1. Aging Cognition Evaluation A Unique Opportunity in understanding age related disorders

2. u Improve understanding of the biology of memory disorder with concurrently collected serial: u Cognitive data u Biological samples u Clinical events u Potential applications across other pathologies u Discover predictive biomarkers

3. u Establish robust baseline cognition score u Identify meaningful changes in cognition u Follow cognition deficits and rate of change u Correlate changes in cognition score with changes in biology u Identify well characterized patients for further evaluation Objectives

4. BIOLOGICAL u Genomic DNA u RNA from PAXGene u PBMCs ~4ml u Serum 0.5ml u Plasma 0.5ml u Urine 5ml u CSF 0.5ml (subpopulation) PSYCHOMETRIC u Semantic memory u Working memory u Executive function u Concentration u Response speed u MMSE DEMOGRAPHIC u Family History u Current Meds u Ethnic History u Education u Smoking u Alcohol u Clinical events Outputs

5. u 6-monthly serial follow-up of up to 5000 healthy subjects >60 y/o. u Collection of biological fluid samples including CSF (subpopulation) with simultaneous clinical and cognition evaluations using a CDR cognition battery at each 6 monthly visit. Protocol

6. The ACE Solution: identify MCI using… …evidence of progressive cognitive decline

7. 6 Monthly report to subject

8. Protocol design Age 60-75 Able to present for a blood draw every 6 months Generally healthy Cognitively normal Consent CDR Cognition Battery training Con Meds Con Diagnoses Family history ECG Other tests Cognition Battery Con Meds Con Diagnoses Blood Draw Spinal Tap (subpopulation) Cognition Battery Con Meds Con Diagnoses Blood Draw Spinal Tap (subpopulation) 6 months Controls Cognition diminished SCR.V.1 V.2 Cognition normal

9. ActivityScreening Visit Visit 1 BASELINE Subsequent 6 Monthly Visits Informed consent document signed X Subject and Visit Identification XXX DemographicsX Subject/Family historyXXX Concomitant Medications XXX Overnight fastXX Blood/urine Sample for banking XX Optional Spinal Tap for banking XX CDR Cog. Battery, MMSE X**XX Medication change since previous visit XX Clinical events since previous visit XX * Subpopulation ** Training Protocol design Contd: