Parkinson's Disease Dementia Group Research Articles

Neuropsychiatric symptoms profile and markers of Alzheimer disease–type pathology in patients with Lewy body dementias

BackgroundTo determine whether Lewy body dementia (LBD) patients with likely copathology of Alzheimer’s disease (AD) exhibit greater neuropsychiatric symptom (NPS) compared to those without likely AD-type copathology. MethodsWe enrolled 69 individuals diagnosed with Lewy body dementia (LBD), comprising both dementia with Lewy bodies (DLB) (n = 36) and Parkinson's disease dementia (PDD) (n = 33). These participants had accessible cerebrospinal fluid (CSF) markers related to Alzheimer's disease (AD) and cognitive data. We assessed CSF levels of β-amyloid 42 (Aβ42), phosphorylated tau (p-tau), and total tau (t-tau). Employing autopsy-validated CSF thresholds (t-tau/Aβ42 ratio > 0.3, n = 69), we categorized individuals into LBD with AD pathology (LBD + AD, n = 31) and LBD without apparent AD co-pathology (LBD - AD, n = 38). Moreover, the Hamilton Depression Scale (HAMD24), Hamilton Anxiety Scale (HAMA14), and Neuropsychiatric Inventory Questionnaire (NPI-Q) was used to assess the NPS. Spearman correlations were utilized to explore links between NPS and CSF marker profiles. ResultsIn terms of neuropsychiatric symptoms, LBD + AD patients demonstrated notably elevated levels of depressive symptoms (HAMD24) in comparison to LBD - AD patients (P < 0.001). However, based on PDD and DLB groups, no significant variations were noted in the neuropsychiatric symptoms(P＞0.05). Moreover, CSF-derived biomarkers of Aβ42, and t-tau/Aβ42 were also associated with HAMD24 total scores in the LBD + AD subsample (P < 0.05). ConclusionThere is an association between AD pathological markers and the NPS of LBD. The biologically based classification of LBD may be more advantageous in elucidating clinical heterogeneity than clinically defined syndromes.

Associations of Alzheimer's-related plasma biomarkers with cognitive decline in Parkinson's disease.

Parkinson's disease (PD) is associated with cognitive decline through multiple mechanisms, including Alzheimer's disease (AD) pathology and cortical Lewy body involvement. However, its underlying mechanisms remain unclear. Recently, AD-related plasma biomarkers have emerged as potential tools for predicting abnormal pathological protein accumulation. We aimed to investigate the association between AD-related plasma biomarkers and cognitive decline in PD patients. Plasma biomarkers were measured in 70 PD patients (49 with nondemented Parkinson's disease (PDND) and 21 with Parkinson's disease dementia (PDD)) and 38 healthy controls (HCs) using a single-molecule array. The study evaluated (1) the correlation between plasma biomarkers and clinical parameters, (2) receiver operating characteristic curves and areas under the curve to evaluate the discrimination capacity of plasma biomarkers among groups, and (3) a generalized linear model to analyze associations with Addenbrooke's Cognitive Examination-Revised and Montreal Cognitive Assessment-Japanese version scores. Plasma glial fibrillary acidic protein significantly correlated with cognitive function tests, including all subdomains, with a notable increase in the PDD group compared with the HC and PDND groups, while plasma neurofilament light chain captured both cognitive decline and disease severity in the PDND and PDD groups. Plasma beta-amyloid 42/40 and pholphorylated-tau181 indicated AD pathology in the PDD group, but plasma beta-amyloid 42/40 was increased in the PDND group compared with HCs and decreased in the PDD group compared with the PDND group. AD-related plasma biomarkers may predict cognitive decline in PD and uncover underlying mechanisms suggesting astrocytic pathologies related to cognitive decline in PD.

Lawton's Instrumental Activities of Daily Living for Greek-Speaking Adults with Cognitive Impairment: A Psychometric Evaluation Study with Additional Receiver Operating Characteristic Curve Analysis.

