Table 4.
Top 10 adjusted associations from model D, bilateral means of MD and FA from dMRI vs. visit 1 exposures: serum 25(OH)D, folate and cobalamin (overall and stratified analysis) with uncorrected P < 0.05: ordinary least square brain scan-wide analyses on HANDLS 2004–2009 and HANDLS-SCAN 2011–2015a.
| Outcome (vscan) | Outcome description | Exposure (v1) | Stratum | (N) | β | (SE) | P | Standardized Beta (b) | q-value | Passes FW Bonferroni correction | Standardized Beta (b): SAb | Puncorr: SA |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OVERALL | ||||||||||||
| alic_b_tr | Anterior limb of the internal capsule, Mean diffusivity, bilateral mean | FOL | __ | (240) | −5.64e-06 | (1.56e-06) | 3.8e-04 | −0.23 | 0.074d | Yes | −0.26 | 0.003 |
| cgc_b_fa | Cingulum (Cingulate Gyrus), fractional anisotropy, bilateral mean | 25(OH)D | __ | (185) | +0.0007 | (0.0002) | 4.1e-04 | +0.31 | 0.074d | Yes | +0.28 | 0.002 |
| alic_b_fa | Anterior limb of the internal capsule, fractional anisotropy, bilateral mean | 25(OH)D | __ | (185) | +0.0006 | (0.0002) | 9.7e-04 | +0.29 | 0.12d | No | +0.22 | 0.005 |
| mcp_b_tr | Middle cerebellar peduncle, mean diffusivity, bilateral mean | B-12 | __ | (240) | −1.45e-07 | (4.81e-08) | 2.8e-03 | −0.19 | 0.22 | No | −0.18 | 0.019 |
| mfowm_b_tr | Middle Fronto-Orbital WM, mean diffusivity, bilateral mean | FOL | __ | (240) | −5.68e-06 | (1.93e-06) | 3.7e-03 | −0.19 | 0.22 | No | −0.23 | 0.019 |
| cgh_b_fa | Cingulum (Hippocampus), fractional anisotropy, bilateral mean | 25(OH)D | __ | (185) | +0.0006 | (0.0002) | 3.9e-03 | +0.25 | 0.22 | No | +0.21 | 0.023 |
| icp_b_fa | Inferior cerebellar peduncle, fractional anisotropy, bilateral mean | FOL | __ | (240) | +0.0009 | (0.0003) | 4.5e-03 | +0.19 | 0.22 | No | +0.22 | 0.015 |
| ss_b_fa | Sagittal Stratum, fraction anisotropy, bilateral mean | 25(OH)D | __ | (185) | +0.0004 | (0.0002) | 4.9e-03 | +0.25 | 0.22 | No | +0.20 | 0.010 |
| mowm_b_tr | Middle Occipital WM, mean diffusivity, bilateral mean | FOL | __ | (240) | −4.13e-06 | (1.50e-06) | 6.5e-03 | −0.18 | 0.22 | No | −0.17 | 0.024 |
| put_b_tr | Putamen, mean diffusivity, bilateral mean | FOL | __ | (240) | −4.22e-06 | (1.54e-06) | 6.5e-03 | −0.18 | 0.22 | No | −0.26 | 0.004 |
| STRATIFIED | ||||||||||||
| alic_b_fa | Anterior limb of the internal capsule, fractional anisotropy, bilateral mean | 25(OH)D | Whites | (109) | +0.0009 c | (0.0002) | 8.6e-05 | +0.37 | 0.11d | No | +0.32 | 0.001 |
| bcc_b_tr | Body of corpus callosum, Mean diffusivity, bilateral mean | 25(OH)D | BP | (52) | −0.00002 c | (4.43e-06) | 8.7e-05 | −0.53 | 0.11d | No | −0.61 | 0.001 |
| cgc_b_fa | Cingulum (Cingulate Gyrus), fractional anisotropy, bilateral mean | 25(OH)D | Whites | (109) | +0.0008 | (0.0002) | 1.1e-04 | +0.39 | 0.11d | No | +0.36 | < 0.001 |
| sowm_b_fa | Superior Occipital WM, fractional anisotropy, bilateral mean | FOL | Males | (103) | +0.0016 c | (0.0004) | 2.1e-04 | +0.39 | 0.12d | No | +0.31 | 0.007 |
| unc_b_tr | Uncinate Fasciculus, mean diffusivity, bilateral mean | FOL | AA | (98) | 2.2e-04c | (2.33e-06) | 3.4e-04 | −0.40 | 0.12d | No | −0.39 | 0.004 |
| alic_b_tr | Anterior limb of the internal capsule, Mean diffusivity, bilateral mean | FOL | AP | (163) | −6.44e-06 | 1.72e-06 | 4.6e-04 | −0.27 | 0.12d | No | −0.30 | 0.004 |
| scc_b_tr | Splenium of Corpus Callosum, Mean diffusivity, bilateral mean | 25(OH)D | BP | (52) | −0.000015 c | (3.80e-06) | 3.0e-04 | −0.50 | 0.12d | No | −0.63 | 0.001 |
| sowm_b_tr | Superior Occipital WM, mean diffusivity, bilateral mean | FOL | Males | (103) | −0.00001c | (3.53e-06) | 4.6e-04 | −0.37 | 0.15d | No | −0.38 | < 0.001 |
| alic_b_tr | Anterior limb of the internal capsule, Mean diffusivity, bilateral mean | FOL | >50 years | (96) | −0.00001c | (2.92e-06) | 2.8e-04 | −0.36 | 0.15d | No | −0.44 | 0.011 |
| cgc_b_fa | Cingulum (Cingulate Gyrus), fractional anisotropy, bilateral mean | 25(OH)D | BP | (52) | +0.00150 | 0.00040 | 5.8e-04 | +0.57 | 0.17d | No | +0.59 | 0.003 |
25(OH)D, 25-hydroxyvitamin D; AP, Above poverty; B-12, serum cobalamin (vitamin B-12); FOL, serum folate; FWER, FamilyWise Error Rate; GM, Gray Matter; SA, Sensitivity Analysis; SE, Standard Error; WM, White Matter.
Values are adjusted linear regression coefficients β with associated SE, standardized beta, uncorrected p-values, corrected q-values (false discovery rate) and results of sensitivity analysis. (N) is the sample size in each analysis. Bolded rows correspond to statistically significant associations after correction for multiple testing, FWER < 0.05.
Based on a sensitivity analysis further adjusting for selected socio-demographic, lifestyle and health-related factors after screening using machine learning techniques (see Supplemental Methods 2). Note that for visit 1 25(OH)D, no additional covariates were selected. For Folate and B-12 a reduced set of additional covariates were included and are listed in Supplemental Methods 2.
P < 0.10 for null hypothesis that exposure × stratifying variable 2-way interaction term is =0 in the unstratified model with exposure and socio-demographic factors included as main effects.
Finding considered a trend for passing FDR q-value correction at type I error of 0.10 per vitamin, model and stratification status while failing the FWER criterion, due to a standardized effect size (in absolute value) ≥0.20.