We know that Parkinson's patients have difficulties with memory and thinking throughout their disease process - from mild problems in a minority of patients when they are first diagnosed to eventual dementia in a significant number of patients later in the disease. Identifying those patients who are most likely to have these kind of problems is important for arranging appropriate support and making plans for the future. But more than this, it is key (as with all neurodegenerative disease) for identifying those who may benefit from future treatments as well as understading the underlying mechanism.
Whilst the PREDICT model aims to identify high risk groups in a non-invasive way, one of the most important biomarkers in the dementia field is increasingly cerebrospinal fluid (CSF). In Alzheimer's Disease, the most common form of dementia, it is well established that low levels of protein amyloid beta (Ab42) and elevated protein tau (t-tau and p-tau) in the CSF are the "signature" of the disease, reflecting the underlying proteins that accumulate in the brain. In Parkinson's disease the situation is less clear.
This study was a meta-analysis of 16 cohort studies looking at the CSF in Parkinson's patients. They included a number of different types of study including prospective, retrospective and cross-sectional studies and were able to compare different groups including those with mild cognitive impairment and Parkinson's Disease Dementia. A cautious note should be struck due to significant differences between the studies - for example levels of amyloid beta in patients with normal cognition ranged hugely from 322 to 971.6pg/ml. However, the finding of significantly lower amyloid beta in Parkinson's patients with dementia but not those with mild cognitive impairment and higher t-tau levels in Parkinson's patients with dementia and again not those with cognitive impairment is interesting.
We can't say from this study whether the CSF has a predictive value but if the "signature" of the CSF in Parkinson's Disease dementia is indeed similar to that in Alzheimer's Disease, it suggests similarities in the underlying pathophysiology that may be amenable to similar treatment approaches.
https://www.ncbi.nlm.nih.gov/pubmed/28808876
Abstract
The cerebrospinal fluid (CSF) signature of reduced amyloid beta 1-42 (Aβ42), elevated total tau (t-tau), and phosphorylated tau181 (p-tau) is important for the early diagnosis of Alzheimer's disease (AD). Aβ42, 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 Aβ42, 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 Aβ42, 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 Aβ42 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 Aβ42 (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.
Whilst the PREDICT model aims to identify high risk groups in a non-invasive way, one of the most important biomarkers in the dementia field is increasingly cerebrospinal fluid (CSF). In Alzheimer's Disease, the most common form of dementia, it is well established that low levels of protein amyloid beta (Ab42) and elevated protein tau (t-tau and p-tau) in the CSF are the "signature" of the disease, reflecting the underlying proteins that accumulate in the brain. In Parkinson's disease the situation is less clear.
This study was a meta-analysis of 16 cohort studies looking at the CSF in Parkinson's patients. They included a number of different types of study including prospective, retrospective and cross-sectional studies and were able to compare different groups including those with mild cognitive impairment and Parkinson's Disease Dementia. A cautious note should be struck due to significant differences between the studies - for example levels of amyloid beta in patients with normal cognition ranged hugely from 322 to 971.6pg/ml. However, the finding of significantly lower amyloid beta in Parkinson's patients with dementia but not those with mild cognitive impairment and higher t-tau levels in Parkinson's patients with dementia and again not those with cognitive impairment is interesting.
We can't say from this study whether the CSF has a predictive value but if the "signature" of the CSF in Parkinson's Disease dementia is indeed similar to that in Alzheimer's Disease, it suggests similarities in the underlying pathophysiology that may be amenable to similar treatment approaches.
https://www.ncbi.nlm.nih.gov/pubmed/28808876
Neurol Sci. 2017 Aug 14. doi: 10.1007/s10072-017-3088-1. [Epub ahead of print]
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.
Hu X, Yang Y, Gong D
Abstract
The cerebrospinal fluid (CSF) signature of reduced amyloid beta 1-42 (Aβ42), elevated total tau (t-tau), and phosphorylated tau181 (p-tau) is important for the early diagnosis of Alzheimer's disease (AD). Aβ42, 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 Aβ42, 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 Aβ42, 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 Aβ42 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 Aβ42 (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.
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