Parkinson's Disease Dementia Patients Research Articles

Pimavanserin for psychosis in Parkinson's Disease dementia: Subgroup analysis of the HARMONY Trial

IntroductionPimavanserin is FDA-approved to treat Parkinson's disease (PD) psychosis. We analyzed the effect of pimavanserin on psychosis in the PD dementia (PDD) subgroup from the phase 3 HARMONY trial. MethodsThis subgroup analysis included PDD patients enrolled in an international, multicenter, randomized discontinuation study of pimavanserin for dementia-related psychosis. PDD patients with moderate-to-severe psychosis, age 50–90 years, received pimavanserin 34 mg/day for 12 weeks (open-label period). Those with a sustained psychosis response to pimavanserin at weeks 8 and 12 were randomized during the double-blind period to continue pimavanserin or receive placebo. Primary efficacy endpoint was time to psychosis relapse as measured by the SAPS-H + D and CGI-I. Safety was assessed, as were effects on motor symptoms and cognitive abilities using the ESRS-A and MMSE. Results392 patients were enrolled in HARMONY (mean age: 72.6 years; 38.8 % female): 59 had PDD; 49/59 remained on pimavanserin during the open-label period (safety analysis set), and 36/49 were randomized to pimavanserin (n = 16) or placebo (n = 20) in the double-blind phase (intent-to-treat analysis set). Risk of psychosis relapse was lower with pimavanserin 34 mg compared with placebo in the double-blind phase (HR = 0.052; 95 % CI 0.016–0.166; 1-sided nominal p < 0.001). During the open-label period, 46.9 % experienced a treatment-emergent adverse event; event incidence was similar across arms in the double-blind period. Pimavanserin did not adversely affect motor or cognitive function in either treatment phase. ConclusionsPimavanserin significantly reduced risk of psychosis relapse in patients with PDD, was well tolerated, and did not worsen motor or cognitive function.

Proteomic comparison between non-purified cerebrospinal fluid and cerebrospinal fluid-derived extracellular vesicles from patients with Alzheimer's, Parkinson's and Lewy body dementia.

Dementia is a leading cause of death worldwide, with increasing prevalence as global life expectancy increases. The most common neurodegenerative disorders are Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD). With this study, we took an in-depth look at the proteome of the (non-purified) cerebrospinal fluid (CSF) and the CSF-derived extracellular vesicles (EVs) of AD, PD, PD-MCI (Parkinson's disease with mild cognitive impairment), PDD and DLB patients analysed by label-free mass spectrometry. This has led to the discovery of differentially expressed proteins that may be helpful for differential diagnosis. We observed a greater number of differentially expressed proteins in CSF-derived EV samples (N=276) compared to non-purified CSF (N=169), with minimal overlap between both datasets. This finding suggests that CSF-derived EV samples may be more suitable for the discovery phase of a biomarker study, due to the removal of more abundant proteins, resulting in a narrower dynamic range. As disease-specific markers, we selected a total of 39 biomarker candidates identified in non-purified CSF, and 37 biomarker candidates across the different diseases under investigation in the CSF-derived EV data. After further exploration and validation of these proteins, they can be used to further differentiate between the included dementias and may offer new avenues for research into more disease-specific pharmacological therapeutics.

Risk factors for dementia in Parkinson's Disease - the overuse of anticholinergic drugs.

