Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis
Abstract
:1. Introduction
2. Materials and Methods
2.1. Search Strategy
2.2. Study Criteria
2.3. Data Extraction
2.4. Statistical Analysis
2.5. Data Analysis
3. Results
3.1. Effect of PPAR-γ Agonists on Cognition Based on the Observational Studies
3.2. Effect of PPAR-γ Agonists on Cognition Based on Clinical Trials
3.2.1. Neuropsychological Outcomes/Neuropsychological Scales
3.2.2. Metabolic Outcomes
3.2.3. AEs
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Design/Reference | Participants | Drugs | Outcome Measure | Effect on Cognition | ||||
---|---|---|---|---|---|---|---|---|
Number | Median Age | Basic Disease | Name | Treatment Dose | Duration | |||
Case–Control [29] | 8276 | 79.7 | DM | Glitazone | NR | NR | (ICD-10: F01, F03, G30) | OR = 0.80 [0.68–0.95] |
Cohort [30] | 19,203 | ≥60 | DM | pioglitazone | >0.83 DDDs | >252 days | ICD-9-CM | pioglitazone user HR = 0.77 [0.62–0.95] <0.83 DDDs HR = 0.90 [0.66–1.23] 0.83–1.00 DDDs HR = 0.89 (0.58–1.36) >1.00 DDDs HR = 0.64 (0.47–0.87) |
Cohort [31] | 145,717 | 60 | DM | Rosiglitazone | NR | NR | NR | HR = 0.94, p = 0.004 |
Cohort [32] | 145,928 | ≥60 | DM and non-DM | Rosiglitazonepioglitazone | NR | NR | Tenth Revision [ICD-10] | Diabetes & PIO < 8 HR = 1.16 [0.87–1.55] Diabetes & PIO ≥ 8 HR = 0.53 [0.30–0.94] Rosiglitazone HR = 0.84 [0.59–1.18] |
Case–Control [33] | 7086 | ≥65 | DM | Thiazolidinedione | Prescriptions 1–9 10–9 ≥30 | 45–90 days | NR | Thiazolidinedione prescriptions 1–9 OR = 0.89 [0.42–1.86] 10–9 OR = 0.97 [0.45–2.07] ≥30 OR = 0.87 [0.31–2.40] |
Cohort [34] | 91,219 | ≥60 | T2DM | Thiazolidinedione | NR | 11 years | Tenth Revision [ICD-10] | Dementia HR=0.79 [0.77, 0.81] Alzheimer’s dementia HR = 0.80 [0.77, 0.83] Vascular dementia HR = 0.78 [0.75, 0.82] Thiazolidinedione HR = 0.76 [0.55, 1.05] |
Cohort [35] | 335 | 79.7 | DM | Thiazolidinedione | NR | NR | Tenth Revision [ICD-10] | HR = 0.64 [0.40–1.03] |
Cohort [36] | 11,011 | 58.7 | T2DM | pioglitazone | NR | 20 months | Tenth Revision [ICD-10] | HR = 0.72 [0.54–0.94] |
Cohort [37] | 5048 | 61.2 | T2DM | Rosiglitazone | NR | NR | Tenth Revision [ICD-10] | HR = 0.89 [0.69–1.15] |
Design/Reference | Participants | Intervention | Drugs | Outcome Measure | AEs | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Number | Median Age | Cognitive Function | APOE- 4 | Control | Case | Dose | Duration | Cognitive | Metabolic | ||
RCT [16] | 56 | 74.5 | MCI | NR | 1507 | 1531 | PIO 0.8 mg/day | 6 months | MMSE | NR | √ |
RCT [17] | 29 | 74.9 | AD | NR | 15 | 14 | PIO 15 mg | 6 months 12 months 18 months | ADAS-Cog NPI NOSGER ADFACS CDR-SB | NR | √ |
RCT [18] | 693 | 72.5 | Mild to moderate AD | √ | 165 | 166 | PIO 2/8/10 mg | 24 weeks | MMSE ADAS-Cog | NR | √ |
