Table 4.
Adjusted cognitive decline in subgroups according to TDP-43, HS, and APOE ε4
| Advanced TDP-43 |
HS |
APOE ε4 carrier |
n | TDP-43 burden (sd) | MMSE proximate to death (sd) |
Adjusted global cognitive decline per year (sd) |
Adjusted global cognition proximate to death (sd) |
|---|---|---|---|---|---|---|---|
| NO | NO | NO | 516 | 0·11 (0·21) | 23·0 (7·8) | 0·006 (0·079) | 0·10 (0·92) |
| YES | 137 | 0·12 (0·22) | 20·8 (9·0) | −0·005 (0·097) | 0·10 (1·05) | ||
| YES | NO | NO | 154 | 1·43 (0·81) | 19·5 (9·0) | 0·016 (0·075) | 0·07 (0·90) |
| YES | 77 | 1·65 (1·00) | 15·8 (10·6) | −0·013 (0·089) | −0·20 (1·12) | ||
| YES | YES | NO | 42 | 2·56 (0·82) | 14·0 (9·8) | −0·047 (0·090) | −0·86 (1·04) |
| YES | 35 | 2·64 (0·84) | 11·9 (9·7) | −0·052 (0·094) | −0·60 (1·06) |
Advanced TDP-43 was defined as TDP-43 stage 2 or 3. TDP-43 burden, unadjusted MMSE proximate to death, adjusted global cognitive decline per year (random slope of global cognition additionally adjusted for Aβ, PHFtau, age at death, sex, and years of education), and adjusted global cognition proximate to death (global cognition proximate to death adjusted for Aβ, PHFtau, and demographics) are shown for each subgroup. We aimed to capture the cognitive trajectory not explained by AD pathology or demographics with adjusted global cognitive decline per year and adjusted global cognition proximate to death. To calculate adjusted global cognitive decline, we first derived random slope of global cognition from linear mixed models with annual global cognitive function as the longitudinal outcome, adjusting for age at baseline, sex, and years of education. This random slope was additionally adjusted for Aβ and PHFtau to derive adjusted global cognitive decline per year. Data shown here are from a subset of participants with non-missing data for all variables displayed. We note that there were only 15 participants (four APOE ε4 carriers) who had HS but did not have advanced TDP-43, and this small subgroup (not displayed in this table) had the following characteristics: TDP-43 burden 0·11 (sd 0·17), unadjusted MMSE proximate to death 17·7 (sd 12·4), adjusted global cognitive decline −0·013 (sd 0·061), and adjusted global cognition proximate to death −0·10 (sd 0·80). Aβ=β-amyloid, HS=hippocampal sclerosis, MMSE=mini-mental state exam, PHFtau=paired helical filament tau, sd=standard deviation, TDP-43=TAR-DNA binding protein-43kDa proteinopathy.