Effect of olfactory impairment and white matter hyperintensities on cognition in Parkinson's disease
Introduction
The olfactory dysfunction occurs in early stages of clinical Parkinson's disease and in asymptomatic relative of PD patient with a prevalence of approximately 90% [1]. As the olfactory system is one of induction sites for α-synuclein, neurodegenerative changes in this system occur early in the course of PD [2], [3]. Importantly, recent studies have demonstrated a close association between olfactory dysfunction and cognitive status as well as ongoing cognitive decline in patients with PD [4]. Therefore, olfactory performance in the early stage of PD seems to play an important role in modulation of PD-related cognitive performance.
Previous studies have shown that microstructural or gross abnormality around white matter regions of olfactory system appear to negatively influence on olfactory performance in several disease entities, including idiopathic hyposmic subjects [5], and mild cognitive impairment (MCI) [6]. Similarly, microstructural alterations in the white matter of the central olfactory system that are associated with impaired olfaction are present in early stage PD patients [7]. Additionally, the burden of white matter hyperintensities (WMH) is a major contributor to the development of dementia in patients with PD-MCI [8]. These studies suggest that the concurrent presence of white matter pathologies and olfactory dysfunction may have a negative additive impact on cognitive performance in patients with PD.
Based on magnetic resonance imaging (MRI) scans, WMH may be categorized as deep WMH (DWMH), or patchy areas of WMH in subcortical white matter, and periventricular WMH (PWMH), which are adjacent to the cerebral ventricles [9]. These WMH subtypes exhibit different neuropathologies [10] and etiological mechanisms [9], [11]. Thus, the present study investigated the effects of WMH on olfactory dysfunction and cognitive impairments according to WMH type in patients with non-demented PD. Additionally, this study evaluated whether the concurrent presence of WMH and olfactory dysfunction has an additive influence on cognitive performance by analyzing neuropsychological test data according to WMH severity and the degree of olfactory dysfunction.
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Subjects
The present study was retrospective and utilized 171 patients with non-demented PD who were recruited from a university hospital between January 2008 and January 2013. Of patients enrolled in this study, 54 and 35 patients participated in our previous studies dealing with olfaction and white matter hyperintensities in PD [2], [8], respectively, and 23 patients participated in both previous studies. PD was diagnosed according to the clinical diagnostic criteria of the United Kingdom PD Society
Demographic characteristics and neuropsychological data
The demographic characteristics of the subjects are provided in Table 1. No significant differences age, in gender, vascular risk factors, or vascular events were found between PD and normal controls. General cognitive deficits were significantly greater in PD (27.0) than in control subjects (28.3). The mean duration of PD was 32 months and the mean scores for parkinsonian motor severity and the CCSI were 22.6, and 6.2, respectively. The WMH severity scores for DWMH (5.3 versus 3.6, p = 0.029),
Discussion
The present study investigated the effects of the simultaneous presence of WMH and olfactory dysfunction on cognitive performance in non-demented patients with PD. The major findings of this study were that (1) the influence of WMH on olfactory performance was more prominent in PD with DWMH than in those with PWMH, (2) DWMH severity had a negative impact on semantic fluency, and (3) when severe olfactory dysfunction and high-grade DWMH existed at a same time there was an increased risk for
Acknowledgment
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HI14C0093).
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