Abstract

ObjectiveWe aimed to develop a sex-specific risk scoring system, abbreviated as SRSS-CNMCI, for the prediction of the conversion of cognitively normal (CN) people into patients with Mild Cognitive Impairment (MCI) to provide a reliable tool for the prevention of MCI.MethodsCN at baseline participants 61–90 years of age were selected from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database with at least one follow-up. Multivariable Cox proportional hazards models were used to identify the major risk factors associated with the conversion from CN to MCI and to develop the SRSS-CNMCI. Receiver operating characteristic (ROC) curve analysis was used to determine risk cutoff points corresponding to an optimal prediction. The results were externally validated, including evaluation of the discrimination and calibration in the Harvard Aging Brain Study (HABS) database.ResultsA total of 471 participants, including 240 female (51%) and 231 male participants (49%) aged from 61 to 90 years, were included in the study cohort. The final multivariable models and the SRSS-CNMCI included age, APOE e4, mini mental state examination (MMSE) and clinical dementia rating (CDR). The C-statistics of the SRSS-CNMCI were 0.902 in the female subgroup and 0.911 in the male subgroup. The cutoff point of high and low risks was 33% in the female subgroup, indicating that more than 33% female participants were considered to have a high risk, and more than 9% participants were considered to have a high risk in the male subgroup. The SRSS-CNMCI performed well in the external cohort: the C-statistics were 0.950 in the female subgroup and 0.965 in the male subgroup.ConclusionThe SRSS-CNMCI performs well in various cohorts and provides an accurate prediction and a generalization.

Highlights

  • Alzheimer’s disease (AD) is a neurodegenerative disease that progresses over time (Alzheimer’s disease facts and figures, 2020)

  • We presented a sex-specific scoring system (SRSS-CNMCI) for the prediction of the risk of the conversion to Mild Cognitive Impairment (MCI) within 12 years in cognitively normal participants aged from 61 to 90 years

  • This result indicated that specific monitoring and treatment plans should be implemented in men and women, respectively

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Summary

Introduction

Alzheimer’s disease (AD) is a neurodegenerative disease that progresses over time (Alzheimer’s disease facts and figures, 2020). According to the latest Alzheimer’s disease report 2020, the number of people aged 65 years and older with AD is projected to reach 152 million worldwide by 2050 (Alzheimer’s disease facts and figures, 2020). The total annual payments for health care and long-term care for patients with AD have been approximately $305 billion in 2020 and were estimated to be more than $1.1 trillion in 2050 (Alzheimer’s disease facts and figures, 2020), which may impose an enormous financial burden on patient families and society. Between 2015 and 2019, The total health-economic cost of AD increased by about 1.5 times in the last 5 years and was estimated to be about $4218 million (Shon and Yoon, 2021). According to the above data, AD has become a central public health issue in China, South Korea, Japan and other East Asian countries and even the whole world

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