Our study found an association between myopia and cognitive dysfunction, relative to emmetropia. This association was independent of age, sex, BMI, income, education, and reading/writing. The association of myopia with cognitive impairment was not related to confounding by cataract. Our results provide preliminary evidence on a novel association between myopia and cognitive dysfunction that should be further studied and need to be replicated in other cohorts.
Reduced vision in older adults has been postulated to affect cognitive function by reducing participation in social, physical, and cognitively stimulating activities that protect against dementia,
24,25 while increasing the risk of depression and anxiety,
26 conditions associated with incident dementia.
27 However, correcting for best-corrected visual acuity and uncorrected refractive errors did not change the association between myopia and cognitive dysfunction significantly, suggesting that other mechanisms may be responsible.
What are possible explanations for the association between myopia and cognitive dysfunction? First, it is possible that pathogenic processes in dementia may affect refraction. Some studies have shown that β-amyloid, a key pathogenic feature of cognitive dysfunction, may also accumulate in the lens.
7 Amyloid deposition in the lens can increase lens thickness and curvature, as well as promote lens crystalline aggregation, all of which can increase the refractive index.
8,9 Another possible mechanism is that acetylcholine deficiency, which occurs early in the course of cognitive dysfunction,
28 may reduce parasympathetic input to the ciliary muscle, decreasing the amplitude of accommodation.
29 Suboptimal accommodation during near work leads to hyperopic defocus on the retina, which has been shown to accelerate axial growth.
30 Reduced accommodation in adults has been correlated with myopia progression in some studies, although this was not reported in other studies.
31–33 Second, the association may be due to uncontrolled confounding by other chronic or age-related conditions (i.e., poor general health). Further studies on environmental, pathological genetic, correlates of myopia, and cognitive dysfunction may provide additional insights.
It is noteworthy that education did not significantly modify the association between myopia and cognitive dysfunction in our participants (
P for interaction = 0.899). Years of education, socioeconomic indicators like income and type of housing, or reading were not significantly different between myopic and nonmyopic individuals in our study (all
P > 0.05). Most of our older population received elementary education or less (89.5%), and results should be interpreted cautiously when generalizing to more recent birth cohorts, as education and reading, which are frequently associated with myopia in children, are also putative protective factors against cognitive decline in later life.
10
The strengths of our study include standardized protocols for obtaining refraction and lens opacity measurements. There are some limitations to this study that may have affected the results. First, our study is cross-sectional in nature and the temporality of myopia and cognitive dysfunction is not clear. Second, only ethnic Malay adults were examined in this study and the findings may vary in other ethnic groups. Third, although the AMT is a well-validated screening instrument for cognitive impairment,
34 misclassification may occur, likely biasing OR estimates toward the null hypothesis and inflating their SEs,
35 thereby making actual associations more difficult to detect. Fourth, there may be residual confounding due to factors that we have not controlled for (e.g., depressive symptoms, general well-being, and status of Alzheimer's disease or Parkinson's disease), and categorization of continuous exposure variables (e.g., education level, hours of reading/writing). Fifth, the current sample may not represent the source population due to the high rates of persons with missing cognitive testing (20.2%) and visual impairment (11.4%) data that may introduce bias in this study. Finally, the AMT was administered in the participant's preferred language, and a systematic difference is possible between test scores taken in English versus Malay.
In summary, we report a novel finding from population-based data showing an association between myopia and cognitive dysfunction. The specific underlying mechanisms of this association are unknown; however, our results may provide insights into possible common pathways of myopia and cognitive dysfunction.