TABLE 3.

AL_total and AL_comp (at v₁) and their association with baseline plasma NfL and annualized change in plasma NfL between v₁ and v₃, overall and by sex and race: mixed-effects linear regression models; HANDLS, 2004–2017¹

	Overall (n = 608)	Women (n = 352)	Men (n = 256)	P sex  2	White adults (n = 257)	African American adults (n = 351)	P race  3
Model 1A
ALtotal, γ0a	−0.038 ± 0.015*	−0.029 ± 0.019	−0.039 ± 0.023	0.52	−0.005 ± 0.023	−0.057 ± 0.020**	0.15
ALtotal × Time, γ1a	+0.0066 ± 0.0018***	+0.006 ± 0.002**	+0.008 ± 0.003*	0.75	+0.004 ± 0.003	+0.008 ± 0.002**	0.25
Model 2A
ALtotal, γ0a	−0.033 ± 0.015*	−0.027 ± 0.018	−0.037 ± 0.024	0.68	−0.003 ± 0.023	−0.050 ± 0.019*	0.65
ALtotal × Time, γ1a	+0.0067 ± 0.0018***	+0.006 ± 0.002**	+0.008 ± 0.003*	0.75	+0.004 ± 0.003	+0.008 ± 0.002**	0.19
Model 1B
WHR, γ0a	+0.053 ± 0.033	+0.063 ± 0.030*	−1.247 ± 0.465**	<0.001	+0.065 ± 0.032	−1.047 ± 0.349**	0.008
WHR × Time, γ1a	+0.004 ± 0.004	+0.003 ± 0.004	+0.119 ± 0.062	0.066	+0.0035 ± 0.0040	+0.074 ± 0.045	0.084
Model 2B
WHR, γ0a	+0.053 ± 0.032	+0.064 ± 0.029*	−1.179 ± 0.474*	0.001	+0.064 ± 0.032	−0.991 ± 0.345**	0.008
WHR × Time, γ1a	+0.005 ± 0.004	+0.003 ± 0.004	+0.112 ± 0.063	0.077	+0.0034 ± 0.0039	+0.0711 ± 0.044	0.064
Model 1C
ALB, γ0a	−0.092 ± 0.064	+0.045 ± 0.078	−0.301 ± 0.106**	0.004	−0.064 ± 0.101	−0.127 ± 0.083	0.90
ALB × Time, γ1a	+0.014 ± 0.008	+0.003 ± 0.010	+0.029 ± 0.014*	0.14	+0.010 ± 0.012	+0.017 ± 0.011	0.56
Model 2C
ALB, γ0a	−0.107 ± 0.064	+0.007 ± 0.077	−0.303 ± 0.107**	0.006	−0.062 ± 0.102	−0.146 ± 0.082	0.81
ALB × Time, γ1a	+0.013 ± 0.008	+0.003 ± 0.010	+0.027 ± 0.014	0.17	+0.007 ± 0.012	+0.017 ± 0.011	0.46
Model 1D4
hsCRP, γ0a	−0.008 ± 0.008	−0.015 ± 0.010	+0.004 ± 0.014	0.19	−0.010 ± 0.012	−0.008 ± 0.011	0.90
hsCRP × Time, γ1a	+0.004 ± 0.002*	+0.006 ± 0.002**	+0.001 ± 0.003	0.059	+0.005 ± 0.003*	+0.003 ± 0.002	0.53
Model 2D4
hsCRP, γ0a	−0.008 ± 0.008	−0.015 ± 0.010	+0.003 ± 0.015	0.24	−0.010 ± 0.013	−0.018 ± 0.011	0.88
hsCRP × Time, γ1a	+0.004 ± 0.002*	+0.006 ± 0.002**	+0.001 ± 0.003	0.074	+0.005 ± 0.002*	+0.004 ± 0.002	0.54
Model 1E
HbA1c, γ0a	+0.026 ± 0.019	+0.032 ± 0.025	+0.015 ± 0.028	0.78	+0.080 ± 0.025**	−0.035 ± 0.027	0.007
HbA1c × Time, γ1a	+0.0078 ± 0.0023**	+0.0098 ± 0.0052**	+0.0061 ± 0.0036	0.35	+0.0084 ± 0.0030**	+0.0068 ± 0.0034*	0.70
Model 2E
HbA1c, γ0a	+0.030 ± 0.019	+0.030 ± 0.024	+0.021 ± 0.029	0.98	+0.076 ± 0.025**	−0.024 ± 0.028	0.021
HbA1c × Time, γ1a	+0.0076 ± 0.0023**	+0.0099 ± 0.0030**	+0.0055 ± 0.0037	0.30	+0.0088 ± 0.0029**	+0.0051 ± 0.0035	0.60
Model 1F
CHOL, γ0a	−0.0004 ± 0.0004	+0.0001 ± 0.0005	−0.0011 ± 0.0007	0.13	−0.0004 ± 0.0006	−0.0004 ± 0.0006	0.89
CHOL × Time, γ1a	+0.00014 ± 0.00005**	+0.00006 ± 0.00006	+0.00025 ± 0.00009**	0.069	+0.00016 ± 0.00007*	+0.00012 ± 0.00007	0.66
Model 2F
CHOL, γ0a	−0.0004 ± 0.0004	+0.0001 ± 0.0005	−0.0011 ± 0.0007	0.17	−0.0004 ± 0.0006	−0.0004 ± 0.0006	0.87
CHOL × Time, γ1a	+0.00014 ± 0.00005**	+0.00006 ± 0.00006	+0.00026 ± 0.00009**	0.060	+0.00017 ± 0.00007*	+0.00014 ± 0.00007	0.69
Model 1G
HDL-C, γ0a	+0.0034 ± 0.0010**	+0.0029 ± 0.0013*	+0.0037 ± 0.0017*	0.35	+0.0031 ± 0.0019	+0.0034 ± 0.0012**	0.88
HDL-C × Time, γ1a	−0.00017 ± 0.00014	−0.00030 ± 0.00016	−0.00002 ± 0.00023	0.33	−0.00010 ± 0.00024	−0.00018 ± 0.00017	0.80
Model 2G
HDL-C, γ0a	+0.0030 ± 0.0010**	+0.0025 ± 0.0013	+0.0036 ± 0.0017*	0.54	+0.0030 ± 0.0019	+0.0028 ± 0.0013*	0.89
HDL-C × Time, γ1a	−0.0002 ± 0.0001	−0.00032 ± 0.00017	−0.00001 ± 0.00024	0.31	−0.00019 ± 0.00024	−0.00013 ± 0.00017	0.81
Model 1H
RHR, γ0a	−0.0017 ± 0.0015	−0.0031 ± 0.0020	−0.00043 ± 0.0024	0.43	−0.00205 ± 0.00231	−0.0018 ± 0.0020	0.99
RHR × Time, γ1a	+0.00087 ± 0.00019***	+0.00077 ± 0.00024**	+0.00096 ± 0.00031**	0.60	+0.00069 ± 0.00028*	+0.00100 ± 0.00026***	0.47
Model 2H
RHR, γ0a	−0.0019 ± 0.0015	−0.0029 ± 0.0019	−0.0005 ± 0.0024	0.51	−0.00213 ± 0.00230	−0.0017 ± 0.0020	0.89
RHR × Time, γ1a	+0.00087 ± 0.00019***	+0.00081 ± 0.00024**	+0.00096 ± 0.00031**	0.68	+0.00062 ± 0.00028*	+0.0010 ± 0.0002***	0.46
Model 1I
SBP, γ0a	−0.0033 ± 0.0011**	−0.0037 ± 0.0013**	−0.0023 ± 0.0019	0.67	−0.0052 ± 0.0016**	−0.0013 ± 0.0016	0.023
SBP × Time, γ1a	+0.00040 ± 0.00014**	+0.00019 ± 0.00016	+0.00074 ± 0.00025**	0.062	+0.00024 ± 0.00019	+0.00056 ± 0.00020**	0.36
Model 2I
SBP, γ0a	−0.0030 ± 0.0011**	−0.0035 ± 0.0013**	−0.0020 ± 0.0010	0.64	−0.0049 ± 0.0016**	−0.0007 ± 0.0016	0.019
SBP × Time, γ1a	+0.00039 ± 0.00014**	+0.0002 ± 0.0002	+0.00070 ± 0.00026**	0.063	+0.00021 ± 0.00019	+0.00053 ± 0.00020**	0.27
Model 1J
DBP, γ0a	−0.0052 ± 0.0017**	−0.0082 ± 0.0021***	−0.0012 ± 0.0027	0.047	−0.0104 ± 0.0026***	−0.0015 ± 0.002	0.002
DBP × Time, γ1a	+0.0005 ± 0.0002*	+0.0003 ± 0.0003	+0.0007 ± 0.0003*	0.32	+0.0003 ± 0.0003	+0.00063 ± 0.00027*	0.50
Model 2J
DBP, γ0a	−0.0045 ± 0.0017**	−0.0071 ± 0.0021**	−0.0010 ± 0.0027	0.069	−0.0098 ± 0.0027***	−0.0005 ± 0.0021	0.002
DBP × Time, γ1a	+0.00048 ± 0.00021*	+0.00034 ± 0.00027	+0.00068 ± 0.00034	0.32	+0.0002 ± 0.0003	+0.00056 ± 0.00028*	0.38

