Table.
Demographic data and biomarker levels at baseline for carriers of pathogenic variants and non-carriers
| Non-carriers (n=91) | Presymptomatic carriers of pathogenic variants (n=100) | Symptomatic carriers of pathogenic variants (n=48) | p value | ||
|---|---|---|---|---|---|
| Age, years | 36·3 (11·4) | 34·15 (9·5) | 46·8 (9·7) | <0·0001* | |
| Sex | |||||
| Female | 54 (59%) | 55 (55%) | 25 (52%) | 0·69 | |
| Male | 37 (41%) | 45 (45%) | 23 (48%) | 0·69 | |
| Ethnicity | |||||
| White† | 72 (89%) | 77 (85%) | 33 (79%) | 0·53 | |
| Latin American | 7 (9%) | 8 (9%) | 6 (14%) | 0·53 | |
| Asian | .. | 4 (4%) | 2 (5%) | 0·53 | |
| Other‡ | 2 (3%) | 1 (2%) | 1 (3%) | 0·53 | |
| APOE ɛ4 carrier | 31 (34%) | 33 (33%) | 17 (35%) | 0·96 | |
| EYO, years | −10·0 (12·1) | −13·8 (9·8) | 1·9 (6·6) | <0·0001§ | |
| Mean follow up, years | 3·4 (1·8) | 3·4 (1·8) | 2·7 (1·7) | 0·062 | |
| Number of visits with soluble TREM2 determination | .. | .. | .. | 0·074 | |
| 2 | 63 | 64 | 23 | .. | |
| 3 | 17 | 25 | 13 | .. | |
| 4–6 | 11 | 11 | 12 | .. | |
| Mini-mental state examination, score | 28·9 (1·37) | 29·1 (1·22) | 24·4 (4·4) | <0·0001* | |
| Cognitive composite, z-score | −0·1 (0·9) | −0·2 (0·1) | −2·9 (1·7) | <0·0001* | |
| Years of education | 15·0 (2·3) | 15·0 (2·8) | 14 (3·8) | 0·11 | |
| CSF variables | |||||
| Aβ42, pg/mL | 749·6 (263·1) | 741·1 (417·0) | 381·3 (162·5) | <0·0001* | |
| Aβ40, pg/mL | 8484·8 (2792·6) | 9028·6 (3305·9) | 8636·2 (2711·0) | 0·56 | |
| Ratio of Aβ42 to Aβ40 | 0·1 (0·01) | 0·1 (0·03) | 0·04 (0·01) | <0·0001* | |
| t-tau, pg/mL | 267·9 (117·2) | 406·5 (289·8) | 752·3 (373·2) | <0·0001¶ | |
| p-tau, pg/mL | 29·8 (16·8) | 53·02 (49·0) | 127·0 (69·6) | <0·0001¶ | |
| Soluble TREM2, ng/mL | 2·7 (1·2) | 3·4 (1·6) | 4·1 (1·3) | <0·0001‖ | |
| Total cortical PiB-PET uptake, SURV | 1·07 (0·2) | 1·6 (0·8) | 3·0 (1·1) | <0·0001¶ | |
| Precuneus cortical thickness, mm | 2·4 (0·1) | 2·4 (0·2) | 2·1 (2·2) | <0·0001* | |
| Hippocampal volume, mm3 | 8815·9 (631·5) | 8871·4 (752·4) | 7497·6 (1246·4) | <0·0001* | |
Data are mean (SD) or n (%). All p values regarding demographics are based on analysis of raw data (ANOVA). All p values regarding cognitive data (ie, Mini-Mental State Examination and cognitive composite) are adjusted for age and education and based on analysis of raw data (ANCOVA). Categorical variables (ie, sex, APOE status, and visits) were analysed by the χ2 test. The p values regarding biochemical markers were based on an analysis (ANCOVA) that considered log-transformed variables and, for raw data, the rest of the variables and neuroimaging markers were adjusted by age and sex. Hippocampal volume was corrected per participant by total brain volume. p values with no footnote relate to comparisons with ANOVA or ANCOVA. EYO=estimated years to symptom onset according to parental onset. PiB-PET=Pittsburgh compound B PET. p-tau=phosphorylated tau on threonine 181. SUVR=standardised uptake value ratio. t-tau=total tau.
Symptomatic carriers of pathogenic variants versus non-carriers of pathogenic variants and presymptomatic carriers of pathogenic variants, p<0·0001.
Ethnicity data were available for 214 participants.
Australian aboriginal or native Hawaiian.
Symptomatic carriers of pathogenic variants versus non-carriers of pathogenic variants and presymptomatic carriers of pathogenic variants, p<0·0001; presymptomatic carriers of pathogenic variants versus non-carriers of pathogenic variants, p=0·034.
Symptomatic carriers of pathogenic variants versus non-carriers of pathogenic variants and presymptomatic carriers of pathogenic variants, p<0·0001; presymptomatic carriers of pathogenic variants versus non-carriers of pathogenic variants, p<0·0001.
Non-carriers of pathogenic variants versus presymptomatic carriers, p=0·0026; non-carriers of pathogenic variants versus symptomatic carriers of pathogenic variants, p<0·0001; and presymptomatic carriers of pathogenic variants versus symptomatic carriers of pathogenic variants, p=0·0052. One participant was excluded because of incomplete data.