Adeline Su Lyn Ng

THE ROLE OF COMPREHENSIVE INVESTIGATION IN THE DIAGNOSTIC WORK-UP OF YOUNGER PATIENTS WITH COGNITIVE IMPAIRMENT

and adjusted for age. WM tracks that significantly correlated with EYO were further evaluated with pathological biomarkers (cerebrospinal fluid (CSF) amyloid and tau). Results:Significant changes in mean diffusivity and radial diffusivity were seen within parietal and frontal regions for MC CDR>0 compared to other groups (Fig1). Within the MC group, three WM tracks were significantly associated with EYO: forceps major (FMaj), cingulum, and posterior corpus callosum (PCC). Initial decline in WM for MC and NC occur around 10 years prior to EYO. A significant interaction was observed for mutation status and EYO in the cingulum. CSF amyloid correlated with average mean fractional anisotropy (FA; p1⁄40.02) but not with any specific WM track. CSF T-tau correlated with FA for the PCC (p1⁄40.04) and FMaj (p1⁄40.001). Conclusions: This data reveals that WM integrity in ADAD is most strongly affected in posterior/parietal white matter with more advanced disease. These changes suggest that structural decline may initiate just before EYO that associates with the underlying pathology.

MEDIAL TEMPORAL ATROPHY IN AMYLOID-NEGATIVE, YOUNG-ONSET DEMENTIA IS ASSOCIATED WITH HIGH WHITE MATTER HYPERINTENSITY

AV1451 change based on PiB status in OA. Mixed effects models showed significant differences in AV1451 change over time between AD and OA in Braak III/IV (mean AD AV1451-APC1⁄44.38%, p<0.05; Fig.2) and Braak V/VI (AD AV1451-APC1⁄45.14%, p<0.05), but not Braak I/II (AD AV1451-APC1⁄4-0.66%, p>0.3). Voxelwise analyses of AV1451 change in AD showed significant increases in lateral and medial frontal lobes (p<0.001, uncorrected; Fig.3A), while atrophy over the same interval was more widespread (Fig.3B). In OA, AV1451 binding significantly increased in bilateral temporal lobe and retrosplenial cortex (p<0.001, cluster FWE p<0.05; Fig.4A). There were no voxelwise differences related to sex, PiB, or APOE. Atrophy in OAwas observed in temporal and parietal lobes with limited frontal involvement (FWE p<0.05; Fig.4B). Conclusions: Our findings provide evidence of in vivo tau accumulation in OA especially in regions associated with early tau deposition. Tau accumulation in OA occurs mostly in regions where cortex is thinning (Fig.5). In AD, tau accumulation is more severe across the brain and group-level increases are in regions associated with ‘later’ tau pathology.

DIFFERENTIATING FRONTAL VARIANT ALZHEIMER'S DISEASE FROM BEHAVIOURAL VARIANT FRONTOTEMPORAL DEMENTIA

prepare sites and investigators for FTLD clinical trials. Clinical, biomarker, genetic and imaging data from ARTFL and LEFFTDS will soon be available to investigators worldwide. Kipp Right frontal, mean (s) 2.2 (1.1) 2.2 (1.1) 0.98 Kipp Left frontal, mean (s) 2.3 (0.9) 2.0 (0.7) 0.56 Kipp Right anterior temporal, mean (s) 1.6 (1.2) 2.0 (0.7) 0.55 Kipp Left anterior temporal, mean (s) 1.9 (0.9) 2.0 (0.7) 0.85 Kipp Right posterior temporal, mean (s) 1.6 (0.7) 2.0 (0.7) 0.24 P2-304 DIFFERENTIATING FRONTALVARIANT

CEREBROSPINAL FLUID TAU/AMYLOID β42 RATIO CORRELATES TO CEREBRAL ATROPHY IN AD

gradient-echo-planar sequence sensitive to blood oxygen level-dependent(BOLD) contrast were collected. The subgroup analyses were conducted using SPM and REST, with PCC being selected as the seed region. Results: The SCD group had intact default mode network (Fig. 1). However, the connectivity between PCC and prefrontal cortex and middle temporal cortex had been attenuated compared with control aging group (Fig 2a). We found progressively reduced connectivity in MCI and AD groups in prefrontal cortex, PCC and MTL (medial temporal lobe). (Fig 2b and 2c). Conclusions:Our pilot study is the first to detect the brain connectivity alterations in SCD, and found the connectivity between PCC and other DMN regions being attenuated in the progression of cognitive impairment (from SCD to MCI to AD). PCCDMN connectivity alteration might be a sensitive biomarker of early cognitive impairment and is worthy of further investigation on a larger-scale longitudinal study. References: 1. He Y, et al. 2007;35:488-500. 2. Sorg C, et al. 2007;104:18760-18765. 3. Fransson P, et al. 2008;42:1178-1184. 4. Fransson P. 2005;26: 15-29.

