PREDOMINANT SUBCORTICAL 18F-AV-1451 BINDING IN BEHAVIORAL VARIANT FRONTOTEMPORAL DEMENTIA

Poster Presentations: Sunday, July 16, 2017 Background: Patients who had a cerebrovascular event are at higher risk of developing vascular dementia, especially in older age. However, some patients appear resilient to cognitive impairment even at advanced age. One possible explanation is that they have resistance to small vessel disease, particularly white matter hyperintensities (WMH) detectable on MRI. We studied the relevance of WMH to cognition in relation to age in patients who had a TIA/non-disabling stroke, particularly the older-old (>80). Methods: 570 consecutive patients with recent TIA/nondisabling stroke from the Oxford Vascular Study underwent multimodal MRI and cognitive assessment with the Montreal Cognitive Assessment scale (MoCA). They were divided into two age groups (<80, N¼461; 80, N¼109) and three cognitive groups according to their MoCA score: no vascular cognitive impairment (NoCI, MoCA>24, N¼384), mild vascular cognitive impairment (MildVCI, MoCA¼20-24, N¼143) or severe vascular cognitive impairment (SevereVCI, MoCA<20, N¼43). WMH were automatically segmented on FLAIR images using BIANCA (Griffanti et al., Neuroimage 2016) and the relative WMH volumes calculated. A two-way between groups factorial ANOVA was performed on the WMH volumes to test the interaction between age and cognition. Voxel-wise correlational analyses were then performed on the binarised, normalized, smoothed maps of WMH using non-parametric permutation test in FSL to explore if lower MoCA score would be associated with higher probability of WMH in different localization in the younger relative to the older-old patients. Results: A 2x3 between-group factorial ANOVA on WMH volumes showed significant main effects of age (F¼29.04, p<0.001) and cognitive group (F¼5.71, p¼0.004), and a significant age/cognition interaction (F¼4.67,p¼0.010), in that differences across cognitive groups were significant in the younger but not in the olderold group. Accordingly, the voxel-wise analysis showed a significant negative correlation (voxel-corrected p<0.05) between WMH probability and MoCA score in the younger group only, mainly in periventricular frontal areas (figure). Conclusions: WMH in patients aged 80 years with TIA/minor stroke is unrelated to cognition suggesting that the presence of WMH (i) does not undermine resilience to dementia in the older-old and (ii) should not prompt consideration of a diagnosis of vascular cognitive impairment in the older old.

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PREDOMINANT SUBCORTICAL 18F-AV1451 BINDING IN BEHAVIORAL VARIANT FRONTOTEMPORAL DEMENTIA

Hanna Cho1, Hee Jin Kim2, Jae Yong Choi1, Young Hoon Ryu1, Myung Sik Lee1, Duk L. Na3, Sang Won Seo2, Chul Hyoung Lyoo1, 1Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of South Korea; 2 Samsung Medical Center, Seoul, Republic of South Korea; 3 Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of South Korea. Contact e-mail: [email protected] Background: To investigate topographic binding pattern of 18F-AV-

1451 positron emission tomography (PET) in behavioral variant frontotemporal dementia (bvFTD). Methods: We included 23 bvFTD, 20 Alzheimer’s disease (AD) and 20 age-matched healthy controls matched for this study. All participants underwent neuropsychological tests, magnetic resonance imaging, tau PET scan with 18F-AV-1451 and amyloid PET scan with 18F-florbetaben. Based on participant-specific cortical and subcortical volumes-ofinterest, regional standardized uptake value ratio (SUVR) values for each cortical and subcortical gray and white matter were compared between groups. To investigate laminar binding pattern of 18F-AV-1451 across the cortical layers, surface-based SUVR maps for each cortical layers were extracted and compared between groups. Results: Compared to controls, bvFTD patients showed increased 18F-AV-1451 binding in the putamen, globus pallidus, and inferior frontal and orbitofrontal cortices. 18F-AV-1451 binding in the subcortical white matter regions underlying the frontal, inferior parietal, precuneus, and cingulate cortices was highly increased in bvFTD patients. Contrary to highly increased 18F-AV-1451 binding in cortical gray matter in AD patients, bvFTD patients showed increased binding predominantly in the subcortical white matter underlying inferior, superior and orbitofrontal cortices and insula cortex. However, no cortical and subcortical regions of bvFTD showed correlation between the 18F-AV-1451 binding and severity of cognitive dysfunction. Conclusions: The bvFTD patients showed predominate subcortical 18F-AV-1451 binding pattern, which was distinct from the pattern in AD. However, increased 18F-AV-1451 binding was almost confined to the frontal subcortical white matter and basal ganglia even with the volume atrophy in the widespread frontotemporal cortices and striatum. This suggests that 18F-AV1451 has limitations for tau imaging in bvFTD due to variability of tau isoforms in diverse tauopathies, pathologic heterogeneity other than tauopathy, and lower affinity to non-AD tau.

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Figure 1. Voxel-wise analysis of WMH. Negative correlation between WMH and MoCA score for subjects < 80 years (red-yellow) and for older-old (> 80 years, blue-light blue)

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WEIGHT LOSS MIGHT BE A NONCOGNITIVE SIGN OF PRECLINICAL ALZHEIMER’S DISEASE

Jordi Pegueroles1,2,3, Amanda Jimenez4,5, Victor Montal1,2,3, Eduard Vilaplana1,2,3, Maria Carmona-Iragui1,2,3,6, Daniel Alcolea1,2,3, Ignacio Illan-Gala1,2,3, Frederic Sampedro1,2,3,7, Judith Molero5, Anna Casajoana4,5, Jordi Clarimon1,2,3, Josep Vidal4,5,8, Raquel Bravo4,5, Alberto Lleo1,2,3, Rafael Blesa1,2,3, Juan Fortea1,2,3,6, 1Centre of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), Madrid, Spain; 2Hospital de la Santa Creu i Sant Pau, Barcelona, Spain; 3Biomedical Research Institute Sant Pau (IIB Sant Pau), Barcelona, Spain; 4Institut d’Investigacions Biomediques August Pi Sunyer (IDIBAPS), Barcelona, Spain; 5Hospital Clinic de Barcelona, Barcelona,