Early Parkinson's Disease Group Research Articles

Changes in substantia nigra and locus coeruleus in patients with early-stage Parkinson's disease using neuromelanin-sensitive MR imaging

Neuromelanin-sensitive magnetic resonance imaging is able to visualize changes associated with neuronal loss in the substantia nigra pars compacta (SNc) and locus coeruleus (LC) in patients with Parkinson's disease (PD). However, the diagnostic accuracy of this technique in the early stages of PD remains unknown. Therefore, changes in the SNc and LC observed using neuromelanin imaging were evaluated in patients with early PD. The signal intensities of the lateral, central, and medial parts of the SNc and that of the LC were measured, and the contrast ratios (CRs) were calculated against the adjacent white matter structures. CRs in the lateral part of the SNc and in the LC were significantly reduced in the early PD group when compared with the controls. Sensitivities and specificities in discriminating early PD patients from healthy controls were 73% and 87% in lateral SNc and 82% and 90% in LC, respectively. Neuromelanin imaging can depict signal alterations in the lateral part of the SNc and in the LC in patients with PD, even in its early stage, and can discriminate between these patients and healthy individuals with high sensitivities and specificities.

Parkinson's disease symptoms: The patient's perspective

Patients suffering from Parkinson's disease (PD) will typically experience a range of motor and nonmotor symptoms during the course of their illness, each of which will affect a particular individual to varying degrees. However, patients' perceptions of troublesome symptoms often differ from the clinician's view, and these discrepancies can hamper effective management of PD. In this study, we have assessed 265 consecutive PD patients by asking them to rank their three most troublesome symptoms in the last 6 months, so to gain further insight from the impact of illness on patients' quality of life. Patients were divided into early (<6 years) and late PD groups (>/=6 years) from symptom onset. The division at 6 years was based on the mean time from symptom onset to the development of motor complications. In the early PD group, the 5 most prevalent complaints (ranked in descending order) are slowness, tremor, stiffness, pain, and loss of smell and/or taste. In the advanced PD group, fluctuating response to their medication (most common: wearing-off phenomenon followed by dyskinesia), mood changes, drooling, sleep problems (most common: middle and late night insomnia followed by daytime sleepiness), and tremor were the top 5. Our findings provide further evidence for the diversity of experience in PD and suggest that as the disease advances the most troublesome issues that patients perceive are the lack of response to medication and the nonmotor aspects of the disease, highlighting the importance of assessment and patient-centered management in the follow-up of these patients.

Screening for two SNPs of LINGO1 gene in patients with essential tremor or sporadic Parkinson's disease in Chinese population

Two markers rs9652490 and rs11856808 both located in intron 3 of the LINGO1 gene have been nominated recently to be associated with essential tremor (ET). Although ET and Parkinson's disease (PD) are considered as different entities, they have many overlapping clinical and pathological features. We aimed to evaluate the role of rs9652490 and rs11856808 in the development of ET and PD. To this point, we sequenced the region involving the two markers in 109 ET cases, 425 sporadic Parkinson's disease (SPD) cases and 430 controls in Chinese population. After stratification by age, the rs9652490G allele suggested protective role in the early onset PD (EOPD, age at onset ≤50 years) group compared with age matched controls (OR = 0.56, 95% CI: 0.35–0.90, p = 0.015). No other significant association was found. We concluded that the two markers rs9652490 and rs11856808 were not strongly related to the development of ET or late onset SPD, but the rs9652490G allele might be a protective factor for EOPD in Chinese population.

Association between high-sensitivity C-reactive protein and risk of early idiopathic Parkinson’s disease

Although neuroinflammation is known to play an important role in the pathogeneses of neurodegenerative diseases, few studies have been conducted on the association between Parkinson's disease (PD) and high-sensitivity C-reactive protein (hs-CRP), which is the most studied biomarker of systemic inflammation. Therefore, we conducted this study to determine the clinical correlates of hs-CRP levels in early PD patients by comparing findings with those of normal controls. Sixty-three drug-naïve patients with early PD and 117 healthy subjects were recruited, and hs-CRP level differences were investigated in these two groups. It was found that hs-CRP levels in the early PD group were higher than those of healthy controls. Furthermore, when compared with normal controls, the odds ratio for PD based on hs-CRP level cut-off of 0.5 was 2.094 (95% CI = 1.017-4.311, P = 0.045). In this study, our findings support the hypothesis that neuroinflammatory reactions play an important role in the pathogenesis of PD.

