We analysed a total of 5721 participants with no cognitive impairment at baseline. This includes 816 (14.3%) subjects with hearing impairment and 4905 (85.7%) subjects without hearing impairment. Among 816 participants with hearing impairment, 562 were classified as hearing aid users while 138 were not using hearing aids. Note that we considered only participants who reported hearing aid usage at every consecutive visit. Out of 5721 participants, 689 converted to MCI during follow-up. The baseline characteristics of participants are shown in Table 1.
While evaluating the impact of hearing impairment on the progression from healthy to MCI (Scenario 1), 21.8% of individuals aged 70 and older were diagnosed with hearing impairment while among participants aged < 70, only 5.7% had hearing loss (P < 0.001). There was an equal proportion of males and females in the group of participants with hearing impairment whereas most of the subjects without hearing loss were women (70.2%). Those with hearing impairment had significantly higher CDRSB scores (P < 0.001). In Scenario 2, investigating the effect of the use of hearing aids on the healthy-to-MCI conversion, we observed significant differences in usage of hearing aids between age groups (P < 0.001). In Scenario 3, we found significant age (P < 0.001) and gender (P < 0.001) differences. Furthermore, hearing aid users had significantly more years of education (P = 0.03) than those with no hearing impairment.
Hearing Impairment and Risk of Incident MCI
The mean normal-to-MCI conversion period (standard deviation) was 2.6 (1.9) years for patients with hearing impairment and 3.4 (2.7) for those with normal hearing (P < 0.001). Hearing-impaired individuals were at substantially higher risk of developing MCI (HR 1.4, 95%CI, 1.16-1.68, FDR P < 0.001; Fig. 2A). In addition, the overall incidence rates for MCI diagnosis in Scenario 1 were significantly lower for women (HR 0.79, 95%CI, 0.67-0.92, FDR P = 0.004) and higher for participants aged 70 and older (HR 2.88, 95%CI, 2.41-3.45, FDR P < 0.001) and those with higher CDRSB score at baseline (HR 1.71, 95%CI, 1.56-1.87, FDR P < 0.001).
Hearing Aid Status and Risk of Incident MCI
The mean time of healthy-to-MCI progression (SD) for hearing aid users was 2.7 (1.9) years. The mean time to incident MCI diagnosis for non-users of hearing aids was significantly shorter, i.e., 1.8 (1.2) years (P < 0.001). In the multivariable Cox proportional hazards regression model, the use of hearing aids was associated with a lower risk of progression from healthy to MCI (HR, 0.33; 95% CI, 0.23-0.47; FDR P < 0.001; Fig. 2B). Participants at increased risk for normal-to-MCI conversion were 70 years of age and older (HR 4.05, 95%CI, 2.12-7.75, FDR P < 0.001) and with a higher CDRSB score at baseline (HR 1.92, 95%CI, 1.46-2.53, FDR P < 0.001).
Normal hearing versus corrected hearing loss
Since the use of hearing aids was negatively associated with the incidence of MCI diagnosis, we compared survival time for participants without hearing impairment and hearing-impaired adults that reported use of hearing aids (Scenario 3). We found no statistically significant differences in risk of progression from healthy to MCI between these two groups (HR, 1.23; 95% CI, 0.99-1.5; FDR P = 0.08; Fig. 2C). Finally, we compared the incidence rate for MCI diagnosis in group of participants with normal hearing and those with hearing loss that did no use hearing aid. We found that hearing-impaired individuals without hearing aids were at significantly higher risk of conversion from healthy to MCI (HR, 3.94; 95% CI, 2.90-5.36; FDR P < 0.001).
The baseline characteristics of participants in propensity score matched groups are shown in Table 2. The results from propensity score analyses revealed similar results to the findings of the primary analyses (Fig. 4). First, we reported a higher risk of conversion from healthy to MCI for patients with hearing impairment (HR, 1.38; 95% CI, 1.08-1.75; FDR P = 0.015; Fig. 3A). Second, the use of hearing aids was associated with reduced risk of progression to MCI when compared to non-use of hearing aids (HR, 0.29; 95% CI, 0.17-0.49; FDR P < 0.001; Fig. 3B). Finally, we found no statistically significant differences in time to incident MCI diagnosis between patients without hearing impairment and hearing-impaired individuals that reported use of hearing aids (HR, 1.03; 95% CI, 0.77-1.38; FDR P = 0.95; Fig. 3C).
Given that our project is a non-randomized study on causal associations, we also assessed the robustness of our results with respect to unmeasured confounding (Table 3). Sensitivity analysis for unmeasured confounding performed for Scenario 1 showed that hearing-impaired individuals were at substantially higher risk of developing MCI compared to participants with normal hearing for all considered values of the strength of the confounder-outcome association, and the prevalence of potential confounder in the population. The results of sensitivity analyses obtained for Scenario 2 were also consistent with those from the primary analysis i.e., the use of hearing aids was associated with lower risk of incident MCI in Scenario 2. In Scenario 3, only when larger proportion of patients with normal hearing have the unmeasured predictor and when the unmeasured predictor has effect 2-fold larger than the existing predictor i.e., ‘normal hearing/hearing aid used’, the unmeasured confounder may have impact on the effect of ‘normal hearing/hearing aid used’ predictor on the outcome.
Longitudinal Changes in Cognitive Function
To assess the effect of hearing impairment and hearing aid usage on cognitive function, we performed the longitudinal analyses for Scenarios 1-3 using linear mixed effects regression models with individual CDRSB test scores as dependent variables. We examined the impact of hearing impairment on cognitive decline in Model 1, the impact of hearing aid usage on cognitive decline in Model 2; and in Model 3, we compared the cognitive function in participants without hearing loss and hearing-impaired adults using hearing aids.
Model 1 showed a considerable variation in estimated individual intercepts, with the variance of 0.12 units change in the CDRSB score. We found that for every one-year increase, CDRSB was expected to increase by 0.14 (P < 0.001). On average, individuals with hearing impairment tended to have 0.13 points higher CDRSB score compared to those without hearing loss (P = 0.005). Cognitive decline was also positively associated with the time and hearing impairment interaction (P < 0.001) meaning that participants without hearing impairment showed less time‐related decline than hearing-impaired subjects (Fig. 4A).
Within Model 2, we found a significant effect of longitudinal follow-up time (P < 0.001) and hearing aid status (P < 0.001) on the CDRSB score. For every one-year increase, CDRSB was shown to increase on average by 0.55. The CDRSB score reported for hearing-impaired participants using hearing aids was, on average, 0.4 points lower than for non-users of hearing aids. Most importantly, the interaction between follow-up time and hearing aid status was statistically significant (P = 0.004), with the time‐related increase in cognitive scores steeper for participants not using hearing aids (Fig. 4B).
In Model 3, we observed a significant effect of follow-up time on the CDRSB score (P < 0.001), with the average annual rate of change in CDRSB of 0.14 points. However, neither the average CDRSB score for individuals without hearing loss and hearing-impaired adults using hearing aids nor temporal changes in the CDRSB score for these two groups of participants were found statistically significant (P = 0.33 and P = 0.06 respectively).