Table 4.
Mean decline between B vitamin and placebo groups: effect modification by major risk factors for cognitive decline*
| Characteristics | Mean difference in cognitive decline † [Folic acid / B6 / B12 Group - Placebo Group] (95% CI) | |||
|---|---|---|---|---|
|
| ||||
| Global Score | Verbal Score | TICS | Category fluency | |
| Age at 1st assessment | ||||
| ≤ 72 years (n= 987) | 0.05 (−0.02, 0.13) | 0.07 (−0.02, 0.15) | 0.11 (−0.27,0.49) | −0.10 (−0.66, 0.46) |
| > 72 years (n= 1022) | 0.01 (−0.08, 0.09) | −0.01 (−0.10, 0.08) | 0.21 (−0.19, 0.61) | −0.16 (−0.69, 0.36) |
| P† | P=0.20 | P=0.71 | P=0.87 | |
| Dietary folate intake | ||||
| <279 mg/day (n= 293) | 0.14 (−0.01, 0.29) | 0.14 (−0.04, 0.31) | 1.24 (0.47,2.00) | −0.19 (−0.61, 0.24) |
| ≥279 mg/day (n=1,637) | 0.01 (−0.05, 0.07) | 0.00 (−0.06, 0.07) | −0.04 (−0.34, 0.26) | 0.00 (−0.99, 0.99) |
| P=0.11 | P=0.16 | P=0.002 | P=0.73 | |
| Dietary vitamin B6 intake | ||||
| < 1.9 mg/day (n= 524) | 0.02 (−0.05, 0.08) | 0.07 (−0.05, 0.20) | 0.56 (0.03, 1.10) | −0.69 (−1.43, 0.05) |
| ≥1.9 mg/day (n=1,406) | 0.05 (−0.06, 0.15) | 0.01 (−0.07, 0.08) | 0.00 (−0.33, 0.33) | 0.03 (−0.43, 0.49) |
| P=0.63 | P=0.35 | P=0.08 | P=0.10 | |
| Dietary vitamin B12 intake | ||||
| <2.4 μg/day (n= 82) | 0.19 (−0.06, 0.44) | 0.10 (−0.21, 0.41) | 1.35 (0.16, 2.54) | 1.62 (0.11, 3.13) |
| ≥2.4 μg/day (n=1848) | 0.02 (−0.04, 0.08) | 0.02 (−0.04, 0.09) | 0.10 (−0.18, 0.39) | −0.24 (−0.64, 0.17) |
| P=0.19 | P=0.62 | P=0.05 | P=0.02 | |
| Overall dietary vitamin B intake | ||||
| “Low” ‡ (n= 573) | 0.09 (−0.01, 0.20) | 0.12 (0.00, 0.24) | 0.74 (0.23, 1.25) | −0.39 (−1.10, 0.32) |
| “Adequate”‡ (n=1357) | 0.00 (−0.07, 0.06) | −0.02 (−0.09, 0.06) | −0.10 (−0.43, 0.24) | −0.07 (−0.54, 0.40) |
| P=0.11 | P=0.06 | P=0.01 | P=0.46 | |
| 1st cognitive assessment score ‡ | ||||
| Low (n=201) | 0.11 (−0.14, 0.37) | 0.01 (−0.24, 0.26) | 1.00 (−0.16, 2.17) | 0.17 (−1.05, 1.40) |
| Normal (n= 1808) | 0.02 (−0.03, 0.07) | 0.04 (−0.03, 0.10) | 0.07 (−0.20, 0.33) | −0.10 (−0.49, 0.28) |
| P=0.49 | P=0.82 | P=0.12 | P=0.67 | |
| Highest attained education∥ | ||||
| LPVN/AD/RN (n=1,330) | 0.04 (−0.03, 0.10) | 0.03 (−0.04, 0.11) | 0.34 (0.00, 0.67) | −0.07 (−0.54, 0.41) |
| BA, MA, DR (n= 560) | 0.02 (−0.09, 0.13) | 0.02 (−0.10, 0.15) | −0.12 (−0.65, 0.41) | −0.38 (−1.11, 0.34) |
| P=0.77 | P=0.90 | P=0.15 | P=0.47 | |
| Cigarette smoking | ||||
| Never smoker (n= 946) | 0.02 (−0.06, 0.10) | 0.05 (−0.04, 0.14) | 0.16 (−0.25, 0.56) | 0.50 (−1.04, 0.04) |
| Ever smoker (n=1,063) | 0.04 (−0.04, 0.11) | 0.01 (−0.08, 0.09) | 0.16 (−0.21, 0.54) | 0.21 (−0.33, 0.75) |
| P=0.79 | P=0.46 | P=0.98 | P=0.07 | |
| Alcohol drinking | ||||
| Non-drinker (n= 1006) | 0.02 (−0.06, 0.10) | 0.02 (−0.07, 0.10) | 0.06 (−0.33, 0.46) | 0.02 (−0.52, 0.55) |
