Skip to main content
Download PDF

A comprehensive evaluation on the associations between hearing and vision impairments and risk of all-cause and cause-specific dementia: results from cohort study, meta-analysis and Mendelian randomization study

BMC Medicine volume 22, Article number: 518 (2024) Cite this article

Abstract

Background

Epidemiological studies show inconsistent links between hearing/vision impairment and dementia risk. Using multisource data, we investigated how single or combined sensory impairments relate to risks of all-cause and specific types of dementia.

Methods

We employed a triangulation approach combining three methodologies. We analyzed 90,893 UK Biobank (UKB) adults to explore single and joint effects of hearing and vision impairments on all-cause and Alzheimer’s disease (AD), vascular dementia (VD) and non-AD non-VD (NAVD). A meta-analysis of prospective studies involving 937,908 participants provided stronger evidence. Finally, we conducted Mendelian randomization (MR) analysis using genome-wide association studies from UKB (361,194 participants) and FinnGen (412,181 participants) to validate relationships between sensory impairments and dementia occurrence.

Results

In the UKB cohort study, compared to participants with normal hearing, those in the mild and severe hearing impairment groups had progressively and significantly higher risk of all-cause dementia (mild: HR1.52, 95%CI 1.31–1.77; severe: HR1.80, 95%CI 1.36–2.38), AD (mild: HR1.63, 95%CI 1.30–2.04; severe: HR2.18, 95%CI 1.45–3.27), VD (mild: HR1.68, 95%CI 1.19–2.37; severe: HR1.47, 95%CI 1.22–1.78), and NAVD (mild: HR1.47, 95%CI 1.22–1.78; severe: HR1.98, 95%CI 1.43–2.75). Besides, vision impairment was associated with an increased risk of all-cause dementia (HR1.55, 95%CI 1.18–2.04) and NAVD (HR1.51, 95%CI 1.07–2.13). Furthermore, dual sensory impairment was associated with stepwise increased risks of all-cause and cause-specific dementia than single hearing or vision impairment. In the meta-analysis of 31 prospective cohort studies, risks of all-cause dementia and AD were elevated in participants with single hearing impairment (all-cause dementia: HR1.30, 95%CI 1.21–1.40; AD: HR1.30, 95%CI 1.21–1.40) and dual sensory impairment (all-cause dementia: HR1.63, 95%CI1.14–2.12; AD: HR 2.55, 95%CI 1.19–3.91), while single vision impairment only associated with higher risk of all-cause dementia (HR1.43, 95%CI 1.16–1.71) but not AD. Finally, the MR analysis revealed a significant association between hearing impairment and all-cause dementia (OR1.74, 95%CI 1.01–2.99), AD (OR1.56, 95%CI 1.09–2.23), and NAVD (OR1.14, 1.02–1.26), as well as vision impairment and NAVD (OR1.62, 95%CI 1.13–2.33).

Conclusions

Our findings showed significant associations between hearing and vision impairments and increased risks of all-cause and cause-specific dementia. Standardized hearing and vision assessment and intervention should be emphasized in dementia prevention strategies.

Peer Review reports

Background

Dementia remains a serious challenge for healthcare systems worldwide. By the year 2050, dementia is predicted to affect 150 million people worldwide, contributing to 115.8 million disability-adjusted life years [1]. Pharmaceutical approaches that target neuropathological processes, such as Alzheimer’s disease (AD), offer limited benefits beyond symptom modification [2]. Preventive strategy that reduces risk factors of dementia may be more beneficial than pharmacologic therapy after clinical expression of neuropathology changes [3]. Studies estimate that more than one-third of dementia cases could be prevented by taking precautionary measures that address modifiable risk factors [1].

Hearing and vision impairments, identified as potentially modifiable risk factors for dementia, warrant focused attention. Both functional increasing dementia risk through several mechanisms, such as changes in brain structure and function, increased cognitive load [4, 5], depression [6, 7], social isolation [8,9,10,11], and reduced physical activity [12,13,14]. The prevalence of these impairments is remarkably high among the elderly population, with an estimated 50% of individuals over 60 years reporting either hearing or vision impairment, and 11.3% of those over the age of 80 reporting having both, referred to as dual sensory impairment [15]. The significance of addressing these impairments is underscored by the fact that they will affect a growing proportion of the population due to increased longevity [16]. Given the high prevalence and modifiable nature of most hearing and vision impairments, targeting sensory impairment has emerged as a promising intervention strategy for the prevention of dementia [1, 4].

Despite the growing body of research on the association between sensory impairment and dementia, significant evidence gaps persist, particularly regarding the differential impact of hearing and vision impairments on dementia subtypes and their combined effect on dementia risk. Previous studies have primarily focused on hearing impairment, with the 2020 Lancet Commission report estimating that nearly 8% of all-cause dementia cases worldwide may be attributable to hearing loss. However, the associations between hearing impairment and specific dementia subtypes, such as AD and vascular dementia (VD), remain a subject of ongoing debate [17, 18]. Furthermore, the role of vision impairment in dementia risk is less well-characterized, with inconsistent findings reported across studies. While some US cohort studies have observed a significant association between vision impairment and dementia risk [19, 20], other US and European longitudinal studies have failed to replicate these findings [21,22,23]. Moreover, the potentially heightened risk of dementia in individuals with dual sensory impairment has not been adequately explored, and few studies have rigorously examined the impact of joint hearing and vision impairments and their potential interaction effects on the risk of dementia and its subtypes. Given the high clinical and cost-effectiveness of interventions aimed at optimizing hearing and vision, it is imperative to address these evidence gaps and develop a more comprehensive understanding of the role of hearing and vision impairments in the prevention of all-cause and cause-specific dementia [19, 24, 25].

Our overarching objective was to shed light on the intricate associations between hearing and vision impairments and the risk of dementia by combining multiple real-world data (Fig. 1). We began by exploring the association between (i) individual hearing or vision impairment and (ii) the additive combination of dual sensory impairment, with the risk of all-cause dementia and its subtypes (AD, VD, and non-AD non-VD [NAVD]) in UK Biobank (UKB). Genetic susceptibility to dementia, reverse causation bias, and competing mortality risk were accounted to ensure the robustness of our findings. Furthermore, we conducted a meta-analysis of previous prospective studies to provide a second verification of the associations. We also performed Mendelian randomization (MR) analyses using genome-wide association studies (GWAS) summary statistics to thirdly verify the relationships.

Fig. 1
figure 1

Schematic diagrams illustrating the study designs. Panel A A cohort study with 90,893 participants from UK Biobank. Panel B A meta-analysis based on 93,7908 participants from 31 prospective cohort studies. Panel C A two-sample Mendelian Randomization analysis based on GWAS summary statistics derived from FinnGen (N = 41,218) and UK Biobank (N = 361,194); MR-PRESSO, Mendelian randomization pleiotropy residual sum and outlier; CI, confidence intervals

Full size image

Methods

A prospective UKB cohort study

Study design and participants

The UKB is a prospective population-based cohort, recruited over 500,000 volunteers aged 40–69 years between 2006 and 2010 (https://www.ukbiobank.ac.uk/) [26]. Individuals were invited to attend one of the 22 centers across England, Scotland, and Wales for baseline assessment. Written informed consent was obtained for collection of questionnaire and biological data. UKB was undertaken with ethical approval from the North West Multi-Center Research Ethics Committee of the UK (ref11/NW/0382). This research was conducted under UKB application number 107217. We excluded those with missing data on hearing or vision impairment, a prior diagnosis of dementia at baseline, resulting in 90,893 participants in our analyses (Additional file 1: Figure S1). This study is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines (Additional file 1: Table S1).

Assessment of exposure, outcome, and covariates

The exposures of interest were hearing and vision impairments. Hearing ability was assessed by speech reception threshold in noise (SRTn) score out of the left and right ear without aids. Hearing status was categorized as “normal ([SRTn] <  − 5.5decibels [dB]), “mild impaired” (SRTn ≥  − 5.5 to <  − 3.5 dB), and “severe impaired” (SRTn ≥  − 3.5 dB) [27]. Vision ability was assessed by the corrected lower logarithm of the minimum angle of resolution (LogMAR) value of either left or right eye with the use of aids. Vision status was categorized as “normal” (LogMAR ≤ 0.3) and “impaired” (LogMAR > 0.3). Specific information on assessment of hearing and vision impairments was presented in Additional file 2: Supplementary Methods.