One of the components of a dementia diagnosis is the assessment of functional abilities. These abilities are measured via screeners, such as the Instrumental Activities of Daily Living (IADL) scale. The IADL scale is a valid tool that has been adapted in many languages. This study aimed to provide a cut-off point and validate the Greek version of the IADL scale in populations with cognitive impairment. IADL data were collected from 132 individuals: 24 PD patients, 24 Parkinson's disease dementia (PDD) patients, and 24 AD patients. The remaining 60 participants were cognitive healthy adults (CHAs). The CHA group and the PD group served as the cognitively unimpaired group (CUG), while the PDD and AD groups served as the cognitively impaired group (CIG). Additionally, the MMSE, the AMTS, the Clock Drawing Test CDT, the Arizona Battery for Communication Disorders of Dementia (ABCD), the NPI, and the GDS-15 were administered to the participants. Statistically significant differences in the IADL scores were exhibited between all subgroups. The IADL scale showed high internal consistency (Cronbach's alpha = 0.890). A threshold equal to 6.00 (AUC = 0.888, p < 0.001) was estimated between the CUG and the CIG. Significant positive correlations were observed between IADL and MMSE (r = 0.764, p < 0.001), IADL and AMTS (r = 0.724, p < 0.001), IADL and ABCD (r = 0.702, p < 0.001), and IADL and CDT (r = 0.627, p < 0.001) results. Given the obtained results, the IADL scale is a valid tool for clinical use with high reliability and sensitivity. Also, the IADL scale is a valuable instrument for screening functional abilities associated with cognitive impairment.

Identification of key genes and signaling pathways associated with dementia with Lewy bodies and Parkinson's disease dementia using bioinformatics.

Dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are collectively known as Lewy body dementia (LBD). Considering the heterogeneous nature of LBD and the different constellations of symptoms with which patients can present, the exact molecular mechanism underlying the differences between these two isoforms is still unknown. Therefore, this study aimed to explore the biomarkers and potential mechanisms that distinguish between PDD and DLB. The mRNA expression profile dataset of GSE150696 was acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) between 12 DLB and 12 PDD were identified from Brodmann area 9 of human postmortem brains using GEO2R. A series of bioinformatics methods were applied to identify the potential signaling pathways involved, and a protein-protein interaction (PPI) network was constructed. Weighted gene co-expression network analysis (WGCNA) was used to further investigate the relationship between gene co-expression and different LBD subtypes. Hub genes that are strongly associated with PDD and DLB were obtained from the intersection of DEGs and selected modules by WGCNA. A total of 1,864 DEGs between PDD and DLB were filtered by the online analysis tool GEO2R. We found that the most significant GO- and KEGG-enriched terms are involved in the establishment of the vesicle localization and pathways of neurodegeneration-multiple diseases. Glycerolipid metabolism and viral myocarditis were enriched in the PDD group. A B-cell receptor signaling pathway and one carbon pool by folate correlated with DLB in the results obtained from the GSEA. We found several clusters of co-expressed genes which we designated by colors in our WGCNA analysis. Furthermore, we identified seven upregulated genes, namely, SNAP25, GRIN2A, GABRG2, GABRA1, GRIA1, SLC17A6, and SYN1, which are significantly correlated with PDD. The seven hub genes and the signaling pathways we identified may be involved in the heterogeneous pathogenesis of PDD and DLB.

Neurological, Cognitive, and Clinical Biomarkers of Lewy Body Dementia Subtypes: A Literature Review

