Table 4.
Associations between nut exposure and cognitive declinea
| Nut exposure | Change in cognitive function | Decline in cognitive function | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Model 1 | Model 2 | Model 3 | Model 1 | Model 2 | Model 3 | |||||||
| β (95% CI) | P-value | β (95% CI) | P-value | β (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | OR (95% CI) | P-value | |
| Dietary marker | ||||||||||||
| Nut intake | 0.19 (0.00, 0.38) | 0.046 | 0.25 (0.05, 0.46) | 0.014 | 0.25 (0.04, 0.46) | 0.018 | 0.87 (0.73, 1.04) | 0.12 | 0.79 (0.63, 1.00) | 0.05 | 0.78 (0.61, 0.99) | 0.043 |
| Urinary markers | ||||||||||||
| Urolithin A | 0.86 (0.10, 1.61) | 0.026 | 1.00 (0.24, 1.76) | 0.010 | 0.85 (0.04, 1.66) | 0.040 | 0.41 (0.19, 0.90) | 0.027 | 0.37 (0.16, 0.82) | 0.015 | 0.37 (0.15, 0.88) | 0.024 |
| Urolithin A glucuronide | 0.64 (−0.04, 1.33) | 0.06 | 0.90 (0.20, 1.60) | 0.013 | 0.86 (0.15, 1.56) | 0.018 | 0.74 (0.45, 1.20) | 0.22 | 0.68 (0.40, 1.16) | 0.16 | 0.69 (0.40, 1.19) | 0.18 |
| Urolithin A sulphate | 0.96 (0.17, 1.75) | 0.017 | 1.21 (0.40, 2.01) | 0.004 | 1.14 (0.32, 1.95) | 0.007 | 0.52 (0.27, 1.01) | 0.05 | 0.41 (0.19, 0.86) | 0.019 | 0.43 (0.20, 0.91) | 0.028 |
| Urolithin A sulphoglucuronide | 0.64 (−0.12, 1.41) | 0.10 | 0.97 (0.18, 1.76) | 0.017 | 0.86 (0.05, 1.68) | 0.039 | 0.69 (0.38, 1.25) | 0.23 | 0.54 (0.27, 1.08) | 0.08 | 0.57 (0.28, 1.16) | 0.12 |
| Urolithin B | 1.23 (0.43, 2.04) | 0.003 | 1.33 (0.47, 2.19) | 0.003 | 1.28 (0.37, 2.20) | 0.007 | 0.48 (0.23, 1.01) | 0.05 | 0.38 (0.16, 0.89) | 0.027 | 0.38 (0.15, 0.92) | 0.032 |
| Urolithin B glucuronide | 0.92 (0.24, 1.61) | 0.009 | 0.94 (0.20, 1.68) | 0.014 | 0.88 (0.11, 1.65) | 0.026 | 0.56 (0.32, 0.98) | 0.041 | 0.50 (0.26, 0.95) | 0.036 | 0.49 (0.25, 0.96) | 0.037 |
| Hydroxyhippuric acid | −0.24 (−1.21, 0.73) | 0.62 | −0.13 (−1.15, 0.90) | 0.81 | 0.11 (−0.98, 1.20) | 0.84 | 0.98 (0.52, 1.87) | 0.96 | 0.85 (0.42, 1.72) | 0.65 | 0.66 (0.30, 1.45) | 0.30 |
| Hydroxyphenylacetic acid | 0.74 (−0.05, 1.53) | 0.06 | 0.65 (−0.14, 1.45) | 0.11 | 0.67 (−0.14, 1.49) | 0.10 | 0.46 (0.26, 0.83) | 0.010 | 0.47 (0.25, 0.86) | 0.015 | 0.45 (0.24, 0.87) | 0.017 |
| Dodecanedioic acid | 0.83 (−0.00, 1.66) | 0.05 | 1.17 (0.30, 2.04) | 0.009 | 1.00 (0.08, 1.93) | 0.033 | 0.69 (0.38, 1.23) | 0.21 | 0.48 (0.25, 0.95) | 0.035 | 0.51 (0.25, 1.02) | 0.06 |
| Dimethylglutaric acid | 1.50 (0.34, 2.66) | 0.011 | 1.75 (0.57, 2.94) | 0.004 | 1.77 (0.56, 2.98) | 0.005 | 0.38 (0.16, 0.94) | 0.036 | 0.29 (0.11, 0.78) | 0.014 | 0.29 (0.10, 0.79) | 0.016 |