Dementia diagnoses were ascertained using hospital inpatient recorders (Hospital Episode Statistics for England, Morbidity Record for Scotland and Patient Episode Database for Wales) and death register data (National Health Service [NHS] Digital, NHS Central Register, and National Records). Participants with incident all-cause dementia, including AD, VD, and NAVD were identified using International Classification of Diseases-10th (ICD-10) or 9th (ICD-9) codes specified by the UKB dementia algorithm. The detailed information on all-cause dementia and AD, VD, and NAVD definitions is provided in Additional file 1: Table S2.

We included the following factors in the analyses as covariates according to evidence from previous studies [28, 29]: age at baseline, ethnicity, years of education, Townsend index of deprivation, smoking status, alcohol intakes, physical activity, body mass index (BMI), hypertension status, diabetes status, cardiovascular disease (CVD) status, social isolation, loneliness, depressive symptoms. We evaluated genetic susceptibility to dementia according to apolipoprotein E (APOE) allele status and family history of dementia. Detail information on covariates is presented in Additional file 2: Supplementary Methods and Additional file 1: Table S2 provided the field ID of covariates above.

Statistical analysis

Baseline summary statistics are presented as proportions for categorical data and means with standard deviations (SD) for continuous variables. Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) between baseline hearing or/and vision status and the risk of dementia (all-cause dementia, AD, VD, and NAVD). The proportional hazards (PH) assumption was deemed met based on a log cumulative hazard plot showing approximately parallel curves for the compared groups. Hospital inpatient data were censored on 31 October 2022 (England), 31 August 2022 (Scotland), and 31 May 2022 (Wales). Follow-up time for all participants started from date of recruitment to date when dementia was diagnosed, date of death, date of loss to follow-up, which occurred first. Four models were generated for the analysis: Model 1, adjusted for age; Model 2, further adjusted for sex, ethnicity, socioeconomic status variables of education and Townsend index of deprivation; Model 3 further adjusted for smoking status, alcohol intake, physical activity level and BMI; Model 4 (full adjusted model) further adjusted for diseases histories of hypertension status, diabetes status, CVD status, APOE, and family history of dementia.

We conducted several sensitivity analyses to test the robustness of our study. First, to minimize potential reverse causation, we performed an analysis after excluding those whose dementia occurred within 5 years of follow-up. Second, considering the differences in the prevalence of dementia among different age groups, we only included population who were aged 50 years or old at baseline. Third, death is likely to have acted as a competing risk mechanism for dementia, competing risk analysis was performed with death as a competing event. We also examined the dose–response associations between hearing or vision impairment and dementia risk by analyzing SRTn and LogMAR scores as continuous variables. Further, the mediation effect of loneliness, social isolation, and depressive symptoms, and the interaction effect of socioeconomic, behavioral, medical, and genetic factors with hearing or/and vision impairments on the risk of dementia were analyzed. More details were presented in Statistical Analysis Plan (Additional file 2: Supplementary Methods). SAS 9.4 was used in all statistical analyses above. The PHREG procedure was used to fit the Cox proportional hazards regression models. A two-sided P value of 0.05 or less was considered to indicate statistical significance.

Meta-analysis

Literature search and study selection

We searched PubMed, MEDLINE, and Web of Science on December, 2023, for prospective cohort studies using the following search terms: hearing impairment, hearing loss, hearing disorders, auditory disorders, auditory impairment, visual impairment, visual loss, vision disorders, visual disorders, vision impairment, sensory impairment, sensory disorders, dementia, Alzheimer, cognitive impairment, cognitive decline, cognitive disorders. Detailed search strategies are presented in Additional file 1: Table S3. In addition, a manual reviewing of the reference lists of all relevant articles was conducted to identify any other relevant literature. We conducted the meta-analysis under the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines (Additional file 1: Table S4).

Inclusion and exclusion criteria

The inclusion criteria were as follows: (1) prospective studies; (2) outcomes related to all-cause dementia or dementia subtypes; (3) exposure to hearing impairment, visual impairment, or dual sensory impairment; (4) articles providing measures of association such as relative risk (RR), HR, odds ratio (OR), or other computable effect estimates along with their 95% CI. Exclusion criteria encompass: (1) duplicated studies; (2) studies categorized as reviews, guidelines, meta-analyses, editorials, case reports, comments, letters to the editor, and other communications that did not include original data; (3) animal or in vitro studies; (4) studies with incomplete data records, unconvertible data, or fundamental design flaws that compromise the validity of the results; (5) inaccessible full-text articles.

Data extraction and quality assessment

Two reviewers (SW and HJ) extracted data from the Microsoft Excel spreadsheet using a standardized data extraction checklist. The form included the primary author, year of publication, study design, sample size, assessment of outcomes and exposures, follow-up time, and covariables. Two authors (LW and TL) independently evaluated the quality of included studies according to the Scottish Intercollegiate Guidelines Network (SIGN) 50 guideline 2019 edition [30]. All researchers discussed and settled any differences in the assessment results.

Data analysis

The meta-analysis was conducted using R version (R Foundation for Statistical Computing, Vienna, Austria). HR and corresponding 95%CI were adopted to meta-analyze the risk estimates for all-cause and cause-specific dementia for individual hearing or visual impairment and dual sensory impairment. The random-effect approach was adopted when I2 > 50% or when P < 0.05 indicated a high degree of heterogeneity across the articles; otherwise, a fixed-effect model was applied.

Subjects in these studies were stratified into sub-groups on the basis of continents (North America, Asia, Europe, Australia), assessment methods of hearing and vision impairments (self-reported or objective evaluation). The forest plot was used for the graphical display of the results from the meta-analyses. Additionally, we performed a leave-one-out (LOO) analysis in which studies were systematically excluded one at a time to assess the influence of individual studies on the overall estimate. P < 0.05 was used to indicate statistical significance in 2-sided statistical testing.

Mendelian randomization

Data source

We used a two-sample MR approach that applies MR methods to summary statistics derived from two independent population samples on hearing or visual impairment and dementia, respectively [31, 32]. Furthermore, this method is appropriate even within one sample setting for large biobanks, such as the UKB and FinnGen [33]. All studies included have collected relevant ethical approvals. Candidate genetic variants of outcome (dementia) were obtained from the FinnGen [34]. For exposure (hearing and vision impairment), the GWAS summary statistics were derived from the UKB [35] and FinnGen. Detailed information on the data sources is presented in Additional file 2: Supplementary Methods.

Data analysis

The instrumental variables were included based on the following criteria: (1) genome-wide significance (P < 5 × 10−6) [36, 37]; (2) not in linkage disequilibrium (R2 < 0.001, window size = 1000 kilobases [kb]) [38]. Our primary MR analysis employed a two-sample design to estimate the association between sensory impairment and the risk of dementia. Firstly, in the main study, the random-effects inverse variance weighted (RE-IVW) method was used to estimate the effect. Secondly, a series of robust methods, including inverse-variance weighted (IVW), MR-Egger regression, simple median, and weighted median (WME), as well as Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) method, were performed to assess the robustness of the results. These methods relax the MR assumption to various extent and have been proven to evaluating the robustness of the results effectively. The estimated effects were OR expressed per genetically predicted 1-unit-higher log-odds of liability to sensory impairment. We used the MR-Egger intercept test and MR-PRESSO test to assess for the existence of potential horizontal pleiotropy. For those variants that showed evidence of horizontal pleiotropy or outliers, we removed the corresponding genetic variants and performed the whole main and sensitivity analysis [39]. Third, as the threshold of 5 × 10−6 used in our primary analyses is not a standard threshold, we performed additional analyses using the standard threshold of P < 5 × 10⁻⁸ for instrument selection to check the robustness of our findings. Fourth, to further validate our assumption, we considered several potential confounders from our cohort studies, including educational attainment, smoking habits, alcohol consumption, physical activity levels, BMI, diabetes status, CVD history, hypertension, and depressive symptoms. Using GWAS summary data for these confounders, we first identified genetic variants associated with each confounder at a significance threshold of P < 5 × 10−6, consistent with the threshold used for the exposures (hearing and vision impairments) in the main study. Genetic variants that were strongly associated with any of those confounders were excluded prior to clumping the instrumental variables for each exposure. We then performed additional MR analyses using the independent clumped instrumental variables, ensuring they were not associated with the potential confounders. In addition, to evaluate the influence of each single-nucleotide polymorphism (SNP), we conducted LOO analysis by discarding each exposure-associated SNP and repeatedly performing IVW analysis. Finally, we performed a bidirectional two-sample MR study to evaluate the reverse causality. Additional details on the MR analyses are presented in Additional file 2: Supplementary Methods. We performed MR analyses with the R version 4.3.1. P < 0.05 was used to indicate statistical significance in 2-sided statistical testing. All analyses were corrected for multiple comparisons using the Benjamini–Hochberg false discovery rate (FDR) methods. We conducted the MR analyses under the STrenghtening the Reporting of Observational studies in Epidemiology-MR (STROBE-MR) guidelines (Additional file 1: Table S5).

