TABLE 3.
MMSE scores, CSF levels of AD and neuroinflammation biomarkers, and anti‐HSV IgG titers at baseline and after 28 days of high‐dose valacyclovir treatment
| Correlation | ||||||
|---|---|---|---|---|---|---|
| Biomarker | n pairs | Before treatment | After treatment | P value for difference | r | P value |
| MMSE score, median (IQR) a | 33 | 23 (19–26) | 24 (20–27) | .023 | 0.864 | < .001 |
| CSF Aβ42, pg/ml, mean ± SD | 32 | 363.2 ± 130.0 | 376.1 ± 115.4 | .204 | 0.902 | < .001 |
| CSF Aβ40, pg/ml, mean ± SD | 33 | 10344.9 ± 3715.7 | 10650.1 ± 3502.5 | .245 | 0.918 | < .001 |
| CSF Aβ42/40 ratio, median (IQR) | 32 | 0.34 (0.29–0.42) | 0.33 (0.30–0.42) | .112 | 0.990 | < .001 |
| CSF t‐tau, pg/ml, mean ± SD | 33 | 720.8 ± 342.8 | 727.7 ± 326.6 | .653 | 0.967 | < .001 |
| CSF p‐tau, pg/ml, mean ± SD | 32 | 97.1 ± 47.1 | 97.6 ± 46.55 | .819 | 0.971 | < .001 |
| CSF NfL, pg/ml, mean ± SD | 32 | 1768.8 ± 680.4 | 1816.3 ± 702.4 | .520 | 0.822 | < .001 |
| CSF sTREM2, pg/ml, mean ± SD | 33 | 2483.6 ± 917.4 | 2674.6 ± 889.3 | .028 | 0.861 | < .001 |
| CSF YKL40, ng/ml, mean ± SD | 28 | 179.0 ± 65.0 | 183.0 ± 61.9 | .488 | 0.893 | < .001 |
| CSF IL‐6, pg/ml, mean ± SD | 32 | 0.93 ± 0.34 | 0.86 ± 0.23 | .568 | 0.334 | .062 |
| CSF IL‐8, pg/ml, mean ± SD | 32 | 38.9 ± 9.9 | 41.7 ± 13.3 | .374 | 0.581 | < .001 |
| Serum anti‐HSV IgG, titer, median (IQR) | 33 | 6400 (6400–25600) | 6400 (6400–25600) | .157 | 0.921 | < .001 |
| CSF anti‐HSV IgG, titer, median (IQR) b | 32 | 64 (16–64) | 16 (16–64) | .083 | 0.870 | < .001 |
| Serum/CSF anti‐HSV IgG ratio, median (IQR) b | 31 | 400 (100–400) | 400 (100–400) | .655 | 0.701 | < .001 |
Note: The data include repeat assessments. Mean differences and correlations were tested using the paired‐samples t test and Pearson analysis, respectively, except for the MMSE score; CSF Aβ42/40 ratio; CSF IL‐6, IL‐8, and anti‐HSV IgG levels; serum anti‐HSV IgG level; and serum/CSF‐anti‐HSV IgG ratio, for which the Wilcoxon signed rank test and Spearman correlation analysis were used to accommodate ordinal data or non‐normality.
Abbreviations: Aβ, amyloid beta; AD, Alzheimer's disease; CSF, cerebrospinal fluid; HSV, herpes simplex virus; IgG, immunoglobulin G; IL, interleukin; IQR, interquartile range; MMSE, Mini‐Mental State Examination; NfL, neurofilament light chain; p‐tau, phosphorylated tau; SD, standard deviation; sTREM2, soluble triggering receptor expressed on myeloid cells 2; t‐tau, total tau.
Mean MMSE change = 0.88 ± 1.96 points.
Three participants had undetectable CSF anti‐HSV IgG concentrations, recorded as 0.