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 4 Plasma δNfL and its relation to all-cause mortality, overall, and by sex: 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= δNfL;M= BMI
Total effect	+ 0.201 ± 0.170	0.24	+ 0.680 ± 0.386	0.079	− 0.052 ± 0.208	0.80
CDE	+ 0.264 ± 0.171	0.12	+ 0.750 ± 0.417	0.072	+ 0.090 ± 0.173	0.60
IR	− 0.043 ± 0.044	0.33	− 0.025 ± 0.086	0.77	− 0.126 ± 0.138	0.36
IM	+ 0.015 ± 0.017	0.36	+ 0.016 ± 0.060	0.79	+ 0.011 ± 0.017	0.52
PM	− 0.036 ± 0.024	0.14	− 0.064 ± 0.058	0.27	− 0.027 ± 0.032	0.40
X= δNfL;M= AL
Total effect	+ 0.229 ± 0.179	0.20	+ 0.637 ± 0.389	0.10	+ 0.056 ± 0.228	0.81
CDE	+ 0.230 ± 0.182	0.20	+ 0.567 ± 0.405	0.15	+ 0.059 ± 0.213	0.78
IR	+ 0.001 ± 0.011	0.91	+ 0.011 ± 0.050	0.82	+ 0.015 ± 0.072	0.84
IM	− 0.002 ± 0.020	0.90	+ 0.019 ± 0.052	0.71	− 0.004 ± 0.021	0.84
PM	− 0.000 ± 0.018	0.99	+ 0.019 ± 0.047	0.68	− 0.014 ± 0.023	0.55
X= δNfL;M= WHR
Total effect	+ 0.866 ± 2.644	0.74	+ 1.33 ± 5.07	0.79	+ 0.096 ± 0.249	0.70
CDE	+ 0.198 ± 0.180	0.27	+ 0.55 ± 0.57	0.34	+ 0.090 ± 0.255	0.72
IR	+ 0.798 ± 2.986	0.79	+ 0.98 ± 6.12	0.87	+ 0.019 ± 0.065	0.77
IM	− 0.117 ± 0.353	0.74	− 0.18 ± 0.90	0.84	− 0.003 ± 0.032	0.92
PM	− 0.012 ± 0.074	0.87	− 0.02 ± 0.17	0.91	− 0.011 ± 0.020	0.60
X= δNfL;M= ALB
Total effect	+ 0.107 ± 0.167	0.52	+ 0.651 ± 0.382	0.088	− 0.170 ± 0.185	0.36
CDE	+ 0.090 ± 0.170	0.60	+ 0.605 ± 0.383	0.11	− 0.133 ± 0.189	0.48
IR	+ 0.021 ± 0.058	0.71	+ 0.047 ± 0.127	0.71	− 0.026 ± 0.122	0.83
IM	− 0.005 ± 0.014	0.69	− 0.001 ± 0.011	0.94	− 0.013 ± 0.029	0.66
PM	− 0.002 ± 0.005	0.75	− 0.000 ± 0.005	0.99	+ 0.002 ± 0.007	0.80
X= δNfL;M= CRP
Total effect	+ 0.164 ± 0.175	0.35	+ 0.578 ± 0.362	0.11	− 0.032 ± 0.217	0.88
CDE	+ 0.171 ± 0.174	0.33	+ 0.669 ± 0.371	0.072	− 0.036 ± 0.228	0.88
IR	− 0.008 ± 0.002	0.65	− 0.100 ± 0.107	0.35	+ 0.008 ± 0.038	0.84
IM	− 0.000 ± 0.003	0.88	− 0.024 ± 0.037	0.52	+ 0.003 ± 0.015	0.83
PM	+ 0.001 ± 0.006	0.87	+ 0.034 ± 0.037	0.35	− 0.007 ± 0.020	0.71
X= δNfL;M= HBA1C
Total effect	+ 0.079 ± 0.183	0.67	+ 0.393 ± 0.425	0.36	− 0.091 ± 0.222	0.68
CDE	+ 0.159 ± 0.155	0.31	+ 0.470 ± 0.370	0.20	+ 0.011 ± 0.191	0.95
IR	− 0.077 ± 0.095	0.42	− 0.058 ± 0.135	0.67	− 0.103 ± 0.145	0.48
IM	+ 0.056 ± 0.023	0.014	+ 0.042 ± 0.036	0.25	+ 0.061 ± 0.034	0.071
PM	− 0.059 ± 0.041	0.15	− 0.061 ± 0.080	0.44	+ 0.059 ± 0.050	0.23
X= δNfL;M= CHOL
Total effect	+ 0.312 ± 0.195	0.11	+ 0.682 ± 0.400	0.089	+ 0.116 ± 0.244	0.64
CDE	+ 0.303 ± 0.194	0.12	+ 0.535 ± 0.381	0.16	+ 0.168 ± 0.264	0.52
IR	− 0.003 ± 0.046	0.95	+ 0.101 ± 0.147	0.49	− 0.045 ± 0.064	0.48
IM	+ 0.023 ± 0.018	0.20	+ 0.042 ± 0.046	0.37	+ 0.011 ± 0.019	0.55
PM	− 0.012 ± 0.015	0.43	+ 0.004 ± 0.025	0.87	− 0.018 ± 0.022	0.42
X= δNfL;M= HDL
Total effect	+ 0.230 ± 0.182	0.21	+ 0.699 ± 0.411	0.089	+ 0.016 ± 0.216	0.94
CDE	+ 0.222 ± 0.171	0.20	+ 0.736 ± 0.402	0.067	− 0.000 ± 0.230	1.00
