Race, APOE genotypes, and cognitive decline among middle-aged urban adults

Beydoun, May A.; Weiss, Jordan; Beydoun, Hind A.; Hossain, Sharmin; Maldonado, Ana I.; Shen, Botong; Evans, Michele K.; Zonderman, Alan B.

doi:10.1186/s13195-021-00855-y

Alzheimer's Research & Therapy

Table 2 APOE2 and APOE4 allelic dosages and their association with cognitive performance at v1 and change over time: overall and race-specific mixed-effects linear regression models: HANDLS 2004–2013

From: Race, APOE genotypes, and cognitive decline among middle-aged urban adults

	APOE2 allelic dosage		APOE4 allelic dosage
	Model 1	Model 2	Model 1	Model 2
	γ ± SE	γ ± SE	γ ± SE	γ ± SE
Overall	(N = 1770, k = 1.7)	(N = 1770, k = 1.7)	(N = 1770, k = 1.7)	(N = 1770, k = 1.7)
Outcome = Cognitive performance test score
Normalized MMSE
Exposure, γ_0a	− 0.652 ± 0.813	− 0.129 ± 0.696	+ 0.041 ± 0.616	− 0.082 ± 0.528
Exposure × TIME, γ_1a	− 0.394 ± 0.202*	− 0.429 ± 0.196*	+ 0.190 ± 0.153	+ 0.175 ± 0.149
CVLT-List A
Exposure, γ_0a	− 0.290 ± 0.369	− 0.150 ± 0.343	+ 0.151 ± 0.282	+ 0.121 ± 0.263
Exposure × TIME, γ_1a	+ 0.081 ± 0.100	+ 0.054 ± 0.099	− 0.111 ± 0.076 ^b	− 0.121 ± 0.076 ^b
CVLT-DFR
Exposure, γ_0a	− 0.211 ± 0.173	− 0.164 ± 0.163	− 0.001 ± 0.132	− 0.037 ± 0.125
Exposure × TIME, γ_1a	+ 0.081 ± 0.041	+ 0.073 ± 0.041	− 0.025 ± 0.032 ^b	− 0.024 ± 0.032 ^b
BVRT
Exposure, γ_0a	− 0.167 ± 0.269	− 0.203 ± 0.250	+ 0.359 ± 0.203	+ 0.376 ± 0.190*
Exposure × TIME, γ_1a	+ 0.066 ± 0.062	+ 0.058 ± 0.062	− 0.020 ± 0.047	− 0.018 ± 0.047
BTA
Exposure, γ_0a	+ 0.011 ± 0.122	+ 0.039 ± 0.116	− 0.094 ± 0.092	− 0.079 ± 0.087
Exposure × TIME, γ_1a	+ 0.007 ± 0.029	+ 0.007 ± 0.029	+ 0.031 ± 0.022 ^b	+ 0.029 ± 0.022 ^b
AF
Exposure, γ_0a	− 0.053 ± 0.292	+ 0.041 ± 0.276	+ 0.094 ± 0.221	+ 0.044 ± 0.209
Exposure × TIME, γ_1a	− 0.063 ± 0.057	− 0.064 ± 0.057	− 0.001 ± 0.043	− 0.001 ± 0.044
DS-F
Exposure, γ_0a	− 0.037 ± 0.121	+ 0.001 ± 0.110	− 0.004 ± 0.092	− 0.024 ± 0.084
Exposure × TIME, γ_1a	+ 0.005 ± 0.024	+ 0.007 ± 0.024	+ 0.039 ± 0.018*	+ 0.038 ± 0.018*
DS-B
Exposure, γ_0a	− 0.093 ± 0.119	− 0.051 ± 0.106	0.054 ± 0.090	+ 0.043 ± 0.080
Exposure × TIME, γ_1a	− 0.002 ± 0.024	− 0.003 ± 0.024	0.005 ± 0.019	+ 0.001 ± 0.018
CDT
Exposure, γ_0a	+ 0.011 ± 0.067	+ 0.017 ± 0.065	− 0.039 ± 0.051	− 0.042 ± 0.050
Exposure × TIME, γ_1a	− 0.011 ± 0.018	− 0.011 ± 0.018	− 0.009 ± 0.014	− 0.010 ± 0.014
TRAILS A
Exposure, γ_0a	− 1.876 ± 2.248	− 1.626 ± 2.237	+ 0.699 ± 1.700	+ 0.702 ± 1.694
Exposure × TIME, γ_1a	0.685 ± 0.688	+ 0.643 ± 0.689	− 0.191 ± 0.524	− 0.261 ± 0.525
TRAILS B
Exposure, γ_0a	+ 2.899 ± 8.257	+ 1.548 ± 7.698	+ 2.330 ± 6.243 ^a	+ 2.434 ± 5.826^a
Exposure × TIME, γ_1a	− 1.362 ± 1.922	− 1.570 ± 1.925	0.110 ± 1.456 ^b	+ 0.130 ± 1.461^b
Whites	(N = 794, k = 1.8)	(N = 794, k = 1.7)	(N = 794, k = 1.8)	(N = 794, k = 1.7)
Outcome = Cognitive performance test score
Normalized MMSE
Exposure, γ_0a	− 0.160 ± 1.368	− 0.390 ± 1.112	+ 0.371 ± 1.043	+ 0.334 ± 0.853
Exposure × TIME, γ_1a	− 0.402 ± 0.356	− 0.366 ± 0.344	+ 0.291 ± 0.260^d	+ 0.337 ± 0.254
CVLT-List A
Exposure, γ_0a	+ 0.528 ± 0.645	+ 0.442 ± 0.592	+ 0.414 ± 0.495	+ 0.446 ± 0.454
Exposure × TIME, γ_1a	+ 0.062 ± 0.192	+ 0.047 ± 0.189	− 0.370 ± 0.139**	− 0.363 ± 0.137**
CVLT-DFR
Exposure, γ_0a	+ 0.115 ± 0.297	+ 0.074 ± 0.278	+ 0.070 ± 0.228	+ 0.080 ± 0.213
Exposure × TIME, γ_1a	+ 0.103 ± 0.078	+ 0.105 ± 0.077	− 0.127 ± 0.057*	− 0.115 ± 0.056*
BVRT
