TABLE 3.
Cox regression analysis evaluating the effect of genotype on the development of dementia
| Group | Total PD, Na | PDD, N (%) | Adjusted HR (95% CI) | P |
|---|---|---|---|---|
| APOE-ε4 | ||||
| ε4 Non-carriers | 665 | 169 (25.4) | Ref. | |
| ε4 Carriers | 281 | 109 (38.8) | 3.57 (2.15–5.93)b | <0.001 |
| APOE ⋆ time | 0.88 (0.79–0.99)b | 0.028 | ||
| APOE-ε4 subgroupsc | ||||
| Carriers of one ε4 allele | 261 | 99 (37.9) | 3.14 (1.96–5.02)b | <0.001 |
| Carriers of two ε4 alleles | 20 | 10 (50.0) | 6.39 (2.53–16.12)b | <0.001 |
| APOE ⋆ time | 0.91 (0.82–0.99)b | 0.047 | ||
| GBA | ||||
| Non-carriers | 867 | 239 (27.6) | Ref. | |
| GBA mutation carriersd | 100 | 42 (42.0) | 1.76 (1.26–2.46) | 0.001 |
| GBA subgroupsc | ||||
| Risk or mild mutation carriers | 81 | 32 (39.5) | 1.56 (1.07–2.26) | 0.020 |
| Severe mutation carriers | 13 | 7 (53.8) | 2.71 (1.26–5.82) | 0.011 |
| MAPT | ||||
| H2 carriers | 294 | 81 (27.6) | Ref. | |
| H1/H1 carriers | 676 | 200 (29.6) | 1.17 (0.90–1.52) | 0.248 |
| SNCA rs356219 | ||||
| A-allele carriers | 775 | 217 (28.0) | Ref. | |
| GG carriers | 181 | 62 (34.3) | 1.21 (0.91–1.60) | 0.199 |
| APOE-ε4 and GBA subgroups | ||||
| Non-carriers of APOE-ε4 and GBA mutations | 577 | 139 (24.1) | Ref. | |
| Carriers of both APOE-ε4 and GBA mutations | 23 | 14 (60.9) | 5.19 (2.88–9.38) | <0.001 |
Models adjusted for sex, age at baseline, education and stratified for study cohort.
Numbers include participants who had information available for education and time to event or censoring after the baseline visit.
Model includes interaction between the APOE variable and time. The presented HRAPOE for the APOE-ε4 variable refers to the hazard ratio for the respective carriers at time = 0 years (baseline). HR at any point of disease duration can be calculated: HRAPOE ⋆ (HRAPOE ⋆ time)t, where t defines the time point of interest in years.
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: PD, Parkinson’s disease; PDD, Parkinson’s disease dementia; N, number; HR, hazard ratio; CI, confidence interval; Ref., reference; APOE, apolipoprotein E gene; GBA, glucocerebrosidase gene; MAPT, microtubule-associated protein tau gene; SNCA, alpha synuclein gene.