Many patients with Parkinson's disease develop mild cognitive impairment ( MCI ) or dementia. Identifying biomarkers for cognitive impairment could be instrumental in facilitating both early diagnosis of MCI and developing new cognitive-enhancing treatments.
New research has indicated that lower concentrations of alpha-synuclein in cerebrospinal fluid ( CSF ) is associated with reduced performance on several cognitive tests.
This is the largest study exploring the association between CSF biomarkers and cognition in Parkinson's disease, and one of few to explore if alpha-synuclein is associated with cognitive impairment.
CSF markers beta-amyloid42 ( abeta42 ), total tau protein ( t-tau ), phosphorylated tau protein ( p-tau ), and alpha-synuclein reflect pathophysiological changes relevant to cognition in Parkinson's disease.
If changes in these biomarkers can predict cognitive decline, patients could be informed to seek possible treatments.
Part of the Parkinson's Progression Markers Initiative ( PPMI ), an international project focusing on development of biomarkers of progression in Parkinson's disease, this study was comprised of 414 patients with untreated Parkinson without dementia and 196 health control subjects from 24 clinical sites worldwide.
The patients were evaluated for multiple cognitive skills, including visuospatial functions, verbal memory, executive function, and attention.
Patients were defined as having MCI if they showed impairment on two or more tests, while patients not fulfilling criteria for MCI were classified as having normal cognition.
The Unified Parkinson's Disease Rating Score ( UPDRS ) was used to evaluate the progression of the disease in the patients with Parkinson's disease.
The investigation determined that lower alpha-synuclein was associated with reduced performance in cognition testing in the whole Parkinson-group.
Abeta42 was significantly decreased in Parkinson's disease with mild cognitive impairment compared with controls, while values in Parkinson's disease without MCI were identical to the controls.
After analyzing demographics and the results of CSF analysis, there were no significant differences in gender, age, or education between Parkinson and control patients.
Among the patients with Parkinson's disease, 140 MCI subjects were significantly older, had less formal education, and had higher UPDRS scores than the 274 subjects with Parkinson having normal cognition.
The association between reduced CSF alpha-synuclein concentrations and cognition suggests that alpha-synuclein pathology contributes to early cognitive impairment in Parkinson's disease, in particular to executive-attentional dysfunction.
Longitudinal analyses are needed to determine if this and other CSF biomarkers in early Parkinson's disease are associated with the risk of future cognitive decline and dementia. ( Xagena )
Source: Journal of Parkinson's Disease, 2016