To characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.
Bibliographical noteFunding Information:
This research was supported by the Brain Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning (2016M3C7A1913844), National Research Council of Science & Technology (NST) grant by the Korea government (MSIP) (No. CRC-15-04-KIST), grant of the Korean Health Technology R&D Project, Ministry of Health & Welfare, Republic of Korea (HI18C0335, HI19C1132) and Chonnam National University Hospital Biomedical Research Institute (BCRI20012). Data used in preparation of this article were obtained from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database (adni.loni.usc.edu). As such, the investigators within the ADNI contributed to the design and implementation of ADNI and/or provided data but did not participate in analysis or writing of this report. A complete listing of ADNI investigators can be found at: http://adni.loni.usc.edu/wp-content/uploads/how_to_apply /ADNI_Acknowledgement_List.pdf.
© 2021, The Author(s).
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