A VISUAL COGNITIVE ASSESSMENT TOOL FOR THE DIAGNOSIS OF YOUNG-ONSET DEMENTIA: A BIOMARKER-SUPPORTED STUDY

P3-432 AVISUAL COGNITIVE ASSESSMENT TOOL FOR THE DIAGNOSIS OF YOUNG-ONSET DEMENTIA: A BIOMARKER-SUPPORTED STUDY Levinia Lim, Jayne Yi Tan, Eveline Silva, Shahul Hameed, Simon Ting, Adeline Su Lyn Ng, Nagaendran Kandiah, National Neuroscience Institute, Singapore, Singapore; Duke-NUS Graduate Medical School /Neurology, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore. Contact e-mail: levinia_lim@nni. com.sg

DEVELOPMENT OF THE MDS-QOL: TOWARD A MORE RELEVANT QUALITY-OF-LIFE MEASURE IN MILD DEMENTIA

Background:Health related quality of life (QOL) is a robust feedback measure of treatment efficacy. It gives good indication of patient’s coping and adaptation to the disease. Existing QOL instruments do not sufficiently consider various factors that impact patient with mild dementia and by extension their well-being. It is often overlooked that patients with mild dementia do have insight. Hencewe developed a more comprehensivemeasure; Mild Dementia Singapore Quality of Life (MDS-QOL) and present our preliminary findings. Methods:A 40-item questionnaire (MDS-QOL) was developed from a preliminary list of 71 items. This 71-item field version was conceived after a thorough review of existing literature and focus group discussions with dyads of dementia patients and caregivers. 6 domains were identified: Functional Status, Impairment of Cognition, Life Opportunities, Health Perception, Safety in Environment and Overall QOL. The field version was reviewed separately by Subject Matter Experts (SMEs) and also by a pilot group of 10 patients. These reviews aid in assessing relevance and conversion into a compact 40-item (MDS-QOL) questionnaire. The MDS-QOL was administered to participants whose responses

CSF NEUROFILAMENT LIGHT CHAIN LEVELS CORRELATE WITH MARKERS OF MICROGLIAL ACTIVATION (YKL-40) AND GLOBAL COGNITIVE MEASURES IN MCI, ALZHEIMER’S DISEASE, AND FRONTOTEMPORAL DEMENTIA

Background: Accumulation of ubiquitinated proteins and UPSassociated protein is a common feature in many neurodegenerative diseases. To address the link between proteasome impairment, AD and LBD pathology, cognition decline and noncognitive symptom, the reduction of RPT6 and the alteration of the other proteasome components and activities were investigated in to identify clinico-pathological correlations, these includes: i) Possible relationships between reduction of RPT6 and the alteration of the other proteasome components and semi-quantitative scores of AD and LBD pathology in different brain areas. ii) Possible relationships between proteasome dysfunction and the cognition function and non-cognitive symptom in LBD and AD. Methods:The analysis of the relationships between non-cognitive behaviours and mood and proteasome markers were exploratory and unbiased as there were no compelling hypotheses linking them. Furthermore, due to the different regional patterns for the protein changes and the linkage of particular behavioural symptoms to a specific brain area, each brain region was analysed separately. Results:Reductions in RPT6 and proteasome activities were found to be associated with the semi-quantitative scores for plaques and neurofibrillary tangles. Semi-quantitative plaque scores were significantly predicted by RPT6 in BA9, 40 and 24. Semi-quantitative tangle scores were significantly predicted by RPT6 in BA40 and 24. Semi-quantitative a-synuclein scores were significantly predicted by RPT6 in BA9 only. Cognitive impairment was significantly predicted by RPT6 in BA9, 40 and 24. Persecution was significantly predicted by RPT6 expression in brain regions BA9 and BA40. Depression was significantly predicted by RPT6 expression in BA9. Conclusions:Our results indicated reductions in the key proteasome component RPT6 and proteasome activity. These reductions were associated with cognitive decline, non-cognitive symptoms and protein aggregates. These data suggested that the activating of the UPS could be a therapeutic target for treating DLB, PDD and AD.

