Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women

Beydoun, May A.; Noren Hooten, Nicole; Weiss, Jordan; Beydoun, Hind A.; Hossain, Sharmin; Evans, Michele K.; Zonderman, Alan B.

doi:10.1186/s12916-022-02425-x

Table 3 Plasma NfL_v1 and its relation to all-cause mortality among women: mediating and interactive effects of BMI, AL, and co-morbidity index using 4-way decomposition^a,b,c

From: Plasma neurofilament light and its association with all-cause mortality risk among urban middle-aged men and women

	Overall (N = 694), β ± SE	P	Women (N = 401), β ± SE	P	Men (N = 293), β ± SE	P
X= NfL_v1;M= BMI
Total effect	+ 0.397 ± 0.264	0.13	+ 0.877 ± 0.602	0.15	+ 0.138 ± 0.345	0.69
CDE	+ 0.173 ± 0.222	0.44	+ 0.712 ± 0.465	0.13	− 0.073 ± 0.228	0.75
IR	+ 0.083 ± 0.090	0.36	− 0.048 ± 0.191	0.80	+ 0.089 ± 0.198	0.65
IM	+ 0.106 ± 0.071	0.14	+ 0.276 ± 0.207	0.18	+ 0.031 ± 0.073	0.67
PM	+ 0.035 ± 0.050	0.48	− 0.064 ± 0.094	0.50	+ 0.090 ± 0.065	0.16
X= NfL_v1;M= AL
Total effect	+ 0.283 ± 0.220	0.20	+ 0.835 ± 0.585	0.15	+ 0.120 ± 0.267	0.65
CDE	+ 0.282 ± 0.219	0.20	+ 0.857 ± 0.586	0.14	− 0.009 ± 0.253	0.97
IR	+ 0.000 ± 0.011	1.00	− 0.013 ± 0.037	0.72	+ 0.079 ± 0.115	0.49
IM	+ 0.004 ± 0.015	0.80	+ 0.004 ± 0.018	0.84	+ 0.033 ± 0.036	0.36
PM	− 0.003 ± 0.015	0.83	− 0.011 ± 0.021	0.59	+ 0.017 ± 0.032	0.61
X= NfL_v1;M= WHR
Total effect	+ 0.540 ± 2.051	0.79	+ 0.592 ± 1.976	0.76	+ 0.097 ± 0.307	0.75
CDE	+ 0.246 ± 0.246	0.32	+ 0.609 ± 1.02	0.55	+ 0.068 ± 0.293	0.82
IR	+ 0.400 ± 2.391	0.87	+ 0.114 ± 1.672	0.95	+ 0.005 ± 0.059	0.93
IM	− 0.095 ± 0.360	0.79	− 0.051 ± 0.429	0.91	+ 0.008 ± 0.041	0.84
PM	− 0.012 ± 0.099	0.91	− 0.080 ± 0.294	0.79	+ 0.016 ± 0.030	0.61
X= NfL_v1;M= ALB
Total effect	+ 0.239 ± 0.210	0.25	+ 0.728 ± 0.485	0.13	− 0.002 ± 0.242	1.00
CDE	+ 0.236 ± 0.214	0.27	+ 0.773 ± 0.484	0.11	− 0.007 ± 0.250	0.98
IR	− 0.003 ± 0.026	0.91	− 0.039 ± 0.069	0.58	− 0.041 ± 0.060	0.50
IM	+ 0.019 ± 0.022	0.42	− 0.010 ± 0.022	0.66	+ 0.046 ± 0.034	0.17
PM	− 0.011 ± 0.021	0.61	+ 0.003 ± 0.015	0.85	− 0.000 ± 0.049	0.99
X= NfL_v1;M= CRP
Total effect	+ 0.376 ± 0.245	0.13	+ 0.829 ± 0.585	0.16	+ 0.132 ± 0.289	0.65
CDE	+ 0.399 ± 0.244	0.10	+ 1.109 ± 0.543	0.041	+ 0.045 ± 0.310	0.88
IR	− 0.017 ± 0.029	0.55	− 0.274 ± 0.162	0.091	+ 0.074 ± 0.110	0.50
IM	+ 0.015 ± 0.022	0.49	+ 0.064 ± 0.058	0.27	+ 0.025 ± 0.029	0.39
PM	− 0.021 ± 0.021	0.32	− 0.071 ± 0.053	0.18	− 0.013 ± 0.022	0.57
X= NfL_v1;M= HBA1C
Total effect	+ 0.275 ± 0.222	0.22	+ 0.884 ± 0.565	0.12	+ 0.082 ± 0.277	0.77
CDE	+ 0.264 ± 0.224	0.24	+ 0.864 ± 0.564	0.13	+ 0.084 ± 0.278	0.76
IR	− 0.001 ± 0.012	0.94	− 0.007 ± 0.022	0.74	+ 0.001 ± 0.023	0.98
IM	+ 0.001 ± 0.008	0.93	+0.003 ± 0.015	0.82	− 0.005 ± 0.014	0.74
PM	+ 0.011 ± 0.014	0.43	+ 0.023 ± 0.024	0.34	+ 0.002 ± 0.016	0.89
X= NfL_v1;M= CHOL
Total effect	+ 0.244 ± 0.220	0.27	+ 0.727 ± 0.478	0.13	− 0.002 ± 0.277	0.99
CDE	+ 0.247 ± 0.219	0.26	+ 0.715 ± 0.481	0.14	+ 0.043 ± 0.258	0.87
IR	− 0.000 ± 0.015	0.98	+ 0.017 ± 0.059	0.78	− 0.053 ± 0.071	0.46
