Abstract
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 case-control 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.
Highlights
Dementia is a severely debilitating health condition that imposes burdensome social and economic costs, and rapidly aging populations have increased the prevalence of dementia worldwide [1]
Our results revealed that the following conditions were positively associated with the incidence of Late-onset Alzheimer’s disease dementia (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)
The present study aims to determine prior diseases associated with LOAD simultaneously, and construct pathways analysis for these diseases associated with LOAD
Summary
Dementia is a severely debilitating health condition that imposes burdensome social and economic costs, and rapidly aging populations have increased the prevalence of dementia worldwide [1]. Pathological manifestation in head injury have been linked to the risk of LOAD, including increased amyloid-beta and tau pathology, neuroinflammation, and axonal and cytoskeletal changes in the brain [15,16,17]. Hearing loss has been reported as a risk factor for dementia [18,19,20,21], where even mild levels suggest a link [22, 23]. Patients with hearing loss may suffer from social isolation, depression, disability, and increased risk of dementia [24,25,26,27]. Recent studies in animals have demonstrated that the microbiome-gut-brain axis may be involved in the pathogenesis of Alzheimer’s disease [28,29,30]
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