Highlights
- •WMHs and cerebrospinal fluid CSF markers were determined in 39 PD patients (19 with dementia) and 12 healthy controls;
- •Cross-sectionally, parieto-occipital WMHs were independently associated with PD-dementia and decreasing CSF Aβ levels;
- •Longitudinally, moderate-to-severe parieto-occipital WMHs and low CSF Aβ were associated with progression to dementia;
- •Combined assessment of parieto-occipital WMHs and CSF Aβ might be a PD-dementia risk marker.
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 18 months. 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 18 months 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.
Keywords
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Article info
Publication history
Published online: June 10, 2016
Accepted:
June 3,
2016
Received in revised form:
April 24,
2016
Received:
February 15,
2016
Footnotes
☆Funding: Fundació la Marató de TV3 2006 (N-2006-TV060510).
Identification
Copyright
© 2016 Published by Elsevier B.V.
