themselves under the supervision of the specialists. Conclusions: Training course of evaluation and management of dementia is useful methods for the better understanding of dementia especially for the non-specialists.

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.

A DATA TRANSFORMATION TECHNIQUE FOR MULTI-SCANNER MRI STUDIES: APPLICATION TO MCI PATIENT CLASSIFICATION

20-29 123 0 5 0.46 0.87 0 2 30-39 236 0 10 0.68 1.39 0 2 40-49 296 0 6 0.82 1.89 0 3 50-59 290 0 11 1.57 2.05 1 4 60-69 293 0 15 2.25 2.36 2 5 70-79 169 0 15 4.02 3.21 4 9 80-90 32 0 14 4.47 3.49 4 9 Yu Yong Choi, Balaji Kannappan, Jang Jae Lee, Kyu Yeong Choi, Hyangmi Kim, Byeong Chae Kim, Kun Ho Lee, National Research Center for Dementia, Chosun University, Gwangju, Republic of South Korea, Department of Premedics, Chosun University, Gwangju, Republic of South Korea; National Research Center for Dementia, Chosun University, Gwangju, Republic of South Korea; Department of Life Sciences, Gwangju, Republic of South Korea; National Research Center for Dementia, Gwangju, Republic of South Korea; National Research Centre for Dementia, Gwangju, Republic of South Korea; Chonnam National University Medical School, Gwangju, Republic of South Korea; Department of Life Science, Chosun University, Gwangju, Republic of South Korea. Contact e-mail: yuyongchoi@gmail.com

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.