114 Chapter 5 Figure 2. Associations between genetic variants and biomarkers Values given are odds ratio (95% confidence interval) corrected for age, sex and population substructure, as estimated by logistic regression (predictor: APOE ε4 allele or normalized PRS; outcome: A. dichotomous biomarker status for A, T and N separately (reference = negative biomarker status), B. eight-profile ATN classification (reference = A-TN-), C. three-category ATN classification (reference = Normal AD biomarkers)). The odds ratio for the PRS reflects the odds of having an abnormal biomarker status or being classified in one of the ATN profiles with abnormal biomarkers, per one standard deviation increase in the PRS. APOE ε4 is per allele. * p-value <0.05. OR = odds ratio; PRS = polygenic risk score. Progression to dementia Next, we performed Cox proportional hazards analyses to investigate the association between genetic risk factors and the risk of dementia. A higher score on the PRS was not associated with a higher risk of all-type dementia (HR 1.0 (95%CI 0.7-1.4), Table 2). However, when analyzing AD and non-AD as separate outcomes, we found that a higher PRS predicted progression to AD dementia specifically (HR 1.7 (1.1-2.8), n progression=25), while individuals with a higher PRS had a lower risk of non-AD dementia (HR 0.5 (0.3-0.9), n progression=16). Additionally, the APOE ɛ4 allele was associated with a higher risk of progression to all-type dementia (HR 2.0 (1.3-3.2). When AD dementia and other types of dementia were analyzed separately, the APOE