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Biomarkers for cognitive impairment in Lewy body disorders: Status and relevance for clinical trials
Author(s) -
Siderowf Andrew,
Aarsland Dag,
Mollenhauer Brit,
Goldman Jennifer G.,
Ravina Bernard
Publication year - 2018
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.27355
Subject(s) - dementia with lewy bodies , lewy body , dementia , alpha synuclein , parkinson's disease , clinical trial , medicine , disease , movement disorders , cognitive decline , pathology , biomarker , psychology , neuroscience , biology , biochemistry
Biomarkers have the potential to improve diagnosis and prognosis, and guide clinical treatment decisions. In research, biomarkers can be used for patient selection and as outcome measures in clinical trials. A range of biochemical and imaging biomarkers are relevant to patients with Lewy body disorders, including PD, PD dementia, and dementia with Lewy bodies. Dopaminergic imaging is used for differential diagnosis of parkinsonian disorders versus tremor disorders without dopamingeric deficits, and also to differentiate dementia with Lewy bodies from Alzheimer's disease. Markers of underlying Alzheimer's disease pathology have been applied to PD patients experiencing cognitive decline to determine the extent of mixed pathology in these cases. Assessment of alpha‐synuclein species in spinal fluid is possible, and more specific assays attempt to identify alpha‐synuclein aggregates or phosphorylated alpha‐synuclein. While alpha‐synuclein markers are intended to measure the pathology most central to PD dementia and dementia with Lewy bodies, convincing evidence of robust reliability and validity from multiple laboratories is lacking. Similarly, alpha‐synuclein imaging by PET or single‐photon emission computed tomography, while an important research goal, is not yet available. In addition to their uses in the clinic, biomarkers have natural uses in therapeutic trials that target cognitive and neuropsychiatric features of Lewy body disorders. The biomarkers most likely to be incorporated into trials are dopaminergic and amyloid imaging for the purpose of accurate patient selection, and possibly to demonstrate the utility of antiamyloid treatments in Lewy body disorders patients with mixed pathology. © 2018 International Parkinson and Movement Disorder Society