Kang Ko

SLEEP QUALITY IN YOUNG AND MIDDLE AGE-PERIOD IS ASSOCIATED WITH CEREBRAL AMYLOID BURDEN IN COGNITIVELY NORMAL ELDERLY PEOPLE

trate the regions of significance. Results:The association between baseline levels of cognition and inflammation was greater in the Tg than Wt rats in the right nucleus accumbens, whereas in the opposite was seen in the right inferior colliculus. The association between baseline levels of inflammation and change in cognition at follow-up, several regions including the left retrosplenial cortex, right hippocampus, and the right posterior commissure showed higher decrease in cognition of the Tg animals compared to the Wt (Figure 1). Conclusions:At baseline, there is no association between neuroinflammation and cognitive performance; however in more aged rats, baseline levels of PBR is able to predict cognitive decline. The results provide a framework that could potentially be applied in human studies focusing on the detrimental roles of neuroinflammation in AD.

ASSOCIATION OF SERUM THYROID HORMONE WITH CEREBRAL AMYLOID DEPOSITION AND REGIONAL CEREBRAL GLUCOSE METABOLISM IN COGNITIVELY NORMAL, CLINICALLY EUTHYROID ELDERLY INDIVIDUALS

Hyo Jung Choi, Min Soo Byun, Dahyun Yi, Hyewon Baek, Jun Ho Lee, Hyun Jung Kim, Young Min Choe, Bo Kyung Sohn, Jee Wook Kim, Younghwa Lee, Hyunwoong Ko, Na Young Han, Seung Hoon Lee, Kang Ko, Jong Inn Woo, Dong Young Lee, Seoul National University Hospital, Seoul, The Republic of Korea; 2 Medical Research Center Seoul National University, Seoul, The Republic of Korea; Ulsan University Hospital, Ulsan, The Republic of Korea; SMG-SNU Boramae Medical Center, Seoul, South Korea; 5 Hallym University Dongtan Sacred Hospital, Seoul, The Republic of Korea. Contact e-mail: jung830313@hanmail.net

MODERATING EFFECT OF COGNITIVE RESERVE PROXIES ON THE ASSOCIATION BETWEEN IN VIVO AD PATHOLOGIES AND COGNITION

n 174 22 128 71 Beta-amyloid Global Pib (SUVR) 1.627 60.530 1.609 60.412 0.857 1.648 60.539 1.573 60.472 0.304 Neurodegeneration ADT (mm) 2.600 60.284 2.518 60.260 0.205 2.596 60.311 2.562 60.234 0.376 HVa (mm) -206461225 -2396 6947 0.146 -2004 61262 -2362 6 1109 0.047 50 % intracranial stenosis Number of intracranial stenosis 2 StenosisStenosis+ P-value StenosisStenosis+ P-value n 178 21 161 38 Beta-amyloid Global Pib (SUVR) 1.646 60.522 1.415 60.411 0.052 1.640 60.536 1.544 60.414 0.234 Neurodegeneration ADT (mm) 2.584 60.290 2.579 60.254 0.940 2.598 60.292 2.521 60.252 0.136 HVa (mm) -2087 6 1202 -2515 61327 0.128 -2021 61227 -2602 6 1080 0.008

THE DIRECT AND RISK-MODERATION EFFECT OF MIDLIFE LIFESTYLE ACTIVITIES ON ALZHEIMER`S DISEASE BIOMARKERS

igure 2. Results of moderated mediation model. (A) CA moderated relaonship between APOE4 and HV. (B) PA had significant direct effect on Mglu. Only significant interaction and moderating path were included ut are not shown here for display simplicity. APOE4: Apolipoprotein E 4; CA: Cognitive activity; HV: Hippocampal volume; PA: Physical activy; CMglu: Cerebral glucose metabolism Poster Presentations: Saturday, July 21, 2018 P120

Synergistic interaction between APOE and family history of Alzheimer’s disease on cerebral amyloid deposition and glucose metabolism

