Subjective cognitive decline, APOE genotype, and incident Alzheimer’s disease: The AGES‐Reykjavik Study

Authors: Mirjam I. Geerlings, Lotte Gerritsen, Jet M.J. Vonk, Vilmundur Gudnason, Lenore J. Launer

Published: 2020-12-07

Abstract

AbstractBackgroundSubjective cognitive decline (SCD) may be a marker of preclinical Alzheimer’s disease (AD) in some individuals and is related to biomarkers of AD. We investigated the longitudinal associations of SCD and APOE genotype with incidence of dementia and AD.MethodData are from 4,349 older adults (76±5 years, 59% women) without dementia who participated in the population‐based AGES‐Reykjavik Study. SCD was assessed with the question ‘Has your memory gotten worse in the past 12 months’. A 1.5T brain MRI was performed in all participants. Five mutually exclusive groups were defined: 1) normal (i.e. no SCD, no MCI, no dementia)/APOE e4 negative (n=2039); 2) normal/APOE e4 positive (n=711); 3) SCD/APOE e4 negative (n=806); 4) SCD/APOE e4 positive (n=355); 5) MCI (regardless of APOE) (n=438). MCI and dementia, including AD, were assessed according to international criteria. We used Cox regression analyses adjusted for age, sex, and education to estimate the Hazard Ratios of each group with incident dementia, including AD and non‐AD dementia.ResultDuring on average 9 years of follow‐up, 843 persons developed dementia, including 397 with AD. Within the normal/APOE e4 negative group conversion rate to dementia was 13%; these rates were 20%, 20%, 30%, and 38% for groups 2 through 5, respectively. For AD, the conversion rates for groups 1 through 5 were 6%, 12%, 10%, 21%, and 23%. Cox regression analyses showed that compared to the normal/APOE e4 negative group, the normal/APOE e4 positive group had 2.48 times higher risk of AD (95% CI 1.84‐3.34), the SCD/APOE e4 negative group 1.78 times higher (1.31‐2.42), the SCD/APOE e4 positive group 5.23 times higher (3.83‐7.16), and the MCI group 4.43 times higher (3.24‐6.06) (Figure 1).ConclusionSubjective cognitive decline and APOE e4 positivity each increased the risk of AD development, but the combination of a subjective cognitive symptom and a biomarker posed the strongest risk for AD, comparable to that of MCI. These findings may help to identify high‐risk groups in the population to target for preventive or therapeutic interventions.