Relationship Between Brain Nutrient Concentrations and Cognition
Scores of the first five NPs were not statistically different between demented and non-demented subjects (data not shown). However, among non-demented subjects, subjects who had mild cognitive impairment (GDS 3, n = 11) had significantly lower NP2 score than that of cognitively intact subjects (GDS 1–2, n = 12, p = 0.002), but not for other NPs. The difference remained statistically significant after an adjustment for sex, education, hypertension, diabetes, and presence of APOE ε4 allele (p = 0.004).
A heat map was constructed to provide Pearson's partial correlation coefficients between NP scores or nutrient concentrations and scores on cognitive domains, depression, and activities of daily living in all subjects (Figure 2A, p-values provided in Supplementary Table 4A). Pearson's partial correlations were adjusted for sex, education, diabetes, hypertension, and presence of APOE ε4 allele. No consistent relationship between NPs and cognitive domain scores that reached statistical significance was observed.
Figure 2  Heat map of Pearson's correlation coefficients between nutrient pattern (NP) scores or nutrient concentrations and scores on cognitive domains, depression, and activities of daily livings in (A) all subjects (n = 47) and (B) non-demented subjects (Global Deterioration Scale = 1–3, n = 23). Correlations are adjusted for sex, education, diabetes, hypertension, and APOE ε4 allele (#p < 0.10, *p < 0.05). SFA, saturated fatty acid; MUFA, monounsaturated fatty acid; PUFA, polyunsaturated fatty acid; trans-FA, trans-fatty acid. A subset analysis among non-demented subjects (GDS 1–3) was performed and Pearson's coefficients are illustrated in a heat map (Figure 2B, p-values provided in Supplementary Table 4B). In the models adjusted for covariates among the five NPs representing the highest variances, NP2 was consistently associated with higher scores on global cognition (r = 0.38, p = 0.070), memory (r = 0.38, p = 0.073), language (r = 0.42, p = 0.046), and lower depression score (r = −0.40, p = 0.090) (Figure 3). After additional adjustment for antidepressant use, the correlation with lower depression score remained borderline significant (r = −0.35, p = 0.100). Since NP2 is mainly described by carotenoids, significant correlations were also consistently observed between lutein, zeaxanthin, β-carotene and scores on global cognition, memory, language, and depression. Other notable associations included NP3 and NP5 and higher depression. Additional adjustment for antithrombotic use was performed for PK and MK-4 and their correlations with different cognitive domain composite scores remained statistically non-significant (p > 0.05) for all six cognitive domains and activities of daily living, while the correlation between MK-4, but not PK, and depression remained statistically significant (Supplementary Table 4B).
Figure 3  The relationship between nutrient pattern 2 (NP2) score and composite scores of (A) global cognition, (B) memory, (C) language, and (D) depression among non-demented subjects (Global Deterioration Scale = 1–3, n = 23). Pearson's correlation coefficients are adjusted for sex, education, diabetes, hypertension, and APOE ε4 allele.