Exploring prior diseases associated with incident late-onset Alzheimer’s disease dementia

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 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.

Deep phenotyping of Alzheimer’s disease leveraging electronic medical records identifies sex-specific clinical associations

“…While many efforts have evaluated the association of individual risk factors with AD, unbiased approaches to these associations are limited. Prior work, largely hypothesis-driven, focused on select comorbidities associated with AD, such as hypertension 16 , vascular disorders 17 , diabetes 18 , obesity 19 , and others 20 – 22 . However, how sex modulates AD complexity and heterogeneity has still not been fully explored.…”

Altered Gut Microbial Load and Immune Activation in a Drosophila Model of Human Tauopathy

“…Thus, the reduced GI motility and increased bacterial load shown in the present study may apply to other types of degeneration. Although digestive disorders, including irritable bowel syndrome, have also been associated with AD and related dementias ( Liao et al, 2020 ), tau-mediated enteric nervous system changes remain poorly understood in tauopathies ( Chalazonitis and Rao, 2018 ; Derkinderen et al, 2021 ). As such, the present study provides a potential role of tau in enteric nervous system degeneration, perhaps contributing to gastrointestinal symptoms, including reduced gut motility.…”

Mapping morbidity 10 years prior to a diagnosis of young onset Alzheimer's disease

“…Taiwanese study of 4600 LOAD cases and 4600 controls found that anxiety, functional digestive disorder, psychopathology-specific symptoms, disorders of the vestibular system, concussion, disorders of the urinary system, disorders of refraction and accommodation, and hearing loss were positively associated with LOAD. 25 Likewise, a study based on the Baltimore Longitudinal Study of Aging found depression, erectile dysfunction, gait abnormalities, hearing loss, and nervous and musculoskeletal symptoms positively associated with LOAD. 26 While some of these overlap with associations found in the present study (hearing loss, depression, disorders of the urinary system), others were not commonly found in our cohort (disorders of the vestibular system, disorders of refraction etc.…”