To determine the risk factors for dementia in a group of patients with Parkinson's Disease (PD), especially the effect of the anticholinergic burden assessed according to the Anticholinergic Cognitive Burden scale (ACB) and the CRIDECO Anticholinergic Load Scale (CALS). To provide information about factors associated with Parkinson's Disease dementia (PDD), especially the anticholinergic burden and testing the effect of both scales in an assessment of the anticholinergic burden in this group of patients. A retrospective and cross-sectional analysis of medical records of patients with Parkinson's Disease admitted to the Neurology Department of the Medical University of Silesia, Katowice, Poland between 2019 and 2021 was performed. We found 418 patients with a diagnosis of PD, but 80 were excluded due to lack of a cognitive function assessment. Based on MMSE score, the remaining 338 patients were divided into two groups of patients with, and without, PDD. Next, demographic and clinical data was collected. The anticholinergic burden was assessed using the ACB and the CALS scales. According to the authors of these scales, : if a scale score is of three or more points, this should be considered as a significant anticholinergic burden. Multiple logistic regression with backward elimination was used to assess factors significantly related to the presence of dementia, and two different models were used for both scales assessing the anticholinergic burden. 62 (18.3%) patients were diagnosed with PDD. Overall significant anticholinergic burden (≥ 3 points) was found in 31.95% of patients using CALS and in 18.93% using ACB. Anticholinergic burden was higher in patients with dementia (CALS 50 vs. 27.90%, p < 0.001, ACB 43.5 vs. 13.41%, p < 0.001). According to both models, the factors significantly related to dementia were: age (ACB OR 1,114 (1.062-1.170), p < 0.001, CALS OR 1.123 (1.070-1.178), p < 0.001), significant anticholinergic burden (ACB OR 3.433 (1.746-6.750), p < 0.001, CALS OR 2.166 (1.157-4.055), p = 0.016) disease severity in the Hoehn-Yahr scale (ACB OR 1.752 (1.197-2.565), p = 0.004, CALS OR 1.831 (1.256-2.670), p = 0.002) and atrial fibrillation (ACB OR 5.593 (1.417-22.083), p = 0.014, CALS OR 5.159 (1.314-20.254), p = 0.016). The anticholinergic burden is larger in PDD patients compared to PD patients without dementia. CALS or ACB scales are helpful in this risk assessment and might be crucial to avoid the development of PDD, especially in older PD patients with multimorbidities.

Safety, tolerability, and preliminary efficacy of SYN120, a dual 5-HT6/5-HT2A antagonist, for the treatment of Parkinson disease dementia: A randomized, controlled, proof-of-concept trial

BackgroundSYN120 is a dual serotonin receptor (5-HT6/5-HT2A) antagonist hypothesized to improve cognition and psychiatric symptoms. ObjectivesWe evaluated the safety, tolerability, and efficacy of SYN120 in patients with Parkinson disease dementia (PDD). MethodsIn a multicenter, double-blind, parallel-group, 16-week phase 2a proof-of-concept trial in PDD with concomitant cholinesterase inhibitor use, eligible patients were randomized to oral SYN120 (100 mg/day) or placebo. Adverse events (AEs), Unified Parkinson's Disease Rating Scale (UPDRS) scores, and discontinuations assessed safety and tolerability. The primary and key secondary efficacy measures were the Cognitive Drug Research (CDR) computerized assessment system Continuity of Attention and Quality of Episodic Memory scores. Other efficacy measures were: Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog), Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change (ADCS-CGIC), Brief Penn Parkinson's Daily Activity Questionnaire-15 (PDAQ-15), Scales for Outcomes in Parkinson's Disease-Sleep Scale (SCOPA-Sleep), and Neuropsychiatric Inventory (NPI). ResultsEighty-two patients were randomized to SYN120 (N = 38) or placebo (N = 44), AEs occurred in 74% and 77% of patients, and treatment discontinuation in both groups was 16%. Nausea and vomiting were more frequent, and motor symptoms (UPDRS) worsened in the SYN120 group. At week 16, the SYN120 and placebo groups did not differ significantly for any cognitive assessment. Cognitive activities of daily living (PDAQ-15) and the NPI-Apathy/Indifference scores improved nominally in the SYN120 group compared with placebo (unadjusted p = 0.029 and 0.028). ConclusionsSYN120 was adequately tolerated, mild worsening of motor symptoms was noted and it did not improve cognition in PDD patients. Its potential benefits for cognitive activities of daily living and apathy warrant further study. RegistrationClinicaltrials.gov as NCT02258152.

Morphological characteristics differentiate dementia with Lewy bodies from Parkinson disease with and without dementia.

