PREDICTION OF CEREBRAL AMYLOID POSITIVITY BASED ON NEUROPSYCHOLOGICAL TEST PERFORMANCE IN NON-DEMENTED ELDERLY INDIVIDUALS

Podium Presentations: Tuesday, July 26, 2016

Using longitudinal neuropsychological assessment, we detected both mutation-specific as well as more general FTD predictive neuropsychological patterns. Our results confirm the prognostic value of neuropsychological assessment as potential clinical biomarker in the presymptomatic phase of familial FTD.

O3-09-05

THE DIAN-NACC UDS COMPARISON STUDY: RATES OF COGNITIVE DECLINE

Virginia Buckles1, Chengjie Xiong2, Hua Weng3, Randall Bateman2, Jasmeer P. Chhatwal4, Bernardino Ghetti5, Alison Goate6, Neill R. Graff-Radford7, Jason Hassenstab3, Richard Mayeux8, Colin L. Masters9, Eric McDade2, Krista L. Moulder2, Katrina L. Paumier2, John M. Ringman10, Stephen Salloway11, Peter W. Schofield12, John C. Morris2 and the Dominantly Inherited Alzheimer Network, 1Knight Alzheimer Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA; 2Washington University School of Medicine, St. Louis, MO, USA; 3Washington University School of Medicine, St Louis, MO, USA; 4Massachusetts General Hospital and the Athinoula A Martinos Center for Biomedical Imaging, Boston, MA, USA; 5Indiana University School of Medicine, Indianapolis, IN, USA; 6Mount Sinai School of Medicine, New York, NY, USA; 7Mayo Clinic, Jacksonville, FL, USA; 8 Columbia University, New York, NY, USA; 9University of Melbourne, Melbourne, Australia; 10Keck School of Medicine at USC, Los Angeles, CA, USA; 11Butler Hospital & Alpert Medical School of Brown University, Providence, RI, USA; 12University of Newcastle, Newcastle, Australia. Contact e-mail: [email protected] Background: The Dominantly Inherited Alzheimer Network

(DIAN) is a comprehensive longitudinal biomarker study of autosomal dominant Alzheimer disease (ADAD). Previous studies in DIAN (NEJM 2012;367:795-804; Neuropsychology 2014;28:1929) found clinical and psychometric differences in asymptomatic mutation carriers 5-10 years prior to the expected age of symptom onset. To learn whether cognitive changes in ADAD are similar to those of late onset AD we compared ADAD mutation carriers with sporadic AD participants entered into the National Alzheimer Coordinating Center (NACC). Methods: Uniform Data Set cognitive measures from mutation carriers in DIAN (n¼129) and sporadic AD participants (who were CDR0 at baseline but developed cognitive decline due to probable AD, n¼853) was analyzed with respect to age at symptom onset (NACC) and estimated age at onset (DIAN). Cohort differences (30-40 years age difference) compli-

Mean Age at Baseline (SD) Mean Age at Symptom Onset (SD) Mean Years of follow up (SD) Gender (% Female) Mean Years Education (SD) Mutation (PSEN1:PSEN2:APP) CDR at Baseline CDR 0 (%) CDR 0.5 (%) CDR 1 (%) % ApoE4+ 1 E4 2 E4

NACC participants N¼853

DIAN Mutation Carriers N¼129

78.0 (8.9) 80.7 (9.1) 5.4 (2.1) 61.7 15.3 (3.0) 0

41.5 (10.2) 44.2 (8.8) 2.5 (1.0) 59.7 13.9 (2.9) 101:6:22

853 (100) 0 0

64 (49.6) 45 (34.9) 16 (12.4)

24.9 4.1

24.8 4.7

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cate direct comparisons. Rates of change were analyzed both before and after “symptom onset”. Results: Prior to symptom onset, mutation carriers had no significant rate of change in Logical Memory Delayed Recall (p¼0.7931) and MMSE (p¼0.6705), whereas those who later developed sporadic AD already declined significantly (p<0.0001 for both), resulting in statistically significant differences between the two disease sub-types (p<0.0001 for both MMSE and Logical Memory Delayed Recall). For WAIS Digit symbol, however, both mutation carriers and those who developed sporadic AD declined significantly prior to the symptom onset, and their difference on the rate of change is close to statistical significance (p¼0.0644, with sporadic AD declining faster). After symptom onset, the rates of change in MMSE, WAIS Digit symbol, Logical Memory Delayed Recall, and CDR sum-of-boxes did not differ between ADAD mutation carriers and sporadic ADs (p>0.3059). Conclusions: There are statistically significant differences in the rates of cognitive change leading to the symptomatic onset between ADAD and sporadic AD, but the rates of cognitive decline are similar between the two disease subtypes after the symptomatic onset. NOTE: Different methods of determining symptom onset require cautious interpretation of results.