¹Values are fixed effects γ ± SE. Models 1A–1J included each of v₁ AL_total and AL_comp, separately as the main predictor for v₁ NfL and NfL annualized rate of change over time, using a series of mixed-effects linear regression models, carried out in the overall population, and stratified by sex and by race, separately. These models adjusted only for age, sex, race, poverty status, educational attainment, and the inverse Mills ratio. Models 2A–2J followed a similar approach but adjusted further for selected lifestyle and health-related factors, namely current drug use, current tobacco use, Healthy Eating Index-2010, total energy intake, and the Center for Epidemiologic Studies-Depression total score. *P < 0.05; **P < 0.010; ***P < 0.001 for null hypothesis that fixed effect γ = 0. ALB, albumin; AL_comp, allostatic load continuous components; AL_total, allostatic load total score; CHOL, total cholesterol; DBP, diastolic blood pressure; HANDLS, Healthy Aging in Neighborhoods of Diversity Across the Life Span; HbA1c, glycated hemoglobin; HDL-C, HDL cholesterol; hsCRP, high-sensitivity C-reactive protein; NfL, neurofilament light chain; RHR, resting heart rate; SBP, systolic blood pressure; v₁, visit 1; v₃, visit 3; WHR, waist:hip ratio.

²Based on separate models testing the statistical significance for Sex × AL and Sex × AL × Time in models unstratified by sex or race in which these 2-way and 3-way interaction terms were included for each sociodemographic factor, separately.

³Based on separate models testing the statistical significance for Race × AL and Race × AL × Time in models unstratified by sex or race in which these 2-way and 3-way interaction terms were included for each sociodemographic factor, separately.

⁴Log_e transformed. All the continuous predictors, including main exposure variables, were centered at their respective means.