Exposure, γ_0a	+ 0.121 ± 0.421	+ 0.218 ± 0.364	+ 0.346 ± 0.321	+ 0.291 ± 0.278
Exposure × TIME, γ_1a	+ 0.090 ± 0.098	+ 0.106 ± 0.097	+ 0.053 ± 0.071	+ 0.044 ± 0.071
BTA
Exposure, γ_0a	− 0.041 ± 0.197	− 0.062 ± 0.186	− 0.086 ± 0.147	− 0.050 ± 0.139
Exposure × TIME, γ_1a	0.040 ± 0.051^d	+ 0.024 ± 0.050^d	− 0.043 ± 0.038	− 0.043 ± 0.037
AF
Exposure, γ_0a	+ 0.562 ± 0.507	+ 0.460 ± 0.461	+ 0.212 ± 0.387	+ 0.263 ± 0.350
Exposure × TIME, γ_1a	− 0.065 ± 0.108	− 0.083 ± 0.110	− 0.032 ± 0.079	− 0.026 ± 0.080
DS-F
Exposure, γ_0a	− 0.038 ± 0.207	− 0.099 ± 0.181	− 0.198 ± 0.158	− 0.215 ± 0.137
Exposure × TIME, γ_1a	− 0.004 ± 0.045	− 0.010 ± 0.046	0.046 ± 0.033	+ 0.047 ± 0.034
DS-B
Exposure, γ_0a	− 0.100 ± 0.211	− 0.172 ± 0.181	+ 0.045 ± 0.162	+ 0.041 ± 0.139
Exposure × TIME, γ_1a	+ 0.003 ± 0.044	+ 0.002 ± 0.043	+ 0.022 ± 0.033	+ 0.015 ± 0.032
CDT
Exposure, γ_0a	− 0.021 ± 0.105	− 0.050 ± 0.104	− 0.022 ± 0.083	− 0.011 ± 0.080
Exposure × TIME, γ_1a	− 0.039 ± 0.031^d	− 0.043 ± 0.031	− 0.038 ± 0.023	− 0.032 ± 0.023
TRAILS A
Exposure, γ_0a	− 1.800 ± 2.293	− 1.139 ± 2.250	2.521 ± 1.751	+ 2.428 ± 1.715
Exposure × TIME, γ_1a	+ 0.096 ± 0.755	+ 0.095 ± 0.754	− 0.379 ± 0.556	− 0.491 ± 0.555
TRAILS B
Exposure, γ_0a	+ 3.770 ± 11.488	+ 7.185 ± 10.406	+ 19.112 ± 8.730*	+ 19.258 ± 7.937*
Exposure × TIME, γ_1a	− 3.513 ± 2.701	− 3.187 ± 2.663	− 4.140 ± 2.000*	− 4.408 ± 1.981*
African American	(N = 976, k = 1.8)	(N = 976, k = 1.8)	(N = 976, k = 1.8)	(N = 976, k = 1.8)
Outcome = Cognitive performance test score
MMSE
Exposure, γ_0a	− 1.094 ± 1.005	− 0.079 ± 0.894	− 0.09 ± 0.758	− 0.274 ± 0.675
Exposure × TIME, γ_1a	− 0.360 ± 0.246	− 0.432 ± 0.242	+ 0.139 ± 0.190	+ 0.110 ± 0.186
CVLT-List A
Exposure, γ_0a	− 0.767 ± 0.437	− 0.472 ± 0.413	+ 0.077 ± 0.335	+ 0.044 ± 0.316
Exposure × TIME, γ_1a	+ 0.104 ± 0.115	+ 0.073 ± 0.115	+ 0.016 ± 0.089	+ 0.004 ± 0.089
CVLT-DFR
Exposure, γ_0a	− 0.405 ± 0.209	− 0.314 ± 0.200	− 0.015 ± 0.160	− 0.022 ± 0.153
Exposure × TIME, γ_1a	+ 0.078 ± 0.048	+ 0.072 ± 0.048	+ 0.027 ± 0.038	+ 0.020 ± 0.038
BVRT
Exposure, γ_0a	− 0.322 ± 0.348	− 0.423 ± 0.336	+ 0.293 ± 0.262	+ 0.342 ± 0.253
Exposure × TIME, γ_1a	0.058 ± 0.083	+ 0.042 ± 0.083	− 0.053 ± 0.064	− 0.046 ± 0.064
BTA
Exposure, γ_0a	0.027 ± 0.156	+ 0.089 ± 0.150	− 0.088 ± 0.118	− 0.086 ± 0.114
Exposure × TIME, γ_1a	− 0.005 ± 0.036	− 0.005 ± 0.036	+ 0.065 ± 0.028*,^d	+ 0.064 ± 0.028*^,d
AF
Exposure, γ_0a	− 0.383 ± 0.347	− 0.257 ± 0.338	+ 0.087 ± 0.262	+ 0.038 ± 0.255
Exposure × TIME, γ_1a	− 0.061 ± 0.066	− 0.050 ± 0.066	+ 0.032 ± 0.054	+ 0.006 ± 0.051
DS-F
Exposure, γ_0a	− 0.044 ± 0.148	+ 0.021 ± 0.139	+ 0.117 ± 0.111	+ 0.095 ± 0.105
Exposure × TIME, γ_1a	+ 0.004 ± 0.028	+ 0.007 ± 0.028	+ 0.033 ± 0.021	+ 0.032 ± 0.021
DS-B
Exposure, γ_0a	− 0.100 ± 0.139	− 0.014 ± 0.127	+ 0.060 ± 0.105	+ 0.045 ± 0.096
Exposure × TIME, γ_1a	− 0.006 ± 0.029	− 0.009 ± 0.029	− 0.002 ± 0.022	− 0.006 ± 0.022
CDT
Exposure, γ_0a	+ 0.033 ± 0.086	+ 0.060 ± 0.084	− 0.041 ± 0.065	− 0.043 ± 0.064^c
Exposure × TIME, γ_1a	− 0.002 ± 0.022^d	− 0.003 ± 0.022^d	+ 0.005 ± 0.017^d	+ 0.003 ± 0.017^d
TRAILS A
Exposure, γ_0a	− 1.798 ± 3.475	− 1.611 ± 3.472	− 0.322 ± 2.610	− 0.167 ± 2.612
Exposure × TIME, γ_1a	+ 1.004 ± 1.023	+ 0.985 ± 1.030	− 0.089 ± 0.790	− 0.100 ± 0.793
TRAILS B
Exposure, γ_0a	+ 3.643 ± 11.608	− 1.801 ± 10.944	− 7.672 ± 8.726	− 6.498 ± 8.229
Exposure × TIME, γ_1a	− 0.761 ± 2.638	− 1.087 ± 2.651	+ 2.928 ± 2.162	+ 2.710 ± 2.021

