White matter hyperintensities, cerebrospinal amyloid-β and dementia in Parkinson's disease

Abstract

White-matter hyperintensities (WMHs) have been related to small-vessel disease, but also to amyloid-β (Αβ) vascular deposition, particularly in parieto-occipital regions. Low cerebrospinal fluid (CSF) Aβ [1-42] levels (biomarker of parenchymal and/or vascular Aβ deposition) and WMHs have been associated with Parkinson's disease (PD) and related dementia (PDD), separately but not in combination. We studied 50 subjects: 38 PD patients (19 non-demented [PDND]+19 PDD) and 12 healthy-controls. Baseline regional WMHs from FLAIR MRI-sequences were dichotomized into none-to-mild vs. moderate-to-severe by an expert radiologist blind to clinical and CSF data using an adaption of the Age-Related White Matter Changes scale. Baseline CSF α-synuclein, τ and Aβ [1-42] levels were determined with ELISA techniques. Progression to dementia in PDND patients was clinically evaluated at 18months. For analyses purposes patients were considered altogether (PDND+PDD) and separately (PDND vs. PDD). At baseline, moderate-to-severe parieto-occipital WMHs were significantly more frequent in PDD than in PDND (p=0.049) and controls (p=0.029), without significant differences in other regions. In regression models CSF Aβ was significantly associated in the entire PD cohort with moderate-to-severe parieto-occipital WMHs independently of age, vascular risk factors, APOE-4 and dementia. There were no associations with CSF α-synuclein and τ. Progression to dementia at 18months was more frequent in patients with moderate-to-severe parieto-occipital WMHs and low CSF Aβ vs. those with none-to-mild parieto-occipital WMHs and normal CSF Aβ (p=0.007). It remains to be seen whether the relationship between CSF Aβ and WMHs in PD and their association with PD-dementia is a reflection of not only parenchymal, but also vascular Αβ deposition.