Table 4. Hazard Ratios (95% CIs) Examining the Associations of RBC Folate, Vitamin B12, and Sulfur Amino Acids Using Quartiles (With Quartile 1 as Reference) With Incident Dementia and Incident Alzheimer Diseasea.
| Variable | Incident Dementia | Incident Alzheimer Disease | ||||
|---|---|---|---|---|---|---|
| Quartile 2 | Quartile 3 | Quartile 4 | Quartile 2 | Quartile 3 | Quartile 4 | |
| RBC Folate | ||||||
| Multiadjusted HRb | 1.03 (0.71-1.48) | 0.92 (0.63-1.36) | 1.01 (0.72-1.43) | 0.76 (0.48-1.22) | 0.75 (0.46-1.22) | 0.76 (0.49-1.18) |
| Adjusting also for APOEε4 statusc | 0.90 (0.61-1.33) | 0.97 (0.64-1.44) | 1.06 (0.74-1.52) | 0.73 (0.45-1.18) | 0.77 (0.46-1.29) | 0.75 (0.47-1.20) |
| Vitamin B12 | ||||||
| Multiadjusted HRb | 0.88 (0.60-1.31) | 0.98 (0.66-1.46) | 0.93 (0.62-1.40) | 0.97 (0.59-1.59) | 1.14 (0.69-1.89) | 0.81 (0.47-1.38) |
| Adjusting also for APOEε4 statusc | 0.97 (0.65-1.46) | 1.00 (0.66-1.51) | 0.96 (0.63-1.45) | 1.06 (0.63-1.78) | 1.24 (0.74-2.06) | 0.85 (0.49-1.49) |
| Holotranscobalamin | ||||||
| Multiadjusted HRb | 0.95 (0.64-1.40) | 0.74 (0.49-1.12) | 0.89 (0.60-1.34) | 1.08 (0.66-1.77) | 0.91 (0.54-1.52) | 0.84 (0.49-1.44) |
| Adjusting also for APOEε4 statusc | 1.00 (0.67-1.49) | 0.74 (0.48-1.14) | 0.92 (0.60-1.40) | 1.09 (0.65-1.81) | 0.90 (0.53-1.53) | 0.87 (0.48-1.48) |
| Homocysteine | ||||||
| Multiadjusted HRb | 1.04 (0.65-1.65) | 1.50 (0.97-2.32)d | 1.60 (1.01-2.55)d | 1.56 (0.60-2.21) | 1.90 (1.05-3.46)d | 2.33 (1.26-4.30)d |
| Adjusting also for APOEε4 statusc | 1.15 (0.71-1.88) | 1.52 (0.95-2.42)e | 1.67 (1.02-2.72)d | 1.30 (0.66-2.58)d | 1.92 (1.01-3.66)d | 2.42 (1.25-4.68)d |
| Methionine | ||||||
| Multiadjusted HRb | 0.80 (0.57-1.13) | 0.58 (0.39-0.86)d | 0.54 (0.36-0.81)d | 1.13 (0.73-1.73) | 0.74 (0.45-1.22) | 0.62 (0.36-1.06)e |
| Adjusting also for APOEε4 statusc | 0.81 (0.57-1.16) | 0.58 (0.38-0.86)d | 0.53 (0.34-0.80)d | 1.14 (0.73-1.79) | 0.70 (0.41-1.18) | 0.61 (0.35-1.06)e |
| Cystathionine | ||||||
| Multiadjusted HRb | 1.50 (0.93-2.42) | 1.71 (1.07-2.72)c | 1.37 (0.83-2.45) | 1.52 (0.79-2.91) | 1.94 (1.05-3.60)c | 1.57 (0.82-3.02) |
| Adjusting also for APOEε4 statusc | 1.63 (0.99-2.71)d | 1.84 (1.13-2.99)c | 1.45 (0.86-2.44) | 1.85 (0.91-3.78)d | 2.37 (1.20-4.66)c | 1.89 (0.93-3.86)d |
| Cysteine | ||||||
| Multiadjusted HRb | 0.93 (0.54-1.60) | 1.47 (0.89-2.42) | 1.51 (0.89-2.55) | 0.84 (0.41-1.71) | 1.41 (0.74-2.69) | 1.58 (0.81-3.07) |
| Adjusting also for APOEε4 statusc | 0.99 (0.56-1.76) | 1.48 (0.87-2.53) | 1.60 (0.92-2.78) | 0.89 (0.42-1.88) | 1.37 (0.68-2.73) | 1.62 (0.80-3.27) |
| Glutathione | ||||||
