Voice Disorders as Early Biomarkers of Cognitive Decline

Dementia affects greater than 57 million people worldwide. With an aging population and limited disease-curing treatments available, early identification of biomarkers is crucial. The 2020 Lancet Commission identified hearing loss as the largest modifiable risk factor for dementia globally, and a randomized controlled trial found that hearing intervention reduced 3-year cognitive change in older adults who were at increased risk for cognitive decline. Similarly, studies have found that abnormalities in acoustic measures of voice are correlated with cognitive status and can potentially predict decline. The association between hearing loss and cognitive decline might have both social and neurological mechanisms. Dysphonia might pose similar problems. Socially, voice disorders may reduce engagement in social and cognitively stimulating activities. Neurologically, one example is in Parkinson's disease in which the vagus nerve is one of the earliest sites of Lewy body pathology in Braak staging, and dysphonia and dysarthria can precede motor symptoms by years. Voice changes have been associated with different neurological conditions such as amyotrophic lateral sclerosis, multiple system atrophy, and Alzheimer's disease. Despite this, no prior large-scale study has examined whether diagnosed voice disorders are associated independently with incident cognitive decline. Our study is the first to examine this potential association, using the TriNetX US Collaborative Health Network platform to compare patients with diagnosed voice disorders and matched controls, with a hearing loss cohort as a standard of comparison given that it is the largest established modifiable risk factor for dementia, as dysphonia is also a modifiable condition.

This study included 833,417 total patients in the voice disorders and control cohorts. Voice disorders were associated with a significantly elevated risk of incident cognitive decline compared to controls (HR=1.291, 95% CI 1.155-1.443, P<0.0001). Hearing loss alone was associated with a slightly lower risk of cognitive decline (HR=1.267, 95% CI 1.203-1.334, P<0.0001). Voice disorders without concurrent hearing loss were associated with an elevated risk of incident cognitive decline compared to hearing loss alone (HR=1.261, 95% CI 1.121-1.419, P=0.0001), while voice disorders with hearing loss were associated with the highest risk among all cohorts (HR=2.038 vs controls; HR=1.545 vs hearing loss). Both voice disorder subgroups did not differ when compared with each other (HR=1.088, P=0.376).

The results from our study indicate that voice disorders are associated with an elevated risk of incident cognitive decline and may represent a stronger early biomarker than hearing loss alone. These findings highlight otolaryngology and family medicine/internal medicine encounters as potential entry points for cognitive assessment, and early voice treatment needs to be investigated for possible beneficial cognitive effect.