Dementia with Lewy bodies (DLB) and Parkinson disease (PD) with and without dementia are entities of a spectrum of Lewy body diseases. About 26.3% of all PD patients develop dementia increasing up to 83%. Parkinson disease-dementia (PDD) and DLB share many clinical and morphological features that separate them from non-demented PD (PDND). Clinically distinguished by the temporal sequence of motor and cognitive symptoms, the pathology of PDD and DLB includes variable combinations of Lewy body (LB) and Alzheimer (AD) lesions, both being more severe in DLB, but much less frequent and less severe in PDND. The objective of this study was to investigate the morphological differences between these three groups. 290 patients with pathologically confirmed PD were reviewed. 190 of them had clinical dementia; 110 met the neuropathological criteria of PDD and 80 of DLB. The major demographic and clinical data were obtained from medical records. Neuropathology included semiquantitative assessment of LB and AD pathologies including cerebral amyloid angiopathy (CAA). PDD patients were significantly older than PDND and DLB ones (83.9 vs 77.9years, p < 0.05); the age of DLB patients was between them (80.0years), while the disease duration was shortest in DLB. Brain weight was lowest in DLB, which showed higher Braak LB scores (mean 5.2 vs 4.2) and highest Braak tau stages (mean 5.2 vs 4.4 and 2.3, respectively). Thal Aβ phases were also highest in DLB (mean 4.1 vs 3.0 and 1.8, respectively). Major findings were frequency and degree of CAA, being highest in DLB (95% vs 50% and 24%, with scores 2.9 vs 0.7 and 0.3, respectively), whereas other small vessel lesions showed no significant differences. Striatal Aβ deposits also differentiated DLB from the other groups. This and other studies of larger cohorts of PD patients indicate that the association of CAA and cortical tau-but less-LB pathologies are associated with more severe cognitive decline and worse prognosis that distinguish DLB from PDD and PDND. The particular impact of both CAA and tau pathology supports the concept of a pathogenic continuum ranging from PDND to DLB + AD within the spectrum of age-related synucleinopathies.

Validation study of Arizona Battery for Communication Disorders of Dementia in Greek monolingual cognitively impaired patients

The evaluation of cognitive-communication disorders is performed with several types of assessment methods. These methods include different types of cognitive and language tests such as the Arizona Battery for Communication Disorders of Dementia (ABCD). The present study aimed to validate the ABCD in the Greek language. 132 individuals participated in the study: 60 adults in cognitive health (ACH) and 72 patients [24 Parkinson Disease (PD) patients without cognitive impairment, 24 with Parkinson Disease Dementia (PDD) and 24 with Alzheimer's Disease (AD)]. The cognitive and mental status of all participants was estimated by means of the Mini Mental State Examination (MMSE), the Abbreviated Mental Test Score (AMTS), the Clock Drawing Test (CDT), the Instrumental Activities of Daily Living (IADL), the Neuropsychiatric Inventory (H-NPI) the Geriatric Depression Scale -15 (GDS-15) and the ABCD. Statistically significant differences were found between all tests administered with the PDD and AD patients having the lower scores. The ABCD showed good psychometric properties, internal consistency (Cronbach alpha=0. 901) and discriminatory ability. It was significantly correlated with the AMTS, CDT, IADL, and MMSE.The Greek version of the ABCD demonstrated good validity, sensitivity, and discriminatory ability. The ABCD is a valuable instrument to assess cognitive-communication dis-orders.

N200 and P300 component changes in Parkinson's disease: a meta-analysis.

Cognitive impairment can seriously affect the quality of life of Parkinson's disease (PD) patients. Although numerous studies showed that N200, P300 latency and amplitude are correlated with cognitive functions, there is a sufficient amount of controversial results. Therefore, it is necessary to conduct a meta-analysis of N200, P300 latency and amplitude data of event-related potential (ERP) in PD. We systematically searched on PubMed and Web of Science for PD-related ERP studies published before December 2021. Standard mean difference (SMD) and 95% confidence interval (CI) estimates of N200 and P300 components were compared among PD patients, PD dementia (PDD) patients, PD non-dementia (PDND) patient, and healthy control (HC). Our meta-analysis showed prolonged N200 latency at the Fz, Cz electrode sites, prolonged P300 latency at the Fz sites in PD patients, compared to HC; prolonged N200 latency at the Cz, Pz electrode sites in PDND patients, compared to HC; prolonged P300 latency at the Cz site in PDD patients, compared to PDND patients; and reduced P300 amplitude at the Fz electrode site in PDND patients, compared to HC. N200 and P300 component may be potential electrophysiological biomarkers of early cognitive impairment in PD patients. Future studies are needed to confirm this conclusion. Estimates of N200 and P300 component can be a valuable support for clinicians in diagnosis of early cognitive impairment in PD patients due to the simplicity and non-invasiveness of the procedure.