Introduction: Diagnosing the etiology underlying dementia symptoms can be difficult because of the broad nature of shared cognitive impairments across dementia subtypes. Therefore, we sought to differentiate the cognitive profiles of Alzheimer’s disease (AD) from vascular dementia (VaD) and Lewy body dementia (LBD). Methods: PubMed, ScienceDirect, Web of Science, Google Scholar, and PsychINFO were searched for studies comparing the cognitive profile of AD to those of VaD and LBD along the domains of memory, language, and executive function. Results: Short-term and episodic memory were more severely impaired in AD than VaD and LBD. Semantic memory was more impaired in AD than LBD, but it was similarly impaired in AD and VaD. Semantic fluency was worse in AD than in VaD, and phonemic fluency was worse in AD compared to VaD and LBD. Naming was more impaired in AD compared to VaD and LBD. Executive function impairments were similar or less severe in AD relative to VaD and LBD. Discussion: Findings may be explained through neuropathological correlates of each disease. Tau proteins targeting the medial temporal lobes and synaptic loss in prefrontal cortices in AD may explain greater memory deficits in AD relative to VaD and LBD. In those with AD, the temporal lobes undergo greater atrophy than in those with VaD and LBD, possibly contributing to the greater semantic fluency impairments in AD. Greater white matter loss in frontal lobes in VaD may be a reason for a worse phonemic fluency in VaD relative to AD. Executive function impairments may be attributable to more deep white matter hyperintensities in those with VaD and more dopaminergic dysfunction of the basal ganglia in those with LBD relative to those with AD. Conclusion: Understanding the cognitive profiles that differentiate AD from VaD and LBD would aid in more efficient and accurate diagnoses of dementia etiologies. Diagnoses could be further improved by using cognitive assessment in addition to neural and physiological measures. This knowledge may help identify individuals at risk of developing dementia, helping clinicians intervene early and prevent progression to severe stages.

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.

Impairment of EEG functional connectivity in dementia during recognition of emotional facial expression

AbstractBackgroundThe performance of facial expression recognition is affected both in neurocognitive disorders and in healthy elderly. Emotional content processing is expected to be adversely affected in dementia and as well in Parkinson's disease patients. The present study aims to compare the impaired facial expression recognition between different types of dementia patients, functional connectivity changes in patients with mild cognitive impairment, and patients with dementia were investigated by event‐related EEG‐coherence.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. EEG was recorded while angry, happy, and neutral facial expressions were presented. The artifacts were rejected by using Independent‐Component‐Analysis and Current‐Source‐Density. Magnitude‐squared coherence values of theta (4‐7Hz, 50‐400ms) responses were calculated. Inter‐hemispheric and intra‐hemispheric (frontal and central centered) pairs of F3, F4, C3, C4, T7, T8, Tp7, Tp8, P3, P4, O1, O2 channels were used. Two separate inter and intra hemispheric repeated‐measures‐ANOVA models were used for group comparisons.ResultThere were no group differences for intra‐hemispheric comparisons, but GroupXLocation comparison (p=.040) was significant, HE and MCI groups had higher coherence values in central‐ temporal, central‐ temporoparietal, and central‐ occipital connections compared to PDMCI, PDD, and AD patient groups (Figure 1). FaceXGroup (p=.009) interaction was significant for inter‐hemispheric coherence values, HC and MCI groups had higher interhemispheric coherence values than the PDMCI, PDD, and AD, especially during recognition of "angry" facial expression.ConclusionThe connectivity between the central and posterior regions increased with emotional face content; this increase seems to be preserved in MCI. On the other hand, it wasn't maintained in patients with more severe neurocognitive impairment; PDMCI, PDD, and AD groups had reduced central‐posterior connectivity and interhemispheric connectivity during the facial expression recognition paradigm. The decrease in inter and intra‐connectivity in the posterior regions is consistent with behavioral scores and may indicate neural losses as a phenomenon.

