Vascular and amyloid pathologies in memory clinic patients: Synergetic or independent?

P62 IC-P-088 Poster Presentations: IC-P ASSOCIATIONS OF THE LOCUS COERULEUS, EDUCATION, AND DIGIT SPAN SCORE: A STUDY OF MAGNETIC RESONANCE IMAGING Takashi Kato1, Kaori Iwata1, Izumi Kuratsubo1, Kimiko Kato2, Masahiko Bundo1, Yutaka Arahata1, Yoshitaka Inui1, Kengo Ito1, Akinori Nakamura1, MULNIAD, 1National Center for Geriatrics and Gerontology, Obu, Japan; 2Aichi Shukutoku University, Nagakute, Japan. Contact e-mail: tkato@ncgg.go.jp Background: The locus coeruleus (LC) is a brainstem nucleus that has widespread projections to modulate states of attention. It has been shown that tau pathology is frequently seen in the LC in individual under 30 years of age, suggesting Alzheimer’s disease (AD)-associated tau pathology begins in the LC. The magnetic resonance (MR) T1-signal derived from neuromelanin (NM) is considered to be a surrogate maker for the neural density of the LC. The purpose of this study was to investigate associations of a cognitive function, years of school education, and MR signal of the LC. Methods: Subjects were 58 cognitively normal elderly subjects (69.4(60-79)y.o., MMSE mean(range): 28.8(25-30)) who underwent T1-wieghted high resolution MR imaging of the brain stem and 3D T1-weighted whole brain MR imaging. The brain stem image was coregistrated to the whole brain image and spatially normalized with DARTEL. The mean signal intensity of LC was calculated using regions of interest (ROI) that were placed on the hyperintensity derived from NM of the LC at -26.0 to -19.0 in Z coordinate in the MNI stereotactic space. The mean signal ratio (mSR) of the LC was calculated as mSR¼(SLC–SDS)/SDS, where SLC and SDS are the signal intensities of the LC and superior cerebellar peduncle decussation, respectively. Single and multiple regression analyses were done for digit span backward score, age, years of school education (Education), and mSR. Results: The mSR declined a mean of 0.289 unit per year in a single regression analysis (p¼0.028). Digit span backward score had a positive association with mSR (p¼0.028, R^2¼0.083) in a single regression. In a multiple regression analysis to predict the digit span backward score, statistically significant terms were mSR (p¼0.026) and mSR x Education (p¼0.003). Adding the interaction term improved the goodness of fit from F¼5.095 (p¼0.028) to F¼7.921 (p¼0.001). The single term of Education was not significant (p¼0.071). Conclusions: The results suggest NM in the LC shows age-related decline. Higher educational attainment supports working memory and attention control tasks like digit span backward mainly through the interaction with the LC. Center, Amsterdam, Netherlands; 5Radboud University Medical Center, Radboud Alzheimer Center, Donders Institute for Brain, Cognition and Behaviour, Nijmegen, Netherlands; 6Radboud University Medical Center, Nijmegen, Netherlands. Contact e-mail: w.freeze@maastrichtuniversity.nl Background: Cerebral small vessel disease and amyloid-beta deposition are two important biomarkers of dementia. We examined whether these types of pathology interact and to what extent they contribute to medial temporal lobe atrophy (MTA) and cognitive decline in a sample of elderly memory clinic patients. Methods: 94 memory clinic patients from the Dutch multicenter LeARN study were included. At baseline, 25 patients were diagnosed as having possible or probable Alzheimer’s disease, 5 as having vascular dementia, 27 as having mild cognitive impairment (MCI) and 37 as having subjective cognitive impairment (SCI). Baseline cerebrovascular pathology was determined by white matter hyperintensity (WMH) volume on magnetic resonance images, and baseline amyloid pathology as cerebrospinal fluid derived amyloid-beta 42 (Ab42). Baseline MTA was scored bilaterally using a visual rating scale (score 04). Cognition was assessed with a neuropsychological test battery (including cognitive tests of immediate and delayed verbal memory recall, verbal fluency, attention and processing speed, concept shifting, inhibition and working memory) at baseline and at 2 year follow-up. Main effects and interactions of WMH and Ab42 on MTA score and cognition were computed with multivariate regression analyses, adjusted for age, sex, education, intracranial volume and baseline diagnosis (SCI, MCI or dementia). Results: Cross-sectionally, there was no correlation between WMH and Ab42. Higher MTA score was associated with larger WMH volume (standardized beta¼0.35, p¼0.003), but not with Ab42 and there was no interaction effect. There were no associations between baseline cognition measures and WMH or Ab42. Longitudinally, lower baseline Ab42 was independently associated with decline in both immediate (standardized beta¼0.32, p¼0.011) and delayed (standardized beta¼0.29, p¼0.022) memory recall. Baseline WMH volume did not predict memory decline and there was no interaction with Ab42. There were no associations between Ab42 or WMH with decline in any other cognitive domain, nor was there any interaction effect between Ab42 and WMH. Conclusions: These findings suggest that WMH, but not amyloid pathology, contributes to medial temporal lobe neurodegeneration in an independent way. On the contrary, baseline amyloid level seems to be a better predictor of memory decline in memory clinic patients than baseline WMH volume. IC-P-090 IC-P-089 VASCULAR AND AMYLOID PATHOLOGIES IN MEMORY CLINIC PATIENTS: SYNERGETIC OR INDEPENDENT? Whitney Freeze1, Saartje Burgmans1, Pauline Aalten2, Lies Clerx1, Stephanie Vos1, Ed Gronenschild1, Mark van Buchem3, Jeroen van der Grond3, Frederik Barkhof4, Wiesje M. van der Flier4, Bart N.M. van Berckel4, Rik Ossenkoppele4, Marcel Verbeek5, Marcel G.M. Olde Rikkert6, Walter Backes1, Frans R.J. Verhey1 on behalf of the Learn Consortium, 1Maastricht University Medical Center, Maastricht, Netherlands; 2Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands; 3Leiden University Medical Center, Leiden, Netherlands; 4VU University Medical INCREASED RADIOLIGAND BINDING TO TRANSLOCATOR PROTEIN CORRELATES WITH WORSENED CLINICAL SEVERITY AND ATROPHY IN ALZHEIMER’S DISEASE William Charles Kreisl1,2, Chul Hyoung Lyoo2,3, Monica Wei2, Joseph Snow2, Kimberly J. Jenko2, Cheryl L. Morse2, Sami S. Zoghbi2, Jeih-san Liow2, Amanda M. DiBattista4, G. William Rebeck4, Victor W. Pike2, R. Scott Turner4, Robert B. Innis2, 1Columbia University Medical Center, New York, NY, USA; 2National Institute of Mental Health, Bethesda, MD, USA; 3Gangnam Severance Hospital, Seoul, South Korea; 4 Georgetown University, Washington, DC, USA. Contact e-mail: wck2107@cumc.columbia.edu Background: We previously demonstrated that radioligand binding to the 18 kDa translocator protein (TSPO), a marker for