Results

Cohort study in UKB

A total of 90,893 participants with a mean (SD) age at baseline of 56.7 (8.1) years were included in the analyses, of which 53.6% were female and the majority (91.5%) were white. Mild and severe hearing impairments were present in 10.6% (9674) of participants, while 2.5% (2308) had vision impairment. Prevalence of hearing or vision impairment increased with age and was more common in females. Participants with hearing or vision impairment were more likely to have lower socioeconomic status and unhealthier lifestyle behaviors, including smoking and less physical activity, have obesity, loneliness, social isolation and depressive symptoms, and have comorbidities such as hypertension, diabetes, and CVD (Table 1). After 12.9 (SD 1.7) years follow-up, 1170 study participants were diagnosed with dementia.

Table 1 Characteristics of participants by hearing and vision status, n (%)
Full size table

Compared to participants with normal hearing, those with mild and severe hearing impairment had 52% and 80% higher risk of all-cause dementia, separately (mild impairment: HR1.52, 95%CI 1.31–1.77; severe impairment: HR1.80, 95%CI 1.36–2.38) (Table 2, Additional file 1: Table S6-S8). A dose–response association was found, with the risk of all-cause dementia significantly increasing as the severity of hearing impairment increased (Ptrend < 0.001). This dose–response association was further confirmed when analyzing SRTn scores as a continuous variable instead of categorical groups (Additional file 1: Table S9). Similar risk association and dose–response association between hearing impairment and dementia were consistent across dementia subtypes (Table 2, Additional file 1: Table S6-S8).

Table 2 Separate and joint association of hearing and vision impairments with risk of all-cause and cause-specific dementia—Model 4
Full size table

Compared to participants with normal vision, significantly higher risks of all-cause dementia (HR1.55, 95%CI 1.18–2.04) and NAVD (HR1.51, 95%CI 1.07–2.13) were found in the vision impaired group (Table 2, Additional file 1: Table S6-S8). A dose–response association was also observed between vision impairment severity (reflected by LogMAR scores) and the risk of all-cause and cause-specific dementia (Ptrend < 0.001) (Additional file 1: Table S9).

With increased severity of dual sensory impairment, participants had a progressively and significantly higher risk of all-cause dementia (Ptrend < 0.001) (Table 2). A significant positive gradient of association between hearing impairment and dementia risk was found regardless of vision status, whereas the significant association of vision and increased dementia risk was just found in participant who experienced normal hearing but not in participants with mild or severe hearing impairment. (Additional file 1: Table S10).

In the sensitivity analyses excluding participants diagnosed with dementia events at least 5 years after baseline (Additional file 1: Table S11), and those aged < 50 years old at baseline (Additional file 1: Table S12), the association between hearing or/and vision impairments and dementia remained significant. Also, the estimates remained stable when we adopted competing risk analysis considering death as a competing event (Additional file 1: Table S13). The effects of hearing or vision impairment on dementia risk were mediated by social isolation and loneliness (Additional file 1: Table S14-S15). No interaction effect was found between most of the covariates and hearing or/and vision impairments in the risk of all-cause and cause-specific dementia (Additional file 1: Table S16-S27), except for APOE4 allele (Additional file 1: Figure S2).

Meta-analysis

In total, 1092 potentially eligible articles were identified, and 31 studies with 937,908 participants were considered for meta-analysis [17, 18, 20,21,22,23, 28, 40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61,62,63]. Additional file 1: Figure S3 presents the flow chart exhibiting the process of the detailed literature selection. Characteristics and methodological quality of meta-analyses for these studies are provided in Additional file 1: Table S28.1-S28.2. Figure 2 displays the forest plot illustrating the association between single hearing or vision impairment and dual sensory impairment with all-cause dementia and AD. Hearing impairment was associated with 30% higher risk of all-cause dementia (HR1.30, 95%CI 1.21–1.40) and 45% higher risk of AD (HR1.45, 95%CI 1.01–1.88). Vision impairment was significantly associated with all-cause dementia (HR1.43, 95%CI 1.16–1.71) but not with AD (HR1.39, 95%CI 0.98–1.80). All-cause dementia and AD risk were further elevated when hearing and vision impairment occurred together (All-cause dementia: HR1.63, 95%CI 1.14–2.12; AD: HR 2.38, 95%CI 1.45–3.31).

Fig. 2
figure 2

Meta-analyses on the relationship of hearing and visual impairment with all-cause dementia and AD. Panel A shows the results of association between hearing impairment with all-cause dementia and panel B for AD. Panel C shows the results of association between vision impairment with all-cause dementia and panel D for AD. Panel E shows the results of association between dual sensory impairment with all-cause dementia and panel F for AD. AD, Alzheimer’s disease; CI, confidence interval; MD, mean difference

Full size image

In general, the results from our sensitivity analyses, stratifying the studies based on several different factors, were not substantially different from those of the main analysis. Our meta-analysis summary estimate for studies using self-reported hearing and vision status was lower than that using objective measurement (hearing impairment: HRself-reported1.16, 95%CI 1.08–1.24; HRmeasured1.20, 95%CI 1.12–1.28; vision impairment: HRself-reported1.19, 95%CI 1.06–1.32; HRmeasured1.97, 95%CI 1.09–2.85), but the differences were not statistically significant (Additional file 1: Figure S4-S5). Differences were observed when stratified by continents (Phearing < 0.01; Pvision = 0.02; Pdual sensory = 0.02). The overall pooled HR appeared to be lower in studies conducted in Europe (HRhearing1.19,95%CI 1.13–1.25; HRvision1.00, 95%CI 0.91–1.09; HRdual sensory1.15, 95%CI 1.06–1.24) and higher in those conducted in North America (HRhearing1.22, 95%CI 1.14–1.31; HRvision1.68, 95%CI 1.25–2.11; HRdual sensory2.02, 95%CI 1.32–2.72) and Asia (HRhearing1.30, 95%CI 1.16–1.45; HRvision1.41, 95%CI 1.06–1.76) (Additional file 1: Figure S6-S8). In LOO analysis, we did not observe a great change in HR, which proved that heterogeneity does not come from a single article and our analysis results were robust (Additional file 1: Figure S9-S11).