Cognitive Stimulation Therapy for People with Parkinson's Disease Dementia

<h3>Research Objectives</h3> To investigate the effect of Cognitive Stimulation Therapy (CST) for people with Parkinson's disease dementia (PDD) and their caregivers. <h3>Design</h3> Within-subjects pre-test post-test design. <h3>Setting</h3> Community-based, in partnership with the local American Parkinson Disease Association chapter. <h3>Participants</h3> Eighteen participants: 9 people with possible PDD (MoCA score < 21), and 9 caregivers. <h3>Interventions</h3> A 7-week program of bi-weekly 45-minute long CST group classes for people with PDD. CST is an intervention for people with dementia involving group activities and conversations that stimulate cognitive and social skills. <h3>Main Outcome Measures</h3> PDD participants completed the Montreal Cognitive Assessment (MoCA), Neuro Quality of Life Cognition Short Form (NeuroQOL Cog SF), Geriatric Depression Scale (GDS), Parkinson's Disease Questionnaire-39 (PDQ-39) and Relationship Assessment Scale (RAS). Caregivers completed the Caregiver Burden Scale (CBS) and RAS. After the course, both groups completed the Client Satisfaction Questionnaire (CSQ-8). <h3>Results</h3> The PDD group's MoCA scores improved from pre to post intervention (pre: M = 19.11, SD = 2.57; post: M = 21.22, SD = 2.95; p = 0.01). All other measures, except the PDD RAS and CBS, showed pre-post improvement, although these were not significant. The PDD participants and their caregivers reported high satisfaction with the program, as indicated by the CSQ-8 (M = 3.5 [out of 4 possible], SD = 0.16), with 72% of participants rating all items positively. <h3>Conclusions</h3> Participation in a group CST course resulted in improved cognition in this small sample of people with PDD. In addition, individuals with PDD and their caregivers were highly satisfied with the program. Although larger studies are needed, these findings suggest that CST may benefit cognition among people with PDD and is an acceptable program for people with PDD and their caregivers. <h3>Author(s) Disclosures</h3> The authors have no disclosures to report.

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).

Expression of nAChRα7 receptor in model rats with Parkinson’s disease dementia

To investigate the expression and role of nicotinic acetylcholine α7 subunit (nAChRα7) in the hippocampus of rats with Parkinson's disease (PD) and Parkinson's disease dementia (PDD). PD model was established with 6-hydroxydopa. Then, methyllycaconitine was further used to prepare a PDD model. The behavioral indexes and malondialdehyde (MDA) and superoxide dismutase (SOD) levels were measured. The mRNA level and protein level of nAChRα7 in hippocampus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western-blot, respectively. The α7nAchR and NeuN protein was detected by immunofluorescence. Compared with the PD model group, the escape latency of the PDD model group was significantly prolonged while the times of crossing platforms was significantly reduced (p < 0.05). The SOD level in the PDD and PD group decreased as compared with the control group (p < 0.05), while the MDA content increased (p < 0.05). The mRNA level and protein expression of nAChRα7 in the PDD and PD model group was significantly lower than that in the control group (p < 0.05). There was a significant difference in the nAChRα7 protein level between the PDD and PD model group (p < 0.05). Together, the nAChRα7 receptor level was significantly decreased in the PDD model group, indicating that the decrease in the nAChRα7 receptor levels is a possible mechanism of the pathogenesis of PDD.

Electrophysiological differences in cortical excitability in different forms of dementia: A transcranial magnetic stimulation and laboratory biomarkers study

The aim of the present study was to identify neurophysiologic markers to differentiate between Alzheimer dementia (AD), Vascular dementia (VaD), and Parkinson's disease dementia (PDD), and to examine their relationship to levels of transforming growth factor β1 (TGFβ1). The study included 15 patients with each type of dementia (AD, VaD, PDD) and 25 control subjects. Dementia patients were diagnosed according to the DiagnosticandStatisticalManualofMentalDisorders4thedition-revised(DSM-IV-R). Modified Mini Mental State Examination (MMMSE), motor cortex excitability including resting and active motor thresholds (rMT, aMT), input-output (I/O) curve, contralateral and ipsilateral silent periods (cSP, iSP), short-interval intracortical inhibition (SICI) at 1,2 and 4ms, and serum levels of TGFβ1 were examined. There were no significant differences between groups with regards to age, sex, education or socioeconomic level. There was significant neuronal hyperexcitability in the form of reduced rMT and aMT and a shallower I/O curve in all three groups of dementia compared with the control group. The durations of cSP and iSP were longer in AD and PDD groups compared with the control group, whereas there were no significant differences in VaD. SICI was less effective in the three dementia groups than in the control group at intervals of 4ms. Serum levels of TGFβ1 were significantly elevated in all dementia groups in comparison with the control group. There was a significant negative correlation between serum level of TGFβ1 and cSP, iSP, and SICI across all patients and a significant negative correlation between serum level of TGFβ1 and iSP duration in AD. Although motor thresholds were reduced in all patients, measures of SICI, cSP and iSP could distinguish between dementia groups. Serum level of TGFβ1 negatively correlated with iSP specifically in the AD group. This suggests that levels of TGFβ1 may relate to GABAergic dysfunction in dementia.

