HARMONY Study of Dementia in Swedish Twins health Hälsa genes ARv environment Miljö and Och newNY NIA grant R01AG08724 and the Alzheimer’s Association

The Swedish Twin Registry Middle Cohort Born (13,665 pairs) Questionnaires: 1961, 1963, 1967 (1970) Questionnaire: 1973 Old Cohort Born (10,945 pairs) Computer Assisted Telephone Interviews: N = 20,269 Individuals aged 65+ (MZ, same sex DZ, and opposite sex DZ)

HARMONY Screening Phase ALL TWINS ,435individuals NOT SUSPECT NOT PARTNER NORMAL CONTROL SAMPLE PARTNER TO DEMENTED SUSPECT DIAGNOSTIC WORKUP NOT FOLLOWED

HARMONY Clinical Phase NEUROIMAGING FINAL CLINICAL DIAGNOSIS LONGITUDINAL FOLLOW UP AUTOPSY DIAGNOSTIC REVIEW BOARD PRELIMINARY JUDGMENT CLINICAL WORK UP 1557 individuals CONSENSUS DIAGNOSIS

Swedish Twin Data for Studies of Cognitive Aging and Dementia Old Middle SATSA SALZA Gender I Cohort Cohort OCTO-Twin Swedish Twin Registry HARMONY

Registry Linkage Swedish Twin Registry Cause of Death Registry Inpatient Discharge Registry Cancer Registry Inpatient Psychiatric Registry

Dependent Variable Clinically diagnosed Alzheimer’s disease Clinically diagnosed dementia –Cases screened as “suspects” and diagnosed with dementia –Controls screened as “not suspects” “Cognitive dysfunction” –Screening outcomes Registry diagnosed dementia

Samples for Analysis of Dementia Case-control –N = 547 cases, controls Co-twin control –140 pairs Discordant MZ pairs –Enhanced by registry linkage –106 twin pairs Prospective dementia cohort

Summary of published results Basic description of study Heritability Cognitive screening Age of onset Early life risk factors Occupation Cancer Education Personality