Uric acid associates with cognition in Parkinson's disease

doi:10.1016/j.parkreldis.2007.11.001

Parkinsonism & Related Disorders

Volume 14, Issue 7, November 2008, Pages 576-578

https://doi.org/10.1016/j.parkreldis.2007.11.001 Get rights and content

Abstract

Cognitive dysfunction is common in Parkinson's disease (PD). Low plasma uric acid level is a risk factor for PD but its association with cognitive impairment in PD has not been previously studied. In the present study urine uric acid level as well as plasma uric acid- and homocysteine levels were measured in 40 patients with PD. Comprehensive neuropsychological tests including computerized tasks were performed on all. Both low plasma and low urine uric acid levels associated with decreased neuropsychological performance. In multiple linear regression low urine uric acid level predicted worse performance in the Picture completion subtest of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) (p = 0.003) and in the Rule shift cards test of the Behavioral Assessment of the Dysexecutive Syndrome (BADS) (p = 0.04). Low plasma uric acid level predicted worse performance both in the Picture completion (p = 0.02) and Similarities subtest of the WAIS-R (p = 0.02). Reaction time and the time spent on cognitive processing in the Statement verification task were inversely correlated with the uric acid levels (p = 0.0001). There was no correlation between the homocysteine level and neuropsychological performance. Instead, the plasma uric acid and homocysteine levels correlated significantly and their possible association in PD is discussed.

Introduction

Subtle cognitive changes are often detected early in Parkinson's disease (PD) [1] and poor initial performance on neuropsychological tests measuring verbal fluency [2] and in the Picture completion subtest of the WAIS-R [3] have been shown to predict subsequent dementia. The reasons for cognitive decline in PD are unclear though several risk factors have been identified [1], [4].

Low plasma uric acid level has been found to be a risk factor for PD [5], but its association with cognition has not been previously studied in PD. In the present study we measured plasma and daily urine uric acid concentrations in PD patients and assessed their cognition with comprehensive neuropsychological testing. The associations of the uric acid levels with cognitive changes and plasma homocysteine were examined.

Section snippets

Materials and methods

The characteristics of the study population (40 PD patients, mean age 60.8 years, 23 men and 17 women with post-diagnostic disease duration not more than 10 years) have been described previously in detail [6]. All patients signed a written informed consent. The study was approved by the Ethics Committee of Helsinki and Uudenmaa Health District Area. The neuropsychological testing and the laboratory sampling took place from February to October 2005.

The plasma uric acid levels were assessed from

Results

The median (range) plasma uric acid level was 287.5 mmol/l (153–467), urine uric acid level was 3.2 mmol/l (1.1–5.8) and homocysteine level was 9.3 μmol/l (6.4–21.6). Plasma uric acid level correlated with urine uric acid (r = 0.4, p = 0.02) and homocysteine (r = 0.40, p = 0.01) levels. The cognitive scores did not correlate with plasma homocysteine but several correlations with the uric acid levels were observed (Table 1).

As expected, education correlated with several neuropsychological parameters

Discussion

The present study shows that low plasma and urine uric acid levels associate with worse cognitive performance in PD. The finding is in accordance with the view that uric acid has neuroprotective properties, probably due to its action as both an antioxidant and iron chelator [7]. The Picture completion and Block design subtests are considered sensitive to subcortical damage, as they require both visuospatial and visuoconstructive abilities, sustained attention and good executive control. The

Acknowledgements

The study was supported by Jorvi Hospital Science Fund. We thank Dr. Marjatta Pohja for her comments on the manuscript.

