Table 3.
Summarize the mainly effects of the mitophagy inducers in the included studies.
| Study (year) | Summarize the effects of the mitophagy inducers in outcome |
|---|---|
| Resveratrol vs placebo | |
| Moussa (2017) |
RGM (resveratrol, glucose, and malate combination) treatment were similar on all of the screening variables. At 12 months treatment duration, change scores on ADAS-cog, MMSE, ADAS-ADL, or NPI fields all showed less deterioration in the RGM than the control group. However, none of the change scores reached statistical significance (p > 0.05). |
| Turner (2015) |
Resveratrol and its major metabolites were measurable in plasma and CSF. The most common adverse events were nausea, diarrhea, and weight loss. CSF Aβ40 and plasma Aβ40 levels declined more in the placebo group than the resveratrol-treated group, resulting in a significant difference at week 52. Brain volume loss was increased by resveratrol treatment compared to placebo. |
| Zhu (2019) |
Compared to the placebo-treated group, at 52 weeks, resveratrol markedly reduced CSF MMP9 and increased macrophage-derived chemokine (MDC), interleukin (IL)-4, and fibroblast growth factor (FGF)-2. Compared to baseline, resveratrol increased plasma MMP10 and decreased IL-12 P40, IL12 P70, and RANTES. In this subset analysis, resveratrol treatment attenuated declines in MMSE scores, change in ADCS-ADL scores, and CSF Aβ42 levels during the 52-week trial, but did not alter tau levels. |
| NADH vs placebo or base line | |
| Demarin (2004) |
After 6 months of treatment, subjects treated with NADH (10 mg) showed no evidence of progressive cognitive deterioration and had significantly higher total scores on the MDRS compared with subjects treated with placebo (p < 0.05), such as better performance on verbal fluency (p = 0.019), visual-constructional ability (p = 0.038) and abstract verbal reasoning. |
| Rainer (2000) |
No clinically relevant changes versus baseline were seen in the GDS, the cognitive parameters, or any of the three subscores of the ADAS-Cog that capture memory, orientation and language in the group as a whole. Moreover, none of the minute changes that where observed in these parameters achieved statistical significance or indicated a statistical trend. |
| Birkmayer (1996) |
NADH improved the MMSE and GDS scores compared to the placebo group, need more rigorously controlled studies to confirm in future. |
| Metformin vs placebo | |
| Koening (2017) |
Metformin was found to be safe, well-tolerated, and measureable in CSF. Metformin was associated with improved executive functioning, and trends suggested improvement in learning/memory and attention. No significant changes in CBF were observed, though post-hoc completer analyses suggested an increase in orbitofrontal CBF with metformin exposure. |
| Luchsinger (2016) |
Metformin could not be tolerated by 7.5% of participants. There were no serious adverse events related to metformin. The 7.5% of persons who did not tolerate metformin reported gastrointestinal symptoms. After adjusting for baseline ADAS-cog, changes in total recall of the SRT favored the metformin group. Differences for other outcomes were not significant. |
| Sodium selenite vs placebo | |
| Cardoso (2019) |
Supranutritional selenium supplementation was well tolerated and yielded a significant increase in CSF selenium. Reclassifying subjects as either responsive or non-responsive based on elevation in CSF selenium concentrations revealed that responsive group did not difference in Mini-Mental Status Examination (MMSE) as non-responsive group. |
| Malpas (2016) |
VEL015 (sodium selenate) at doses up to 30 mg per day for 24 weeks was safe and well-tolerated in patients with AD, however no difference in the fields of MMSE, ADAS-cog et al cognition tests. |
| NA vs placebo | |
| Phelan (2017) |
There were no significant effects of NA on the primary or secondary endpoints. A mild effect of low compliance was observed on word recall and command tasks. There were no differences in adverse events experienced by NA- and placebo-treated groups. |
ADAS-cog: Alzheimer’s Disease Assessment Scale-cognitive; ADCS Activities of Daily Living Scale (ADCS-ADL); and Neuropsychiatric Inventory (NPI); MDRS: Mattis Dementia Rating Scale; MMSE: Mini Mental State Examination; Cerebral blood flow: CBF; GDS: global deterioration scale.