Changes of cerebrospinal fluid Aβ42, t-tau, and p-tau in Parkinson's disease patients with cognitive impairment relative to those with normal cognition: a meta-analysis

The cerebrospinal fluid (CSF) signature of reduced amyloid beta 1-42 (A beta(42)), elevated total tau (t-tau), and phosphorylated tau181 (p-tau) is important for the early diagnosis of Alzheimer's disease (AD). A beta(42), t-tau, and p-tau have been reported in numerous studies to contribute to predicting cognitive impairment in Parkinson's disease (PDCI). However, no consistent conclusion can be drawn so far. Literatures regarding A beta(42), t-tau, and p-tau in CSF were systematically reviewed, and a meta-analysis was thus performed to evaluate the changes of these biomarkers in PDCI patients, including PD with mild cognitive impairment (PDMCI) and PD dementia (PDD) patients, relative to PD with normal cognition (PDNC) patients. Databases of PubMed, EBSCO, and Springer were retrieved for articles concerning A beta(42), t-tau, and p-tau in PDCI patients relative to those in PDNC patients published from January 1, 2000 to February 1, 2017. The following keywords were set, namely, dementia or cognitive impairment or mild cognitive impairment and cerebrospinal fluid and Parkinson*. Sixteen articles comprising 590 PDCI patients and 1182 PDNC patients were included. The results showed that CSF A beta(42) level in PDCI cohort was lower than that in PDNC cohort (pooled Std.MD = -0.44, 95% CI [-0.61, -0.26], p < 0.00001). Reduced A beta(42) (pooled Std.MD = -0.60, 95% CI [-0.75, -0.45], p < 0.00001) as well as elevated t-tau (pooled Std.MD = 0.21, 95% CI [0.06, 0.35], p = 0.006) and p-tau (pooled Std.MD = 0.36, 95% CI [0.02, 0.69], p = 0.04) could be observed in PDD cohort compared with PDNC cohort. Therefore, amyloid pathology and tauopathy may participate in the development of PDD, which is similar to AD.