Deep Brain Stimulation of the Nucleus Basalis of Meynert for Parkinson's Disease Dementia: A 36 Months Follow Up Study.

ABSTRACTBackgroundDegeneration of the nucleus basalis of Meynert (NBM) and cortical cholinergic dysfunction are hallmarks of Parkinson's disease dementia (PDD). There is no effective therapy for PDD. Deep brain stimulation of the NBM (NBM‐DBS) has been trialed as a potential treatment.ObjectiveOur primary aim was to evaluate the sustained tolerability of NBM‐DBS in PDD, and its impact on global cognition, behavioral symptoms, quality of life and caregiver burden and distress. Second, we aimed to determine whether baseline measures of arousal, alertness, and attention were predictive of the three year response to NBM‐DBS in PDD patients.MethodsFive of the six PDD patients who completed the baseline assessment participated in a 3 year follow up assessment. We assessed the participants after three years of NBM‐DBS on the Mini Mental State Examination, Dementia Rating Scale‐2, Blessed Dementia Rating Scale, Neuropsychiatric Inventory, and the SF36.ResultsThe five patients showed varying trajectories of cognitive decline, with two showing a slower progression over the three‐year follow‐up period. A slower progression of decline on global cognition was associated with higher baseline accuracy on the Posner covert orienting of attention test, and less daytime sleepiness.ConclusionsWhether slower progression of cognitive decline in two patients was in any way related to individual variability in responsiveness to NBM‐DBS requires confirmation in a larger series including an unoperated PDD control group. Higher accuracy in covertly orienting attention and better sleep quality at baseline were associated with better cognitive outcomes at 36 months assessment. These results require validation in future studies with larger samples.

Cerebral microbleeds is associated with dementia in Parkinson's disease.

Emerging evidence suggests that cerebral small vessel disease (CSVD) may worsen cognitive functions in Parkinson's disease (PD). However, the effect of microbleeds on cognitive function in patients with PD remains unknown. This study explored the association between the presence, number and location of microbleeds with dementia in PD patients. This cross-sectional study included 431 patients with PD from Beijing Tiantan Hospital from May 2016 to August 2019. Cognition assessments (MMSE, MoCA) were performed for these patients. MRI imaging sequences were obtained and reviewed independently by two well-trained readers who were blind to all clinical data. Spearman's correlation analysis and logistic regression model analysis were further used for the assessments. An association between cerebral microbleeds with cognitive ability and dementia in PD patients was revealed. A significance was observed between the total number of microbleeds and two widely used scores of cognitive assessments (Spearman R = - 0.120 to MMSE with a p = 0.016, and - 0.117 to MoCA with a p = 0.020). In detail, infratentorial microbleeds were associated with the level of cognition in PD patients (Spearman R = - 0.099 to MMSE with a p = 0.049, and - 0.116 to MoCA with a p = 0.021). Furthermore, logistic regression analysis results also confirmed such correlations between the number of microbleeds and cognitive ability after adjusting for age, cholesterol level, Hamilton Anxiety Scale, Hamilton Depression Scale, and white matter hyperintensity Fazekas score (OR 3.28, p = 0.035, 95% CI 1.090-9.892). The occurrence of microbleeds, especially in the infratentorial locations, may worsen the cognitive function of PD patients and result in dementia. Management of cerebral vascular disease could be beneficial to patients with PD.

Effect of cognitive reserve on cognitive function in Parkinson's disease.

