Table 2.
Clinical studies testing anti-inflammatory molecules with potential therapeutic value for Alzheimer disease treatment. Other: other symptoms or biomarkers evaluated. NT (not tested); U (unspecified). Acetate, propionate and butyrate are short-chain fatty acids. ADAS-Cog: Alzheimer disease assessment scale–cognitive; ADFACS: Alzheimer’s Disease Functional Assessment and Change Scale; ADCS-ADL: ADCS Activity of Daily Living; CDR: Clinical Dementia Rating; MMSE: Mini Mental Status Evaluation Test; NPI: Neuropsychiatric Inventory; PAL-WMS-R: Paired-Associate Learning Wechsler Memory Scale.
| Compound (Dose) | Source | Patients (Years Old) | Study Design | Inflammatory/AD Biomarkers | Cognitive Effect | Other | Citation Year |
|---|---|---|---|---|---|---|---|
| Metformin (200 mg/day) | Galega officinalis plant | 20 (55–80) | 8 weeks | = Aβ42 levels | ↑ Learning and memory (CANTAB PAL scale) | Crosses the BBB | [46] 2017 |
| = phospho-TAU levels | ↑ Attention (DMS Percent Correct Simultaneous) | ||||||
| = total TAU levels | |||||||
| Lactoferrin (250 mg/day) | Milk | 50 (>65) | 3 months | ↑ IL-10 levels | [50] 2019 |
||
| ↑ GSH levels | ↑ Ach levels | ||||||
| ↓ IL-6 levels | ↑ 5-HT levels | ||||||
| ↓ Aβ42 levels | ↑ AKT levels | ||||||
| ↓ Caspase-3 levels | ↑ MMSE score | ↑ phospho- AKT(S473) levels | |||||
| ↓ Cholesterol levels | ↑ ADAS-Cog11 score | ↑ PI3K levels | |||||
| ↓ HSP90 levels | |||||||
| ↓ TAU pTAU(181) | ↓ PTEN levels | ||||||
| ↓ NO levels | ↓ MAPK1 levels | ||||||
| ↓ MDA levels | |||||||
| Vitamin B12 (25 μg/day) + Folic acid (800 μg/day) | Vitamin B12: animal products Folic acid: broccoli, peas, chickpeas, leafy green vegetables |
240 (>65) | 6 months | ↓ IL-6 levels | - | [54] 2019 |
|
| ↓ TNF-α levels | ↑ Full Scale IQ (FSIQ) score | ||||||
| ↓ MCP-1 levels | ↑ Verbal intelligence quotient (VIQ) score | ||||||
| ↓ Homocysteine levels | ↑ Information and Digit Span | ||||||
| Vitamin B12 + Risperidone and Quetiapine (atypical antipsychotic drugs) | Risperidone: and Quetiapine are synthetic |
102 (>65) | U | ↑ TGF-β score ↓ IL-8 levels ↓ TNF-α levels ↓ CD68 levels |
NT | ↓ Pain (VAS scale) | [55,56] 2018 |
| Nilvadipine (8 mg/day) | Pyridine (crude coal tar) | 511 (>50) | 18 months | NT | = ADAS-Cog 12 = CDR-sb = DAD |
- | [62] 2018 |
| Simvastatin 80 mg/day | Statins (Fungus Aspergillus terreus) | 80 (>50) | 18 months | ↓ IL-6 levels | - | [63] 2017 |
|
| ↓ IL-1β levels | ↑ ADAS-Cog score | ||||||
| ↓ ACT levels | ↑ MMSE score | ||||||
| ↓ TNF-α levels | ↑ Dependence Scale score | ||||||
| ↓ APP levels | ↑ ADCS-ADL score | ||||||
| ↓ BACE1 levels | ↑ NPI score | ||||||
| ↓ Aβ levels | |||||||
| Simvastatin 40 mg/day | 406 (>50) | 18 months | ↓ CRP levels | = ADAS-Cog score | ↑ HDL levels | [64] 2011 |
|
| = MMSE score | |||||||
| = Dependence Scale score | ↓ Total cholesterol levels | ||||||
| = ADCS-ADL score | |||||||
| = NPI score | ↓ LDL levels | ||||||
| Atorvastatin 40 mg/day | Statins | 178 (45–60) | 18 months | ↓ IL-1β levels ↓ IL-6 levels ↓ TNF-α levels ↓ CRP levels ↓ MCP-1 levels |
NT | ↓ Lipid levels | [65] 2016 |
| Atorvastatin 80 mg/day | 640 (50–90) | 18 months | NT | = ADAS-Cog score | [66] 2010 |
||
| = ADCS-CGIC score | ↓ Total cholesterol levels | ||||||
| = MMSE score | |||||||
| = CDR-SB score | ↓ LDL-C levels | ||||||
| = ADFACS score | ↓ Triglycerides levels | ||||||
| = NPI score | |||||||
| Tetrahydrocannabinol (4.5 mg/day) |
Cannabis plant | 50 (78–79) | 3 weeks | NT | = NPI score = Cohen-Mansfield Agitation Inventory = Quality of Life-Alzheimer’s Disease = Barthel Index score = PAL WMS-R score |
[67] 2015 |