RCT [19] | 32 | 76.5 | 12 AD/3 MCI | NR | 17 | 15 | PIO 15–30 mg | 6 months | MMSE ADAS-Cog WMSR | FPG Insulin HOMA% | √ |
RCT [20] | 34 | 77 | mild AD with T2DM | √ | 17 | 17 | PIO 15–30 mg | 6 months | ADAS-Cog | TNF CRP IL-6 | NR |
RCT [21] | 1393 | 74.1 | AD | √ | 496 | 494 | RSG 2, 8 mg | 48 weeks | MMSE ADAS-Cog CDR-SB | NR | √ |
RCT [21] | 1429 | 73.2 | AD | √ | 487 | 790 | RSG 2, 8 mg | 48 weeks | MMSE ADAS-Cog CDR-SB | NR | √ |
RCT [22] | 49 | 66.0 | MCI | √ | 25 | 25 | RSG 30 mg | 6 months | MMSE ADAS-Cog DST | TNF FPG Insulin CRP IL-6 | NR |
RCT [23] | 511 | 70.7 | Mild to moderate AD | NR | 122 | 131 | RSG 2, 4, 8 mg | 24 weeks | ADAS-Cog MMSE | NR | √ |
RCT [24] | 145 | 60.2 | T2DM | NR | 70 | 66 | RSG 4 mg | 4 weeks | DST SWMR RAVLT | Insulin FPG HOMA % | NR |
RCT [25] | 42 | 77.5 | mild AD DM | NR | 21 | 21 | PIO 15–30mg | 6 months | MMSE ADAS-cog WMSR | FPG Insulin HOMA% | NR |
RCT [26] | 80 | 72.2 | Mild to moderate AD | NR | 29 | 31 | RSG 8 mg | 12 months | ADAS-cog | FDG-PET | NR |
RCT [27] | 30 | 73.0 | AD | NR | 10 | 20 | RSG 4 mg | 6 months | MMSE | Insulin FPG | NR |
RCT [28] | 579 | NR | Mild to moderate AD | √ | 165 | 166 | RSG 2, 8 mg | 24 weeks | NR | NR | √ |
Neuropsychological | Results | |||
---|---|---|---|---|
SMD | 95% CI | I2 | ||
1. ADAS-COG | −0.07 | −0.13, −0.01 | 11.5% | |
Drug | PIO | −0.39 | −0.70, −0.08 | 28.6% |
RSG | −0.06 | −0.12, 0.00 | 0% | |
Dose | L | −0. 08 | −0.16, 0.00 | 0% |
M | −0.03 | −0.12, 0.06 | 0% | |
H | −0.39 | −0.70, −0.08 | 28.6% | |
Disease | Mild to moderate AD | −0.05 | −0.12, 0.01 | 0% |
AD with DM | −0.82 | −1.35, −0.28 | 33.3% | |
AD | −0.11 | −0.27, 0.05 | 0% | |
Duration | 24 weeks | −0.11 | −0.21, 0.00 | 31.8% |
L | −0.05 | −0.22, 0.12 | 0% | |
M | −0.09 | −0.26, 0.09 | 0% | |
H | −0.53 | −0.90, −0.16 | 43.2% | |
48 weeks | −0.05 | −0.12, 0.02 | 0% | |
L | −0.09 | −0.19, 0.01 | 46.7% | |
M | −0.01 | −0.11, 0.09 | 0% | |
H | −0.13 | −0.91, 0.64 | - | |
72 weeks | −0.04 | −0.82, 0.75 | - | |
M | 0.29 | −0.22, 0.80 | - | |
H | −0.04 | −0.82, 0.75 | - | |
Region | America | −0.06 | −0.12, −0.00 | 0% |
Europe | 0.29 | −0.22, 0.80 | - | |
Asia | −0.73 | −1.16, −0.30 | 0% | |
2.CDR-SB | −0.06 | −0.14, 0.01 | 43.3% | |
Drug | PIO | 0.22 | −0.14, 0.58 | 0% |
RSG | −0.07 | −0.15, −0.00 | 60.8% | |
Dose | L | −0.14 | −0.25, −0.04 | 72.0% |
M | −0.00 | −0.11, 0.10 | 0% | |
H | 0.22 | −0.14, 0.58 | 0% | |
Disease | Mild to moderate AD | −0.07 | −0.15, −0.00 | 60.8% |
AD with DM | 0.40 | −0.21, 1.02 | - | |
AD | 0.12 | −0.33, 0.57 | 0% | |
Duration | 24 weeks | 0.17 | −0.30, 0.65 | 28.6% |
48 weeks | −0.07 | −0.14, −0.00 | 59.6% | |
72 weeks | 0.04 | −0.74, 0.83 | - | |
Region | America | −0.07 | −0.14, 0.00 | 40.4% |
