Table 4.
Results of human studies testing the effect of lithium (a), rapamycin (b), rifampicin & doxycycline (c) and nilotinib (d) on cognition.
| Author, year | Cognitive tests | Outcome | Significance | |
|---|---|---|---|---|
| a | Pomara et al., 1983 | Buschke selective reminding test | [2pt]No quantitative data reported—“None of the psychometric measures showed either consistent, significant increases or decreases” | ± |
| Digit span/supraspan test | ||||
| Sperling test of iconic memory | ||||
| Word fluency tasks | ||||
| Wechsler Memory Scale | ||||
| a | Macdonald et al., 2008 | Change in MMSE | Li−4.8 (5.5), ctrl−4.0 (5.0) | ± |
| a | Hampel et al., 2009 | MMSE | Li−23.6 (1.6) -> 22.6 (3.5) | ± |
| PBO−23.6 (1.7) -> 23.2 (2.7) | ||||
| ADAS-Cog | Li−15.8 (4.2) -> 15.6 (4.4) | ± | ||
| PBO−5.4 (5)-> 16.6 (5.1) | ||||
| ADAS-Cog % with improvement >4 points | Li−28.6%, PBO−14.3% | NR | ||
| a | Leyhe et al., 2009 | ADAS-Cog | Li 19.2 (5.7) -> 17.7 (5.8) | + |
| PBO 16.5 (5.1) -> 18.0 (5.1) | ||||
| a | Forlenza et al., 2011 | ADAS-Cog | Li 11.0(6.7)->12.6(6.6), PBO 10.7(5.1)-> 13.9(8.5) | + |
| CDR–SoB | Li 1.4(1.3) -> 2.2(1.8), PBO 1.9(1.4) -> 2.8(2.3) | ± | ||
| Delayed recall | Li 4.8(2.1) -> 4.8(2.2), PBO 4.2(2.3) -> 4.5(2.3) | ± | ||
| Figure recall | Li 2.3(1.2) -> 2.0(1.3), PBO 1.9(1.1) -> 1.6(1.2) | ± | ||
| Sequence letters & numbers | Li 6.4(2.1) -> 6.0(2.9), PBO 6.3(2.6) -> 5.1(2.6) | + | ||
| Trail making test A (s) | Li 69.1(44.2) -> 62.8(31.5), PBO 89.9(67.4) -> 63.6(41.9) | ± | ||
| Trail making test B | Li 171.8(83.9) -> 184.9(78.1), PBO 207.1 (79.6) -> 190.7 (92.8) | ± | ||
| Conversion MCI->AD | Li (n = 20) Stable = 16, Progress = 4 | ± | ||
| PBO (n = 20) Stable = 13, Progress = 7 | ||||
| MCI->AD converters CDR-SoB | Li 3.3(1.3) -> 4.4(1.5), PBO 3.4(1.4) -> 5.6(1.5) | + | ||
| a | Nunes et al., 2013 | MMSE | Li 19.48 (0.67) -> 19.82 (0.9) | +++ |
| PBO 17.95 (0.73) -> 14 (1.326) | ||||
| b | Kraig et al., 2018 | Pre-post test change | ||
| EXIT25 | PBO 0.38 (-1.84, 2.61), rapa−0.1 (-3.31, 3.11) | ± | ||
| SLUMS | PBO 0.38 (-2.03, 1.26), rapa−0.8 (-3.92, 2.32) | ± | ||
| TAPS | PBO−1 (-3.18, 1.18), rapa 1.44 (-1.68, 4.57) | ± | ||
| c | Molloy et al., 2013 | SADAS-Cog | Rif−0m = 22, 12m = 27.5 | — |
| Doxy – 0m = 21, 12m = 25.5 | — | |||
| Rif + Doxy−0m = 22, 12m = 28 | — | |||
| PBO−0m = 21, 12m = 25 | ||||
| CDR-SoB mean | Rif−0m = 6, 12m = 8.5 | ± | ||
| Non-Rif−0m = 5.75, 12m = 7.75 | ||||
| Doxy – 0m = 6, 12m = 8.5 | ± | |||
| Non-Doxy – 0m = 5.75, 12m = 7.8 | ||||
| SMMSE | ns vs. placebo, data NR | ± | ||
| Qmci | Rif worse than PBO, data NR | — | ||
| d | Pagan et al., 2016 | MMSE (change 0w->24w) | 150mg–+3.85, 300mg–+3.5 | NR |
| SCOPA-Cog (change 0w->24w) | 150mg–+1.85, 300mg–+2.00 |
+++ favoring intervention, highly significant p < 0.001. ++ favoring intervention, significant p < 0.01. + favoring intervention, significant p < 0.05. +/± trend favoring intervention, p < 0.1. ± not significant. +/± trend favoring control, p < 0.1. - favoring control, significant p < 0.05. – favoring control, significant p < 0.01. — favoring control, highly significant p < 0.001. EXIT25, Executive interview; NR, p-value not reported; PBO, placebo; RoB, Cochrane risk of bias; SLUMS, St Louis University Memory Status; TAPS, Texas Assessment of Processing Speed.