| Multiadjusted HRb | 1.07 (0.74-1.53) | 0.81 (0.54-1.22) | 1.17 (0.79-1.73) | 1.07 (0.68-1.66) | 0.65 (0.38-1.11) | 1.07 (0.65-1.76) |
| Adjusting also for APOEε4 statusc | 1.10 (0.76-1.61) | 0.81 (0.53-1.23) | 1.14 (0.76-1.72) | 1.07 (0.67-1.70) | 0.71 (0.41-1.22) | 1.03 (0.61-1.72) |
| Methionine to Homocysteine Ratio | ||||||
| Multiadjusted HRb | 0.77 (0.55-1.09) | 0.53 (0.35-0.80)c | 0.44 (0.27-0.71)c | 0.88 (0.58-1.36) | 0.44 (0.25-0.77)c | 0.43 (0.23-0.80)c |
| Adjusting also for APOEε4 statusc | 0.72 (0.50-1.03)d | 0.51 (0.34-0.77)c | 0.41 (9.25-0.67)c | 0.85 (0.54-1.32) | 0.44 (0.25-0.77)c | 0.41 (0.21-0.80)c |
| Cystathionine to Homocysteine Ratio | ||||||
| Multiadjusted HRb | 1.07 (0.72-1.61) | 0.83 (0.55-1.28) | 0.98 (0.65-1.48) | 1.16 (0.70-1.91) | 0.66 (0.38-1.16) | 0.91 (0.54-1.52) |
| Adjusting also for APOEε4 statusc | 1.13 (0.74-1.71) | 0.84 (0.54-1.30) | 0.98 (0.64-1.49) | 1.21 (0.72-2.04) | 0.70 (0.39-1.25) | 0.98 (0.58-1.68) |
Abbreviations: HR, hazard ratio; RBC, red blood cell.
The first to fourth quartile categories were, respectively, as follows: for red blood cell folate: 82.5 ng/mL or less, 82.6 to 104.1 ng/mL, 104.02 to 138.7 ng/mL, and greater than 138.7 ng/mL; for vitamin B12: 364.6 pg/mL or less, 364.7 to 470.3 pg/mL, 470.4 to 618.1 pg/mL, and greater than 618.2 pg/mL; for holotranscobalamin: 43.0 pmol/L or less, 43.1 to 61.0 pmol/L, 61.1 to 89.0 pmol/L, and greater than 89.0 pmol/L; for total homocysteine: 10.5 μmol/L or less, 10.6 to 12.8 μmol/L, 12.9 to 16.0 μmol/L, and greater than 16.0 μmol/L; for methionine: 19.5 μmol/L or less, 19.6 to 22.9 μmol/L, 23.0 to 26.8 μmol/L, and greater than 26.8 μmol/L; for cystathionine: 205 nmol/L or less, 206 to 288 nmol/L, 289 to 434 nmol/L, and greater than 434 nmol/L; for cysteine: 290 μmol/L or less, 291 to 320 μmol/L, 321 to 358 μmol/L, and greater than 358 μmol/L; for glutathione: 2.75 μmol/L or less, 2.76 to 3.44 μmol/L, 3.45 to 4.20 μmol/L, and greater than 4.20; for methionine to total homocysteine ratio: 1.35 or less, 1.36 to 1.79, 1.80 to 2.35, and 2.35 or greater; and for cystathionine to total homocysteine ratio: 0.016 or less, 0.017-0.023, 9.924 to 0.032, and greater than 0.032.
The multiadjusted model was adjusted for age, sex, educational level, creatinine level, systolic blood pressure, use of vitamins, albumin level, smoking status, and history of cardiovascular conditions and stroke.
Data on APOEε4 status were available in 2364 individuals from the original 2570 who had available data on RBC folate. For the rest, data on APOE-ε4 status were available in 2237 participants of the original 2355 with available data on vitamin B12 and sulfur amino acid status.
P < .05.
P < .10.