Mild cognitive impairment (MCI) is one of the common non-motor symptoms in patients with Parkinson’s disease (PD). MCI is the transition stage between normal aging and full-blown dementia and is also ...a powerful predictor of dementia. Although the concept of MCI has been used to describe some of the PD symptoms for many years, there is a lack of consistent diagnostic criteria. Moreover, because of the diverse patterns of the cognitive functions, each cognitive impairment will have a different progression. In this review, we overviewed the diagnostic criteria for PD-MCI, primarily focused on the heterogeneity of PD-MCI patients’ cognitive function, including various types of cognitive functions and their progression rates. A review of this topic is expected to be beneficial for clinical diagnosis, early intervention, and treatment. In addition, we also discussed the unmet needs and future vision in this field.
Monoamine neurotransmitters play essential roles in the regulation of arousal and sleep. Impaired metabolism of monoamine neurotransmitters could result in the accumulation of neurotoxic aldehyde ...metabolites and, hence, neuronal degeneration. Aldehyde dehydrogenases play an important role in the metabolism of the neurotoxic aldehyde metabolites, including the aldehyde metabolites of dopamine, serotonin, and noradrenaline. Deficient aldehyde dehydrogenase 2 (ALDH2) has been suggested to result in the accumulation of these biogenic aldehydes. An ALDH2 single nucleotide polymorphism (SNP), rs671 (A), results in significantly reduced ALDH2 enzyme activity. A total of 83 Parkinson's disease (PD) patients were recruited in this study. In addition to the genotypes of rs671, the patients were assessed with the PD sleep scale-2nd version (PDSS-2) and the Epworth sleepiness scale (ESS) for symptoms of daytime and nocturnal sleep disturbances. The patients carrying rs671 (A) had more frequent dozing while lying down to rest in the afternoon (ESS item5) (F = 7.308, p = 0.008) than the rs671 (GG) patients. The patients with rs671 (A) reported a trend toward more frequent difficulty staying asleep than the patients with rs671 (GG). (F = 3.278, p = 0.074). The results indicate that patients carrying allele rs671 (A) are more likely to experience impairment in the regulation of arousal and sleep. The results also support the hypothesis that the accumulation of neurotoxic monoamine neurotransmitter aldehyde metabolites secondary to reduced ALDH2 enzyme activity may cause more severe monoaminergic neuronal loss and, hence, more severe symptoms in the regulation of wakefulness and sleep.
Elevated levels of interleukin 1β (IL‐1β) have been identified in patients with chronic viral hepatitis and have been associated with depressive symptoms. Given the high prevalence of depression in ...this patient population, this study sought to explore the potential influence of IL‐1β genetic variations on the severity of depressive symptoms. In a cohort of 181 Taiwanese patients with chronic viral hepatitis, we investigated the impact of five common IL‐1β single nucleotide polymorphisms (SNPs), including rs16944, rs1143627, rs1143630, rs1143643, and rs3136558, on depressive symptoms using the Beck's Depression Inventory‐II. Additionally, we analyzed the primary domains of IL‐1β‐related depressive symptoms according to Beck's six symptom categories of depression. Our analysis revealed significant associations between depressive symptoms and three intronic IL‐1β SNPs. After controlling for age, sex, marital status, and education level, patients with the rs1143630 GG, rs1143643 CC, and rs3136558 AA genotypes demonstrated higher severity of depressive symptoms in the domains of indecision (p = 0.004), agitation (p = 0.001), and feelings of punishment (p = 0.005), respectively, compared to rs1143630 GA+AA, rs1143643 CT, and rs3136558 AG+GG genotypes. According to Beck's categorization, these symptoms can be classified into three dimensions: disturbances in emotion regulation, energy, and cognition. Our findings demonstrate the association between IL‐1β polymorphisms and depressive symptoms and suggest a potential underlying mechanism for specific depressive symptoms within the chronic viral hepatitis population. These insights could improve our understanding and treatment of depressive symptoms in individuals with viral hepatitis.