MR analysis

In the primary analyses, sensorineural hearing loss was associated with increased risk of AD (OR1.56, 95%CI 1.09–2.22) and NAVD (unspecified dementia) (OR1.14, 95%CI 1.02–1.28). Visual disturbances were associated with NAVD (dementia in other diseases classified elsewhere) (OR1.39, 95%CI 1.11–1.74) (Fig. 3). The association between visual disturbances and NAVD was still significant after FDR correction. After validating the associations above in the UKB and FinnGen GWAS for hearing and vision impairment, the effect of sensorineural hearing loss on the risk of AD (OR1.56, 95%CI 1.09–2.23) and NAVD (OR1.14, 95%CI 1.02–1.26), and visual disturbances on NAVD (OR1.62, 95%CI 1.13–2.33) were still robust. Furthermore, the analysis identified self-reported hearing problems were associated with an increased risk of all-cause dementia (Dementia, including avohilmo) (OR1.74, 95%CI 1.01–2.99). Estimates from MR analyses with MR-Egger intercept test and MR-PRESSO for horizontal pleiotropy are presented in Additional file 1: Table S29 (FinnGen GWAS) and Additional file 1: Table S30 (UKB and FinnGen GWAS). Scatter plots and LOO plots are presented in Additional file 1: Figure S12-S27. Sensitivity analysis under a tense threshold for selecting significant instruments (P < 5 × 10−8) yielded similar results as the primary finding (Additional file 1: Table S31). After excluded genetic variants of potential confounders, the results were similar with the primary findings (Additional file 1: Table S32-S33). In the reverse direction, we did not find evidence of associations between all-cause and cause-specific dementia and hearing or visual impairments, suggesting no potential bidirectional causality between the traits (Additional file 1: Table S34, Figure S28-S35).

Fig. 3
figure 3

MR analyses for the effects of hearing and vision impairment on the risk of all-cause and cause-specific dementia by using RE-IVW method based on GWAS of FinnGen and UKB. Panel A with the only FinnGen GWAS for exposure. Panel B with the UKB and FinnGen GWAS for exposure. Dots, mean odds radio; Horizontal lines, 95%CI; Arrows, the confidence interval extends beyond the displayed range; MR, Mendelian randomization; RE-IVW, random-effects inverse-variance weighted; UKB, UK Biobank

Full size image

Discussion

This comprehensive study, leveraging a triangulation approach with a large prospective cohort, meta-analysis, and MR analyses, provides compelling evidence for the associations between hearing and vision impairments and the increased risk of all-cause and cause-specific dementia. The UKB cohort study demonstrated dose–response relationships between the severity of hearing impairment and the risk of AD, VD, and NAVD, while vision impairment was significantly associated with a higher risk of NAVD. Notably, the combination of hearing and vision impairments resulted in a striking six-fold increase in AD risk compared to those without sensory impairments. The meta-analysis corroborated these findings, showing that hearing, vision, and dual sensory impairments were associated with a 30%, 43%, and 63% increased risk of all-cause dementia, respectively. MR analyses further supported these associations. These robust findings underscore the critical importance of sensory health in dementia prevention and highlight the need for increased attention to sensory screening and early intervention strategies in clinical practice and public health initiatives.

The associations of hearing and vision impairments with the risk of dementia have been previously explored in epidemiological studies. Some studies reported that decline in hearing, compared with vision, was a more consistent and pronounced predictor of cognitive changes [1]. In 2020, the result of an observational study involving 3497 participants (aged > 75) from two prospective German old-age cohorts showed that hearing impairment was associated with an increased incidence of all-cause dementia in older adults [21]. There was no excess risk or risk compensation through the additional presence or absence of vision impairment. However, the results were inconsistent, in another cohort study involving 2051 participants in the Ginkgo Evaluation of Memory study, increased risk of all-cause dementia just observed in participants with only vision impairment, but not in those with only hearing impairment [18]. The results of our study explored the associations of individual hearing or vision impairment with higher risk of dementia, and the additive effects of multiple sensory impairments on dementia risk. Consistent with our research, a cohort study involving 4546 participants (aged > 65) who were initially free from all-cause dementia, using data from US National Health and Aging Trends Study similarly concluded that functional hearing or vision impairment and dual sensory impairment were associated with higher hazard of dementia over a 7-year follow-up period [20]. In addition, Philip H. Hwang et al. observed that dual sensory impairment was associated with a greater than 3 times increased risk for AD in the Cardiovascular Health Study involving 2927 participants [17].

Although existing studies provided novel insights into the associations between single or dual sensory impairment and dementia risk, some limitations remain. For example, previous studies mainly used self-reported data to assess hearing and vision impairments which could not deal with impairment severity bias [18, 21, 23, 28, 40, 61, 63, 64]. Especially, compared to pure-tone audiometry (PTA) or subjective self-report measures of hearing loss, a speech-in-noise (SIN) hearing assessment specifically evaluates the listener’s ability to detect and recognize speech in background noise [27, 65, 66]. Previous finding suggests SIN hearing impairment to be a more proximate indicator of AD than peripheral measures such as the PTA [67]. Moreover, most previous studies did not consider genetic predisposition, a critical determinant of dementia incidence which will limit causal inference [68]. Additional concerns, such as less accurate diagnostic criteria for dementia (relying solely on self-reported diagnosis information and measured cognitive performance), lacking consideration for assistive devices among participants, may further weaken the solidity of previous conclusions [22, 28, 48,49,50]. In the current study, we aimed to address these limitations. In particular, we used objectively measured hearing and vision impairments and incorporated genetic susceptibility factors into our analyses. Use of the UKB cohort, with its large sample size (n > 100,000), prolonged follow-up (mean duration of 12 years, with specific event dates), and precise dementia diagnosis (relying on inpatient hospital records and death registers), substantially reinforced the validity of our findings. The meta-analysis summarized evidence of previous cohort studies and enhanced the credibility of the conclusions. Furthermore, we used two-sample MR analyses to allow for investigation of the casual relationship between hearing and vision impairments and dementia risk. Beyond these robust methodological enhancements, our study results also exhibit several compelling features. First, we identified a positive dose–response association between severity of single or dual sensory impairments with all-cause and cause-specific dementia (AD, VD and NAVD) risks. Second, the study showed that hearing and vision impairments have joint positive effects on all-cause dementia, AD and NAVD, while also confirming the absence of an interaction effect between them in relation to dementia risk. Finally, the Meta- and MR analyses provide novel evidence for relationships between hearing and vision impairments with the heighted risk of dementia.

A key concern in studies that investigate risk factors for dementia is reverse causation bias. Dementia pathology progresses several years prior to a formal dementia diagnosis, and this progression can affect other behavioral and physical measures [69]. It is also well established that neurodegeneration caused by the pathophysiological progression of AD occurs several years prior to clinical manifestation of the disease [70, 71]. In the context of the current study, pre-clinical dementia could adversely affect performance on a sensory processing, which in turn would be associated with a future diagnosis of dementia [29]. To address this, we investigated whether associations differed by length of follow-up period in our sensitivity analyses. We found that the associations remained similar to the main findings when restricting to cases that occurred over longer follow-up periods. Similarly, a secondary analysis by Jonathan S. Stevenson restricted to dementia cases that occurred in four separate follow-up periods of ≤ 3, 3.1 to 6, 6.1 to 9, and > 9 years and found that the effect remained significant [29]. To augment the reliability of our findings, we conducted an MR analysis. This approach effectively mitigates confounding factors and eliminates the possibility of reverse causation bias. The MR analyses revealed a significant increase in the risk of dementia with hearing or vision impairment. Conversely, no correlation was observed between the expression of dementia and the risk of sensory impairment.