O3-09-06

PREDICTION OF CEREBRAL AMYLOID POSITIVITY BASED ON NEUROPSYCHOLOGICAL TEST PERFORMANCE IN NON-DEMENTED ELDERLY INDIVIDUALS

Hyunwoong Ko1, Dahyun Yi1, Min Soo Byun1, Hyo Jung Choi1, Hyewon Baek1, Jun Ho Lee1, Hyun Jung Kim1, Younghwa Lee1, Bo Kyung Sohn2, Jun-Young Lee3, Jung Gi Jung1, Chul-Ho Sohn1, Yu Kyeong Kim2, Jong Inn Woo1, Dong Young Lee1, 1Seoul National University Hospital, Seoul, Republic of Korea; 2SMG-SNU Boramae Medical Center, Seoul, Republic of Korea; 3SNU Hospital Boramae, Seoul, South Korea. Contact e-mail: [email protected] Background: Cerebral beta amyloid protein (Ab) deposition is the

core pathological hallmark of Alzheimer’s disease (AD). Although amyloid PET imaging can be used to identify Ab deposition human brains in vivo, it is still very expensive and cannot easily be available in many clinical settings. We aimed to find out neuropsychological tests or their combinations that could predict Ab deposition status in non-demented elderly individuals. Methods: One hundred and eighty-two non-demented (149 cognitively normal and 33 amnestic mild cognitive impairment) elderly individuals (mean age 69.7 years, range 55-87) who participated in the Korean Brain Aging Study for Early Diagnosis & Prediction of Alzheimer’s disease (KBASE), an ongoing prospective cohort study, were included. All subjects underwent comprehensive neuropsychological assessment and11C-labelled Pittsburgh Compound B positron emission tomography (PiB-PET). PiB-PET Images were classified as amyloid-positive if the mean 11C-PiB retention value was over 1.21 in at least one of the four regions, which included the following: the frontal, lateral temporal, lateral parietal, precuneus/posterior cingulate cortices. Results: The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) word list recall/ recognition, the Rey Complex Figure Test (RCFT) 3-/30-minute delays, the Wechsler Memory Scale-IV (WMS-IV) logical memory (LM) immediate/delay/recognition, and the Wechsler Adult Intelligence Scale (WAIS-IV) block design (BD) test, which had significant mean differences between amyloid-positive and amyloidnegative groups, were initially selected. Thereafter, possible combinations of the tests were tested through a series of logistic

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Podium Presentations: Tuesday, July 26, 2016

regression analyses in order to determine the final composite test score with the highest prediction accuracy. The composite score calculated by the summation of WMS-IV LM delayed recall and WAIS-IV BD scores were finally selected. The prediction accuracy of the score for amyloid positivity was 72.5% in overall nondemented group and 78.5% in only cognitively normal subgroup. Conclusions: Our result suggests that the composite score calculated by summing the scores of WMS-IV LM delayed recall and WAISIV BD is useful for prediction of amyloid positivity in clinical practice for non-demented elderly.

TUESDAY, JULY 26, 2016 ORAL SESSIONS O3-10 PSYCHOSOCIAL AND ENVIRONMENTAL: ASSESSMENT AND CARE — DIFFERENT DEMENTIAS, DIFFERENT CULTURES, DIFFERENT STAGES O3-10-01

OBJECT LOCALISATION DEFICITS IN POSTERIOR CORTICAL ATROPHY AND TYPICAL ALZHEIMER’S DISEASE: TRACKING POSITION, MOVEMENT AND FIXATION PATTERNS WITHIN A SIMULATED REAL-WORLD SETTING

Keir Yong1, Amelia M. Carton1, Biao Yang1, Ian McCarthy1, Tatsuto Suzuki1, Catherine Holloway1, Robin Serougne1, Derrick Boampong1, Mary Pat Sullivan2, Nick Tyler1, Sebastian J. Crutch3, 1 University College London, London, United Kingdom; 2Brunel University London, London, United Kingdom; 3UCL, Institute of Neurology, London, United Kingdom. Contact e-mail: [email protected] Background: Dementia friendly design guidelines emphasise the