IM	− 0.007 ± 0.012	0.59	− 0.002 ± 0.008	0.83	− 0.030 ± 0.038	0.43
PM	+ 0.004 ± 0.014	0.79	− 0.003 ± 0.012	0.81	+ 0.037 ± 0.041	0.36
X= NfL_v1;M= HDL
Total effect	+ 0.436 ± 0.280	0.12	+ 1.166 ± 0.714	0.10	+ 0.106 ± 0.332	0.75
CDE	+ 0.298 ± 0.239	0.21	+ 0.672 ± 0.484	0.17	+ 0.083 ± 0.330	0.80
IR	+ 0.072 ± 0.072	0.32	+ 0.365 ± 0.311	0.24	− 0.007 ± 0.036	0.85
IM	+ 0.050 ± 0.038	0.20	+ 0.104 ± 0.098	0.29	+ 0.010 ± 0.060	0.87
PM	+ 0.016 ± 0.024	0.50	+ 0.026 ± 0.036	0.47	− 0.020 ± 0.041	0.63
X= NfL_v1;M= RHR
Total effect	+ 0.310 ± 0.229	0.18	+ 0.725 ± 0.515	0.16	+ 0.215 ± 0.327	0.51
CDE	+ 0.348 ± 0.239	0.15	+ 0.757 ± 0.530	0.15	+ 0.228 ± 0.324	0.48
IR	− 0.029 ± 0.040	0.47	+ 0.020 ± 0.085	0.81	− 0.013 ± 0.113	0.91
IM	+ 0.004 ± 0.009	0.66	− 0.015 ± 0.025	0.55	+ 0.005 ± 0.029	0.87
PM	− 0.014 ± 0.016	0.39	− 0.037 ± 0.037	0.32	− 0.004 ± 0.020	0.84
X= NfL_v1;M= SBP
Total effect	+ 0.247 ± 0.225	0.27	+ 0.759 ± 0.495	0.13	+ 0.046 ± 0.278	0.87
CDE	+ 0.257 ± 0.227	0.26	+ 0.769 ± 0.495	0.12	+ 0.044 ± 0.284	0.88
IR	+ 0.003 ± 0.012	0.83	− 0.000 ± 0.008	0.97	+ 0.015 ± 0.058	0.79
IM	− 0.006 ± 0.017	0.71	+ 0.001 ± 0.037	0.99	− 0.009 ± 0.021	0.67
PM	− 0.007 ± 0.021	0.76	− 0.010 ± 0.049	0.84	− 0.003 ± 0.019	0.88
X= NfL_v1;M= DBP
Total effect	+ 0.268 ± 0.218	0.22	+ 0.812 ± 0.529	0.13	+ 0.093 ± 0.280	0.74
CDE	+ 0.291 ± 0.221	0.19	+ 0.912 ± 0.558	0.10	+ 0.111 ± 0.290	0.70
IR	− 0.002 ± 0.030	0.95	+ 0.029 ± 0.090	0.75	− 0.015 ± 0.072	0.83
IM	− 0.001 ± 0.021	0.97	− 0.090 ± 0.096	0.34	+ 0.001 ± 0.008	0.88
PM	− 0.020 ± 0.021	0.33	− 0.038 ± 0.057	0.51	− 0.004 ± 0.013	0.76
X= NfL_v1;M= HYPERT
Total effect	+ 0.288 ± 0.217	0.19	+ 0.729 ± 0.489	0.14	+ 0.077 ± 0.271	0.78
CDE	+ 0.080 ± 0.232	0.73	+ 0.096 ± 0.347	0.78	+ 0.174 ± 0.354	0.62
IR	+ 0.199 ± 0.159	0.21	+ 0.600 ± 0.379	0.11	− 0.092 ± 0.167	0.58
IM	+ 0.006 ± 0.013	0.64	+ 0.020 ± 0.053	0.71	− 0.003 ± 0.010	0.76
PM	+ 0.003 ± 0.008	0.69	+ 0.013 ± 0.034	0.71	− 0.002 ± 0.008	0.81
X= NfL_v1;M= DIAB
Total effect	+ 0.370 ± 0.244	0.13	+ 0.714 ± 0.485	0.14	+ 0.158 ± 0.314	0.62
CDE	+ 0.484 ± 0.295	0.10	+ 0.760 ± 0.501	0.13	+ 0.314 ± 0.431	0.47
IR	− 0.117 ± 0.120	0.32	+ 0.032 ± 0.225	0.89	− 0.174 ± 0.175	0.32
IM	+ 0.016 ± 0.019	0.38	− 0.007 ± 0.051	0.89	+ 0.012 ± 0.020	0.56
PM	− 0.014 ± 0.019	0.46	− 0.070 ± 0.057	0.21	+ 0.006 ± 0.014	0.68
X= NfL_v1;M= HYPERCHOL
Total effect	+ 0.279 ± 0.244	0.25	+ 0.637 ± 0.481	0.19	+ 0.137 ± 0.338	0.69
CDE	+ 0.270 ± 0.300	0.37	+ 0.566 ± 0.528	0.28	+ 0.182 ± 0.414	0.66
IR	+ 0.006 ± 0.089	0.95	+ 0.078 ± 0.141	0.58	− 0.047 ± 0.091	0.61
IM	− 0.001 ± 0.006	0.83	− 0.010 ± 0.021	0.64	+ 0.000 ± 0.007	0.99
PM	+ 0.004 ± 0.009	0.67	+ 0.003 ± 0.018	0.87	+ 0.002 ± 0.020	0.94
X= NfL_v1;M= CVD
Total effect	+ 0.158 ± 0.213	0.46	+ 0.362 ± 0.414	0.38	+ 0.055 ± 0.282	0.85
CDE	+ 0.078 ± 0.230	0.73	+ 0.260 ± 0.446	0.56	+ 0.007 ± 0.285	0.98
IR	+ 0.080 ± 0.053	0.13	+ 0.102 ± 0.122	0.41	+ 0.049 ± 0.057	0.40
IM	+ 0.002 ± 0.011	0.87	+ 0.002 ± 0.019	0.90	+ 0.000 ± 0.011	1.00
PM	− 0.002 ± 0.012	0.84	− 0.003 ± 0.024	0.90	− 0.000 ± 0.009	0.99

