TABLE 2.
Association between the genotype and the annual change in Mini–Mental State Examination (MMSE) score
| Genotype | Genotype carriers, N (%)a | Main effectb β (95% CI) | P | Interaction with timeb β (95% CI) | P |
|---|---|---|---|---|---|
| APOE-ε4 | |||||
| ε4 Non-carriers | 661 (70.3) | Ref. | Ref. | ||
| ε4 Carriers | 279 (29.7) | −1.07 (−2.90–0.75) | 0.249 | −0.81 (−1.40–−0.21) | 0.008 |
| APOE-ε4 subgroupsc | |||||
| Carriers of one ε4 allele | 259 (27.6) | −1.25 (−3.12–0.63) | 0.192 | −0.81 (−1.42–−0.20) | 0.009 |
| Carriers of two ε4 alleles | 20 (2.1) | 1.17 (−4.67–7.00) | 0.695 | −0.76 (−2.69–1.18) | 0.443 |
| GBA | |||||
| Non-carriers | 862 (89.7) | Ref. | Ref. | ||
| GBA mutation carriersd | 99 (10.3) | −0.07 (−2.77–2.62) | 0.958 | −1.28 (−2.12–−0.44) | 0.003 |
| GBA subgroupsc | |||||
| Risk or mild mutation carriers | 79 (8.3) | 0.97 (−2.00–3.94) | 0.523 | −1.14 (−2.06–−0.22) | 0.015 |
| Severe mutation carriers | 14 (1.5) | −7.79 (−14.66–0.91) | 0.026 | −1.43 (−3.63–0.77) | 0.202 |
| MAPT | |||||
| H2 carriers | 293 (30.4) | Ref. | Ref. | ||
| H1/H1 carriers | 671 (69.6) | −0.03 (−1.81–1.76) | 0.978 | −0.09 (−0.68–0.50) | 0.766 |
| SNCA rs356219 | |||||
| A-allele carriers | 771 (81.3) | Ref. | Ref. | ||
| GG carriers | 177 (18.7) | −0.46 (−2.58–1.65) | 0.668 | −0.72 (−1.41–−0.03) | 0.041 |
| APOE-ε4 and GBA subgroups | |||||
| Non-carriers of APOE-ε4 and GBA mutations | 574 (62.2) | Ref. | Ref. | ||
| Carriers of both APOE-ε4 and GBA mutations | 23 (2.5) | 0.83 (−4.70–6.37) | 0.769 | −2.87 (−4.46–−1.28) | < 0.001 |
Models adjusted for study cohort, age at baseline, sex and education.
Numbers include participants with information for education and Mini-Mental State Examination (MMSE).
Main effect indicates the effect of genotype on the intercept and the interaction with time indicates the effect of genotype on slope (annual change in MMSE score). MMSE scores were transformed before analysis as outlined in Methods.
The models of APOE-ε4 or GBA subgroups include non-carriers of APOE-ε4 or GBA mutations as the reference group, respectively.
GBA carriers include carriers of any GBA mutation, including variants of unknown significance.
Abbreviations: N, number; CI, confidence interval; Ref., reference; GBA, glucocerebrosidase gene; APOE, apolipoprotein E gene; MAPT, microtubule-associated protein tau gene; SNCA, alpha synuclein gene.