Studies have identified prior conditions associated with late-onset Alzheimer's disease dementia (LOAD), but all prior diseases have rarely been screened simultaneously in the literature. Our objective in the present study was to identify prior conditions associated with LOAD and construct pathways for them. We conducted a population-based matched casecontrol study based on data collected in the National Health Insurance Research database of Taiwan and the Catastrophic Illness Certificate database for the years 1997-2013. Prior diseases definitions were based on the first three digits of the codes listed in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Inclusion criteria required that each ICD-code existed for at least 1 year and incurred at least 2 outpatient visits or inpatient diagnosis. The case group comprised 4,600 patients newly diagnosed with LOAD in 2007-2013. The LOAD patients were matched by sex and age to obtain 4,600 controls. Using stepwise multivariate logistic regression analysis, diseases were screened for 1, 2 ., 9 years prior to the first diagnosis of LOAD. Path analysis was used to construct pathways between prior diseases and LOAD. Our results revealed that the following conditions were positively associated with the incidence of LOAD: Anxiety (ICD-code 300), functional digestive disorder (ICD code 564), psychopathology-specific symptoms (ICD-code 307), disorders of the vestibular system (ICD-code 386), concussion (ICD-code 850), disorders of the urethra and urinary tract (ICD-code 599), disorders of refraction and accommodation (ICD-code 367), and hearing loss (ICD-code 389). A number of the prior diseases have previously been described in the literature in a manner identical to that in the present study. Our study supports the assertion that mental, hearing, vestibular system, and functional digestive disorders may play an important role in the pathogenesis of LOAD.
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