Abbreviations: AL allostatic load, ALB albumin, BMI body mass index, CDE controlled direct effect, CES-D Center for Epidemiological Studies-Depression, CHOL total cholesterol, CRP C-reactive protein (high sensitivity), Log_e transformed, CVD cardiovascular disease, DBP diastolic blood pressure, DIAB diabetes, HBA1C glycated hemoglobin, HDL high-density lipoprotein cholesterol, HEI-2010 Healthy Eating Index-2010 version, HYPERT hypertension, HYPERCHOL hypercholesterolemia, IM interaction, mediated, IR interaction, reference, M mediators/effect modifier, NfL plasma neurofilament light chain, Log_e transformed, PM pure mediation, RHR resting heart rate, SBP systolic blood pressure, WHR waist-hip ratio, X exposure
^aSee the “Methods” section and Table 1 for the definition of each NfL exposure (i.e., NfLv1 and δNfL). All exposures (X) and potential mediators/effect modifiers (M) were z-scored for ease of interpretation, with the exception of binary M (coded as 0/1), namely DIAB, HYPERT, HYPERCHOL, and CVD. Control variables were set at their means
^bCox models for which 4-way decomposition was conducted are equivalent to model 2 (Table 2), for continuous exposures, to which M was added and considered as a potential mediator/effect modifier. Control variables included age at v1, sex, race, poverty status, education, HEI-2010 total score, mean energy intake (kcal/day), current tobacco use, current illicit drug use, the CES-D total score, and the inverse mills ratio
^cTotal effects are beta = Log_e(HR) ± SE with associated p-values from Cox PH hazards models associated with each NfL exposure of interest. Hazard ratio (HR) point estimates the exponent of beta. 95% CI for HR can be calculated as follows: lower confidence limit (LCL): exp[Log_eHR − 1.96×SE(Log_eHR)]; upper confidence limit (UCL): exp[Log_eHR + 1.96×SE(Log_eHR)]

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