Table 3 Systematic reviews and meta-analyses of biofluid and genetic biomarkers of cognitive impairment in Parkinson’s disease
Ref. | Study design | Included studies (N, design) | Included subjects (N, diagnosis) | Biomarker | Cognitive dysfunction severity | Group comparisons | Main results | Conclusions | |
|---|---|---|---|---|---|---|---|---|---|
Type | Purpose | ||||||||
Biofluids (CSF) | |||||||||
SR | N: 58, cross-sectional, prospective cohort (14 on PD-CI) | PD-NC: 1696 PD-MCI: 62 PD-D: 136 | ILs, serpin A1, BDNF, Aß1-42; t-tau; p-tau; APO A1/A2/ε; VDBP | Diagnosis Prognosis | PD-MCI or PD-D | PD-MCI/PD-D vs PD-NC | Cross-sectional. Lower CSF Aß1-42 associated with single cognitive domain dysfunction and PD-D. Increased CSF p-tau and t-tau correlate with poorer cognitive performance Longitudinal. Aß1-42 is a predictor of cognitive decline and dementia in PD | CSF amyloid fractions and tau-protein may be associated and have predictive value in the development of CI in PD | |
MA | N: 16, retrospective, prospective and cross-sectional | PD-NC: 1182 PD-CI (PD-MCI or PD-D): 590 | Aß42; t-tau; p-tau | Diagnosis | PD-MCI or PD-D | PD-MCI vs PD-NC PD-D vs PD-NC | Lower CSF Aß42 (SMD: -0.44; 95% CI: [-0.61, -0.26]; p < 0.00001) levels in PD-CI vs PD-NC Lower CSF Aß42 (SMD: −0.60; 95% CI: [−0.75, −0.45]; p < 0.00001), increased t-tau (SMD: 0.21; 95% CI: [0.06, 0.35]; p = 0.006) and p-tau (SMD: 0.36; 95% CI: [0.02, 0.69]; p = 0.04) levels in PD-D vs PD-NC | Amyloid pathology and tauopathy may participate in the development of PD-D | |
Biofluids (plasma/serum) | |||||||||
MA | N: 15, cross-sectional | PD-NC: 843 PD-CI: 573 | Plasma Hcy, vitamin B12, and folate | Diagnosis | PD-CI | PD-CI vs PD-NC | Higher Hcy (MD: 5.05; 95% CI: [4.03, 6.07]), and lower vitamin B12 (MD: -47.58; 95% CI: [-72.07, -23.09]) and folate levels (MD: -0.21; 95% CI: [-0.34, -0.08]) in PD-CI vs PD-NC | Increased Hcy and reduced vitamin B12 and folate levels are potentially associated with PD-CI | |
MA | N: 16, cross-sectional (4 on PD-CI) | PD: 411 | Serum Cys C | Diagnosis | PD-MCI | PD-MCI vs PD-NC | Higher Cys C serum levels (SMD: 1.29; 95% CI: [0.47, 2.10]; p < 0.05) in PD-MCI vs PD-NC | Serum Cys C may be a promising biomarker for PD-CI | |
Biofluids (combined CSF and blood) | |||||||||
MA | N: 51, cross-sectional (7 including PD-D patients) | PD-NC: 414 PD-D: 163 | CSF and blood biomarkers of BBB disruption | Diagnosis | PD-D | PD-D vs PD-NC | Increased blood NfL level (SMD: 0.60; 95% CI: [0.35, 0.84; p < 0.001) and Qalb (SMD: 0.48; 95% CI: [0.19, 0.77]; p = 0.010) in PD-D vs PD-NC | BBB disruption may be involved in CI in PD | |
Genetics | |||||||||
MA | N: 6 case-control | PD | BDNF Val66Met polymorphism | Prognosis | PD-CI | PD-CI vs PD-NC | BDNF Val66Met polymorphism is significantly associated with CI in Caucasian PD populations | BDNF Val66Met polymorphism may be a risk factor for PD-CI among Caucasians | |
MA | N: 6 case-control | PD-NC: 547 PD-CI: 340 | BDNF Val66Met polymorphism | Prognosis | PD-CI | PD-CI vs PD-NC | BDNF Val66Met is associated with increased risk of CI in additive (OR: 3.82; 95% CI: [1.32, 11.08]; p = 0.01) and recessive (OR: 3.81; 95% CI: [1.38, 10.53]; p = 0.01) models in Caucasians | Homozygote BDNF Val66Met may be associated with increased risk of PD-CI among Caucasians | |