The precise mechanisms underlying the sensory impairment and dementia are not yet fully understood. A proposed explanation for the observed associations is that they are mediated by other factors, such as social isolation, loneliness, and depression [14, 72, 73]. However, we just observed that less than 5% of the associations between hearing or vision impairment and increased dementia risk were mediated through social isolation and loneliness, suggesting that the direct effects of hearing and vision impairments on the risk of dementia were dominant. The cognitive load hypothesis theorizes that sensory impairments may causally increase dementia risk through increases in cognitive load [74]. The higher risk associated with multiple sensory impairment, in particular, may also be because of the limited ability of individuals to compensate for single sensory impairment by employing functioning of an unimpaired sensory system [17]. In our study, we observed that individuals with both vision and severe hearing impairment were associated with a greater than 6 times increased risk for AD. The sensory deprivation hypothesis postulates that prolonged reductions in sensory input lead to cognitive deterioration due to neuronal atrophy [75]. Prolonged lack of adequate sensory stimulation may lead to a cascade of neurological effects including reduced neuroplasticity, with fewer or weaker connections forming between neurons in relevant brain areas [74]. As the brain adapts to reduced sensory input, there may be a reduction in gray matter volume, particularly in areas typically responsible for processing sensory information [74, 76]. This neural atrophy may extend beyond primary sensory cortices to affect regions involved in higher-order cognitive processing [77]. Previous evidence suggests that the reduction in multi-sensory input could have broader implications for overall brain function and cognitive capacity, extending beyond the effects of any single sensory deficit [78]. Additionally, sensory impairments may disrupt the brain’s default mode network (DMN), a system crucial for cognitive function and memory consolidation [79]. Altered sensory input could lead to abnormal activation patterns in the DMN, potentially contributing to cognitive decline and increased risk of dementia [80]. This disruption may affect the brain’s ability to efficiently process information and maintain cognitive flexibility [55]. Chronic sensory deprivation could also trigger a cascade of neuroinflammatory responses [81]. The brain’s attempt to compensate for reduced sensory input could lead to chronic microglial activation, resulting in sustained low-grade inflammation [82]. This neuroinflammation has been associated with accelerated cognitive decline and increased risk of neurodegenerative diseases, including various forms of dementia [83]. Our findings do not allow a conclusive choice between these hypotheses, which are not mutually exclusive. Additional studies are necessary to determine the mechanisms underlying these associations. Either mechanism has implications for potential clinical interventions.

There are several strengths in our study. The large sample size, long duration of follow-up, and objective assessment of sensory impairments in UKB, which avoided potential recall and selection bias and misclassification, allowed us to explore a more robust understanding of the associations between hearing and vision impairments and dementia risk. Also, dementia was ascertained from primary care, hospital admissions, and mortality data records, avoiding bias from self-reported data and allowing us to further identify specific dementia type. Meta-analysis made significant contributions to issues by combining the results from current epidemiological studies and increased our confidence in the results. With the uniform results from the UKB and meta-analysis, MR analysis which employed genetic variation as an instrumental variable to discover and quantify causation was also used, thereby overcoming the impact of possible confounding and reverse causality. Our study also has several limitations. First, it was an observational study based on multiple sources; therefore, reverse causality might exist. However, the study rigorously adjusted for confounding factors, did robust sensitivity analysis, and validated the association through MR analysis, thereby addressing this issue to the best extent possible. Secondly, information on date of onset and cause of sensory loss were unavailable. Thus, some quantitative relationships between sensory impairment and risk of dementia could not be analyzed. In addition, we did not take into account possible changes in sensory impairments over time. Although we consider the found associations valid and reliable, we cannot completely rule out undiscovered mechanisms between increasingly declining sensory performance and longitudinal dementia. Third, there was substantial statistical heterogeneity among the included studies in our meta-analysis which must be noted even though we used a random-effects model to pool the effect estimates and reported subgroup analysis to explore heterogeneity. Fourth, while our study evaluated potential overlap between the instrumental SNPs of confounders and those used for our exposures (hearing and vision impairments), testing the exclusion restriction assumption in the context of pleiotropy remains a significant challenge. Last, the majority of UKB participants are white, which may limit the generalizability of the findings to other races.

Conclusions

In conclusion, impairments in hearing and vision were independently and jointly associated with increased risk of all-cause and cause-specific dementia. Our findings are compelling, because addressing hearing and vision loss as particularly attractive intervention targets for dementia is in line with neurobiological perspectives that highlight the role of sensory deprivation in brain function and because it is a potentially cost-effective practice. Implementing strategies through changes in primary and neuropsychiatry care guidelines and population-level interventions to standardize vision and hearing evaluations as part of the prevention, workup, and management of cognitive impairment warrants further investigation.

Data availability

UK Biobank data is available via www.ukbiobank.ac.uk. Syntax for the generation of derived variables and for the analysis used for this study will be submitted to UK Biobank for record.

Abbreviations

AD:

Alzheimer’s disease

APOE:

Apolipoprotein E

BMI:

Body mass index

CI:

Confidence interval

CVD:

Cardiovascular disease

dB:

Decibels

DMN:

Brain’s default mode network

FDR:

False discovery rate

GWAS:

Genome-wide association studies

HR:

Hazard ratio

ICD:

International Classification of Diseases

LogMAR:

Logarithm of the minimum angle of resolution

LOO:

Leave-one-out

MR:

Mendelian randomization

MR-PRESSO:

Mendelian randomization pleiotropy residual sum and outlier

NAVD:

Non-AD-Non-VD

NHS:

National Health Service

OR:

Odds ratio

PRISMA:

Preferred Reporting Items for Systematic Reviews and Meta-Analysis

PTA:

Pure-tone audiometry

RE-IVW:

Random-effects inverse variance weighted

RR:

Relative risk

SD:

Standard deviation

SIGN:

Scottish Intercollegiate Guidelines Network

SIN:

Speech-in-noise

SRTn:

Speech reception threshold in noise

STROBE:

Strengthening the Reporting of Observational Studies in Epidemiology

STROBE-MR:

STrenghtening the Reporting of Observational studies in Epidemiology-MR

UKB:

UK Biobank

VD:

Vascular dementia

WME:

Weighted median

References

  1. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413–46.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Kabir MT, Uddin MS, Mamun AA, Jeandet P, Aleya L, Mansouri RA, et al. Combination Drug Therapy for the Management of Alzheimer’s Disease. Int J Mol Sci. 2020;21(9):3272.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Frisoni GB, Molinuevo JL, Altomare D, Carrera E, Barkhof F, Berkhof J, et al. Precision prevention of Alzheimer’s and other dementias: Anticipating future needs in the control of risk factors and implementation of disease-modifying therapies. Alzheimers Dement. 2020;16(10):1457–68.

    Article  PubMed  Google Scholar 

  4. Whitson HE, Cronin-Golomb A, Cruickshanks KJ, Gilmore GC, Owsley C, Peelle JE, et al. American Geriatrics Society and National Institute on Aging Bench-to-Bedside Conference: Sensory Impairment and Cognitive Decline in Older Adults. J Am Geriatr Soc. 2018;66(11):2052–8.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Davis A, McMahon CM, Pichora-Fuller KM, Russ S, Lin F, Olusanya BO, et al. Aging and Hearing Health: The Life-course Approach. Gerontologist. 2016;56 Suppl 2(Suppl 2):S256–267.

    Article  PubMed  Google Scholar 

  6. Frank CR, Xiang X, Stagg BC, Ehrlich JR. Longitudinal Associations of Self-reported Vision Impairment With Symptoms of Anxiety and Depression Among Older Adults in the United States. JAMA Ophthalmol. 2019;137(7):793–800.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Li CM, Zhang X, Hoffman HJ, Cotch MF, Themann CL, Wilson MR. Hearing impairment associated with depression in US adults, National Health and Nutrition Examination Survey 2005–2010. JAMA Otolaryngol Head Neck Surg. 2014;140(4):293–302.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Coyle CE, Steinman BA, Chen J. Visual Acuity and Self-Reported Vision Status. J Aging Health. 2017;29(1):128–48.

    Article  PubMed  Google Scholar 

  9. Huang AR, Deal JA, Rebok GW, Pinto JM, Waite L, Lin FR. Hearing Impairment and Loneliness in Older Adults in the United States. J Appl Gerontol. 2021;40(10):1366–71.

    Article  PubMed  Google Scholar 

  10. Shukla A, Cudjoe TKM, Lin FR, Reed NS. Functional Hearing Loss and Social Engagement Among Medicare Beneficiaries. J Gerontol B Psychol Sci Soc Sci. 2021;76(1):195–200.

    Article  PubMed  Google Scholar 

  11. Cruice M, Worrall LE, Hickson L. Personal factors, communication and vision predict social participation in older adults. Advances in Speech Language Pathology. 2005;7:220–32.

    Article  Google Scholar 

  12. Chen DS, Betz J, Yaffe K, Ayonayon HN, Kritchevsky S, Martin KR, et al. Association of hearing impairment with declines in physical functioning and the risk of disability in older adults. J Gerontol A Biol Sci Med Sci. 2015;70(5):654–61.