| Drinker (n= 924) | 0.03 (−0.05, 0.11) | 0.03 (−0.06, 0.12) | 0.25 (−0.15, 0.64) | −0.36 (−0.93, 0.21) |
| P=0.87 | P=0.79 | P=0.52 | P=0.35 | |
| Multivitamin | ||||
| Non-user (n=1546) | 0.02 (−0.04, 0.09) | 0.03 (−0.04, 0.10) | 0.19 (−0.14, 0.51) | −0.21 (−0.64, 0.23) |
| User (n= 463) | 0.05 (−0.05, 0.16) | 0.03 (−0.10, 0.15) | 0.09 (−0.44, 0.61) | 0.12 (−0.69, 0.93) |
| P=0.65 | P=0.96 | P=0.76 | P=0.49 | |
| Prevalent CVD event/Risk factors¶ | ||||
| CVD event (n=1525) | 0.01 (−0.05, 0.07) | 0.02 (−0.06, 0.09) | 0.02 (−0.31, 0.34) | −0.15 (−0.59, 0.29) |
| Risk factors (n= 484) | 0.09 (−0.01, 0.20) | 0.07 (−0.04, 0.19) | 0.63 (0.12, 1.14) | −0.06 (−0.82, 0.71) |
| P=0.19 | P=0.44 | P=0.05 | P=0.83 | |
| Incident Cardiovascular disease** | ||||
| Absent (n=1624) | 0.03 (−0.02, 0.09) | 0.03 (−0.03, 0.10) | 0.15 (−0.13, 0.43) | −0.11 (−0.50, 0.28) |
| Present (n= 385) | −0.01 (−0.14, 0.12) | 0.00 (−0.15, 0.15) | 0.31 (−0.27, 0.89) | −0.41 (−1.32, 0.50) |
| P=0.54 | P=0.72 | P=0.59 | P=0.52 | |
Characteristics as of randomization, except for incident cardiovascular disease which occurred during follow-up;
From longitudinal linear models of least square means of change in cognitive performance from baseline at each assessment and averaged over the follow-up. The number of subjects in each assessment is shown in Table 2 ; P =p value for interaction for testing effect modification in longitudinal linear models.
“Low” overall dietary vitamin B intake is defined as those with low intakes in at least one of the three B vitamins: folate (<279 mg/day) or vitamin B6 (<1.9 mg/day) or vitamin B12 (<2.4 μg/day); “Adequate” overall dietary vitamin B intake was defined as adequate intakes of all three B vitamins (folate ≥279 mg/day and vitamin B6 ≥1.9 mg/day and vitamin B12≥2.4 μg/day)
Participants with “Low” score for the global score (n=201), verbal score (n=201) and animal score (n=197) were those who were in the lowest 10% of scores; for “Low” TICS score, we used the established cutpoint of 31 (n=199).
LPVN: Licensed practical or vocational nurse; AD: Associates degree; RN: Registered nurse; BA: Bachelor's degree; MA: Masters degree; DR: Doctoral degree
“Prevalent CVD” events included myocardial infarction, stroke, revascularization procedures (percutaneous transluminal angioplasty, coronary artery bypass graft, carotid endarterectomy, and peripheral artery surgery), and symptomatic angina pectoris or transient cerebral ischemia. “Risk factors” included current tobacco use, hypertension, high cholesterol, diabetes, parental history of premature MI, or obesity (BMI ≥ 30 kg/m2)
Incident cardiovascular disease includes all non-fatal MI, non-fatal stroke, revascularization surgery, or cardiovascular death that occurred during follow-up, updated at each cognitive assessment