Europe | 0.40 | −0.21, 1.02 | - | |
3. DST | 1.01 | 0.78, 1.42 | 95.7% | |
4. MMSE | 0.37 | −0.09, 0.83 | 0% | |
5. RAVLT | −0.15 | −0.44, 0.13 | 0% | |
Metabolic | Results | |||
SMD | 95% CI | I2 | ||
1. FPG (mg/dL) | −0.07 | −0.13, −0.01 | 0% | |
2. HOMA %(-) | 0.13 | −0.14, 0.41 | 85.5% | |
3. Insulin (μU/mL) | 0.02 | −0.29, 0.32 | 80.4% | |
4. TNF-α (pg/mL) | −0.60 | −1.04, −0.15 | 19.8% | |
5. IL-6 (pg/mL) | −0.30 | −0.73, 0.14 | 0% | |
6. CRP (mg/L) | −0.18 | −0.62, 0.25 | 73.4% |
AEs | Results | ||||
---|---|---|---|---|---|
RR | 95% CI | I2 | Risk | ||
1. Any AEs | 0.82 | 0.78, 0.86 | 96.9% | ||
Drug | PIO | 0.21 | 0.17, 0.25 | 85.0% | |
RSG | 1.06 | 1.01, 1.11 | 57.3% | ||
Dose | 0.8 mg | 0.98 | 0.94, 1.03 | - | |
2 mg | 1.02 | 0.99, 1.05 | 0% | ||
15 mg | 7.42 | 0.96, 57.44 | 0% | ||
Duration | 24 weeks | 0.97 | 0.88, 1.06 | 57.7% | |
48 weeks | 1.05 | 1.00, 1.11 | 74.8% | ||
72 weeks | 9.60 | 0.56, 163.58 | - | ||
Disease | Mild to moderate AD | 1.06 | 1.01, 1.12 | 28.3% | |
AD with DM | 7.00 | 0.38, 127.69 | - | ||
AD | 0.35 | 0.30, 0.40 | 98.2% | ||
2. Anaemia | 5.96 | 3.25, 10.95 | 35.3% | high | |
Drug | PIO | 1.61 | 0.31, 8.24 | - | |
RSG | 6.80 | 3.51, 13.18 | 28.8% | ||
3. Peripheral oedema | 4.35 | 3.29, 5.75 | 79.9% | high | |
Dose | 2 mg RSG | 2.31 | 1.50, 3.54 | 72.7% | |
8 mg RSG | 6.39 | 4.36, 9.38 | 72.0% | ||
4. Bone fractures | 0.86 | 0.67, 1.11 | 0% | ||
5. Cardiac failure | 0.66 | 0.34, 1.29 | 0% | ||
Drug | PIO | 0.62 | 0.30, 1.28 | - | |
RSG | 1.00 | 0.14, 7.04 | 0% | ||
6. Diarrhoea | 1.05 | 0.78, 1.42 | 0% | ||
7. Dizziness | 1.19 | 0.84, 1.68 | 0% | ||
8. Hepatic disorders | 0.61 | 0.38, 0.98 | 0% | ||
9. Headache | 0.77 | 0.40, 1.48 | 38.3% | ||
10. Hyperlipidaemia | 4.98 | 1.71, 14.50 | 6.8% | high | |
11. Hypoglycaemia | 0.81 | 0.55, 1.19 | 0% | ||
12. Insomnia | 0.64 | 0.23, 1.79 | 0% | ||
13. Muscle pain | 3.26 | 1.81, 5.87 | 37.9% | ||
14. Nasopharyngitis | 1.23 | 0.92, 1.65 | 0% | ||
15. Nausea | 2.07 | 0.75, 5.70 | 0% |
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Zhong, H.; Geng, R.; Zhang, Y.; Ding, J.; Liu, M.; Deng, S.; Tu, Q. Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis. Biomedicines 2023, 11, 246. https://doi.org/10.3390/biomedicines11020246
Zhong H, Geng R, Zhang Y, Ding J, Liu M, Deng S, Tu Q. Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis. Biomedicines. 2023; 11(2):246. https://doi.org/10.3390/biomedicines11020246
Chicago/Turabian StyleZhong, Hongfei, Rulin Geng, Yu Zhang, Jingwen Ding, Miao Liu, Shengfeng Deng, and Qiuyun Tu. 2023. "Effects of Peroxisome Proliferator-Activated Receptor-Gamma Agonists on Cognitive Function: A Systematic Review and Meta-Analysis" Biomedicines 11, no. 2: 246. https://doi.org/10.3390/biomedicines11020246