Executive dysfunction is common in Parkinson's disease (PD) patients. The catechol-O-methyltransferase (COMT) Val158Met polymorphism has been proposed to affect executive functions (EFs) in the ...prefrontal cortex. The present study attempted to explore the influence of the COMT polymorphism on EFs in patients with PD. Fifty-four PD patients were recruited and underwent neuropsychological assessments for three core EFs. The COMT polymorphism was genotyped using the TaqMan SNP Genotyping Assay. Participants were divided into three study groups: Val homozygotes, heterozygotes, and Met homozygotes. The three COMT genotype groups had significantly different performances in set-shifting χ2 (2, 54) = 9.717, p = 0.008 and working memory tasks χ2 (2, 54) = 7.806, p = 0.020. Post-hoc analyses revealed that PD Val homozygotes performed significantly poorer in the set-shifting task than did either the PD Met homozygotes (z = -2.628, p = 0.009) or PD heterozygotes (z = -2.212, p = 0.027). Our explorative results suggest that the putative level of prefrontal dopamine influenced set-shifting through a "cane-shaped" dopamine level-response relationship. Our results have clinical implications, which may influence PD treatment with dopamine in the future because the optimal dopamine level to maximize EFs may vary based on the clinical course and COMT polymorphism status. Further study recruiting a larger number of participants is needed to confirm our preliminary findings.
Our study aimed to examine the contribution of commonly used tools, including the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA), and develop a formula for conversion ...of these tests in the Chinese population. We also create a predictive model for the detection of Chinese patients' mild cognitive impairment (MCI). We recruited 168 patients with Parkinson's disease (PD) from 12 medical centres or teaching hospitals in Taiwan, and each participant received a comprehensive neuropsychological assessment. Logistic regression analysis was conducted to find predictors of MCI with the help of a generalized additive model. We found that patients with an MMSE > 25 or a MoCA > 21 were less likely to have MCI. The discrimination powers of the two tests used for detecting MCI were 0.902 and 0.868, respectively, as measured by the area under the receiver operating characteristic curve (ROC). The best predictive model suggested that patients with a higher MMSE score, delayed recall scores of the 12-item Word Recall Test ≥ 5.817, and no test decline in the visuospatial index were less likely to have MCI (ROC = 0.982). Our findings have clinical utility in MCI detection in Chinese PD and need a larger sample to confirm.
Abstract
The direct impact of chronic hepatitis B and hepatitis C on neurocognition remains elusive due to the frequent comorbidities, and the domains of the neurocognitive functions affected have ...rarely been investigated comprehensively. We cross-sectionally assessed the neurocognitive functions of the individuals with chronic hepatitis B, chronic hepatitis C, treated chronic hepatitis C with a sustained virologic response, and their healthy control counterparts. Laboratory examinations were used to investigate the impact of inflammation on neurocognition, exclude the medical conditions that could interfere with neurocognition assessment, and assess liver function and fibrotic severity of the liver of the participants. This study found the detrimental impact of chronic hepatitis B on language and executive functions. In contrast, individuals with chronic hepatitis C showed deficits in executive functions, psychomotor speed, memory, and attention. Successful elimination of hepatitis C resulted in improved liver function, but not neuropsychological test performance. Moreover, erythrocyte sedimentation rate level was found to mediate the deficits in the attention of individuals with chronic hepatitis C. These results demonstrate the neurocognitive deficits and the difference in the profiles of neurocognitive deficits in individuals with chronic hepatitis B and chronic hepatitis C. Our study also provided results suggesting the mediation by systemic inflammation on the attention deficit in individuals with chronic hepatitis C.
Differences exist regarding post-stroke cognitive outcomes.
The aim of this study investigates the potential factors associated with post-stroke cognitive performance and trajectories.
We performed a ...prospective cohort study using serial monitoring of cognitive function over a 1-year period after a first-ever ischemic stroke. Small vessel disease (SVD) burden and hippocampal atrophy (HA) were evaluated using the modified cerebral small vessel disease scores (mCSVD) and medial temporal atrophy score (MTA) scores. A generalized estimating equation (GEE) model and a group-based trajectory model (GBTM) was used to analyze the potential factors associated with post-stroke cognitive outcomes.
A total of 112 patients were enrolled. The GEE model showed that all patients, regardless of initial cognitive performance, had a tendency to show an increase in the Montreal Cognitive Assessment over time. The cognitive performance was better in male patients with higher education levels (p = 0.046 and p < 0.001, respectively), but tended to be worse in patients with higher SVD burden and HA. The GBTM model grouped patients into low, intermediate, and high performance (LP, IP, and HP) after stroke. A higher SVD burden, rather than HA and initial stroke severity and location, independently predicted a higher odds of poor post-stroke cognitive trajectory (being in the LP group) after stroke (adjusted odds ratio 2.74, 95%CI 1.09-6.86).
