1. Epidemiology of Aging and Dementia in Down syndrome Nicole Schupf, Ph.D. Taub Institute for Research on Alzheimer’s Disease Columbia University Medical Canter

2. Accelerated Aging Factors associated with accelerated aging Telomere length Early menopause (46 vs. 51 years) Factors associated with life span (BMI, lipid profiles, functional measures, intellectual function, increasing Aβ40) The relation of accelerated aging to risk of dementia is a relatively neglected area in research on AD in adults with Down Syndrome

3. Down syndrome and beta amyloid The gene for beta-amyloid precursor protein (APP) is on chromosome 21 Individuals with DS have 3 copies of this gene and over-express APP Triplication and over-expression of APP may be related to increased risk of AD in adults with DS, and there are additional genes that can influence risk BACE2

4. Cumulative Incidence of Alzheimer's Disease in DS

5. Risk Factors influencing formation of Abeta and their relation to risk of AD in Down Syndrome Atypical karyotypes Genetic susceptibility factors Individual differences in Abeta peptide levels Gender and estrogen deficiency Metabolic factors (adiposity, dyslipidemia, insulin resistance, hypertension, T2D)

7. Ischemic Heart Disease (SMR=0.7)

8. Hypertension (SMR=0.1)

9. Diabetes (SMR=0.4)

11. Cumulative incidence of AD by change in AB42 Increasing No Change Decreasing HR= 4.9 HR= 2.6