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Gender-specific effect of urate on white matter integrity in Parkinson's disease
2020, Parkinsonism and Related Disorders
To investigate the potential protective influence of serum uric acid (UA) level on white matter (WM) microstructural changes in de novo Parkinson's disease (PD).
We enrolled a total of 184 patients with drug-naïve de novo PD and 59 age and gender-matched controls that underwent diffusion tensor imaging (DTI). Based on the distribution, serum UA levels were stratified into tertiles in PD patients by gender. Using tract-based spatial statistics (TBSS) analysis, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) were used to compare WM integrity between the groups.
Interaction analysis showed that interaction effect on FA values between gender and UA levels in PD was significant in widespread WM areas, including frontal-parieto-temporal, corpus callosum, bilateral internal and external capsule, and thalamic regions. Multiple regression analysis revealed that FA values had a significantly positive correlation with UA levels across widespread WM areas in male patients. However, there was no significant correlation between DTI measures and UA levels in female patients. In a group comparison in male patients, PD with the lowest UA level (PD-L-UA) group showed significantly lower FA and higher MD and RD values in frontal-parieto-temporal WM regions than PD with the highest UA level (PD-H-UA) group. However, female patients did not show significant difference of DTI measures between PD-L-UA and PD-H-UA groups.
The present study demonstrated that the serum UA levels may have the potentially gender-specific close relationship with WM integrity in the early stage of PD.
Gender-specific effect of uric acid on resting-state functional networks in de novo Parkinson's disease
2018, Parkinsonism and Related Disorders
The pattern of resting-state networks is influenced by several factors besides the underlying pathological changes of Parkinson's disease (PD). Uric acid (UA), as an antioxidant, has a neuroprotective property against PD-related microenvironment; however, this effect would be gender-specific. We aimed to evaluate a gender-sensitive resting-state networks (RSN) according to the UA level in drug naïve de novo patients with PD to elucidate the role of antioxidant in cortical functional networks of PD.
This study enrolled 135 de novo patients with PD underwent functional magnetic resonance imaging (MRI). Based on the distribution, the serum UA level was stratified into tertiles in the PD patients by gender. With a seed-based approach, we investigated the pattern of RSN within the dorsal attention network (DAN), executive control network (ECN), and default mode network (DMN).
Interaction analysis showed a significant interaction between the lowest (PD-L-UA) and the highest UA level (PD-H-UA) groups according to gender within the DAN, ECN, and DMN. Compared to the control subjects, male patients with PD-H-UA had higher cortical functional connectivity (FC), while female patients had lower cortical FC regardless of UA level within all seeds. In a direct comparison, male patients with PD-H-UA had increased FC than did those with PD-L-UA. However, there was no significant difference in FC between PD-L-UA and PD-H-UA in female PD patients.
These data suggest that RSN might be closely and gender-specifically associated with the status of serum UA in de novo PD patients.
Characteristics of gray matter morphological change in Parkinson's disease patients with semantic abstract reasoning deficits
2018, Neuroscience Letters
Citation Excerpt :
We realized that the proportion of female subjects was higher in PDSI than in PDSP, although this discrepancy did not reach statistical significance. It remains unclear whether female gender predicts lower scores on the Similarities test in PD patients [24,25]. A recent genetic study reported that the catechol-O-methyltransferase Met/Met genotype in PD patients might play a role [26].
Semantic abstract reasoning(SAR) is an important executive domain that is involved in semantic information processing and enables one to make sense of the attributes of objects, facts and concepts in the world. We sought to investigate whether Parkinson's disease subjects(PDs) have difficulty in SAR and to examine the associated pattern of gray matter morphological changes.
Eighty-six PDs and 30 healthy controls were enrolled. PDs were grouped into PD subjects with Similarities preservation(PDSP, n = 62) and PD subjects with Similarities impairment(PDSI, n = 24)according to their performance on the Similarities subtest of the Wechsler Adult Intelligence Scale. Brain structural images were captured with a 3T MRI scanner. Surface-based investigation of cortical thickness and automated segmentation of deep gray matter were conducted using FreeSurfer software.
PDs performed notably worse on the Similarities test than controls(F = 13.56, P < 0.001).In the PDSI group, cortical thinning associated with Similarities scores was found in the left superior frontal, left superior parietal and left rostral middle frontal regions. Notable atrophy of the bilateral hippocampi was observed, but only the right hippocampus volume was positively correlated with the Similarities scores of the PDSI group.
PDs have difficulty in SAR, and this limitation may be associated with impaired conceptual abstraction and generalization along with semantic memory deficits. Cortical thinning in the left frontal and parietal regions and atrophy in the right hippocampus may explain these impairments among Chinese PDs.
Biomarkers of Nonmotor Symptoms in Parkinson's Disease
2017, International Review of Neurobiology
Citation Excerpt :
A number of biochemical specimens other than CSF have been investigated. Low plasma and urine uric acid is related to cognitive decline in PD (Annanmaki, Pessala-Driver, Hokkanen, & Murros, 2008). It has been reported that low levels of plasma/serum epidermal growth factor and serum insulin-like growth factor-1 can be potential predictors for subsequent cognitive decline (Chen-Plotkin et al., 2011; Pellecchia et al., 2013, 2014).
