Previous studies on MCI reversion mostly investigated the influence of non-modifiable factors (eg. gender, age, genetics) and life-long factors that can no longer be changed in later age (eg. baseline cognitive functioning, education, co-morbidity, etc.). This study identified several dietary/behavioral factors significantly associated with higher possibility of MCI reversion, including daily consumption of fresh fruits, daily engagement in reading, housework, and mah-jong or other card games. Cigarette smoking and duration of alcohol consumption were identified as risk factors impeding MCI reversion. These factors were extracted from people’s daily life in the studied context, and can potentially be transferred into cost-effective preventive practices.
To increase practical implication of our research findings, we analyzed the specific effect of each single activity on cognitive improvement among population with different demographic characteristics. Three activities, housework, reading books or newspaper, and playing cards or mah-jong, were positively associated with MCI reversion, respectively. These findings provide evidence that cognitive stimulation not only protects cognitive functioning from declining (25–28), but may also help those who already develop MCI achieve reversion to CN. It is noteworthy that, although doing housework was associated with MCI reversion, no significant association was found between outdoor activities and MCI reversion. This may indicate that productive activities contribute more to cognitive functions than physical activities among Chinese older adults (29). A previous national longitudinal study in China has found that interacting with friends, playing mah-jong or other games, infrequently providing help to others and doing sport were beneficial for cognitive functioning among normal middle-aged and older adults (30). Both studies identified the beneficial effect of cognitive games and social interactions, which can be easily transferred into community-based dementia prevention programs.
In terms of dietary factors, frequent consumption of meat was found to be negatively associated MCI reversion, probably explained by high volume of saturated fats in meat (31). Previous research has found significant association between intake of saturated fats and incident Alzheimer’s disease (32), and such findings also apply to MCI reversion. However, previous studies have identified a negative association between high habitual fruit intake and cognitive health (33, 34), while frequent fruit consumption was found to be positively associated with MCI reversion in our study. In contrast, no significant association was found between frequent vegetable intake and MCI reversion. Effect of a single food on cognitive health can be attenuated by existent dietary patterns (35). A plausible explanation for the difference between our findings and previous results may be that vegetable is widely popular in Chinese diet and extra consumption of it may not have additional benefits. The negative effect of fruit on cognitive health found in previous research is mostly caused by extra sugar intake, while excessive sugar consumption is not as prevalent in Chinese diet, attenuating the negative impact of fruit. The benefit of fruit consumption may be explained by abundant Vitamin C intake, which was found to have protective effect on cognitive health (36). Future studies investigating healthy diet need to take into consideration the cultural differences of the research contexts. Cigarette smoking was identified as a risk factor negatively associated with MCI reversion, in consistence with previous research which found it to be a risk factor for dementia incidence (37). Previous studies investigating the effect of alcohol on cognitive health mostly focused on quantity of alcohol consumption and have yielded mixed results (38–40). This study found that duration of alcohol consumption was negatively associated with possibility of MCI reversion, providing a new direction for research on alcohol consumption and cognitive health.
The sub-group analysis investigated how the association between modifiable factors and MCI reversion varies across age and gender. In general, the identified factors have more significant impact on the younger groups (65-89) compared to the older group (90 and above). Particularly, daily fruit intake and daily housework were significantly associated with MCI reversion among people between 65 and 90, but not among those who were above 90. In contrast, watching TV/listening to radio daily, as a passive activity, was only significantly associated with higher possibility of reversion among people above 100 years old. This difference may be explained by the impact of aging on neuroplasticity: younger people may more easily increase neuroplasticity and achieve cognitive improvement through lifestyle changes, while older people may have less opportunity to reverse and need to depend on external mental stimulation (41). In terms of gender difference, doing housework was significantly associated with higher possibility of reversion among male, but not among female. This difference might be caused by cultural norms that require women to routinely do housework, and therefore more frequent involvement does not provide extra stimulation.
Three large-scale RCTs, respectively FINGER (11), MAPT (12), and PreDIVA (13), were conducted to prevent dementia through lifestyle interventions, and only FINGER found positive effects. Which specific factors contributed to these effects, however, were not further studied. This study further analyzed the effect of each specific modifiable factor on cognitive reversion and identified several potential protective factors. Several other studies found some modifiable factors contributing to MCI reversion. A study of 396 MCI participants in Japan found that driving a car, using a map to travel to unfamiliar places, reading books or newspapers, taking cultural classes, attending meetings in the community, participating in hobbies or sports activities and engaging in fieldwork or gardening are all beneficial to cognitive recovery (25). It is noteworthy that the results were only significant in the imputed data which augmented the original sample size from 396 to 37,893 by multiple imputation, rendering the conclusions questionable. Moreover, this study ignored nutritional, cardiometabolic and psychological factors, providing limited guidance on health habits. Two other studies of similar sample size and research design were conducted in Australia (26) and Korea (27). Both studies recommended engagement in social activities for people with MCI, but activities were only measured by number and frequency, leaving the effect of specific activities unknown. Great cultural differences exist in the types of activities researched, and the measurement of activity participation also varies. Such difference compromises the generalizability of these findings in a different context.
This is by far the largest and most comprehensive cohort study on the modifiable factors associated with reversion from MCI to CN. We only included factors that were still modifiable when patients had already suffered from MCI. Therefore, findings of this study can be transferred to practice of secondary prevention of dementia. Moreover, variable selection method was widely used to generate data-driven research hypothesis (42). This study integrated both theory-driven and data-driven methods to generate research hypotheses. We first came up with many research hypotheses by comprehensively reviewing previous study on dementia. Then we used a new variable selection method, LASSO instead of traditional stepwise (back-n-forth) method to avoid multicollinearity in the final model. In sensitivity analysis, we found stepwise (back-n-forth) method failed to detect one significant modifiable factor because it usually provides less stable results than LASSO. The large sample size of this study also allowed us to draw robust conclusions among young old, octogenarians, nonagenarians, and centenarians, providing detailed information of dementia prevention for each age group.