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P1‐048: PLASMA NF‐L AS A BIOMARKER FOR NEURODEGENERATION IN MILD AD SUBJECTS IN THE PHASE 2 NAVIGATE‐AD STUDY
Author(s) -
Wang Hong,
Charil Arnaud,
Shcherbinin Sergey,
Natanegara Fanni,
Chao Georgia,
Evans Cynthia Duggan,
Dage Jeffrey,
Irizarry Michael C.,
Lo Albert,
Sims John R.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.073
Subject(s) - biomarker , neurodegeneration , medicine , oncology , population , placebo , dementia , atrophy , pathology , chemistry , disease , biochemistry , alternative medicine , environmental health
Background: With the ever widening reach of global trials in AD regional differences have become increasingly important to take into account when investigating recruitment challenges, inclusion and exclusion criteria, and efficacy analyses. Previous trials have shown heterogeneous cohort data (Henley et al., 2015; 2014) across regions in later stage populations (MMSE 16-26) however, these longitudinal analyses did not focus on cross-sectional differences and were limited to the randomised subject population. This analysis examines regional referral patterns on the International Shopping List Test (ISLT), a supervisor administered three-trial verbal list learning test with measures of immediate and delayed recall, MMSE and CDR. Methods: Global screening data were pooled from Eisai’s MissionAD 1 & MissionAD2 global phase III trials. Data were gathered for each subject that each site considered suitable for consent based upon the protocol criteria. KolmogorovSmirnov normality test was conducted by region; ANOVA’s were performed to compare means of each measure among 5 regions (North America [NA], Europe/South Africa [E/SA], Japan, Asia Pacific [APAC] and South America [SA]). Results: ANOVA’s showed significant differences on the model for ISLT (F(4, 8467)1⁄435.71, p<0.01) ISRL (F(4,8465)1⁄470.33, p<0.01), MMSE (F(4,8900)1⁄42.86, p1⁄40.02) and CDR-SB (F(4,6291)1⁄417.62, p<0.01). Post hoc analysis indicated significant differences on the ISLT immediate recall and delayed recall were being driven by a less impaired population in NA compared to all other regions (p<0.05 for all relationships). MMSE showed little variation between the regions except for SA showing less impairment compared to NA, E/SA and APAC (p<0.05). CDR-SB regional differences were exclusively driven by higher scores fromNA&E/SA than those from Japan & APAC (p<0.05). Conclusions: Referral patterns into this global program differed by region when examining cognitive screening data. The NA region referred subjects with slightly less impairment on the ISLT compared to E/SA and other regions. In contrast, NA sites referred patients with higher levels of impairment on the CDR-SB. The lack of comparative differences on the MMSE seems to suggest worldwide uniformity to this measure both in clinic and for trial screening. Further analysis is warranted to explore how Western and Asian diagnostic and referral practices may differ.