Previous studies showed inconsistent results for the correlation between cognitive reserve (CR) and cognitive function in Parkinson's disease (PD). Additionally, conflicting results were obtained for the association between CR and risk of longitudinal cognitive decline, longitudinal progression to mild cognitive impairment (MCI), and longitudinal progression to dementia in PD patients. Thus, a meta-analysis is essential to summary these inconsistent results. Articles published before November 2021 were searched in databases as follows: PubMed, Web of Science, Medline, EMBASE, and Google Scholar. We computed Fisher's z score and standard error (SE) of each transformation value of correlation coefficient for the correlation between educational level and cognitive function. Additionally, odds ratios (ORs) or hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed as effect sizes for the correlation between educational level and risk of longitudinal progression to MCI. The present study showed that higher educational levels were related to better general cognitive function, executive function, memory, and information processing speed in PD patients, whereas no significant association was showed between educational levels and visuospatial function, language in PD patients. Additionally, included studies reported a negative association between educational level and risk of longitudinal progression to MCI in PD patients. In conclusion, the study demonstrated that higher CR might be correlated with better cognitive function and lower risk of longitudinal progression to MCI in PD. In addition, large-scale prospective studies are necessary to explore the effect of CR on cognitive function in PD.

Impairment of recognition of facial expressions in different types of dementia

AbstractBackgroundImpairment of facial expression recognition in dementia is one of the cognitive deficits that could affect the social life of dementia patients. The severity of the facial expression recognition in different types of dementia has not been fully addressed. Previous studies showed that EEG event‐related oscillation (ERO) studies could reveal the brain dynamics during successful facial expression recognition. Furthermore, the impairment of facial recognition in Alzheimer's disease patients were represented with abnormal EROs (Güntekin et al., 2019). The present study aims to compare the impaired facial expression recognition between different types of dementia by analysis of event‐related delta responses. The role of delta responses in facial expression and emotional paradigms was reported previously by several researchers (Güntekin and Başar, 2014).Method25 Healthy elderly controls (HC), 25 Mild Cognitive Impairment patients (MCI), 25 patients with Alzheimer's disease (AD), 15 patients with Parkinson's disease with Mild Cognitive Impairment (PDMCI) and 16 patients with Parkinson's disease Dementia (PDD) were included in the study. The electroencephalographic activity was recorded during the perception of the facial expression recognition task (Angry, Happy, Neutral). Delta power and phase‐locking were computed for each facial recognition stimuli and compared among the groups (ANOVA, p&lt;0.05).ResultBoth delta power and delta phase locking were lower in dementia groups than healthy controls being worst in PDD. Figure 1 shows the grand average of delta power in all groups for the right occipital location. PDD (p&lt;0.0001) and AD (p&lt;0.05) had lower delta power than the healthy controls, the reduction of delta responses in PDD and AD were especially found over occipital locations. MCI and PDMCI subjects were found less impaired facial expression recognition compared to AD and PDMCI.ConclusionThe present study showed that dementia patients had severe facial recognition deficits that increased cognitive impairment. Event‐related delta responses successfully showed the impaired recognition of facial expression in different types of dementia groups. Among all dementia subjects, PDD patients had the most reduced delta responses that could be an electrophysiological biomarker of impaired facial expression recognition. Acknowledgments: This work (grant number 218S314) was supported by TUBITAK.

Decrease of event related theta power is more profound in patients with Parkinson's disease dementia in comparison to Alzheimer's disease dementia

AbstractBackgroundAlzheimer's disease dementia (ADD) and Parkinson's disease dementia (PDD) are the most common types of dementia. ADD and PDD have different pathophysiology and clinical profile. It is important to understand mechanisms underlying pathophysiology, clinical symptoms, and the electrophysiological differences between these two types of dementia. Event‐related theta responses during cognitive paradimgs are one of the essential biomarkers that could succfesully show cognitive decline in dementia patients (Yener et al.,2007;Güntekin et al.,2020). The aim of the present study was to investigate the Event‐related theta responses during the visual cognitive task in patients with PDD and ADD in order to find the differentiation between these two types of dementia.MethodEEG recordings of 15 patients with ADD, 15 patients with PDD, and matched 15 healthy elderly controls (HC) were performed during the visual oddball paradigm. Event‐related phase‐locking and power analysis were performed for theta frequency band (4‐7 Hz). Repeated measures of ANOVA was used for statistical analysis (p&lt;0.05).ResultThere were significant differences among groups for both event‐related theta phase‐locking (p=0.004) and theta power (p&lt;0.0001). ADD (p&lt;0.005) and PDD (p&lt;0.005) groups had reduced theta phase‐locking in comparison to the HC group (Figure 1). Especially, this reduction was more pronounced in the PDD group. In addition, the PDD group had decreased theta power as compared to the HC (p&lt;0.0001) and ADD (p&lt;0.005) group (Figure 1). Figure 1 shows the grand average of event‐related theta power (upper part) and phase‐locking (lower part) and in HC, ADD and PDD groups.ConclusionThe present study showed decreased event‐related theta responses during the visual oddball paradigm in patients with dementia. Especially, PDD patients had the worst event‐related theta responses. These findings could be interpreted as the visual cognitive processes are more impaired in PDD patients compared to ADD patients.

