In this prospective study of adults in the UK, higher SSB (> 2 unit/day) and ASB (> 0 unit/day) intake were associated with higher dementia risk, while consuming moderate NSJ (0–1 unit/day) was associated with a lower risk and lower level of suboptimal brain structural markers. These associations were similar across major subgroups but was significantly altered by genetic risk of dementia. In aggregate, the findings of this study underscored the detrimental role of SSB and ASB and the potential beneficial role of moderate intake of NSJ in the prevention of dementia.
To our knowledge, this study is one of the few to explore the relation of type-specific SBs with dementia. Looking at prior findings, among 2,888 participants aged over 60 years10, researchers discovered that higher consumption of ASB is associated with a higher risk of Alzheimer’s disease during 9.5 years of follow-up. The estimated HR was 2.89 (95% CI, 1.18 ~ 7.07) for Alzheimer’s disease, while SSB was not significantly related. Another study conducted among 1,865 participants in Framingham Heart Study26 added that consuming sugar from beverages over 7 servings/week was associated with a substantially higher risk of all-cause dementia (HR = 2.80, 95%CI, 2.24 ~ 3.50). Our study, using data of a well-administered population-based cohort, provided further and strong evidence on brain structure to support the hypothesis that ASB intake as well as SSB intake was associated with a higher risk of dementia, although both HRs were not as high as in previous findings.
In our research on NSJ, which have been consumed as an substitute for SSB 27, moderate intake of it was associated with decreased risk of dementia, which was in concordance with several previous studies. For example, in a prospective study of 1,836 Japanese Americans, drinking juices > = 3 times/week were related to a substantially reduced risk of Alzheimer’s disease28. Other short-term interventional studies also presented similar results that juice intake was associated with slowed cognitive decline and lowered risk of cognitive impairment29,30. In another prior study among men in US, fruit juice intake was related with subjective cognitive decline in a dose-response manner from 0 to 1serving/d 12. Our study extended that while moderate intake of 0 ~ 1 units/d was associated with lower dementia risk, participant taking NSJ > 2 units/d was approximately at an as high dementia risk as those who did not drink any. Given that excessive fruit juice intake could be associated with higher diabetes risk31 or other co-morbidity, there awaits further investigation to define the optimal level.
Although the biological pathway of the relation between SBs and dementia was not fully understood, several possible mechanisms could shed light on the results. For SSB, excessive sugar intake might induce a rapid rise in blood glucose and insulin32, thus causing brain dysfunction33. For ASB, aspartame could be linked to energy production disruption and increased oxidative stress34, and thus contributed to a higher risk of dementia35 Also, the phenylalanine in aspartame could directly affect the synthesis of inhibitory monoamine neurotransmitters and induce neural degeneration36. Therefore, its neurological harm may outweigh benefits from reduced caloric intake. Conversely, rich contents of vitamins37–39, minerals40, carotenoids41–43, and flavornoids44 in NSJ may have advantaged the effects of excessive sugar and thus protected brain health. And oxidative damage caused by the β-amyloid peptide in the pathogenesis of dementia may be hydrogen peroxide mediated45.
Findings in the present study were of timely social and public health significance. For SSB which has long been considered as an excessive energy source, our findings provided evidence of it being a risk factor of dementia. While the food administration department in some western countries has advocated sugar reduction46, the risk of excessive added sugar intake remained inadequately noticed by more developing countries. In the meantime, the widely used artificial sweetener aspartame as a substitution for sugar was quite controversial. Although aspartame has been suggested to be related to neural dysfunction39 through abnormal blood glucose level and direct neurological effect, epidemiological evidence remained very scarce in the past. Our findings suggested that the chronic safety of aspartame needs to be reassessed. For NSJ recommended as a potential healthy beverage alternative, our results also suggest that excessive intake may not play a protective role. Therefore, it is necessary to emphasize a moderate quantity when recommending fruit and vegetable juice intake.
The present study has several strengths. First, the large sample size and relatively long-term follow-up enabled us to explore a comprehensive relation between sugary beverages and dementia incidence. To the best of our knowledge, our research is one of the largest of its kind, and the population-based design with high representativity ensured the generalizability of the results in the UK. The availability of genetic data and brain images in the database also allowed in-depth analyses. Secondly, linkage to registered healthcare records, low rate of loss to follow-up, less affected by selection bias. Insufficient reliability of results due to underestimation of dementia cases in other studies is theoretically avoided in this study. Third, the availability of multiple covariates and careful control in regression models minimized potential confounding effects.
This study has several limitations. First, 24h diet recall was poor at representing a long-term dietary habit. Although using repeated daily records over 2 years, the measurement error was attenuated18,19, and the intake levels in this study were comparable with the national data of UK21, there warrants further investigation using dietary assessments that could better represent a long-term status, such as food frequency questionaire. Secondly, a relatively young age at baseline meant that a large proportion of participants had yet reached an age of prevalent dementia, although subgroup analyses among participants with a baseline age over 60 did demonstrate similar results as that of the whole population. And because the participants undergoing MRI may be healthier and more tolerant to sugar or aspartame than the general population, our results on brain structure need to be further verified. Third, milder dementia cases were likely to be underreported when patients did not acquire medical assistance, considering only participants’ registration data was used to define dementia cases in this study. Moreover, our results may still be subjective to reverse causality, although we have excluded the dementia incidences within the two years after dietary assessment. Due to the long-term development of dementia, early cognitive decline may precede dietary changes, and there awaits further research to confirm these associations and help explain the underlying mechanisms.