TABLE 3.
Conditional associations between each oral hypoglycemic drug class and memory over time by APOE carrier status
| Normal cognition | Amnestic MCI | AD dementia | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Beta [95% CI] | t | df | P‐value | Beta [95% CI] | t | df | P‐value | RR [95% CI] | Z | P‐value | |
| Immediate memory in APOE ε4 carriers | |||||||||||
| Met × time | 0.053 [−0.044, 0.151] | 1.07 | 720.54 | .2855 | 0.013 [−0.14, 0.166] | 0.17 | 409.87 | .8633 | 0.940 [0.866, 1.021] | −1.47 a | .1409 |
| SU × time | 0.014 [−0.055, 0.084] | 0.41 | 671.70 | .6851 | 0.123 [−0.001, 0.246] | 1.95 | 74.00 | .0548 | 1.043 [0.963, 1.131] | 1.04 a | .2998 |
| TZD × time | 0.022 [−0.038, 0.081] | 0.71 | 727.61 | .4761 | −0.052 [−0.144, 0.04] | −1.12 | 87.18 | .2668 | 1.021 [0.924, 1.128] | 0.40 a , b | .6855 |
| Gliptin × time | 0.002 [−0.057, 0.062] | 0.08 | 1067.55 | .9352 | 0.059 [−0.005, 0.124] | 1.81 | 92.86 | .0729 | 1.135 [1.030, 1.251] | 2.55 a | .0107 |
| Immediate memory in APOE ε4 non‐carriers | |||||||||||
| Met × time | 0.058 [0.006, 0.111] | 2.17 | 782.85 | .0307 | −0.029 [−0.113, 0.056] | −0.67 | 491.81 | .5061 | 1.023 [0.945, 1.106] | 0.56 a | .5770 |
| SU × time | −0.016 [−0.057, 0.026] | −0.74 | 684.48 | .4578 | 0.029 [−0.051, 0.109] | 0.72 | 145.69 | .4751 | 1.042 [0.971, 1.119] | 1.14 a | .2544 |
| TZD × time | 0.002 [−0.034, 0.037] | 0.10 | 618.77 | .9213 | 0.027 [−0.079, 0.134] | 0.51 | 116.05 | .6132 | 0.813 [0.714, 0.925] | −3.14 a , b | .0017 |
| Gliptin × time | −0.018 [−0.051, 0.015] | −1.06 | 562.89 | .2917 | 0.037 [−0.035, 0.109] | 1.01 | 108.50 | .3165 | 1.037 [0.930, 1.155] | 0.65 a | .5160 |
| Delayed memory in APOE ε4 carriers | |||||||||||
| Met × time | 0.043 [−0.053, 0.139] | 0.88 | 884.99 | .3788 | 0.051 [−0.085, 0.186] | 0.73 | 435.36 | .4641 | 0.838 [0.734, 0.956] | −2.63 a | .0086 |
| SU × time | 0.018 [−0.05, 0.086] | 0.52 | 782.99 | .6026 | 0.042 [−0.077, 0.162] | 0.69 | 177.41 | .4887 | 1.077 [0.937, 1.239] | 1.05 a | .2942 |
| TZD × time | 0.029 [−0.03, 0.087] | 0.96 | 890.46 | .3364 | 0.01 [−0.076, 0.096] | 0.23 | 129.39 | .8211 | 1.000 [0.819, 1.222] | 0.00 a | .9990 |
| Gliptin × time | 0.058 [0.000, 0.117] | 1.95 c | 1172.29 | .0511 | 0.015 [−0.046, 0.075] | 0.48 | 326.22 | .6298 | 1.189 [1.012, 1.397] | 2.11 a | .0352 |
| Delayed memory in APOE ε4 non‐carriers | |||||||||||
| Met × time | 0.086 [0.035, 0.138] | 3.27 | 935.47 | .0011 | 0.004 [−0.074, 0.082] | 0.11 | 508.85 | .9156 | 0.994 [0.861, 1.148] | −0.08 a | .9344 |
| SU × time | −0.018 [−0.058, 0.023] | −0.86 | 788.86 | .3888 | −0.023 [−0.099, 0.052] | −0.60 | 255.49 | .5471 | 0.979 [0.868, 1.105] | −0.34 a | .7312 |
| TZD × time | −0.002 [−0.037, 0.033] | −0.12 | 1042.39 | .9071 | 0.046 [−0.047, 0.138] | 0.97 | 134.91 | .3355 | 0.762 [0.610, 0.952] | −2.40 a | .0166 |
| Gliptin × time | −0.017 [−0.05, 0.016] | −1.01 c | 841.61 | .3151 | 0.024 [−0.047, 0.094] | 0.66 | 185.60 | .5115 | 1.245 [1.016, 1.527] | 2.11 a | .0350 |
Abbreviations: AD, Alzheimer's disease; APOE, apolipoprotein E; Beta, standardized coefficient; Gliptin, dipeptidyl peptidase‐4 inhibitors; MCI, mild cognitive impairment; Met, metformin; RR, rate ratio (numbers >1 imply better performance over time, numbers <1 imply poorer performance over time); SU, sulfonylurea; TZD, thiazolidinedione.
a
Mixed‐effects zero‐inflated quasi‐Poisson regression (random‐intercepts) was used.
b
Interaction between thiazolidinedione use and APOE ε4 carrier status significant (z = 2.86, P = .0042).
c
Interaction between DPP4 inhibitor use and APOE ε4 carrier status significant (t = 2.19, P = .0290).