    Article  CAS  PubMed  Google Scholar 

  13. Chen DS, Genther DJ, Betz J, Lin FR. Association between hearing impairment and self-reported difficulty in physical functioning. J Am Geriatr Soc. 2014;62(5):850–6.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Crews JE, Campbell VA. Vision impairment and hearing loss among community-dwelling older Americans: implications for health and functioning. Am J Public Health. 2004;94(5):823–9.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Heine C, Browning C. Dual Sensory Loss in Older Adults: A Systematic Review. Gerontologist. 2015;55(5):913–28.

    Article  PubMed  Google Scholar 

  16. Swenor BK, Ramulu PY, Willis JR, Friedman D, Lin FR. The prevalence of concurrent hearing and vision impairment in the United States. JAMA Intern Med. 2013;173(4):312–3.

    Article  PubMed  Google Scholar 

  17. Hwang PH, Longstreth WT Jr, Thielke SM, Francis CE, Carone M, Kuller LH, et al. Longitudinal Changes in Hearing and Visual Impairments and Risk of Dementia in Older Adults in the United States. JAMA Netw Open. 2022;5(5): e2210734.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Hwang PH, Longstreth WT Jr, Brenowitz WD, Thielke SM, Lopez OL, Francis CE, et al. Dual sensory impairment in older adults and risk of dementia from the GEM Study. Alzheimers Dement (Amst). 2020;12(1): e12054.

    PubMed  Google Scholar 

  19. Ehrlich JR, Goldstein J, Swenor BK, Whitson H, Langa KM, Veliz P. Addition of Vision Impairment to a Life-Course Model of Potentially Modifiable Dementia Risk Factors in the US. JAMA Neurol. 2022;79(6):623–6.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Chen SP, Azad AD, Pershing S. Bidirectional Association between Visual Impairment and Dementia Among Older Adults in the United States Over Time. Ophthalmology. 2021;128(9):1276–83.

    Article  PubMed  Google Scholar 

  21. Pabst A, Bär J, Röhr S, Löbner M, Kleineidam L, Heser K, et al. Do self-reported hearing and visual impairments predict longitudinal dementia in older adults? J Am Geriatr Soc. 2021;69(6):1519–28.

    Article  PubMed  Google Scholar 

  22. Brenowitz WD, Kaup AR, Lin FR, Yaffe K. Multiple Sensory Impairment Is Associated With Increased Risk of Dementia Among Black and White Older Adults. J Gerontol A Biol Sci Med Sci. 2019;74(6):890–6.

    Article  PubMed  Google Scholar 

  23. Naël V, Pérès K, Dartigues JF, Letenneur L, Amieva H, Arleo A, et al. Vision loss and 12-year risk of dementia in older adults: the 3C cohort study. Eur J Epidemiol. 2019;34(2):141–52.

    Article  PubMed  Google Scholar 

  24. World Health O. World report on hearing. Geneva: World Health Organization; 2021.

    Google Scholar 

  25. Mukadam N, Anderson R, Knapp M, Wittenberg R, Karagiannidou M, Costafreda SG, et al. Effective interventions for potentially modifiable risk factors for late-onset dementia: a costs and cost-effectiveness modelling study. Lancet Healthy Longev. 2020;1(1):e13–20.

    Article  PubMed  Google Scholar 

  26. Sudlow C, Gallacher J, Allen N, Beral V, Burton P, Danesh J, et al. UK biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age. PLoS Med. 2015;12(3): e1001779.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Dawes P, Fortnum H, Moore DR, Emsley R, Norman P, Cruickshanks K, et al. Hearing in middle age: a population snapshot of 40- to 69-year olds in the United Kingdom. Ear Hear. 2014;35(3):e44–51.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kuo PL, Huang AR, Ehrlich JR, Kasper J, Lin FR, McKee MM, et al. Prevalence of Concurrent Functional Vision and Hearing Impairment and Association With Dementia in Community-Dwelling Medicare Beneficiaries. JAMA Netw Open. 2021;4(3): e211558.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Stevenson JS, Clifton L, Kuźma E, Littlejohns TJ. Speech-in-noise hearing impairment is associated with an increased risk of incident dementia in 82,039 UK Biobank participants. Alzheimers Dement. 2022;18(3):445–56.

    Article  PubMed  Google Scholar 

  30. Scottish Intercollegiate Guidelines Network. SIGN 50 a Guideline developer's Handbook. Edinburgh: Scottish Intercollegiate Guidelines Network, 2019. https://www.sign.ac.uk/media/2038/sign50_2019.pdf. Accessed 6 Nov 2024.

  31. Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37(7):658–65.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet Epidemiol. 2016;40(7):597–608.

    Article  PubMed  PubMed Central  Google Scholar 

  33. Minelli C, Del Greco MF, van der Plaat DA, Bowden J, Sheehan NA, Thompson J. The use of two-sample methods for Mendelian randomization analyses on single large datasets. Int J Epidemiol. 2021;50(5):1651–9.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kurki MI, Karjalainen J, Palta P, et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nat. 2023;613:508–18. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41586-022-05473-8.

  35. Cole JB, Florez JC, Hirschhorn JN. Comprehensive genomic analysis of dietary habits in UK Biobank identifies hundreds of genetic associations. Nat Commun. 2020;11(1):1467. https://doiorg.publicaciones.saludcastillayleon.es/10.1038/s41467-020-15193-0.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Liu B, Lyu L, Zhou W, Song J, Ye D, Mao Y, et al. Associations of the circulating levels of cytokines with risk of amyotrophic lateral sclerosis: a Mendelian randomization study. BMC Med. 2023;21(1):39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Yeung CHC, Schooling CM. Systemic inflammatory regulators and risk of Alzheimer’s disease: a bidirectional Mendelian-randomization study. Int J Epidemiol. 2021;50(3):829–40.

    Article  PubMed  Google Scholar 

  38. Burgess S, Thompson SG. Use of allele scores as instrumental variables for Mendelian randomization. Int J Epidemiol. 2013;42(4):1134–44.

    Article  PubMed  PubMed Central  Google Scholar 

  39. Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J Epidemiol. 2015;44(2):512–25.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Amieva H, Ouvrard C, Meillon C, Rullier L, Dartigues JF. Death, Depression, Disability, and Dementia Associated With Self-reported Hearing Problems: A 25-Year Study. J Gerontol A Biol Sci Med Sci. 2018;73(10):1383–9.

    Article  PubMed  Google Scholar 

  41. Brewster KK, Hu MC, Zilcha-Mano S, Stein A, Brown PJ, Wall MM, et al. Age-Related Hearing Loss, Late-Life Depression, and Risk for Incident Dementia in Older Adults. J Gerontol A Biol Sci Med Sci. 2021;76(5):827–34.

    Article  CAS  PubMed  Google Scholar 

  42. Deal JA, Betz J, Yaffe K, Harris T, Purchase-Helzner E, Satterfield S, et al. Hearing Impairment and Incident Dementia and Cognitive Decline in Older Adults: The Health ABC Study. J Gerontol A Biol Sci Med Sci. 2017;72(5):703–9.

    PubMed  Google Scholar 

  43. Dintica CS, Calderón-Larrañaga A, Vetrano DL, Xu W. Association Between Sensory Impairment and Dementia: The Roles of Social Network and Leisure Activity. J Alzheimers Dis. 2023;94(2):585–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Fischer ME, Cruickshanks KJ, Schubert CR, Pinto AA, Carlsson CM, Klein BE, et al. Age-Related Sensory Impairments and Risk of Cognitive Impairment. J Am Geriatr Soc. 2016;64(10):1981–7.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Ford AH, Hankey GJ, Yeap BB, Golledge J, Flicker L, Almeida OP. Hearing loss and the risk of dementia in later life. Maturitas. 2018;112:1–11.

    Article  PubMed  Google Scholar 

  46. Gallacher J, Ilubaera V, Ben-Shlomo Y, Bayer A, Fish M, Babisch W, et al. Auditory threshold, phonologic demand, and incident dementia. Neurology. 2012;79(15):1583–90.