Mapping of brain acetylcholinesterase alterations in Lewy body disease by PET

To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB). Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis. Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced. Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.

Are dopaminergic pathways involved in theory of mind? A study in Parkinson's disease

The “orbitofrontal” and “cingulate” frontostriatal loops and the mesolimbic dopaminergic system that modulates their function have been implicated in theory of mind (ToM). Parkinson's disease (PD) provides a model for assessing their role in humans. Results of the handful of previous studies of ToM in PD providing preliminary evidence of impairment remain controversial, mainly because the patients included in these studies were not accurately described, making it difficult to determine whether their ToM deficits were due to general cognitive deterioration or to a more specific dopaminergic deficit. The aim of our study was therefore to re-examine previous results highlighting ToM in PD and to explore the involvement of the dopaminergic pathways in ToM. ToM was investigated in 17 newly diagnosed PD patients (early PD group), 27 PD patients in the advanced stages of the disease (advanced PD group) and 26 healthy matched controls (HC), using two ToM tasks: a visual one, which is thought to reflect the “affective” ToM subcomponent (“Reading the Mind in the Eyes”), and a verbal one, which is thought to reflect both the “affective” and the “cognitive” ToM subcomponents (faux pas recognition). Furthermore, the early PD group was studied in two conditions: with and without dopamine replacement therapy (DRT). We failed to find any significant difference in ToM between the early PD patients and the HC group. Furthermore, there was no difference between the early PD patients in the medicated and unmedicated conditions. Conversely, the advanced PD patients scored poorly on the intention attribution question (“cognitive” ToM score) in the faux pas recognition task. The present results suggest that the deficit in ToM only occurs in the more advanced stages of the disease. In addition, our results would appear to indicate that these advanced PD patients present “cognitive” ToM impairment rather than global (“cognitive” and “affective”) ToM impairment. In other words, the ToM deficit would appear to be present in PD patients where the degenerative process has spread beyond the dopaminergic pathways, but not in early PD patients where neuronal loss is thought to be restricted to the nigrostriatal and mesolimbic dopaminergic systems. In conclusion, our results suggest that the dopaminergic pathways are not involved in ToM.

Effects of Parkinson Disease on Two Putative Nondeclarative Learning Tasks

To assess performance on two nondeclarative (implicit) memory tasks of Parkinson disease (PD) patients without dementia in the earlier or later stages of the disease (Hoehn and Yahr Scale scores of 1-2.5 or 3-4, respectively). Different subtypes of nondeclarative memory appear to depend on different components of frontostriatal circuitry. Performance on a probabilistic classification learning (PCL) task was impaired by striatal damage (eg, in PD or Huntington disease) but not by circumscribed frontal lobe damage. On the other hand, performance on the Iowa Gambling Task (IGT) was impaired by damage to the prefrontal cortex. On the PCL, the learning of the control (age- and education-matched) group (n = 19) and the early PD group (n = 16) was comparable with each other, and both groups showed better performance than the later PD group (n = 16). On the IGT, the control group learned better than both of the PD groups. The control and early PD groups were similar on measures from the Wisconsin Card Sorting Test, Stroop Test, Mini-Mental State Examination, and Beck Depression Inventory II. The PCL and IGT tasks appear to rely on different parts of the frontostriatal circuitry in patients with early PD. The current finding that IGT performance was impaired in early PD implies ventromedial prefrontal cortical dysfunction early in the disease.

Cerebrospinal fluid homovanillic acid levels are not reduced in early corticobasal degeneration

To investigate the contribution of nigral degeneration to the development of parkinsonism in the early stages of corticobasal degeneration (CBD), we measured the cerebrospinal fluid (CSF) levels of homovanillic acid (HVA) in patients with early CBD ( n=5), and compared the levels with those in patients with early Parkinson's disease ( n=11) and in normal subjects ( n=13). The mean CSF HVA level in the early CBD group (33.1±6.0 ng/ml) did not differ significantly from that in the control group (37.1±12.7 ng/ml), whereas that in the early Parkinson's disease group (19.0±7.6 ng/ml) was reduced significantly ( P<0.001). This result suggests that neuronal cell loss in the substantia nigra and presynaptic nigrostriatal dopaminergic neuron dysfunction are mild in the early stages of CBD.