1. Update Arg-ADNI Gustavo E. Sevlever, Ricardo F. Allegri (*), Silvia Vázquez, Deborah R. Gustafson, Salvador M. Guinjoan, and Arg-ADNI group. Memory and Aging Center Institute for Neurological Research Buenos Aires, Argentina Washington D.C., July 17, 2015 *speaker

2. www.fleni.org.ar/alzheimer Institute for Neurological Research Institute for Neurological Rehabilitation Center for Molecular Imaging Memory and Aging Center Institute for Neurological Research FLENI Buenos Aires Argentina

3. Update arg-ADNI Preliminary Results Future Tasks Update of Argentine ADNI

5. (*) Stream Chair Management Committee Allegri RF, Sevlever G, Guinjoan S, Gustafson D, Vazquez S. Clinical Stream Cognitive Neurologists Ricardo F. Allegri (*) Patricio Chrem Mendez Maria Julieta Russo Jorge CamposPsychiatrists Salvador GuinjoanNeuropsychologists María Eugenia Martín Florencia Clarens Paula Harris Neuroimaging Stream Silvia Vazquez S (*) Esteban Obenaus German Falasco Leandro Urrutia Fernando Ventrice Laboratory Stream Gustavo Sevlever (*) Horacio Martinetto Ezequiel Surace Miguel Riudavetz Epidemiological Stream Deb Gustafson (*) Study Coordinator Patricio Chrem Mendez Secretary Noelia Egido Data Entry Federico Nahas Study Coordinator Patricio Chrem Mendez Secretary Noelia Egido Data Entry Federico Nahas Arg-ADNI Staff

6. First patient / first visit Q1 2012 Last patient / last visit Q1 2013 First Year 2013 / 2014 Arg-ADNI Study Timeline Month 30 2014 / 2015 Month 48 2015 / 2016 B B 1 1 B B 2,5 4 year

7. Arg-ADNI Patients’ Flowchart Patients Screened at FLENI Nº= 60 Early MCI Nº=12 Healthy Controls Nº= 15 Late MCI Nº= 16 Dementia AD Nº=13 Screening Failure Nº= 7 Patients Screened to ADNI Nº= 108 2 Claustrophobia 1 Psychiatric Disease 1 Cancer 1 Adult ADHD 2 without informant Patients Followed (Baseline) Nº= 56 Dropout Nº= 3 2 removed inform.cons 1 by distance/caregiver Early MCI Nº=10 Healthy Controls Nº= 13 Late MCI Nº= 16 Dementia AD Nº=12 Early MCI Nº=? Healthy Controls Nº= ? Late MCI Nº= ? Dementia AD Nº=? Patients Followed Month 12 Nº= 51 Patients Followed Month 48 Nº= ? New Patients Invited to ADNI Nº= 6 Early MCI Nº=1/10 Healthy Controls Nº= 7/13 Late MCI Nº= 7/16 Dementia AD Nº=4/12 Patients Followed Month 30 Nº= 19/51 Dropout Nº= 5 2 removed inform.cons 2 Cancer 1 Institutionalized

8. 12 30 months months Normal Control (nº=13) did not progress Early MCI (nº=10)1 progressed (10%) Late MCI (nº=16)4 progressed (25%) Arg-ADNI Follow up Rate of Progression

9. Screening / Baseline % compl. Month 12 Month 30 Month 48 Demographic data(+) 100% (+) Clinical, NPS, NPSq(+) 100% (+) Cognitive Reserve (MCI)(+) MCI Blood(+) APOE(+) 100% CSF AB42/Tau(+) 71% (+) MRI (3T)(+) 100% (+) FDG PET Scan(+) 100% (+) PiB PET scan(+) 91% (+) Tau PET scan (AVID) (+) Arg-ADNI Schedule of evaluations.

10. Update arg-ADNI Preliminary Results Future Tasks Update of Argentine ADNI

12. Brain 18 FDG PET scan Uptake Map Hypometabolism Map Brain 11 C-PiB PET scan Healthy AD

13. Arg-ADNI 11 C – PIB - PET imaging

14. Arg-ADNI Cognitive Reserve and Aβ-42 (CSF) in MCI patients Paula Harris, Marcos Fernandez Suarez, Ezequiel Surace. et al., 2015 (in press in Neurospcyhiatric Disease and Treatment) Group 1 (Cut off < 532,5) Group 2 (Cut off  532,5) p Nº1418-- Age70,5 (8,4)65,6 (7,9)ns Education12,9 (4,3)14,5 (3,8)ns MMSE28,5 (1,5)28,5 (0,8)ns CRQ13,3 (5,5)17,2 (2,9) p <0,05 TAP-BA37 (9,9)42,69 (6,2)ns CSF  Aβ1-42 426,0 (87,0)959,0 (251,0) <0,001  TAU-T 501,3 (260,8)200,6 (85,5)<0,001  P-TAU 75,2 (45,8)38,9 (16,2) <0,05  Alz-profile2,6 (7,8)2,0 (0,6)ns Correlation between Cognitive Reserve Questionnaire and A  1-42 level CRQ: Cognitive Reserve Questionnaire (Rami et al., 2011)

15. Arg-ADNI Free Recall and Recognition in MCI patients with amyloid (+) vs amyloid (-) MFlorencia Clarens, María E Martin; Fernanda. Tapajoz et al., 2015 Amyloid (-) Amyloid (+) p Nº1112 Age71.7 (6.7)72.6 (6.3)ns Education13.9 (3.8)12.5 (3.9)ns MMSE28.6 (1.1)27.5 (2.5)ns NPI33.3 (12.2)30.8 (12.5)ns Test Result Variable(s)Area Std. Error(a) Asymptotic Sig.(b) RAVLT total,667,121,187 30 Minute Delay Total,767,111,035 Recognition Score,838,086,008 hipocampo izq,525,128,843 hipocampo der,550,127,692 Demographic data

16. Arg-ADNI FLENI Brain Bank

17. Update arg-ADNI Preliminary Results Future Tasks Update of Argentine ADNI

18. Tau tracer (PETscan) in ADNI Cohort AVID (AV 1451) Start-up: April 2016 Future Tasks Month 48 (+) ADNI cohort (51ptes) Demographic data Clinical, NPS, NPSq Cognitive Reserve (MCI) Blood APOE CSF AB42/Tau MRI (3T) FDG PET Scan PiB PET scan Tau PET scan (AVID)

19. Arg-DIAN (Dominantly Inherited Alzheimer Network) National grant application (CONICET) to study an Argentine DIAN cohort of 40 participant. Start-up: August, 2015 (Prof. J.Morris / Buenos Aires) Future Tasks

20. AD Biomarkers in Down Syndrome PI: Dr. Ezequiel Surace National grant application (CONICET) April 2015 to study an Argentine cohort of 10 participant. Start-up May 2016 Future Tasks

21. Memory and Aging Center

22. Update Arg-ADNI Memory and Aging Center Institute for Neurological Research Buenos Aires, Argentina Washington D.C., July 17, 2015