    Article  PubMed  Google Scholar 

  47. Gates GA, Anderson ML, McCurry SM, Feeney MP, Larson EB. Central auditory dysfunction as a harbinger of Alzheimer dementia. Arch Otolaryngol Head Neck Surg. 2011;137(4):390–5.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Gates GA, Beiser A, Rees TS, D’Agostino RB, Wolf PA. Central auditory dysfunction may precede the onset of clinical dementia in people with probable Alzheimer’s disease. J Am Geriatr Soc. 2002;50(3):482–8.

    Article  PubMed  Google Scholar 

  49. Gates GA, Cobb JL, Linn RT, Rees T, Wolf PA, D’Agostino RB. Central auditory dysfunction, cognitive dysfunction, and dementia in older people. Arch Otolaryngol Head Neck Surg. 1996;122(2):161–7.

    Article  CAS  PubMed  Google Scholar 

  50. Golub JS, Luchsinger JA, Manly JJ, Stern Y, Mayeux R, Schupf N. Observed Hearing Loss and Incident Dementia in a Multiethnic Cohort. J Am Geriatr Soc. 2017;65(8):1691–7.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Gurgel RK, Ward PD, Schwartz S, Norton MC, Foster NL, Tschanz JT. Relationship of hearing loss and dementia: a prospective, population-based study. Otol Neurotol. 2014;35(5):775–81.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Heywood R, Gao Q, Nyunt MSZ, Feng L, Chong MS, Lim WS, et al. Hearing Loss and Risk of Mild Cognitive Impairment and Dementia: Findings from the Singapore Longitudinal Ageing Study. Dement Geriatr Cogn Disord. 2017;43(5–6):259–68.

    Article  PubMed  Google Scholar 

  53. Kim SY, Lim JS, Kong IG, Choi HG. Hearing impairment and the risk of neurodegenerative dementia: A longitudinal follow-up study using a national sample cohort. Sci Rep. 2018;8(1):15266.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Lee ATC, Richards M, Chan WC, Chiu HFK, Lee RSY, Lam LCW. Higher Dementia Incidence in Older Adults with Poor Visual Acuity. J Gerontol A Biol Sci Med Sci. 2020;75(11):2162–8.

    Article  PubMed  PubMed Central  Google Scholar 

  55. Lin FR, Ferrucci L, An Y, Goh JO, Doshi J, Metter EJ, et al. Association of hearing impairment with brain volume changes in older adults. Neuroimage. 2014;90:84–92.

    Article  CAS  PubMed  Google Scholar 

  56. Lin FR, Metter EJ, O’Brien RJ, Resnick SM, Zonderman AB, Ferrucci L. Hearing loss and incident dementia. Arch Neurol. 2011;68(2):214–20.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Lipnicki DM, Crawford J, Kochan NA, Trollor JN, Draper B, Reppermund S, et al. Risk Factors for Mild Cognitive Impairment, Dementia and Mortality: The Sydney Memory and Ageing Study. J Am Med Dir Assoc. 2017;18(5):388–95.

    Article  PubMed  Google Scholar 

  58. Michalowsky B, Hoffmann W, Kostev K. Association Between Hearing and Vision Impairment and Risk of Dementia: Results of a Case-Control Study Based on Secondary Data. Front Aging Neurosci. 2019;11:363.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Osler M, Christensen GT, Mortensen EL, Christensen K, Garde E, Rozing MP. Hearing loss, cognitive ability, and dementia in men age 19–78 years. Eur J Epidemiol. 2019;34(2):125–30.

    Article  PubMed  Google Scholar 

  60. Powell DS, Brenowitz WD, Yaffe K, Armstrong NM, Reed NS, Lin FR, et al. Examining the Combined Estimated Effects of Hearing Loss and Depressive Symptoms on Risk of Cognitive Decline and Incident Dementia. J Gerontol B Psychol Sci Soc Sci. 2022;77(5):839–49.

    Article  PubMed  Google Scholar 

  61. Tran EM, Stefanick ML, Henderson VW, Rapp SR, Chen JC, Armstrong NM, et al. Association of Visual Impairment With Risk of Incident Dementia in a Women’s Health Initiative Population. JAMA Ophthalmol. 2020;138(6):624–33.

    Article  PubMed  Google Scholar 

  62. Uhlmann RF, Larson EB, Rees TS, Koepsell TD, Duckert LG. Relationship of hearing impairment to dementia and cognitive dysfunction in older adults. JAMA. 1989;261(13):1916–9.

    Article  CAS  PubMed  Google Scholar 

  63. Vassilaki M, Aakre JA, Knopman DS, Kremers WK, Mielke MM, Geda YE, et al. Informant-based hearing difficulties and the risk for mild cognitive impairment and dementia. Age Ageing. 2019;48(6):888–94.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Davies HR, Cadar D, Herbert A, Orrell M, Steptoe A. Hearing Impairment and Incident Dementia: Findings from the English Longitudinal Study of Ageing. J Am Geriatr Soc. 2017;65(9):2074–81.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Utoomprurkporn N, Stott J, Costafreda SG, Bamiou DE. Lack of Association between Audiogram and Hearing Disability Measures in Mild Cognitive Impairment and Dementia: What Audiogram Does Not Tell You. Healthcare (Basel). 2021;9(6):769.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Samara M, Thai-Van H, Ptok M, Glarou E, Veuillet E, Miller S, et al. A systematic review and metanalysis of questionnaires used for auditory processing screening and evaluation. Front Neurol. 2023;14:1243170.

    Article  PubMed  PubMed Central  Google Scholar 

  67. Tuwaig M, Savard M, Jutras B, Poirier J, Collins DL, Rosa-Neto P, et al. Deficit in Central Auditory Processing as a Biomarker of Pre-Clinical Alzheimer’s Disease. J Alzheimers Dis. 2017;60(4):1589–600.

    Article  PubMed  PubMed Central  Google Scholar 

  68. Desai R, John A, Saunders R, Marchant NL, Buckman JEJ, Charlesworth G, et al. Examining the Lancet Commission risk factors for dementia using Mendelian randomisation. BMJ Ment Health. 2023;26(1):e300555.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and Management of Dementia: Review. JAMA. 2019;322(16):1589–99.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Murphy C. Olfactory and other sensory impairments in Alzheimer disease. Nat Rev Neurol. 2019;15(1):11–24.

    Article  CAS  PubMed  Google Scholar 

  71. Sperling RA, Aisen PS, Beckett LA, Bennett DA, Craft S, Fagan AM, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–92.

    Article  PubMed  Google Scholar 

  72. Fischer ME, Cruickshanks KJ, Klein BE, Klein R, Schubert CR, Wiley TL. Multiple sensory impairment and quality of life. Ophthalmic Epidemiol. 2009;16(6):346–53.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Resnick HE, Fries BE, Verbrugge LM. Windows to their world: the effect of sensory impairments on social engagement and activity time in nursing home residents. J Gerontol B Psychol Sci Soc Sci. 1997;52(3):S135-144.

    Article  CAS  PubMed  Google Scholar 

  74. Valentijn SA, van Boxtel MP, van Hooren SA, Bosma H, Beckers HJ, Ponds RW, et al. Change in sensory functioning predicts change in cognitive functioning: results from a 6-year follow-up in the maastricht aging study. J Am Geriatr Soc. 2005;53(3):374–80.

    Article  PubMed  Google Scholar 

  75. Lin FR, Yaffe K, Xia J, Xue QL, Harris TB, Purchase-Helzner E, et al. Hearing loss and cognitive decline in older adults. JAMA Intern Med. 2013;173(4):293–9.

    Article  PubMed  Google Scholar 

  76. Peelle JE, Troiani V, Grossman M, Wingfield A. Hearing loss in older adults affects neural systems supporting speech comprehension. J Neurosci. 2011;31(35):12638–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Rutherford BR, Brewster K, Golub JS, Kim AH, Roose SP. Sensation and Psychiatry: Linking Age-Related Hearing Loss to Late-Life Depression and Cognitive Decline. Am J Psychiatry. 2018;175(3):215–24.

