TABLE 4.
Associations of study variables with changes in the MMSE score and CSF sTREM2 level during 28 days of high‐dose valacyclovir treatment (linear regression analysis)
| MMSE change | CSF sTREM2 change | |||||
|---|---|---|---|---|---|---|
| Baseline assessment | B (95% CI) | Stand. β | P value | B (95% CI) | Stand. β | P value |
| Age (years) | 0.13 (−0.29–0.03) | −0.28 | .109 | 35.60 (−2.58–73.79) | 0.32 | .067 |
| Sex (women) | −1.24 (−2.64–0.16) | −0.31 | .081 | 142.86 (−211.55–497.27) | 0.15 | .417 |
| PILRA A/A | 0.14 (−1.83–2.12) | 0.03 | .884 | −456.47 (−907.09–−5.85) | −0.35 | .047 |
| GM 17/17 | 0.42 (−1.74–2.59) | 0.07 | .694 | 99.39 (−427.39–626.16) | 0.07 | .703 |
| Serum anti‐HSV‐2 IgG‐positive | 0.32 (−1.27–1.91) | 0.07 | .684 | −18.67 (−405.56–368.23) | −0.02 | .922 |
| Serum anti‐CMV IgG‐positive | 1.07 (−0.72–2.87) | 0.21 | .231 | 0.26 (−6.45–6.98) | −0.07 | .938 |
| MMSE score | −0.07 (−0.26–0.11) | −0.15 | .419 | 17.28 (−27.47–62.03) | 0.14 | .437 |
| CSF Aβ42, pg/ml | −1.43 × 10−3 (−7.11 × 10−3–4.26 × 10−3) | −0.09 | .612 | −1.58 (−2.84–0.32) | −0.42 | .016 |
| CSF Aβ40, pg/ml | −0.11 × 10−3 (−0.30 × 10−3–0.08 × 10−3) | −0.21 | .235 | −0.05 (−0.10–−0.01) | −0.40 | .020 |
| CSF Aβ42/40 ratio c | −2.26 (−8.13–3.62) | −0.14 | .439 | 152.03 (−1286.49–1590.54) | 0.04 | .831 |
| CSF t‐tau, pg/ml | −0.72 × 10−3 (−2.80 × 10−3‐1.37 × 10−3) | −0.13 | .487 | −0.42 (−0.90‐0.07) | −0.30 | .093 |
| CSF p‐tau, pg/ml | −0.01 (−0.02–0.01) | −0.13 | .465 | −2.12 (−5.85–1.62) | −0.21 | .256 |
| CSF NfL, pg/ml | −1.20 × 10−3 (−2.18 × 10−3–−0.22 × 10−3) | −0.41 | .019 | −0.17 (−0.43–0.08) | −0.24 | .178 |
| CSF sTREM2, pg/ml | −0.66 × 10−3 (−1.41 × 10−3–0.09 × 10−3) | −0.31 | .081 | −0.17 (−0.35–0.02) | −0.32 | .071 |
| CSF YKL40, ng/ml | −0.02 (−0.03–−0.01) | −0.48 | .006 | −2.43 (−5.20–0.33) | −0.32 | .082 |
| CSF IL‐6 a , pg/ml | −2.27 (−6.59–2.05) | −0.19 | .291 | −420.34 (−1476.99–636.30) | −0.15 | .423 |
| CSF IL‐8 a , pg/ml | −0.31 (−1.28–0.66) | −0.12 | .519 | −168.37 (−396.16–59.43) | −0.27 | .142 |
| Serum anti‐HSV IgG, titer | 0.02 × 10−3 (0.05 × 10−3–0.09 × 10−3) | 0.12 | .499 | 0.02 (0.00–0.03) | 0.37 | .036 |
| CSF anti‐HSV IgG, titer b | 0.04 (−0.23–0.31) | 0.06 | .757 | 3.66 (−3.08–10.40) | 0.20 | .276 |
| Serum/CSF anti‐HSV IgG ratio b , c | 1.98 (−1.05–5.01) | 0.16 | .191 | 714.77 (−12.25–1441.79) | 0.25 | .054 |
| MMSE change | CSF sTREM2 change | |||||
|---|---|---|---|---|---|---|
| 28‐day assessment d | B (95% CI) | Stand. β | p value | B (95% CI) | Stand. β | P value |
| Serum acyclovir, μmol/L | −0.03 (−0.09–0.02) | −0.25 | .188 | −7.37 (−19.88–5.15) | −0.22 | .238 |
| CSF acyclovir, μmol/L | −0.08 (−0.40–0.25) | −0.09 | .642 | 6.07 (−72.34–84.48) | 0.03 | .875 |
| CSF/serum acyclovir ratio c | 2.56 (−0.49–5.61) | 0.38 | .096 | 376.00 (−376.29–1128.30) | 0.23 | .316 |
| Serum 9‐CMMG, μmol/L | −0.07 (−0.43–0.28) | −0.08 | .675 | −10.39 (−95.25–74.48) | −0.05 | .804 |
Abbreviations: 9‐CMMG, 9‐carboxymethoxymethylguanine; Aβ, amyloid beta; CI, confidence interval; CMV, cytomegalovirus; CSF, cerebrospinal fluid; GM, γ marker; HSV, herpes simplex virus; IgG, immunoglobulin G; IL, interleukin; MMSE, Mini‐Mental State Examination; NfL, neurofilament light chain; PILRA, paired immunoglobulin‐like type 2 receptor alpha; p‐tau, phosphorylated tau; sTREM2, soluble triggering receptor expressed on myeloid cells 2; t‐tau, total tau.
Square root‐transformed.
Three participants had undetectable CSF anti‐HSV IgG concentrations, recorded as 0.
Base‐10 log‐transformed.
Models adjusted for the time (in minutes) since the last valacyclovir dose (log 10‐transformed).