QUALITY OF LIFE OF PATIENTS WITH MILD DEMENTIA (QOL-MILD DEMENTIA): DEVELOPMENT OF A NOVEL INSTRUMENT

P3-409 QUALITY OF LIFE OF PATIENTS WITH MILD DEMENTIA (QOL-MILD DEMENTIA): DEVELOPMENT OFA NOVEL INSTRUMENT Eveline Silva, Angeline Shi Hui Zhang, Linda Lay Hoon Lim, Kok Pin Ng, Adeline Su Lyn Ng, Nagaendran Kandiah, National Neuroscience Institute, Singapore, Singapore; 2 National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore; Duke-NUS Graduate Medical School, Singapore, Singapore. Contact e-mail: eveline_silva@nni.com.sg

HIGHER PERIPHERAL TREM2 MRNA EXPRESSION LEVELS ARE RELATED TO COGNITIVE DEFICITS AND HIPPOCAMPAL ATROPHY IN ALZHEIMER'S DISEASE AND AMNESTIC MCI

O2-06-06 HIGHER PERIPHERALTREM2 MRNA EXPRESSION LEVELS ARE RELATED TO COGNITIVE DEFICITS AND HIPPOCAMPAL ATROPHY IN ALZHEIMER’S DISEASE AND AMNESTIC MCI Yi Jayne Tan, Adeline Su Lyn Ng, Joseph K. W. Lim, Russell J. Chander, Ji Fang, Yingwei Qiu, Simon Ting, Shahul Hameed, NagaendranKandiah, Juan Zhou, Duke-NUSGraduateMedical School, Singapore, Singapore; 2 National Neuroscience Institute, Tan Tock Seng Hospital, Singapore, Singapore; National Neuroscience Institute, Singapore, Singapore; National Neuroscience Institute (SGH campus), Singapore, Singapore; 5 Agency for Science, Technology and Research, Singapore, Singapore. Contact e-mail: jayne.tan@duke-nus.edu.sg

PREVALENCE OF FAMILY HISTORY OF DEMENTIA IN A SPECIALIST YOUNG-ONSET DEMENTIA CLINIC COHORT

Background:Young-onset dementia (YOD) is defined as dementia occurring before the age of 65. The most common causes include early-onset Alzheimer’s disease (EOAD), frontotemporal dementia (FTD) and vascular dementia (VAD). Pre-dementia syndromes like mild cognitive impairment (MCI) and subjective cognitive impairment (SCI) are also prevalent in YOD clinics. FTD is known to have the highest rate of family history of dementia (40%), more so than EOAD or VAD. Rates of family history in MCI and SCI have been less studied. This cross-sectional study looked at the prevalence of family history of dementia according to disease subtype in a specialist YOD cohort. Methods: All subjects seen at a specialist YOD clinic at the National Neuroscience Institute, Tan Tock Seng Hospital between 2009 and October 2015 had their clinical charts retrospectively analysed. All available demographic, clinical and neuropsychological data were extracted. Diagnoses of EOAD, FTD, VAD, MCI and SCI were made in accordance with international consensus criteria. All subjects consented for their data to be utilized for research, and the study was approved by the Singhealth institutional review board. Statistical analyses (independent t-test and chi-square test) were performed using SPSS v20. Results: A total of 329 subjects were included in the study. Baseline characteristics according to disease subtype are listed in Table 1. The SCI group (n1⁄456) had the highest proportion of subjects with history of dementia in at least one first-degree relative at 30.4%, higher than the MCI (29.8%), AD (24.0%) and FTD (16.7%) groups. There were no significant demographic differences between SCI subjects with family history of dementia and those without, apart from baseline MMSE scores. SCI subjects with family history had a higher mean score of 29.161.0 vs 27.263.9. Conclusions: Up to 1/3 of SCI subjects had dementia history in a first-degree relative, the highest in our cohort. Whether this is the primary cause for anxiety related to subjective cognitive concerns, or if the neuropsychiatric symptoms are true harbingers of a pre-clinical degenerative illness remain to be determined. SCI patients with family history of dementia should be followed-up closely to monitor for progression to an MCI or AD state.