Background/aims Patients with vestibular disease have been observed to have concomitant cognitive and psychiatric dysfunction. We evaluated the association between vestibular vertigo, cognitive impairment and psychiatric conditions in a nationally representative sample of US adults. Methods We performed a cross-sectional analysis using the 2008 National Health Interview Survey (NHIS), which included a Balance and Dizziness Supplement, and questions about cognitive function and psychiatric comorbidity. We evaluated the association between vestibular vertigo, cognitive impairment (memory loss, difficulty concentrating, confusion) and psychiatric diagnoses (depression, anxiety and panic disorder). Results We observed an 8.4% 1-year prevalence of vestibular vertigo among US adults. In adjusted analyses, individuals with vestibular vertigo had an eightfold increased odds of ‘serious difficulty concentrating or remembering’ (OR 8.3, 95% CI 4.8 to 14.6) and a fourfold increased odds of activity limitation due to difficulty remembering or confusion (OR 3.9, 95% CI 3.1 to 5.0) relative to the rest of the US adults. Individuals with vestibular vertigo also had a threefold increased odds of depression (OR 3.4, 95% CI 2.9 to 3.9), anxiety (OR 3.2, 95% CI 2.8 to 3.6) and panic disorder (OR 3.4, 95% CI 2.9 to 4.0). Conclusions Our findings indicate that vestibular impairment is associated with increased risk of cognitive and psychiatric comorbidity. The vestibular system is anatomically connected with widespread regions of the cerebral cortex, hippocampus and amygdala. Loss of vestibular inputs may lead to impairment of these cognitive and affective circuits. Further longitudinal research is required to determine if these associations are causal.

Vestibular function declines with age, and emerging evidence suggests that vestibular loss is associated with cognitive impairment. Whether vestibular dysfunction is associated with age-related cognitive decline is unknown. We used data from the 1999–2002 National Health and Nutrition Examination Surveys to evaluate the influence of vestibular function on cognitive performance in a nationally representative sample of U.S. adults aged ≥60 years ( n = 1,303). Vestibular function was measured with the modified Romberg test, and cognitive function was measured by the digit symbol substitution (DSS) score test. We also developed structural equation models (SEMs) to explore whether vestibular dysfunction and associated cognitive impairment mediate the effect of age on falls and activities of daily living (ADL) difficulty. Vestibular dysfunction was present in 58% of the study population. In multivariate analyses, vestibular dysfunction was associated with a 3.4-point lower DSS score (95% confidence interval: −5.2, −1.6; p < .0001), equivalent to the effect of 5 years of age. Vestibular dysfunction was also associated with a significantly higher odds of ADL difficulty ( p = .001), and with a 2.6-fold increase in the odds of falling ( p = .017). SEMs suggested that vestibular function mediates 14.3% of the effect of age on cognitive performance. Further SEMs suggested that lower cognitive performance mediates the association between vestibular loss and ADL difficulty as well as falls. This study suggests that vestibular dysfunction partially mediates the association between age and cognitive impairment. Moreover, the cognitive impairment that results from vestibular loss may contribute to ADL difficulty and falls in older individuals.

Vestibulo-ocular and vestibulospinal reflexes normally maintain stable gaze and posture during head movement. Individuals with bilateral vestibular deficiency (BVD) often experience oscillopsia (blurring of vision due to image slip across the retinae during head movement), disequilibrium, and postural instability that together confer a 31-fold increase in risk of falling.¹ Most individuals with unilateral vestibular deficiency (UVD) ultimately compensate for their loss by using information from the remaining labyrinth, and those with mild or moderate BVD often compensate by integrating residual labyrinthine input with other sensory cues. However, severe BVD can be devastating if adaptation and compensation strategies fail to overcome the sensory deficit.^2,3 Individuals with BVD often experience chronic imbalance and instability of vision and posture that render routine daily activities such as walking and driving difficult.

Importance Despite the efficacy of immune checkpoint inhibitors (ICIs), cutaneous immune-related adverse events (cirAEs) occur in 20% to 40% of all treated patients. To our knowledge, little is known about the predictive value of these cutaneous eruptions and their subtypes regarding cancer survival. Objective To determine the association of developing cirAEs following treatment with anti–programmed cell death 1 (PD-1) or anti–programmed cell death ligand 1 (PD-L1) therapy with patient survival. Design, Setting, and Participants This retrospective cohort study used data from the TriNetX Diamond Network, a database of health records and claims data from more than 200 million US and European patients, to conduct a population-level cohort analysis. The study included 7008 eligible patients who developed cirAEs after treatment with anti–PD-1 or anti–PD-L1 therapy for malignant neoplasms of digestive organs, bronchus or lung, melanoma of skin, and urinary tract who were identified through the TriNetX Diamond Network along with 7008 matched controls. Exposures Development of cirAEs within 6 months following anti–PD-1 or anti–PD-L1 therapy. Main Outcomes and Measures A 6-month analysis using a Cox proportional hazards model was performed to determine the association of cirAEs with overall survival after adjusting for demographic characteristics, cancer type, and cancer stage. Results A total of 7008 patients (3036 women [43.3%]; mean [SD] age, 68.2 [11.2] years) were matched to 7008 (3044 women [43.4%]; mean [SD] age, 68.3 [11.1] years) controls. Pruritus (hazard ratio [HR], 0.695; 95% CI, 0.602-0.803;P < .001), drug eruption (HR, 0.755; 95% CI, 0.635-0.897;P = .001), xerosis (HR, 0.626; 95% CI, 0.469-0.834;P = .001), nonspecific rashes (HR, 0.704; 95% CI, 0.634-0.781;P < .001), and appearance of any cirAE (HR, 0.778; 95% CI, 0.726-0.834;P < .001) were significantly protective of mortality using a Benjamini-Hochberg correction with a significance level of .05. Additionally, psoriasis (HR, 0.703; 95% CI, 0.497-0.994;P = .045) and lichen planus/lichenoid dermatitis (HR, 0.511; 95% CI, 0.279-0.939;P = .03) were significant. Eczematous dermatitis (HR, 0.612; 95% CI, 0.314-1.195), vitiligo (HR, 0.534; 95% CI, 0.254-1.123), bullous pemphigoid (HR, 0.524; 95% CI, 0.140-1.956), and Grover disease (HR, 0.468; 95% CI, 0.115-1.898) were all associated with strong protective clinical effects. Conclusions and Relevance The results of this cohort study suggest that the development of cirAEs is strongly associated with response to ICI therapy and patient survival.