IR	+ 0.002 ± 0.037	0.95	− 0.024 ± 0.180	0.89	+ 0.014 ± 0.050	0.77
IM	+ 0.001 ± 0.004	0.85	− 0.001 ± 0.012	0.97	− 0.004 ± 0.011	0.72
PM	+ 0.005 ± 0.010	0.65	− 0.013 ± 0.029	0.66	+ 0.006 ± 0.012	0.64
X= δNfL;M= RHR
Total effect	+ 0.223 ± 0.171	0.20	+ 0.599 ± 0.382	0.12	+ 0.032 ± 0.191	0.87
CDE	+ 0.220 ± 0.172	0.20	+ 0.425 ± 0.385	0.27	+ 0.062 ± 0.189	0.74
IR	− 0.022 ± 0.032	0.50	+ 0.085 ± 0.124	0.50	− 0.031 ± 0.070	0.66
IM	− 0.012 ± 0.021	0.58	+ 0.051 ± 0.056	0.36	− 0.031 ± 0.029	0.29
PM	+ 0.036 ± 0.025	0.16	+ 0.037 ± 0.049	0.45	+ 0.032 ± 0.033	0.33
X= δNfL;M= SBP
Total effect	+ 0.211 ± 0.176	0.23	+ 0.654 ± 0.389	0.093	+ 0.009 ± 0.208	0.97
CDE	+ 0.190 ± 0.181	0.29	+ 0.639 ± 0.385	0.097	− 0.0236 ± 0.221	0.92
IR	+ 0.006 ± 0.019	0.76	+ 0.005 ± 0.039	0.89	+ 0.010 ± 0.039	0.80
IM	+ 0.010 ± 0.018	0.58	+ 0.001 ± 0.041	0.83	+ 0.020 ± 0.030	0.52
PM	+ 0.005 ± 0.019	0.79	+ 0.001 ± 0.025	0.98	+ 0.003 ± 0.038	0.94
X= δNfL;M= DBP
Total effect	+ 0.248 ± 0.180	0.17	+ 0.678 ± 0.404	0.094	+ 0.043 ± 0.207	0.84
CDE	+ 0.248 ± 0.184	0.18	+ 0.682 ± 0.398	0.087	− 0.020 ± 0.230	0.93
IR	− 0.010 ± 0.024	0.68	− 0.014 ± 0.042	0.74	+ 0.031 ± 0.086	0.72
IM	− 0.005 ± 0.014	0.74	− 0.002 ± 0.018	0.93	+ 0.015 ± 0.036	0.68
PM	+ 0.015 ± 0.017	0.36	+ 0.011 ± 0.020	0.58	+ 0.017 ± 0.036	0.63
X= δNfL;M= HYPERT
Total effect	+ 0.248 ± 0.185	0.18	+ 0.666 ± 0.392	0.089	+ 0.138 ± 0.259	0.59
CDE	+ 0.322 ± 0.261	0.22	+ 0.252 ± 0.369	0.50	+ 0.377 ± 0.416	0.37
IR	− 0.089 ± 0.140	0.53	+ 0.296 ± 0.338	0.38	− 0.181 ± 0.172	0.30
IM	− 0.016 ± 0.025	0.53	+ 0.047 ± 0.059	0.43	+ 0.043 ± 0.045	0.33
PM	+ 0.031 ± 0.028	0.28	+ 0.071 ± 0.051	0.16	− 0.015 ± 0.042	0.73
X= δNfL;M= DIAB
Total effect	+ 0.153 ± 0.178	0.39	+ 0.644 ± 0.395	0.10	− 0.072 ± 0.222	0.75
CDE	+ 0.037 ± 0.237	0.88	+ 0.206 ± 0.396	0.60	− 0.190 ± 0.336	0.57
IR	+ 0.098 ± 0.096	0.31	+ 0.321 ± 0.258	0.22	+ 0.123 ± 0.134	0.36
IM	+ 0.021 ± 0.021	0.33	+ 0.093 ± 0.084	0.27	+ 0.022 ± 0.026	0.41
PM	− 0.002 ± 0.023	0.94	+ 0.023 ± 0.057	0.69	− 0.026 ± 0.028	0.37
X= δNfL;M= HYPERCHOL
Total effect	+ 0.207 ± 0.178	0.25	+ 0.552 ± 0.380	0.15	+ 0.023 ± 0.209	0.91
CDE	+ 0.128 ± 0.207	0.54	+ 0.407 ± 0.440	0.36	+ 0.003 ± 0.252	0.99
IR	+ 0.081 ± 0.078	0.30	+ 0.136 ± 0.163	0.41	+ 0.023 ± 0.083	0.79
IM	+ 0.006 ± 0.011	0.56	+ 0.023 ± 0.033	0.49	+ 0.001 ± 0.006	0.92
PM	− 0.008 ± 0.012	0.49	− 0.014 ± 0.023	0.55	− 0.004 ± 0.021	0.86
X= δNfL;M= CVD
Total effect	+ 0.203 ± 0.172	0.24	+ 0.542 ± 0.385	0.16	+ 0.047 ± 0.211	0.82
CDE	+ 0.146 ± 0.184	0.43	+ 0.485 ± 0.434	0.26	+ 0.054 ± 0.228	0.81
IR	+ 0.057 ± 0.048	0.23	+ 0.060 ± 0.109	0.58	+ 0.002 ± 0.036	0.96
IM	+ 0.011 ± 0.012	0.34	+ 0.004 ± 0.013	0.75	+ 0.001 ± 0.019	0.95
PM	− 0.010 ± 0.012	0.38	− 0.009 ± 0.017	0.64	− 0.009 ± 0.023	0.68

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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