Patterns of olfactory functional networks in Parkinson's disease dementia and Alzheimer's dementia

Hyposmia is common in Alzheimer's dementia (AD) and Parkinson's disease dementia (PDD). We evaluated the pattern of olfactory functional connectivity (FC) in AD and PDD to uncover neural correlates that are related to olfactory dysfunction. This study enrolled 57 patients with AD and PDD and 25 control subjects. Using a seed-based approach, we compared the resting-state network from the seed-region-of-interest in the olfactory bulb, olfactory tract, piriform cortex, and orbitofrontal cortex (OFC) between groups. The PDD group showed lower FC with striatal-thalamic-frontal regions from the olfactory bulb than the AD group. The PDD group showed lower FC from left OFC with striatal-frontal regions and lower FC from right OFC with left fronto-temporal areas than the AD group. In a correlation analysis, the FC from left OFC with right insula that differed between the PDD and control groups was positively correlated with olfactory function. The present study demonstrated that this distinct olfactory functional network pattern may represent different neural mechanisms for olfactory dysfunction in AD and PDD.

P2‐220: GAIT IMPAIRMENTS IN DEMENTIA SUBTYPES: CONSIDERING THE IMPACT OF ENVIRONMENTAL CONTEXT

Background Gait is a potentially useful clinical tool to aid early diagnosis of dementia. Unique signatures of gait have been shown to discriminate dementia subtypes, such as Alzheimer's disease (AD) and Lewy body disease (LBD; including dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD)), from each other and normal ageing when assessed using “gold-standard” methodology, such as instrumented walkways. Body-worn monitors, such as tri-axial accelerometers, may allow inexpensive measurement of gait in clinical environments, and provide a more ecologically-valid picture of gait in free-living environments, i.e. home and community. The aim of this study was to explore the impact of the environment on gait characteristics for distinguishing AD and LBD from each other and controls. Methods 99 participants were recruited; 32 AD ((mean±SD) Age:77±6; MMSE:23±4), 28 DLB (Age:76±6; MMSE:24±4), 14 PDD (Age:78±6; MMSE:24±4) and 25 controls (Age:74±9; MMSE:29±1). Dementia subtypes ranged from mild cognitive impairment to moderate dementia. A tri-axial accelerometer (Axivity AX3) recorded gait data over six 10-metre walks in the lab, and continuously over seven days in free-living environments. One-way ANOVAs and non-parametric equivalents assessed group differences. Results Preliminary results show that all disease groups had impaired gait compared to controls (p≤.05) in both lab and free-living environments. In the lab, the PDD group demonstrated greater variability and asymmetry of gait (p≤.05) compared to AD and DLB, and in free-living by shorter steps and greater variability of gait (p≤.05). There were no differences between AD and DLB in the lab, however, people with AD had a significantly more asymmetric step length than DLB (p=.017, AUC=.677) in free-living environments. Conclusions This study is the first to provide evidence that gait can distinguish different disease subtypes from normal ageing using inexpensive body-worn monitors. It also highlights the influence of the environment on patterns of gait impairment. Free-living gait analysis may provide a more accurate and discriminative reflection of gait impairment in different disease subtypes, and therefore be a useful clinical tool to aid early differential diagnosis. Different methods of gait analysis may provide different results; future work should validate accelerometery outcomes with gold-standard instruments in the described populations.