Abbreviations: AF animal fluency, APOE Apolipoprotein E genotype, BMI body mass index, BTA Brief Test of Attention, BVRT Benton Visual Retention Test, CDT Clock Drawing Test, CES-D Center for Epidemiologic Studies-Depression, CVLT-DFR California Verbal Learning Test-Delayed Free Recall, CVLT-List A California Verbal Learning Test-List A, DS-B Digits Span-Backward, DS-F Digits Span-Forward, HANDLS Healthy Aging in Neighborhood of Diversity across the Lifespan, HEI-2010 Healthy Eating Index, 2010 version, HS high school, MMSE Mini-Mental State Examination, SD Standard Deviation, TRAILS A Trailmaking Test, Part A, TRAILS B Trailmaking Test, part B, WRAT-3 Wide Range Achievement Test, 3rd revision, X mean
Models 1A.1-1K included each of APOE2 or APOE4 allelic dosages, separately as the main predictor for v1 cognitive performance and cognitive change over time (11 test scores), using a series of mixed-effects linear regression models, carried out in the overall population and stratified by race. These models adjusted only for age, sex, race, poverty status, and the inverse mills ratio. Models 2A.1-2K followed a similar approach but adjusted further for selected socio-demographic, lifestyle, and health-related factors, namely educational attainment, the WRAT-3 score, current drug use, current tobacco use, body mass index, self-rated health, co-morbidity index, HEI-2010, total energy intake, and the CES-D total score
^a p < 0.05 for Race × (APOE2 or APOE4) in models that are unstratified by race to which this 2-way interaction was included
^b p < 0.05 for Race × (APOE2 or APOE4) × TIME in models that are unstratified by race to which this 3-way interaction was included
^c p < 0.05 for Sex × (APOE2 or APOE4) in models that are stratified by race to which this 2-way interaction was included
^d p < 0.05 for Sex × (APOE2 or APOE4) × TIME in models that are stratified by race to which this 3-way interaction was included
*p < 0.05; **p < 0.01, test for null hypothesis of γ = 0. Bolded values passed correction for multiple testing

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ISSN: 1758-9193

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