Table 3.
Longitudinal association of biomarkers of neurodegenerative diseases and subjective cognitive complaints with risk of all-cause dementia (ESTHER cohort, nested case–control study)
| Cases (n = 226), N (%) | Controls, (n = 476), N (%) | Model 1a odds ratio (95%CI), p-valuec | Model 2b odds ratio (95%CI), p-valuec | |
|---|---|---|---|---|
| Subjective cognitive complaints | ||||
| No | 36 (15.9) | 115 (24.2) | Reference | Reference |
| Occasional | 142 (62.8) | 303 (63.7) | 1.22 (0.75–1.96), 0.4220 | 1.26 (0.76–2.08), 0.3748 |
| Persistent | 48 (21.2) | 58 (12.2) | 1.70 (0.93–3.12), 0.0874 | 1.58 (0.82–3.05), 0.1684 |
| GFAP | ||||
| GFAPQ1–3 | 117 (51.8) | 403 (84.7) | Reference | Reference |
| GFAPQ4 | 109 (48.2) | 70 (14.7) | 2.93 (1.94–4.41), < 0.0001 | 3.17 (2.03–4.95), < 0.0001 |
| Subjective cognitive complaints and GFAP | ||||
| No and GFAPQ1–3 | 22 (9.7) | 104 (21.8) | Reference | Reference |
| No and GFAPQ4 | 14 (6.2) | 10 (2.1) | 4.06 (1.41–11.68), 0.0093 | 3.98 (1.27–12.48), 0.0180 |
| Occasional and GFAPQ1–3 | 76 (33.6) | 251 (52.7) | 1.30 (0.74–2.29), 0.3575 | 1.31 (0.73–2.38), 0.3674 |
| Occasional and GFAPQ4 | 66 (29.2) | 51 (10.7) | 2.81 (1.47–5.38), 0.0017 | 3.02 (1.51–6.01), 0.0017 |
| Persistent and GFAPQ1–3 | 19 (8.4) | 48 (10.1) | 1.22 (0.57–2.63), 0.6138 | 0.99 (0.43–2.30), 0.9809 |
| Persistent and GFAPQ4 | 29 (12.8) | 9 (1.9) | 7.39 (2.89–18.88), < 0.0001 | 7.52 (2.79–20.29), < 0.0001 |
| NfL | ||||
| NfLQ1–3 | 136 (60.2) | 388 (81.5) | Reference | Reference |
| NfLQ4 | 90 (39.8) | 85 (17.9) | 1.32 (0.87–2.00), 0.1926 | 1.38 (0.88–2.17), 0.1573 |
| Subjective cognitive complaints and NfL | ||||
| No and NfLQ1–3 | 22 (9.7) | 96 (20.2) | Reference | Reference |
| No and NfLQ4 | 14 (6.2) | 18 (3.8) | 1.35 (0.53–3.41), 0.5273 | 1.52 (0.57–4.07), 0.4025 |
| Occasional and NfLQ1–3 | 83 (36.7) | 249 (52.3) | 1.18 (0.66–2.10), 0.5737 | 1.25 (0.68–2.31), 0.4662 |
| Occasional and NfLQ4 | 59 (26.1) | 53 (11.1) | 1.77 (0.91–3.46), 0.0950 | 1.95 (0.96–3.99), 0.0664 |
| Persistent and NfLQ1–3 | 31 (13.7) | 43 (9.0) | 2.05 (0.99–4.25), 0.0547 | 2.00 (0.91–4.42), 0.0851 |
| Persistent and NfLQ4 | 17 (7.5) | 14 (2.9) | 1.70 (0.66–4.36), 0.2689 | 1.63 (0.60–4.44), 0.3385 |
| p-tau181 | ||||
| p-tau181Q1–3 | 152 (67.3) | 386 (81.1) | Reference | Reference |
| p-tau181Q4 | 74 (32.7) | 90 (18.9) | 1.20 (0.80–1.82), 0.3809 | 1.21 (0.78–1.89), 0.3936 |
| Subjective cognitive complaints and p-tau181 | ||||
| No and p-tau181Q1–3 | 24 (10.6) | 93 (19.5) | Reference | Reference |
| No and p-tau181Q4 | 12 (5.3) | 22 (4.6) | 1.07 (0.42–2.72), 0.8875 | 1.00 (0.37–2.69), 0.9959 |
| Occasional and p-tau181Q1–3 | 97 (42.9) | 248 (52.1) | 1.18 (0.67–2.07), 0.5685 | 1.18 (0.65–2.13), 0.5909 |
| Occasional and p-tau181Q4 | 45 (19.9) | 55 (11.6) | 1.46 (0.74–2.87), 0.2749 | 1.55 (0.76–3.19), 0.2308 |
| Persistent and p-tau181Q1–3 | 31 (13.7) | 45 (9.5) | 1.63 (0.79–3.34), 0.1854 | 1.53 (0.71–3.31), 0.2796 |
| Persistent and p-tau181Q4 | 17 (7.5) | 13 (2.7) | 2.07 (0.79–5.43), 0.1413 | 1.73 (0.62–4.81), 0.2966 |
Percentages might not sum up to 100 because of rounding and missing values
In this sample GFAPQ4 ≥ 122.00 pg/mL; NfLQ4 ≥ 21.20 pg/mL; p-tau181Q4 ≥ 2.06 pg/mL
CI confidence interval, GFAP glial fibrillary acidic protein, NfL neurofilament light chain, p-tau181 phosphorylated tau181, Q quartile
aLogistic regression model 1 adjusted for age (continuous), sex, and educational level
bLogistic regression model 2 additionally adjusted for lifetime history of stroke, myocardial infarction, diabetes, lifetime history of depression, and APOE ε4 genotype
cp-value derived from the logistic regression models