COWAT Performance of Persons with Alzheimer Dementia, Vascular Dementia, and Parkinson Disease Dementia According to Stage of Cognitive Impairment.

The Controlled Oral Word Association Test (COWAT) evaluates frontal lobe and executive function. Therefore, it can be helpful in differentiating cognitive deficits. However, there are no studies comparing the COWAT performance according to the type and stage of cognitive impairment. To compare performance among persons with Alzheimer dementia (AD), vascular dementia (VaD), and Parkinson disease dementia (PDD) on the COWAT according to stage of cognitive impairment. Retrospective chart review. University hospital rehabilitation psychology center. We reviewed the medical records of 246 persons diagnosed with mild cognitive impairment (MCI) or dementia using the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and the Korean-Instrumental Activities of Daily Living (K-IADL). Patients were divided into a control group, Alzheimer groups (amnestic mild cognitive impairment [aMCI] + AD), Vascular groups (vascular mild cognitive impairment [VaMCI] + VaD), and Parkinson groups (Parkinson disease-mild cognitive impairment [PD-MCI] + PDD). Total scores (ie, total number of words produced in 60 seconds on the semantic and phonemic fluency tests of the COWAT) were analyzed. Secondary analysis included calculating percentage scores of words produced during each of the four, 15-second segments from the total number of words produced in each trial. All MCI groups scored significantly lower than the control group on both semantic and phonemic fluency tests. Among the dementia groups, the VaD (mean ± SD, 5.6 ± 5.1) and PDD (5.5 ± 5.5) groups' scores were significantly lower and worse than that of the AD (11.0 ± 8.8) group on the phonemic test (P < .001). The difference in percentage scores was most marked between the PD-MCI (17.0 ± 2.2) and PDD (1.2 ± 3.1) groups, followed by the VaMCI (13.3 ± 1.9) and VaD (5.6 ± 1.8) groups on the latter phonemic test (P = .007). The COWAT is a sensitive test of frontal-lobe and executive function impairment in persons with MCI. Decreased verbal output in the last 15 seconds of phonemic fluency test is significantly decreased and impaired in persons with VaMCI and PD-MCI compared to persons with aMCI as they progress to dementia. III.

No Significant Difference in Cognitive Decline and Mortality between Parkinson's Disease Dementia and Dementia with Lewy Bodies: Naturalistic Longitudinal Data from the Swedish Dementia Registry.

Whether dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) are distinct disorders or two subtypes of the same entity, is not yet fully understood. There is a dearth of knowledge on differences in longitudinal clinical outcomes between DLB and PDD. We aimed to compare longitudinal trend of cognitive decline, mortality, and their determinant factors between patients with DLB and PDD. At baseline, we recruited 1110 DLB, and 764 PDD patients registered in the Swedish dementia registry (SveDem) during 2007-2015. Cognitive status was assessed at baseline and each follow-up visit by mini-mental state examination (MMSE). At least one follow-up MMSE was available for 411 (37.0%) DLB and 229 (30.0%) PDD patients. Rate of cognitive decline and mortality risk were compared between the two groups. After an average of 2-years, the rate of cognitive decline did not differ between DLB (1.1 MMSE unit/year) and PDD (1.2 MMSE unit/year) groups (p = 0.970). There was no significant difference in the median survival time between DLB (4.0 years) and PDD (4.1 years) groups (Log rank p = 0.614). Antipsychotic drug use in DLB and larger number of medications in PDD were the most important determinants of faster annual cognitive decline. Our findings from real-world clinical practice demonstrated that the rate of cognitive decline and mortality do not differ significantly between DLB and PDD at least over 2 years, yet, various factors might determine clinical outcome in these two groups. It seems that DLB and PDD are probably similar synucleinopathies, with phenotypical variations in the order of manifestations rather than course of progression and clinical outcome.

