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
BACE 2 that can influence risk
4. Cumulative Incidence of Alzheimer's Disease in DS
1
Down Syndrome
0.9
0.8
Cumulative Incidence
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
40 50 60 70
AGE
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)
6. Down syndrome: Age associated
Medical Conditions : Low Risk
• Cardiovascular and cerebrovascular disease
– Ischemic Heart Disease (SMR=0.7)
– Hypertension (SMR=0.1)
– Diabetes (SMR=0.4)
– Stroke (SMR= 0.1)
7. Early onset of AD in those with the APOE e4 allele
3/4, 4/4
3/3
2/2, 2/3, 2/4
1
Cumulative Incidence (%)
0.8
0.6
0.4
0.2
0
45 50 55 60 65
AGE
