A Biological Index to Screen Multi-Micronutrient Deficiencies Associated with the Risk to Develop Dementia in Older Persons from the Community

Abstract

Background: Low blood status in several nutritional compounds, including long-chain omega-3 fatty acids (LC n-3 PUFA), carotenoids, and vitamin D, have been associated with a higher risk to develop dementia. Nutritional deficiencies may potentiate each other regarding dementia risk; yet the association of multiple nutritional deficiencies with dementia has been little explored. Objective: To develop an index of micronutritional biological status (MNBS) for the screening of multi-micronutritional deficiencies associated with the risk of dementia in a prospective population-based cohort of older persons. Methods: We included participants from the Bordeaux Three-City study, who were free of dementia at baseline, had blood measurements of LC n-3 PUFA, carotenoids, and 25(OH)D, and who were followed for up to 18 years for dementia. We used penalized splines in Cox models to model dose-response relationships of each nutritional component with the risk of dementia and construct a risk index. Results: 629 participants with an average age of 73.1 years were included in the study. Each increase of 1 SD of the MNBS index was associated with a 46%higher risk of dementia (HR = 1.46, 95%CI 1.23; 1.73). Participants with highest index ([mean+1SD; max]) had a 4-fold increased risk of dementia compared with participants with a low index ([min; mean-1SD]) (HR = 4.17, 95%CI 2.30; 7.57). Conclusion: This index of assessment of micronutritional biological status is a practical tool that may help identify populations with inadequate nutritional status, screen eligible individuals for nutritional prevention in primary care, or for supplementation in preventive trials of dementia.

Concurrent nutrient deficiencies are associated with dementia incidence

“…The 13% of participants with the highest nutrient status index had a four-fold increased chance of developing dementia compared to the 21% with the lowest index scores. 7 Additionally, While this earlier research also demonstrated associations between multiple-nutrient suboptimal statuses and brain aging, direct comparison between results is complicated by differences in components and cut-offs.…”

“…To construct the nutrient status index as used in our study, we combined the approaches of Bowman and colleagues 6 and Neuffer and colleagues. 7 This nutrient status index indicates the number of highrisk statuses for three nutrients: homocysteine (as marker of B vitamin status), vitamin D, and n-3 PUFAs. These nutrient biomarkers were selected a priori on the basis of having a plausible mechanism of action in preventing dementia, having proof from observational studies of the beneficial associations between the nutrient biomarker and dementia risk, 2 Figure 1 shows the dose-response associations between the individual nutrient statuses with dementia.…”

Increased Intake of Vegetables and Fruits Improves Cognitive Function among Chinese Oldest Old: 10-Year Follow-Up Study

“…Notably, associations between multiple nutrients may potentiate the benefits of an individual nutrient [68]. Neuffer et al, for example, assessed plasma levels of LC n-3 PUFA, 25-hydroxyvitamin D, and carotenoids, indicating a fourfold increased risk of dementia among participants who demonstrated higher index values, indicating potential for mitigating cognitive decline through correction of multinutrient deficiencies [69]. In fact, the LipiDiDiet trial tested the efficacy of a multinutrient supplement in preventing Alzheimer's disease progression, with follow-up results after 36 months, revealing significant long-term improvement in cognitive outcomes, brain atrophy, and disease progression among 81 participants (from an initial pool of 311 randomized subjects) [70].…”

Nutrition state of science and dementia prevention: recommendations of the Nutrition for Dementia Prevention Working Group

“…10 A similar index used in the three-City study was also associated with a higher risk of dementia, with a large effect size. 39,40 Effect sizes can be used to estimate sample size (appendix p 10). Importantly, the magnitude of reported associations in the three-city study was high (ie, stronger than the effect size of APOE ε4 status).…”