Heart rate variability and its influencing factors in patients with dementia with Lewy bodies and patients with Parkinson disease dementia

Objective To compare the difference in heart rate variability(HRV)between patients with dementia with Lewy bodies(DLB)and those with Parkinson disease dementia(PDD)and to identify the influencing factors. Methods We retrospectively enrolled 30 patients with DLB(DLB group)and 41 patients with PDD(PDD group)at the outpatient and inpatient services of our hospital from January 2010 to December 2017 in this study, and further recruited 119 normal elderly individuals to serve as the control group.HRV was recorded with 24 h dynamic electrocardiogram and compared between the DLB group and the PDD group.Time domain measures including standard deviation of all normal to normal(NN)intervals(SDNN)and square root of the mean squared differences of successive NN intervals(rMSSD)and frequency domain measures including total power(TP), low frequency(LF), and high frequency(HF)were analyzed with a customized program.The levodopa equivalent dose(LED), mini-mental state examination(MMSE), Montreal Cognitive Assessment(MoCA), Hoehn-Yahr stage(H-Y stage)and the unified Parkinson's disease rating scale Ⅲ(UPDRS Ⅲ), and the Alzheimer's disease Cooperative Study-Activities of Daily Living scale(ADCS-ADL)were assessed in DLB and PDD patients to investigate the influencing factors. Results SDNN, TP, and LF in the DLB group and the PDD group were significantly lower than in the control group(F=14.154, 4.742, 4.897, P 0.05). The DLB group and the PDD group did not differ in HF from the control group(P>0.05). There was no significant difference in any HRV indexes between DLB and PDD patients(P>0.05). Correlation analysis showed no correlation of HRV with cognitive level(MMSE, MoCA), motor disturbance degree(UPDRS Ⅲ, H-Yahr stage), daily living ability(ADCS-ADL), or dosage of anti-PD drugs(each P>0.05). Conclusions DLB and PDD patients present similar impairments in autonomic nervous system function, which are not associated with disease severity. Key words: Dementia; Lewy bodies; Parkinson disease; Heart rate variability

Module differences of glucose metabolic brain network among Alzheimer's disease, Parkinson's disease dementia, Lewy body dementia and health control.

Dementia has become a serious disease in elderly population. Graph theory based brain network analysis method is considered as a popular and universal technique in the field of the neurosciences. It can help neuroscientists to investigate the neuropathology of dementia, especially to understand dementia subtypes. However, brain network analysis for various dementia subtypes at the same time is still limited. The aim at this study is to investigate the similarities and differences in brain network modular parameters of three dementia subtypes: Alzheimer's disease (AD), Parkinson's disease dementia (PDD), Lewy body dementia (DLB). Health control has also been compared. All subjects of health control(HC), AD, PDD and DLB groups were from Huashan Hospital. Using topological analysis algorithms, we found that HC brain was divided into 4 modules; AD brain was divided into 4 modules; PDD brain was divided into 6 modules; and DLB brain was divided into 10 modules, which demonstrated differences in these dementia subtypes. We also found that right thalamus area was scattered in all dementia subtypes. After using the seed point correlation analysis, it can be seen that the connections between right thalamus and subcortical, frontal gyrus were enhanced and the connections with the occipital gyrus was attenuated in dementia subtypes. As a result, findings in this paper are expected to be useful for neuroscientists to further understand the pathology of AD, PDD and DLB.

Neuropsychiatric Symptoms in Parkinson's Disease Dementia Are More Similar to Alzheimer's Disease than Dementia with Lewy Bodies: A Case-Control Study.

