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. Author manuscript; available in PMC: 2020 Feb 1.
Published in final edited form as: Nat Med. 2019 Jan 21;25(2):277–283. doi: 10.1038/s41591-018-0304-3

Fig. 4 |. Prediction of changes in cortical thinning and cognition by baseline serum NfL (retrospective prediction) and serum NfL rate of change (prospective prediction).

Fig. 4 |

a–c, Higher baseline serum NfL levels were significantly associated with an increased rate of change in cortical thickness (n = 125; B(s.e.m.) = −0.105(0.013), P = 4.47 × 10−13) (a), MMSE (n = 132; B(s.e.m.) = −3.980(0.537), P = 2.38 × 10−11) (b), and Logical Memory test (immediate recall, n = 133; B(s.e.m.) = −1.478(0.502), P = 0.004) (c). A similar significance (P = 0.015) was obtained for the Logical Memory test delayed recall. LMEMs (see Methods) were run with all mutation carriers together (n = 125) because of the high degree of overlap in cognitive and biomarker levels between presymptomatic (Presym) and symptomatic (Sym) mutation carriers. However, at least for cortical thickness, separate analyses for presymptomatic and symptomatic mutation carriers were also significant (n = 65, presymptomatic mutation carriers (yellow): B(s.e.m.) = −0.03(0.01), P = 0.047; n = 60, symptomatic mutation carriers (red): B(s.e.m.) = −0.10(0.03), P = 0.002). d–f, In a true prospective design, mutation carriers returning for follow-up visits after the last serum collection were included in the analysis. Individuals’ rates of change in serum NfL levels predicted subsequent cortical thinning (d; n = 30; B(s.e.m.) = −1.867(0.769), P = 0.024). The same predictive associations were also significant for the MMSE (e; n = 37; B(s.e.m.) = −52.23(20.19), P = 0.015) and Logical Memory test scores (f; immediate recall, n = 37; B(s.e.m.) = −75.91(18.07), P = 0.0002). For descriptive purposes, presymptomatic and symptomatic mutation carriers are plotted in yellow and red, respectively. Note that not all participants with baseline NfL measurements had longitudinal MRI imaging and longitudinal cognitive parameters available; thus, sample sizes (n) in a–c are slightly lower than those in Supplementary Table 2. This was also true for the mutation carriers returning for follow-up visits after the last serum collection (d–f). The shaded area around each linear fit line represents one s.e.m. from the LMEMs.