significance of the physical environment in supporting patient autonomy; however, there is limited empirical investigation into this area. Visual characteristics of the environment are of particular interest in the context of dementia-related visual impairment (arising from neurological, not ophthalmological, conditions). Such impairment is diagnostic of posterior cortical atrophy (PCA), a clinico-radiological syndrome involving progressive visual dysfunction owing to neurodegeneration of posterior cortical regions. A common complaint in PCA is pronounced difficulty searching for and finding objects, with similar complaints being noted in typical Alzheimer’s disease (tAD; Mendez et al., 1990). An environmental variable proposed to particularly undermine object localisation and orientation in dementia is visual clutter. This project investigated factors influencing object localisation in PCA and tAD in a simulated real-world environment. Methods: A total of 15 PCA patients, 10 tAD patients and 23 healthy controls participated in a series of tasks involving locating objects in extrapersonal-peripersonal (32 trials) and peripersonal space (36 trials). Participants were asked to pick up target objects under varying conditions of clutter (distractor objects: none, two, five), visual cue (present, absent), starting position and object position. All tasks took place within the UCL Pedestrian Accessibility and Movement Environment Laboratory (PAMELA). Task efficiency was the time taken between trial onset and participants’ first physical contact with the target object. Tracking of gait (inertial measurement units [IMUs]), fixation (Begaze eyetracker), walking paths and body position (dead-reckoning analysis using IMUs; Coda system) was carried out as participants performed each task. Results: PCA and tAD groups were inefficient relative

to controls locating and reaching for objects in extrapersonal and peripersonal space. Assessment of walking paths to objects in extrapersonal space revealed tortuous routes for patients both with PCA and tAD. In peripersonal space, poorer object localisation was identified under increased levels of visual clutter in PCA, but not tAD or control participants. PCA patients demonstrated particularly poor performance when locating objects in peripheral vision. Conclusions: Findings outline differential effects of visual clutter by group. Patterns of patient performance, motion and fixation tracking offer insights into the optimal environmental conditions for patients to find objects.

O3-10-02

MINDFULNESS-BASED INTERVENTION PREVENTS MEMORY DECLINE AND IMPROVES MOOD AND QUALITY OF LIFE IN OLDER ADULTS WITH MILD COGNITIVE IMPAIRMENT: PRELIMINARY FINDINGS

Eddy Larouche1,2, Anne-Marie Chouinard1,2, Sonia Goulet1,2, Carol Hudon1,2, 1Universite Laval, Quebec, QC, Canada; 2Institut Universitaire en Sante Mentale de Quebec, Quebec, QC, Canada. Contact e-mail: [email protected] Background: In the last decade, new pharmacological treatments for Alzheimer’s disease (AD) failed to offer effective, long-lasting solutions, which stimulated the development of prophylactic approaches. Mindfulness-Based Interventions (MBI) promote the strengthening of attention and a non-reactive attitude through mindfulness meditation and philosophy. Such holistic methods show great potential against pathological aging that could lead to AD. The aim of this study was to test the efficacy of a MBI in targeting memory decline, depression, and quality of life, compared to an active control condition, in older adults with mild cognitive impairments (MCI). Methods: In this single-blind randomized controlled trial, older adults with MCI were assigned to a 8-week MBI (n¼11) or control (CTRL; n¼11) condition, which provided psychoeducation about memory and aging. Pre- and post- intervention, all participants were administered a verbal free-recall memory test, the Geriatric depression scale, and the WHO Quality of life BRIEF and OLD scales. Longitudinal mixed model analyses were conducted to compare the evolution of measurements in both conditions. Effect sizes (Cohen’s d) were calculated and an intent-to-treat paradigm was used with an alpha of 5%. Results: Participants, of which 36.4% were women, were aged between 56 and 87 (mean¼71.6, SD¼7.6), with a mean education level of 13.6 years (SD¼2.8). Ten participants in each condition completed the study. T-tests or khi-square analyses showed that there was no baseline difference between groups in terms of age (p¼0.170), education level (p¼0.456), and gender (p¼0.225). Compared to the control group, the MBI group showed less objective memory deterioration preand post- intervention (MBI¼-0,02% p¼0.944, CTRL¼-3,2% p¼0.285; d¼0,99), a greater decrease in the number of depressive symptoms (MBI¼-3,3% p¼0.297, CTRL¼-1,6% p¼0.634; d¼0,43), and increased quality of life (MBI¼+1,9% p¼0.200, CTRL¼+0,0% p¼0.756; d¼1,57). Conclusions: These preliminary findings indicate that MBI can help preventing memory decline and improving mood and quality of life in older adults with MCI. Moderate and large effect sizes obtained for all variables support the effectiveness of MBI in buffering against pathological aging.