Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease

Bäckström, David; Domellöf, Magdalena Eriksson; Lindér, Jan; Olsson, Bob; Öhrfelt, Annika; Trupp, Miles; Zetterberg, Henrik; Blennow, Kaj; Forsgren, Lars

doi:10.1001/jamaneurol.2015.1449

Cited by 159 publications

(136 citation statements)

References 41 publications

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“…Two cross-sectional studies reported an association between low CSF Aβ 42 levels and cognitive impairment in PD 90,91 . In addition, four longitudinal studies reported that reduced Aβ 42 predicted more rapid cognitive decline 92–95 , confirming previous findings 96–98 (TABLE 2). DeNoPa, a multimodal biomarker study in de novo PD 99 , found no link between PD progression and CSF markers, but the results could have been confounded by the low number of participants agreeing to serial CSF sampling, variations in CSF sample preparation, and the demographics of the cohort.…”

Section: Biomarkers Of Cognitive Decline In Pdsupporting

confidence: 87%

Cognitive decline in Parkinson disease

et al. 2017

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Dementia is a frequent problem encountered in advanced stages of Parkinson disease (PD). In recent years, research has focused on the pre-dementia stages of cognitive impairment in PD, including mild cognitive impairment (MCI). Several longitudinal studies have shown that MCI is a harbinger of dementia in PD, although the course is variable, and stabilization of cognition — or even reversal to normal cognition — is not uncommon. In addition to limbic and cortical spread of Lewy pathology, several other mechanisms are likely to contribute to cognitive decline in PD, and a variety of biomarker studies, some using novel structural and functional imaging techniques, have documented in vivo brain changes associated with cognitive impairment. The evidence consistently suggests that low cerebrospinal fluid levels of amyloid-β42, a marker of comorbid Alzheimer disease (AD), predict future cognitive decline and dementia in PD. Emerging genetic evidence indicates that in addition to the APOE*ε4 allele (an established risk factor for AD), GBA mutations and SCNA mutations and triplications are associated with cognitive decline in PD, whereas the findings are mixed for MAPT polymorphisms. Cognitive enhancing medications have some effect in PD dementia, but no convincing evidence that progression from MCI to dementia can be delayed or prevented is available, although cognitive training has shown promising results.

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Section: Biomarkers Of Cognitive Decline In Pdsupporting

confidence: 87%

Cognitive decline in Parkinson disease

et al. 2017

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“…Four studies were performed in North America (Liu et al 2015; Siderowf et al 2010; Stewart et al 2014; Terrelonge et al 2015) and five studies in Europe (Alves et al 2014; Backstrom et al 2015; Compta et al 2013; Hall et al 2015; Parnetti et al 2014). The studies involved 1218 subjects diagnosed with Parkinson's disease (PD).…”

Section: Resultsmentioning

confidence: 99%

Do CSF Biomarkers Predict Progression to Cognitive Impairment in Parkinson’s disease patients? A Systematic Review

Leaver

Poston

2015

Neuropsychol Rev

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Many patients with Parkinson's disease (PD) will develop cognitive impairment. Cross-sectional studies have shown that certain protein levels are altered in the cerebrospinal fluid (CSF) of PD patients with dementia and are thought to represent potential biomarkers of underlying pathogenesis. Recent studies suggest that CSF biomarker levels may be predictive of future risk of cognitive decline in non-demented PD patients. However, the strength of this evidence and difference between specific CSF biomarkers is not well delineated. We therefore performed a systematic review to assess if levels of specific CSF protein biomarkers are predictive of progression to cognitive impairment. Nine articles were identified that met inclusion criteria for the review. Findings from the review suggest a convergence of evidence that a low baseline Aβ42 in the CSF of non-demented PD patients predicts development of cognitive impairment over time. Conversely, there is limited evidence that CSF levels of tau, either total tau or phosphorylated tau, is a useful predictive biomarker. There are mixed results for other CSF biomarkers such as α-synuclein, Neurofilament light chain, and Heart fatty acid-binding protein. Overall the results of this review show that certain CSF biomarkers have better predictive ability to identify PD patients who are at risk for developing cognitive impairment. Given the interest in developing disease-modifying therapies, identifying this group will be important for clinical trials as initiation of therapy prior to the onset of cognitive decline is likely to be more efficacious.

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“…While the effects on cognition were different for the COMT and DRD2 genotypes, none of the genotypes affected cerebrospinal fluid NFL concentration (which has been found predictive of PDD) 35. This suggests that the COMT and DRD2 genotypes did not affect cognition through gross effects on neurodegeneration, at least not as measured by injury of myelinated axons.…”

Section: Discussionmentioning

confidence: 80%

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease

et al. 2017

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ObjectivesCognitive decline is common in Parkinson's disease (PD), but the underlying mechanisms for this complication are incompletely understood. Genotypes affecting dopamine transmission may be of importance. This study investigates whether genotypes associated with reduced prefrontal dopaminergic tone and/or reduced dopamine D2‐receptor availability (Catechol‐O‐methyltransferase [COMT] Val158Met genotype and DRD2 C957T genotype) affect the development of cognitive deficits in PD.Materials and methodsOne hundred and 34 patients with idiopathic PD, participating in a regional, population‐based study of incident parkinsonism, underwent genotyping. After extensive baseline investigations (including imaging and biomarker analyses), the patients were followed prospectively during 6‐10 years with neuropsychological evaluations, covering six cognitive domains. Cognitive decline (defined as the incidence of either Parkinson's disease mild cognitive impairment [PD‐MCI] or dementia [PDD], diagnosed according to published criteria and blinded to genotype) was studied as the primary outcome.ResultsBoth genotypes affected cognition, as shown by Cox proportional hazards models. While the COMT 158Val/Val genotype conferred an increased risk of mild cognitive impairment in patients with normal cognition at baseline (hazard ratio: 2.13, P = .023), the DRD2 957T/T genotype conferred an overall increased risk of PD dementia (hazard ratio: 3.22, P < .001). The poorer cognitive performance in DRD2 957T/T carriers with PD occurred mainly in episodic memory and attention.ConclusionsThe results favor the hypothesis that dopamine deficiency in PD not only relate to mild cognitive deficits in frontostriatal functions, but also to a decline in memory and attention. This could indicate that dopamine deficiency impairs a wide network of brain areas.

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Cerebrospinal Fluid Patterns and the Risk of Future Dementia in Early, Incident Parkinson Disease

Cited by 159 publications

References 41 publications

Cognitive decline in Parkinson disease

Cognitive decline in Parkinson disease

Do CSF Biomarkers Predict Progression to Cognitive Impairment in Parkinson’s disease patients? A Systematic Review

Polymorphisms in dopamine-associated genes and cognitive decline in Parkinson's disease

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