Therapeutic trials in dementia with Lewy bodies: a systematic review of the literature

Cognitive diseases with Lewy bodies occur in two forms: dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD), which follows the progression of Parkinson's disease. There is currently no curative treatment for these cognitive diseases with Lewy bodies. Therapeutic trials in DLB are rare, due to the recent description of the disease as well as its first international diagnostic criteria (1996). This article proposes a synthesis of the therapeutic trials carried out in DLB in the last 5 years, including PDD patients with DLB patients, using the Clinicaltrials.gov and Pubmed.gov databases. We identified 35 therapeutic trials on Clinical Trials and 14 on PubMed. According to our temporal criteria, 21 trials were analyzed. Among the 11 completed trials with reported results, two molecules showed positive results: two trials with zonisamide (phase 2 and 3) showed a gain on parkinsonism and one trial with neflamapimod (phase 2) a gain on cognition and walking. In recent years, there has been an increase in the therapeutic research effort in DLB, which is consistent with the prevalence of this disease - approximately 200,000 patients in France. Compared to other cognitive neurodegenerative diseases, therapeutic research is largely insufficient, whereas the proportion of positive trials is important. An effective disease modifying would have strong consequences for the patient and the relatives.

Odor Recognition Memory in Parkinson's Disease: A Systematic Review.

Olfactory impairment is a central non-motor symptom in Parkinson's disease (PD). Previous studies have demonstrated that olfactory dysfunction is associated with mental illness and impaired cognition. The frequently investigated olfactory functions are odor detection, discrimination, and identification. However, few studies have focused on odor recognition memory (ORM). ORM tasks involves episodic memory which therefore can facilitate the detection of dementia among patients with PD and consequently adjust their treatment. Thus, the aim of this systematic review is to summarize the existing research on ORM in PD. Databases and reference lists were used for data collection. Studies were included in the review if they met the eligibility criteria derived from the PICOS-framework. Quality evaluation of the studies was based on the STROBE-statement. Six studies with small samples were included in the analysis which demonstrated the scarce research on the subject. The studies targeting ORM were heterogenous and involved two main tasks: odor recognition and odor matching. The synthesis of the data demonstrated that PD patients performed significantly lower than controls on both tasks, especially on odor matching task. Only the odor recognition task exhibited a difference between patients with PD vs. Alzheimer's disease (AD). PD patients performed significantly better than AD patients. The findings based on the available limited data support the notion that odor recognition task can be of importance in identifying Parkinson's disease dementia (PDD). To investigate this hypothesis, future research needs to include larger samples of PD, PDD and AD patients executing the same odor recognition task.

Associations of Chinese Herbal Medicine Usage with Risk of Dementia in Patients with Parkinson's Disease: A Population-Based, Nested Case-Control Study.