Biomarkers are helpful for early diagnosis, assessment of disorder severity, prognosis, and prediction of response to therapy. Given that early therapeutic intervention may be useful in forestalling or slowing neurodegenerative conditions, employing reliable biomarkers to identify asymptomatic individuals who are destined to develop clinical Parkinson's disease (PD) is critical. Two important observations have been repeatedly found in persons who eventually develop clinical PD: (1) significant neuronal loss occurs in the substantia nigra and (2) the presence of nonmotor symptoms (NMS). Each of these findings occurs prior to the development of motor signs and symptoms, often preceding the clinical diagnosis of PD by a decade or more. As such, NMS themselves, and factors associated with their development may be useful clinical biomarkers for predicting future development of motor PD. Recently, research criteria for prodromal PD, defined as presence of motor and/or NMS, but not yet fulfilling the classic PD diagnosis, have been proposed by the International Parkinson and Movement Disorder Society Task Force. Although there are a small number of biomarkers associated with NMS of PD, in this chapter, discussion follows concerning the expanding literature associated with clinical, biochemical, imaging, and genetic biomarkers of NMS in patients with PD.
Homocysteine and cognition: A systematic review of 111 studies
2016, Neuroscience and Biobehavioral Reviews
Citation Excerpt :
Two studies with cross sectional analyses of cases were included. In Annanmaki et al. (2008), there was no association between the cognitive function scores and the plasma Hcy levels. Conversely, the study of Martin-Fernandez et al., showed higher Hcy levels in PD patients with levodopa treatment and cognitive impairment compared with those levodopa treated patients without cognitive impairment (Martin-Fernandez et al., 2010).
Elevated plasma homocysteine (Hcy) levels have been associated with cognitive dysfunction in a wide range of conditions. The aim of this review is to establish which cognitive domains and populations are the most affected.
We systematically review the literature and consider all articles that showed any relationship between plasma Hcy levels and scores achieved on cognitive performance tests in both, the general population and patients suffering from central nervous system disorders and other diseases. When effect sizes were available and combinable, several meta-analyses were performed.
We found 111 pertinent articles. There were 24 cohort studies, 18 randomized trials, 21 case-control studies, and 48 cross-sectional studies. This review reveals a positive trend between cognitive decline and increased plasma Hcy concentrations in general population and in patients with cognitive impairments. Results from the meta-analyses also confirm this trend. Treatment with vitamin supplementation fails to show a reduction in cognitive decline.
Further investigations are warranted to clarify this relationship. Earlier detection of the elevated Hcy levels may be an effective intervention to prevent cognitive impairment and dementia.
Association of serum uric acid level with cognitive function among patients with multiple system atrophy
2015, Journal of the Neurological Sciences
Citation Excerpt :
Parkinson's disease (PD), dementia with Lewy bodies and MSA belong to alpha-synucleinopathy diseases. Recently, some studies [16] [17] found uric acid play a key role in decreasing cognitive deficits in PD. Additionally, our previous study found low level of serum uric acid was associated with increased prevalence of MSA in a Chinese population [18].
Oxidative stress is involved in the pathogenesis of multiple system atrophy (MSA) and cognitive impairment. Uric acid has an anti-oxidative effect. Our objective is to clarify the correlations between serum uric acid and cognitive function as well as frontal lobe function in Chinese MSA patients.
All of MSA patients were evaluated using Addenbrooke's Cognitive Examination-Revised (ACE-R), Frontal Assessment Battery (FAB), and Unified MSA Rating Scale (UMSARS). The fasting serum uric acid concentrations of MSA patients were measured.
A total of 89 probable MSA patients with a mean age of 58.6 ± 10.0 years old and disease duration of 2.6 ± 1.5 years were included. Thirty-three patients (37.1%) had global cognitive deficits according to ACE-R. Based on FAB, 35 patients (39.3%) had frontal lobe dysfunction. After adjusting for educational years, patients with cognitive deficits had lower uric acid level than patients without cognitive deficits. Patients with frontal lobe dysfunction had lower uric acid level after adjusting for UMSARS scores. In a forward multiple linear regression, uric acid level and educational years were the variables predicting the ACE-R score (F = 36.540, R² = 0.459, p = 0.0001), uric acid accounting for 14% of the total variables. Uric acid was the only variable contributing to the FAB score (F = 18.551, R² = 0.176, p = 0.0001).
Our study suggested that low level of serum uric acid was associated with cognitive deficits in MSA. Low uric acid level predicting cognitive decline in MSA needs more studies.

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Short communicationUric acid associates with cognition in Parkinson's disease

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Atherosclerosis

A 10-year study of the incidence of and factors predicting dementia in Parkinson's disease

Neurology

Neuropsychological characteristics of preclinical dementia in Parkinson's disease

Neurology

Neuropsychological prediction of dementia in Parkinson's disease

J Neurol Neurosurg Psychiatry

Prevalence and characteristics of dementia in Parkinson disease: an 8-year prospective study

Arch Neurol

Serum uric acid levels and the risk of Parkinson disease

Ann Neurol

Low plasma uric acid level in Parkinson's disease

Mov Disord

Short communication
Uric acid associates with cognition in Parkinson's disease