BackgroundRecently, the field of gene-gene or gene-environment interaction research appears to have gained growing interest, although it is seldom investigated in Alzheimer’s disease (AD). Hence, the current study aims to investigate interaction effects of the key genetic and environmental risks—the apolipoprotein ε4 allele (APOE4) and family history of late-onset AD (FH)—on AD-related brain changes in cognitively normal (CN) middle-aged and older adults.Methods[11C] Pittsburg compound-B (PiB) positron emission tomography (PET) imaging as well as [18F] fluoro-2-deoxyglucose (FDG) PET that were simultaneously taken with T1-weighted magnetic resonance imaging (MRI) were obtained from 268 CNs from the Korean Brain Aging Study for Early Diagnosis and Prediction of AD (KBASE). Composite standardized uptake value ratios were obtained from PiB-PET and FDG-PET images in the AD signature regions of interests (ROIs) and analyzed. Voxel-wise analyses were also performed to examine detailed regional changes not captured by the ROI analyses.ResultsA significant synergistic interaction effect was found between the APOE4 and FH on amyloid-beta (Aβ) deposition in the AD signature ROIs as well as other regions. Synergistic interaction effects on cerebral glucose metabolism were observed in the regions not captured by the AD signature ROIs, particularly in the medial temporal regions.ConclusionsStrong synergistic effects of APOE4 and FH on Aβ deposition and cerebral glucose metabolism in CN adults indicate possible gene-to-gene or gene-to-environment interactions that are crucial for pathogenesis of AD involving Aβ. Other unspecified risk factors—genes and/or environmental—that are captured by the positive FH status might either coexpress or interact with APOE4 to alter AD-related brain changes in CN. Healthy people with both FH and APOE4 need more attention for AD prevention.

HIGH SOCIAL SUPPORTS RELATE WITH LOW IN VIVO ALZHEIMER'S DISEASE PATHOLOGIES IN COGNITIVELY NORMAL ELDERLY INDIVIDUALS

mecamylamine, a combination of 2.5 mg/kg scopolamine and 10 mg mecamylamine, or placebo. Working memory performance was assessed during fMRI and cholinergic challenge using the N-Back Task (NBT). Results:After E2 treatment women without SCD showed a greater increase in frontal activity during theNBT (3-back> 0-back) than women without SCD (p1⁄4 0.01, k1⁄4 200, pcorr1⁄4 0.05). During mecamylamine challenge therewas a significant three-way interaction between SCD status, E2 treatment, and task condition (F(3,480) 1⁄4 2.71, p < 0.05). Women without SCD who received E2 treatment had better 3-back performance during mecamylamine challenge than women who did not receive estradiol (t (16) 1⁄4 2.45, p<0.05: E2 d’ mean 1⁄4 2.41 SD 1⁄4 0.49; no E2 d’ mean 1⁄4 1.82, SD 1⁄4 0.53). Women with SCD who received E2 treatment had worse 3-back performance than women who did not receive E2 treatment (t (16) 1⁄4 -3.68, p<0.05: E2 d’ mean 1⁄4 2.13, SD 1⁄4 0.14; no E2 d’ mean 1⁄4 2.72, SD 1⁄4 0.14). Conclusions: In women without SCD, E2 ameliorated the effects of cholinergic blockade on memory performance. This was not seen in the SCD group. The imaging results further support E2 salutary effects on cholinergic system functioning in normal postmenopausal women but not in womenwith SCD. Postmenopausal SCDmay be amarker of cholinergic vulnerability or E2 unresponsiveness which reduces the cognitive effect of E2.