Background: Patients who have Parkinson's disease (PD) comorbid with dementia is common. With the prolonged life expectancy, dementia is gradually becoming prevalent and affects most patients' life qualities. However, the efficacy of current treatments in dementia of PD is limited. Previous studies indicated the potential roles of Chinese herbal medicine (CHM) in treating dementia, yet the correlation between CHM usage and risk of dementia in PD patients is unclear. Methods: This case-control study was nested within a National Health Insurance database of patients over 50 years with newly diagnosed PD from year 2000 to 2010. Among these PD patients, dementia and nondementia groups were discussed, respectively, in terms of the duration of taking CHM (≥90 vs. <90 days), age (50-64 vs. ≥65 years) and gender. Results: The risk of dementia in patients with PD is lower in CHM users compared with non-CHM users, especially in those taking CHM for more than 90 days (adjusted odds ratio [aOR] 0.58; 95% confidence interval [95% CI] 0.39-0.87). The use of CHM was significantly related to the lower risk of dementia in the subgroups of patients with age ≥65 years for CHM usage <90 days (aOR 0.68; 95% CI 0.53-0.88), patients with age ≥65 years for CHM usage ≥90 days (aOR 0.63; 95% CI 0.42-0.94), female patients using CHM for ≥90 days (aOR 0.43; 95% CI 0.22-0.84), and male patients using CHM for <90 days (aOR 0.62; 95% CI 0.43-0.88). Conclusions: The authors demonstrated the association of CHM usage with lower risk of dementia in patients with PD, especially in women with the usage of CHM for more than 90 days. Since no arbitrary causal conclusions could be drawn from retrospective cohort studies, the finding in this study could be used to generate a hypothesis for a subsequent design of prospective longitudinal study.

Significance of cerebral amyloid angiopathy and other co-morbidities in Lewy body diseases.

Lewy body dementia (LBD) and Parkinson's disease-dementia (PDD) are two major neurocognitive disorders with Lewy bodies (LB) of unknown etiology. There is considerable clinical and pathological overlap between these two conditions that are clinically distinguished based on the duration of Parkinsonism prior to development of dementia. Their morphology is characterized by a variable combination of LB and Alzheimer's disease (AD) pathologies. Cerebral amyloid angiopathy (CAA), very common in aged persons and particularly in AD, is increasingly recognized for its association with both pathologies and dementia. To investigate neuropathological differences between LB diseases with and without dementia, 110 PDD and 60 LBD cases were compared with 60 Parkinson's disease (PD) cases without dementia (PDND). The major demographic and neuropathological data were assessed retrospectively. PDD patients were significantly older than PDND ones (83.9 vs 77.8years; p < 0.05); the age of LB patients was in between both groups (mean 80.2years), while the duration of disease was LBD < PDD < PDND (mean 6.7 vs 12.5 and 14.3years). LBD patients had higher neuritic Braak stages (mean 5.1 vs 4.5 and 4.0, respectively), LB scores (mean 5.3 vs 4.2 and 4.0, respectively), and Thal amyloid phases (mean 4.1 vs 3.0 and 2.3, respectively) than the two other groups. CAA was more common in LBD than in the PDD and PDND groups (93 vs 50 and 21.7%, respectively). Its severity was significantly greater in LBD than in PDD and PDND (p < 0.01), involving mainly the occipital lobes. Moreover, striatal Aβ deposition highly differentiated LBD brains from PDD. Braak neurofibrillary tangle (NFT) stages, CAA, and less Thal Aβ phases were positively correlated with LB pathology (p < 0.05), which was significantly higher in LBD than in PDD < PDND. Survival analysis showed worse prognosis in LBD than in PDD (and PDND), which was linked to both increased Braak tau stages and more severe CAA. These and other recent studies imply the association of CAA-and both tau and LB pathologies-with cognitive decline and more rapid disease progression that distinguishes LBD from PDD (and PDND).

Lipid metabolic dysregulation is involved in Parkinson's disease dementia.