In patients with first-ever mild stroke, cognitive improvement over time was evident. The detrimental impact of the SVD burden may outweigh the effect of HA or acute stroke insult on the post-stroke cognitive trajectory during the 1-year follow-up.
The neuropathology of Parkinson's disease (PD) involves the frontal-subcortical circuit, an area responsible for processing affective theory of mind (ToM). Patients with PD are expected to experience ...deficits in the affective ToM. This study aims to investigate whether the ability to infer emotion in others is affected in either young-onset Parkinson's disease (YOPD) or middle-onset PD (MOPD) patients and to test whether the impairments in affective ToM are associated with the motor symptoms. The affective ToM, global mental abilities, and clinical symptoms were assessed in a total of 107 MOPD, 30 YOPD, and 30 normal controls (NCs). The MOPD patients exhibited deficits in affective ToM to the negative and neutral valences, when compared to the participants in the NCs and YOPD group. By conducting gender-stratified analysis, the deficits in affective ToM was only found in female participants. After adjusting for demographic variables, the multiple linear regression model revealed that affective ToM predicted motor symptoms, especially in female MOPD patients. The present study may aid in the development of medical care programs by advocating for a more comprehensive therapeutic plan that includes continuous disease progression monitoring and social skills training for female MOPD patients or their caregivers.
Background
The commonly used screening tests for Parkinson’s disease (PD) are the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE), both of which only focus on cognitive ...function. A composite assessment that considers both cognitive and social dysfunction in PD would be helpful in detecting mild cognitive impairment (MCI) and PD dementia (PDD).
Objective
We aimed to simplify the commonly used tools and combine cognitive and social functioning tests to detect early MCI and PDD.
Materials and Methods
A total of 166 participants (84 PD patients and 82 healthy) were recruited who completed the MMSE, MoCA, PD social functioning scale (PDSFS), clock drawing test, activities of daily living, comprehensive neuropsychological assessment (e.g., executive, attention, language, memory, and visuospatial functions), and movement disorder society (MDS)-unified PD rating scale. According to the MDS diagnostic criteria, the patients were grouped into PD-nonMCI, PD-MCI, or PDD.
Results
To detect PD-MCI, the optimal cut-off scores for the simplified MoCA and the combined test were 9 and 35. The discrimination values measured by the area under the receiver operating characteristic curve (AUC) of the two tests were 0.767 (
p
< 0.001) and 0.790 (
p
< 0.001). When the simplified MoCA was 7 or the combined test 30, the patients would be classified as having PDD. The AUCs of the two tests were 0.846 (
p
< 0.001) and 0.794 (
p
= 0.003).
Conclusion
We suggest considering both cognitive and social functions when detecting PD-MCI and PDD.
Viral hepatitis is a devastating disease with the risk for cirrhosis and carcinogenicity. Regulatory T cells (Tregs) play important roles in the disease course of viral hepatitis via maintaining the ...balance between overt‐immune responses and viral replications. We hypothesized that genetic polymorphisms of Treg‐related genes, such as interleukin‐2, transforming growth factor‐β 1 (TGF‐β1), forkhead box P3 (FOXP3), and adenylyl cyclase type 9 modulate the hosts' immune regulation under circumstances of viral hepatitis. We examined the effect of five single nucleotide polymorphisms (SNPs) of Treg‐related genes on the levels of C‐reactive protein (CRP) and erythrocyte sedimentation rate (ESR), alanine aminotransferase, and non‐invasive hepatic fibrosis marker (Fibrosis‐4 index) in a total of 138 participants with viral hepatitis. The rs1800469 (a TGF‐β1 SNP) GG genotype is associated with higher serum CRP levels, and the rs3761547 (a FOXP3 SNP) C allele in the females is associated with higher ESR levels. Besides, female participants carrying the rs3761547 C allele had a significantly higher Fibrosis‐4 (FIB‐4) index than the females carrying the TT genotype, while the rs3761547 C allele had the opposite effect in males. With linear‐regression moderation analysis, we found that sex moderated the impact of the FOXP3 SNP on the levels of FIB‐4, whereas the FOXP3 SNP caused the opposite effect between males and females on the severity of hepatic fibrosis. These results provide evidence for the participation of TGF‐β1 and FOXP3 in the inflammatory responses associated with viral hepatitis, where FOXP3 function may be moderated by sex.
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