Participants

We included MCI patients from 65 to 90 years old from the Clinical Research Center for Dementia of South Korea (CREDOS) cohort²³ and the Memory Disorder Clinic in Ewha Womans University Mokdong Hospital (EUMC). We enrolled 3,038 subjects with MCI, including 2,993 from the CREDOS cohort and 45 from EUMC who fulfilled these criteria in this study (Fig. 1). MCI was defined according to Peterson’s²⁴ criteria:

CREDOS: Clinical Research Center for Dementia of South Korea, MCI: mild cognitive impairment, CDR: clinical dementia rating, CDRSB: clinical dementia rating sum of boxes, EUMC: Ewha Womans University Medical Center, BMI: body mass index, SNSB: Seoul Neuropsychological Screening Battery, APOE: apolipoprotein E.

1) cognitive impairment, especially subjective memory complaint by patients or caregivers, 2) evidence of objective memory or other cognitive function impairment in neuropsychological tests, lower than expected for the patient's age and educational level, 3) largely maintained activities of daily living and minimally impaired instrumental activity of daily living (IADL), and 4) absence of dementia in the individual.

Additionally, we included the Clinical Dementia Rating (CDR) and CDR sum of boxes (CDRSB) as inclusion criteria. The CDR score is 0 or 0.5, and the CDRSB should be in the range 0.5–4.0. Patients with a global CDR score of 0 were selected as those with a CDRSB of 0.5, because one or more cognitive domains were lowered to 1SD or less in an objective neuropsychological test. A CDR score of 0.5 indicates a decline in cognitive function, but the IADL remains within the normal range (<0.43). Subjects were excluded for the following reasons:

1) history of significant hearing or visual impairment rendering participation in the interview difficult, 2) history of following neurologic disorder(brain tumor, subarachnoid hemorrhage, epilepsy, encephalitis, and metabolic encephalopathy), 3) severe white matter hyperintensities that might be vascular rather than degenerative, 4) disorder of thyroid gland, syphilis, or vitamin B12 deficiency, 5) history of a psychiatric disorder, including schizophrenia, bipolar disorder, and major depressive disorder and other, 6) history of using psychoactive substances other than alcohol, 7) missing data, such as for sex, education, BMI, neuropsychological tests, and the APOE ε4 genotype.