| Indole-3-acetic acid-O-glucuronide | −0.39 (−1.30, 0.53) | 0.40 | −0.55 (−1.47, 0.37) | 0.24 | −0.60 (−1.52, 0.32) | 0.20 | 1.43 (0.76, 2.67) | 0.27 | 1.52 (0.79, 2.92) | 0.21 | 1.60 (0.81, 3.15) | 0.17 |
| Indoxyl sulphate | 0.19 (−0.49, 0.87) | 0.59 | 0.22 (−0.50, 0.94) | 0.55 | 0.26 (−0.46, 0.98) | 0.48 | 0.98 (0.62, 1.54) | 0.92 | 0.88 (0.52, 1.47) | 0.62 | 0.85 (0.50, 1.45) | 0.56 |
| Dihydroxy--benzoxazinone | 0.61 (−0.32, 1.54) | 0.20 | 0.91 (−0.05, 1.87) | 0.06 | 1.12 (0.13, 2.10) | 0.027 | 0.46 (0.23, 0.94) | 0.033 | 0.39 (0.18, 0.84) | 0.017 | 0.30 (0.12, 0.74) | 0.009 |
| Multimetabolite urinary biomarker panelsb | ||||||||||||
| Model A | 0.004 (0.001, 0.007) | 0.004 | 0.006 (0.003, 0.008) | <0.001 | 0.005 (0.002, 0.007) | 0.002 | 0.997 (0.995, 0.999) | 0.010 | 0.996 (0.994, 0.999) | 0.002 | 0.996 (0.994, 0.999) | 0.003 |
| Model C | 0.004 (−0.001, 0.009) | 0.11 | 0.006 (0.001, 0.011) | 0.029 | 0.006 (0.001, 0.011) | 0.029 | 0.997 (0.993, 1.00) | 0.056 | 0.996 (0.992, 1.00) | 0.028 | 0.995 (0.991, 0.999) | 0.016 |
| Model B | 0.005 (0.002, 0.009) | 0.003 | 0.007 (0.003, 0.011) | <0.001 | 0.006 (0.002, 0.010) | 0.003 | 0.997 (0.995, 1.00) | 0.026 | 0.996 (0.993, 0.999) | 0.008 | 0.996 (0.993, 0.999) | 0.013 |
| Model D | 0.011 (0.001, 0.021) | 0.028 | 0.015 (0.005, 0.025) | 0.004 | 0.012 (0.002, 0.022) | 0.022 | 0.994 (0.987, 1.00) | 0.07 | 0.992 (0.985, 1.00) | 0.047 | 0.993 (0.985, 1.00) | 0.07 |
Linear and logistic regression models were used, and the following three separate models are presented: model 1, which was adjusted for baseline score of cognitive function, sex and age; model 2, which was further adjusted for BMI, energy intake (only diet), alcohol consumption, education, physical activity and smoking status; and model 3, which was further adjusted for depressive symptoms, stroke, cardiovascular disease, hypertension and diabetes.
Multimetabolite urinary biomarkers models evaluated using Tobit models as follows: Model A) all 13 known identified urinary metabolite; Model B) a selection of 7 identified urinary metabolite biomarkers (urolithin A and its three conjugates, urolithin B and its glucuronide, and dodecanedioic acid; Model C) a reduced panel with 4 metabolite biomarkers from Model A (urolithin A glucuronide, hydroxyhippuric acid, hydroxyphenylacetic acid and dimethylglutaric acid); and Model D) a reduced panel with 2 metabolite biomarkers from Model B (urolithin A and its glucuronide).