In this study, we assessed the association between obesity phenotypes defined using BMI quartiles at admission and cognitive function at 3 months post-ischemic stroke onset. To our knowledge, this study is the first to evaluate BMI and domain-specific cognitive outcomes using a comprehensive, standardized, neuropsychological protocol in relation to a multicenter cohort of stroke patients16. Our data analysis indicated that a lower BMI at admission was associated with a higher risk of global cognitive deterioration, while a higher BMI was associated with significantly worse frontal dysfunction post-ischemic stroke. These findings suggest that BMI has differential effects on various cognitive domains following an ischemic stroke.
Previous epidemiologic studies concerning the relationship between BMI and cognitive impairment have yielded controversial findings. The relationship between obesity and long-term cognitive outcomes has alternately been identified as direct, inverse, U-shaped, or even absent21,22. However, as previous studies only performed the MMSE to assess cognition, they might have overlooked the influence of BMI on frontal/executive function, given that the MMSE is not sensitive to evaluating frontal lobe function23. Our results are in line with previous studies showing that a low BMI was significantly associated with a high risk of cognitive decline9.
Despite uncertainly concerning the precise mechanism underlying post-stroke worsening of cognitive function, decreased body weight has been identified as an early indication of declining health and even neurodegeneration24. Moreover, several studies have proposed that leptin, an adipokine produced by adipose tissue, exerts neuroprotective effects through anti-oxidative activity and its promotion of hippocampal progenitor cell proliferation. As underweight patients may have decreased levels of leptin, a lower BMI may result in less neuroprotection after neurological insult25.
Our results also showed that a higher BMI was significantly associated with worse frontal/executive function, specifically in phonemic and semantic fluencies. This finding is in agreement with those of previous studies that have linked obesity to temporal atrophy13. Moreover, one study that used high-resolution 3D MRI scans reported that obese individuals had a significantly lower density of gray matter in the frontal lobe, post-central gyrus, and middle frontal gyrus than control group participants14. Obesity has also been reportedly related to executive dysfunction with other cognitive functions preserved, even in neurologically healthy adults without cognitive impairment15. Specifically, obese adults perform worse on executive function tests, especially those testing verbal interference, than their counterparts with a lower BMI. These findings may indicate vulnerability of the frontotemporal lobe in obese patients to acute stroke, regardless of lesion location.
Our study had some limitations. First, only participants’ height and weight measurements were used to determine the BMI. Other adiposity data, such as abdominal circumference or waist-hip ratio, were unavailable; therefore, we could not address possible differences between leanness and being underweight and their relationships with long-term cognitive outcomes26. Future studies should consider replicating the approach of studies that have investigated the relationship between obesity and Alzheimer’s disease through using the waist-to-hip ratio and waist circumference at multiple sites as a measure of central obesity. Second, we were unable to determine any causal relationships between BMI and cognition because this study spanned a relatively short observational period. Third, restrictions were inevitable concerning the number of participants studied and some of the explanatory variables because this study was the result of a secondary analysis of a multicenter study that aimed to investigate the prevalence of cognitive disorders post-stroke. Consequently, we did not include several image variables such as cerebral atrophy or white matter hyperintensities, which may have affected cognitive function post-stroke. Furthermore, we did not assess temporal changes in BMI from stroke onset. Nonetheless, the main strength of our study is that it is by far the first study to investigate the effects of BMI on each cognitive domain after stroke. These findings may provide additional evidence for pathophysiological aspects of BMI on each neural substrate after ischemic stroke.