Dementia is very common in the late stage of patient with Parkinson's disease (PD). We aim to explore its underlying pathogenesis and identify candidate biomarkers using untargeted metabolomics analysis. Consecutive PD patients and healthy controls were recruited. Clinical data were assessed and patients were categorized into Parkinson's disease without dementia (PDND) and Parkinson's disease dementia (PDD). Fast plasma samples were obtained and untargeted liquid chromatography-mass spectrometry-based metabolomics analysis was performed. Based on the identified differentially-expressed metabolites from the metabolomics analysis, multivariate linear regression analyses and receiver operating characteristic (ROC) curves were further employed. According to the clinical data, the mean ages of PDND and PDD patients were significantly higher than those of healthy controls. The incidence of hypercholesterolemia was decreased in PDD patients. PDD patients also had lower levels of triglyceride, low-density lipoprotein cholesterol, and apolipoprotein B. There were 24 and 57 differentially expressed metabolites in PDD patients when compared with the healthy controls and PDND patients from the metabolomics analysis. Eleven lipid metabolites were simultaneously decreased between these two groups, and can be further subcategorized into fatty acyls, glycerolipids, glycerophospholipids, sphingolipids, and prenol lipids. The plasma levels of the eleven metabolites were positively correlated with MMSE score and can be candidate biomarkers for PDD patients with areas under the curve ranging from 0.724 to 0.806 based on the ROC curves. Plasma lipoproteins are significantly lower in PDD patients. A panel of eleven lipid metabolites were also decreased and can be candidate biomarkers for the diagnosis of PDD patients. Lipid metabolic dysregulation is involved in the pathogenesis of Parkinson's disease dementia.

Effect of cognitive reserve on cognition function in Parkinson's disease: A PRISMA-compliant meta-analysis

Background: Previous studies showed inconsistent results for the correlation between cognitive reserve (CR) and cognitive function in Parkinson's disease (PD). Additionally, conflicting results were obtained for the association between CR and risk of longitudinal cognitive decline, longitudinal progression to mild cognitive impairment (MCI) and longitudinal progression to dementia in PD patients. Thus, a meta-analysis is essential to summary these inconsistent results.

Differential Circulating Levels of Naturally Occurring Antibody to α-Synuclein in Parkinson's Disease Dementia, Alzheimer's Disease, and Vascular Dementia.

Background: Aggregation of alpha-synuclein (α-Syn) is considered to be a significant pathological hallmark and a driving force of Parkinson’s disease (PD). PD dementia (PDD) occurs in a substantial number of PD patients. Naturally occurring antibody against α-Syn (NAb-α-Syn) exists ubiquitously in human blood and is reported to be altered in PD. However, it is not clear yet whether PDD had similar changes of circulating NAb-α-Syn.Methods: In this study, we recruited 61 PDD patients, 52 patients with Alzheimer’s disease (AD), 51 patients with vascular dementia (VaD), and 50 normal controls (NCs). ELISA was used to examine NAb-α-Syn levels in serum.Results: In comparison with NCs, serum levels of NAb-α-Syn were significantly lower in patients with PDD. However, serum levels of NAb-α-Syn were comparable among AD, VaD, and NC groups. Serum levels of NAb-α-Syn were positively correlated with the cognitive function, as reflected by Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Serum levels of NAb-α-Syn were negatively correlated with the severity of PD [as reflected by the Unified Parkinson Disease Rating Scale (UPDRS)] and the duration of PD and PDD. Serum NAb-α-Syn can differentiate PDD patients from AD and VaD patients.Conclusion: These results suggest that circulating NAb-α-Syn might be a potential biomarker of PDD.

Nasal chemosensory tests: biomarker between dementia with Lewy bodies and Parkinson disease dementia.

Dementia with Lewy bodies (DLB) and Parkinson disease dementia (PDD) are progressive and disabling neurodegenerative disorders, which are often misdiagnosed due to theirs overlapping clinical and paraclinical features. Nevertheless, their adequate management requires an accurate differential diagnosis. The main aim of this study was to investigate the usefulness of olfactory and trigeminal nasal testing for the differential diagnosis between DLB and PDD. Odor thresholds to three odorants differentially activating the olfactory and trigeminal systems were assessed in patients with DLB, PDD and healthy controls (n = 20 per group). Odor thresholds were significantly different between the three groups of subjects. More precisely, we found that DLB patients had significantly lower detection threshold performances compared to PDD patients. Moreover, using a standard canonical discriminant analysis, we confirmed a plain differentiation between the three groups. The current study highlights that DLB patients have very poor olfactory and trigeminal detection threshold performances, which are significantly lower, compared to PDD patients. These results suggest that olfactory testing, using odorants that stimulate both the olfactory and trigeminal systems, could constitute an interesting biomarker and contribute to the differential diagnosis of PDD and DLB patients. Further researches, notably on olfacto-trigeminal interactions, are warranted in these populations to support our findings.