Increased risk of chronic diseases and multimorbidity in middle-aged and elderly individuals with early vision, hearing, or dual sensory impairments: insights from prospective cohort studies and Mendelian randomization analysis

Abstract

Background: Sensory impairments (SI), including vision (VI), hearing (HI), and dual sensory impairments (DSI), are prevalent with aging, but their impact on disease risk remains unclear. This study investigates the epidemiological and genetic associations between SIs and 10 chronic disease categories and multimorbidity.

Methods: Using the CHARLS study, participants were classified by their self-reported VI/HI/DSI status in 2011 and 2013 into groups: "new onset, remission, persistent, and no SI." Their chronic disease incidence was tracked until 2018 in sub-cohorts respectively. Mendelian randomization (MR) analyses used genetic instruments from UK Biobank GWAS data on 88,250/504,307 individuals for vision/hearing loss, with outcome datasets from consortia including FinnGen, DIAMANTE, CKDGen, PGC, GWAS Catalog, and International Parkinson's Disease Genomics Consortium.

Results: The cohort study revealed that persistent HI significantly increased the risk of heart disease (P < 0.001, HR 1.63, 95% CI 1.31-2.03), stroke (P 0.004, HR 1.59, 95% CI 1.16-2.18), chronic lung disease (P 0.002, HR 1.53, 95% CI 1.17-1.99), and emotional, nervous, or psychiatric problems (P 0.016, HR 2.03, 95% CI 1.14-3.60). Persistent VI was significantly associated with diabetes or high blood sugar (DM/Hglu) (P 0.012, HR 1.63, 95% CI 1.11-2.38) and chronic lung disease (P 0.042, HR 1.53, 95% CI 1.02-2.31). MR confirmed these strong or suggestive associations, indicating that HI significantly increased the risk of cardiovascular and cerebrovascular events by 61-170%, bronchitis by 160%, and schizophrenia by 36%. In addition, VI significantly raised the risk of hyperglycemia or diabetes by 2-4% and the risk of lung function decline. Additionally, cohort studies confirmed that early DSI significantly raised the risk of multiple diseases, while MR identified genetic links between VI and hepatic failure, Parkinson's, and Alzheimer's disease, and between HI and hypertension, chronic kidney disease, and renal failure.

Conclusions: This study provides evidence from epidemiological or genetic perspectives demonstrates that early exposure to HI/VI/DSI increases the risk of developing chronic diseases. These findings underscore the need for continuous monitoring and timely intervention for SI to manage chronic disease risks in aging populations.

Keywords: Chronic diseases; Cohort study (CS); Dual sensory impairment (DSI); Hearing impairment (HI); Mendelian randomization analyses (MR); Multimorbidity; Vision impairment (VI).

Fig. 1

Overview and detailed workflow diagram of the study design. A Conceptual Diagram: Investigating the Impact of Baseline Exposure to Vision and Hearing Impairments on Chronic Disease Risk Using Prospective Cohort and Mendelian Randomization Studies. B Screening of the study population and establishment of 11 sub-cohorts (10 chronic diseases and multimorbidity) 1Dataset of “Biomarker” includes information of participants’ weight, height, grip strength and physical fitness etc. 2Dataset of “Health_status_and_function ” includes records of participants’ chronic disease onset time, auditory acuity, distance visual acuity, near visual acuity and etc. C Diagram of Mendelian Randomization Assumptions in This Study. Three basic assumptions are required for the genetic variants to qualify as valid instrumental variables (IVs): (Assumption1) they should be robustly associated with the exposure; (Assumption2) they should not be associated with potential confounders of the exposure-outcome association; and (Assumption3) they should not influence the outcome by any variable other than the exposure

Fig. 2

Heatmap of the risk effects (aHR) of self-reported levels of auditory and distance/nearvisual acuity on chronic diseases and multimorbidity. aHR adjusted hazard ratios, *, P < 0.05. Abbreviations: DM/Hglu diabetes or high blood sugar, ENP emotional, nervous, or psychiatric problems

Fig. 3

Forest plots of the risk effects (aHR) of HI/VI/DSI & HI/VI/DSI transition patterns on chronic diseases and multimorbidity. A heart diseases (B) hypertension (C) stroke (D) Diabetes or high blood sugar (E) liver disease (F) kidney disease (G) chronic lung diseases (H) Memory-related disease (I) Asthma (J) Emotional, nervous or psychiatric problems and (K) multimorbidity

Fig. 4

Forest plots of the risk effects (OR, 95%CI) of genetically predicted VI/HI on chronic diseases. A The causal relationship between genetically predicted VI and 24 outcomes by the IVW method. B The causal relationships between HI and the risk of 24 outcomes by the IVW method. The yellow repentant suggestive associations were noted between exposure and outcomes(0.00104<P<0.05), while red repentant strong associations were noted between exposure and outcomes(P<0.00104). 95% CI is presented in the forest plot, with a supplementary forest plot showing wider 99.896% CI calculated using Bonferroni-corrected α_adjusted. Abbreviation: SNP, single nucleotide polymorphism; OR:odds ratio, CI:confidence interval; IVW: inverse‐variance weighted; VI:visual impairment; HI:hearing impairment; AF: Atrial fibrillation and flutter, VHD: valvular heart disease, CHD: Major coronary heart disease event, HF: heart failure, GLU: Blood glucose levels, T2D:type 2 diabetes, F&CL: Fibrosis and cirrhosis of liver, CKD: chronic kidney disease, COPD: chronic obstructive pulmonary disease, PHD: Pulmonary heart disease, FVC:Forced vital capacity, FEV1:Forced expiratory volume in 1-second, PD:Parkinson's disease, AD:alzheimer's disease, MDD:Major depressive disorder, SCZ: schizophrenia

Fig. 5

Key findings from the association analysis of sensory impairments and disease risks: a summary of positive results from cohort studies and mendelian randomization, along with potential pathophysiological mechanisms. A checkmark indicates positive results in the respective studies. In Mendelian randomization analyses, both strong and suggestive associations are encompassed. Abbreviations: HI Hearing Impairment, VI Vision Impairment, DSI Dual Sensory Impairment, ENP Emotional, nervous or psychiatric problems