VOXEL-WISE ANALYSIS OF THE ASSOCIATION BETWEEN FASTING BLOOD INSULIN AND CEREBRAL GLUCOSE METABOLISM IN NONDIABETIC, COGNITIVELY NORMAL ELDERLY INDIVIDUALS

Results:The mean ventricular and sulcal CSF volumes were 31615ml and 276643ml, respectively. The VS ratio was 0.1160.05. Pearson correlation coefficients between the natural log-transformed VS ratio and total brain volume, intracranial volume, brain parenchymal fraction, log-deep WMH, log-periventricular WMH, and age were 0.02 (p1⁄40.52), 0.18, -0.40, 0.21, 0.33, and 0.35, respectively (p-values <0.0001). The VS ratio increased with older age (p<0.0001) independent of sex, total WMH, and ICV. It was also significantly associated with poorer memory performance (b of Z-score1⁄4-1.29; 95% CI -2.41 to -0.17) and poorer executive functioning (b of Z-score1⁄4-1.72; 95% CI -2.78 to -0.67), adjusted for age, sex, log-WMH, and ICV. Conclusions:In this population, a disproportionate increase in ventricular volume relative to sulcal CSF is associated with older age and with poorer memory and executive functioning. Future studies should investigate to what extent this is a biomarker of accelerated cognitive aging.

ASSOCIATION OF HYPERTENSION WITH IN VIVO ALZHEIMER’S DISEASE PATHOLOGIES IN COGNITIVELY NORMAL, MCI AND DEMENTIA INDIVIDUALS

Note : Data Independen CN : Cognit Dementia Rati IN VIVO ALZHEIMER’S DISEASE PATHOLOGIES IN COGNITIVELY NORMAL, MCI AND DEMENTIA INDIVIDUALS So Yeon Jeon, Min Soo Byun, Dahyun Lee, Jun Ho Lee, Young Min Choe, Kang Ko, Seung Hoon Lee, Na Young Han, jee Wook Kim, Bo Kyung Sohn, Jun Young Lee, Dong Young Lee, Seoul National University Hospital, Seoul, Republic of South Korea; Medical Research Center Seoul National University, Seoul, Republic of South Korea; Ulsan University Hospital, Ulsan, Republic of South Korea; Hallym University Dongtan Sacred Hospital, Seoul, Republic of South Korea; SMG-SNU Boramae Medical Center, Seoul, Republic of South Korea; Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of South Korea. Contact e-mail: iris870422@gmail.com

RELATIONSHIP BETWEEN LIFETIME SLEEP EXPERIENCE AND IN VIVO ALZHEIMER’S DISEASE PATHOLOGIES IN COGNITIVELY NORMAL ELDERLY INDIVIDUALS

Dependent variable: beta amyloid positivity 20-39y 0.536 (0.125-2.306) 0.403 1.373 (0.913-2.063) 0.128 40-59y 0.216 (0.067-0.691) 0.010 1.170 (0.804-1.703) 0.412 Recent 0.238 (0.066-0.865) 0.029 0.905 (0.665-1.233) 0.528 Dependent variable: neurodegeneration positivity 20-39y 0.758 (0.224-2.568) 0.656 0.831(0.630-1.097) 0.191 40-59y 0.544 (0.191-1.547) 0.254 0.717(0.545-0.944) 0.018 Recent 1.626 (0.548-4.823) 0.381 0.931(0.735-1.179) 0.551

ASSOCIATION OF SOCIABILITY WITH HIPPOCAMPAL VOLUME IN COGNITIVELY NORMAL MIDDLE- AND OLD-AGED ADULTS

ApoE4 positive. SUVR range was 0.82-1.41 (see Figure). At a cutoff for cortical grey matter SUVR1⁄41.078, 43/240 (17.9%, 95% CI1⁄413-23%) were amyloid positive. Excluding individuals with dementia/neurological/psychiatric disease (n1⁄429), 38/211 (18.0%, 95%CI1⁄413-23%) were amyloid positive. ApoE4 positivity (OR1⁄45.1, 95%CI 2.5-11) was a major risk for amyloid positivity; childhood and midlife cognition were not. Conclusions: In this preliminary analysis the prevalence of amyloid positivity in this population based sample was w18%, slightly lower but not significantly different to that reported in a large meta-analysis of (often self-selected) healthy 70-year-olds (mean 23.1%, 95% CI1⁄419.5-27.2). Further analysis of these data will inform the design of population based approaches to disease prevention.