    Article  PubMed  Google Scholar 

  78. Lindenberger U, Baltes PB. Sensory functioning and intelligence in old age: a strong connection. Psychol Aging. 1994;9(3):339–55.

    Article  CAS  PubMed  Google Scholar 

  79. Ward AM, Schultz AP, Huijbers W, Van Dijk KR, Hedden T, Sperling RA. The parahippocampal gyrus links the default-mode cortical network with the medial temporal lobe memory system. Hum Brain Mapp. 2014;35(3):1061–73.

    Article  PubMed  Google Scholar 

  80. Griffiths TD, Lad M, Kumar S, Holmes E, McMurray B, Maguire EA, et al. How Can Hearing Loss Cause Dementia? Neuron. 2020;108(3):401–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Lazarov O, Mattson MP, Peterson DA, Pimplikar SW, van Praag H. When neurogenesis encounters aging and disease. Trends Neurosci. 2010;33(12):569–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Perry VH, Holmes C. Microglial priming in neurodegenerative disease. Nat Rev Neurol. 2014;10(4):217–24.

    Article  CAS  PubMed  Google Scholar 

  83. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer’s disease. Lancet Neurol. 2015;14(4):388–405.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

The cohort analysis in this study has been conducted using the UK Biobank resource under Application Number 107217 and we express our gratitude to the participants and those involved in building the resource. The Mendelian randomization analysis in this study has been conducted using GWAS data from the UK Biobank database and FinnGen database. We would like to thank all participants and the above-mentioned consortiums for their contribution.

Funding

This paper represents independent research part-funded by grant of National Natural Science Foundation of China (72204143, 82271172, 82071053, 72374156, 72004165, 82371154), the Major Program of National Natural Science Foundation of China (82196821), the Major Fundamental Research Program of the Natural Science Foundation of Shandong Province, China (R2021ZD40), Taishan Scholars Program of Shandong Province-Youth Scholar Program (tsqn202211357), Natural Science Foundation of Shandong Province of China (ZR2022QG081).

Author information

Authors and Affiliations

  1. Shandong Provincial ENT Hospital, School of Public Health, Shandong University, Jinan, Shandong, China

    Fan Jiang, Qiuyue Dong, Na Li, Xiaofei Li, Lei Xu & Haibo Wang

  2. Centre for Health Management and Policy Research, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Fan Jiang, Peipei Fu & Chengchao Zhou

  3. Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Sijia Wu, Xinhui Liu, Hanbing Ji, Le Wang, Tiemei Liu & Hongkai Li

  4. Cambridge Clinical Trials Unit Cancer Theme, University of Cambridge, Cambridge, UK

    Alimu Dayimu

  5. School of Clinical Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China

    Yingying Liu

  6. Department of Health Policy and Management, School of Public Health, Yale University, New Haven, CT, USA

    Peipei Fu

  7. School of Management, Shandong Second Medical University, Weifang, Shandong, China

    Qi Jing

  8. Institute of Population Ageing, University of Oxford, Oxford, UK

    Qi Jing

  9. International Centre for Evidence in Disability, Faculty of Epidemiology and Population Health, The London School of Hygiene & Tropical Medicine, London, UK

    Shanquan Chen

Authors
  1. Fan Jiang
    View author publications

    You can also search for this author inPubMed Google Scholar

  2. Qiuyue Dong
    View author publications

    You can also search for this author inPubMed Google Scholar

  3. Sijia Wu
    View author publications

    You can also search for this author inPubMed Google Scholar

  4. Xinhui Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  5. Alimu Dayimu
    View author publications

    You can also search for this author inPubMed Google Scholar

  6. Yingying Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  7. Hanbing Ji
    View author publications

    You can also search for this author inPubMed Google Scholar

  8. Le Wang
    View author publications

    You can also search for this author inPubMed Google Scholar

  9. Tiemei Liu
    View author publications

    You can also search for this author inPubMed Google Scholar

  10. Na Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  11. Xiaofei Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  12. Peipei Fu
    View author publications

    You can also search for this author inPubMed Google Scholar

  13. Qi Jing
    View author publications

    You can also search for this author inPubMed Google Scholar

  14. Chengchao Zhou
    View author publications

    You can also search for this author inPubMed Google Scholar

  15. Hongkai Li
    View author publications

    You can also search for this author inPubMed Google Scholar

  16. Lei Xu
    View author publications

    You can also search for this author inPubMed Google Scholar

  17. Shanquan Chen
    View author publications

    You can also search for this author inPubMed Google Scholar

  18. Haibo Wang
    View author publications

    You can also search for this author inPubMed Google Scholar

Contributions

HBW attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted. HKL, FJ, QYD, SJW, XHL have directly accessed and verified the underlying data. All the authors were responsible for the decision to submit the manuscript. Concept and design: HBW, SQC, LX, HKL, FJ, AD, QJ. Acquisition of data: QYD (Cohort study and MR analysis), SJW, HBJ, LW, TML (Meta-analysis), XHL (MR analysis). Formal analysis and Interpretation of data: QYD, SJW, XHL, YYL, HKL, FJ, LX, HBW. Statistical analysis: QYD, SJW, XHL. Drafting of the manuscript: FJ, SQC, HKL, LX. Critical revision of the manuscript for important intellectual content: SQC, AD, NL, XFL, CCZ, QJ, PPF. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hongkai Li, Lei Xu, Shanquan Chen or Haibo Wang.

Ethics declarations

Ethics approval and consent to participate

The UK Biobank cohort study obtained ethics approval from the North West Centre for Research Ethics Committee (11/NW/0382). Our Mendelian randomization study only analyzed published studies and consortia that provided publicly available summary statistics. Therefore, no new ethics committee approval was required.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

12916_2024_3748_MOESM1_ESM.docx

Additional file 1: Tables S1-S34, Figures S1-S35. Table S1. STROBE Checklist. Table S2. Exposures, outcomes and covariates’ definitions and descriptions in the UKB cohort study. Table S3. Literature search strategy of Meta-analysis. Table S4. PRISMA. Table S5. STROBE-MR Checklist. Table S6-S8. Associations between hearing/vision impairment and dementia risk—Model 1-3. Table S9. Dose-response associations between hearing/vision impairment and dementia risk. Table S10. Risk of all-cause dementia according to groups of hearing impairment in different category of vision impairment and according to groups of vision impairment in different category of hearing impairment. Table S11-S13. Sensitivity analyses in the UKB cohort study. Table S14-S15. Mediation analyses in the UKB cohort study. Table S16-S27. Subgroup analyses in the UKB cohort study. Table S28.1-S28.2. Characteristics and methodological quality of the included studies in Meta-analysis. Table S29-S30. MR analysis with MR-Egger intercept test and MR-PRESSO estimates for horizontal pleiotropy. Table S31. MR analysis under the threshold of 5×10-8. Table S32-S33. MR analysis after controlling confounders. Table S34. Reverse MR analysis. Figure S1. Study flow charts of UKB cohort study. Figure S2. Association of hearing/vision impairment with all-cause dementia among subjects with different status of genetic susceptibility for dementia. Figure S3. PRSMA flow diagram for study selection in Meta-analysis. Figure S4-S8. Subgroup Meta-analysis. Figure S9-S11. Leave-one-out analysis in Meta-analysis. Figure S12-S35. Scatter plot and leave-one-out tests in MR analysis.

12916_2024_3748_MOESM2_ESM.docx

Additional file 2: Supplementary Methods. Supplementary Method_1. Detailed information on assessment of exposure and covariates in the UK Biobank cohort study. Supplementary Method_2. Statistical analysis plan for the UK Biobank cohort study. Supplementary Method_3. Detailed information on data source and statistical analysis of Mendelian randomization study.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, F., Dong, Q., Wu, S. et al. A comprehensive evaluation on the associations between hearing and vision impairments and risk of all-cause and cause-specific dementia: results from cohort study, meta-analysis and Mendelian randomization study. BMC Med 22, 518 (2024). https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12916-024-03748-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doiorg.publicaciones.saludcastillayleon.es/10.1186/s12916-024-03748-7

Keywords

BMC Medicine

ISSN: 1741-7015

Contact us