Background and purposePrevious studies on the clinical and pathological manifestations of Parkinson’s disease dementia (PDD) have reported findings more similar to dementia with Lewy bodies (DLB) than to Alzheimer’s disease (AD). The aim of this study was to investigate the neuropsychiatric symptoms of PDD compared to DLB and AD.MethodsWe conducted a retrospective case-control study on 125 newly diagnosed consecutive PDD patients and age- and dementia stage-matched controls with either DLB (N = 250) or AD (N = 500) who visited the same hospital over the same period. For each case and control, neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI).ResultsOverall, 513 (58.6%) patients were female and 362 (41.4%) were male. Comparisons of clinical data revealed that the PDD group, similar to the AD group, had a lower NPI total score, NPI caregiver burden score, and rate of antipsychotic use (all p < 0.001) than the DLB group. One or more psychiatric symptoms were reported in 95.2% of the PDD, 99.2% of the DLB, and 96.8% of the AD patients. The PDD group had lower subscores in the items of delusions, hallucinations, agitation, anxiety, irritation, aberrant motor behavior compared to the DLB group. Severe neuropsychiatric symptoms among all dementia patients were associated with younger age, more advanced stage, and a diagnosis of DLB.ConclusionNeuropsychiatric symptoms in PDD were more like those in AD than in DLB. Severe neuropsychiatric symptoms in degenerative dementia were associated with younger age, more advanced stage of dementia, and a diagnosis of DLB.

Long-Term Efficacy of Memantine in Parkinson' Disease Dementia: An 18-Month Prospective Perfusion Single Photon Emission Computed Tomography Preliminary Study.

Background and PurposeAlthough the treatment efficacy of memantine in Parkinson's disease dementia (PDD) has been reported after several weeks of administration, the long-term effects on brain perfusion and clinical symptoms remain unclear. The current study aimed to follow-up PDD patients after 18 months of memantine treatment using 99mTc hexamethylpropylene amine oxime single photon emission computed tomography (SPECT).MethodsA total of 15 patients with PDD and 11 healthy participants were recruited into this study and they were assessed with brain SPECT, Mini-Mental State Examination (MMSE), Clinical Dementia Rating (CDR), Global Deterioration Scale (GDS), and Neuropsychiatric Inventory (NPI). Differences in regional cerebral blood flow (rCBF) between the two groups were evaluated at baseline. After 18 months of memantine administration, changes in brain perfusion, severity of dementia, cognition, and neuropsychiatric disturbances were examined in the patients with PDD.ResultsThe PDD group showed hypoperfusion in most of the cortical, subcortical, and cerebellar areas compared to healthy controls at baseline. At the follow-up, changes in rCBF, CDR (p=0.32), sum of box of CDR (p=0.49), MMSE (p=0.61), GDS (p=0.79), and NPI (p=0.23) were not significant in the PDD patients.ConclusionsOur findings implicate that memantine may delay the progression of brain perfusion deficits and clinical symptoms of PDD in the long term.

Impact of Rivastigmine on Cognitive Dysfunction and Falling in Parkinson's Disease Patients

Background: The purpose of this study was to observe the incidence of falls in Parkinson's disease (PD) patients with different cognitive levels and to investigate the effect of the cholinesterase inhibitor Rivastigmine on cognitive dysfunction and falling in PD patients. Subjects and Methods: Data from 176 PD patients participating in the collaborative PD study between June 2010 and June 2014 were collected; the Chinese edition of the Montreal Cognitive Assessment (MoCA) score was used to evaluate the cognitive function of patients, and falls were recorded. PD patients with cognitive dysfunction were randomly administered either a placebo or Rivastigmine. The cognitive function changes and difference in fall incidence were compared between the 2 groups. Results: The average number of falls per person in PD patients without cognitive impairment dysfunction was significantly lower than that in patients in the PD mild cognitive impairment (PD-MCI) group and that in the PD dementia (PDD) group (p < 0.01, p < 0.001, respectively), and the incidence of falls was significantly lower than that in patients in the PD-MCI and PDD groups (p < 0.01, p < 0.01, respectively). Compared to the PD-MCI group, the incidence of falls of patients in the PDD group (OR 2.45, 95% CI 0.97-6.20, p < 0.01) and the number of falls per person were significantly increased (p < 0.01). After taking the placebo or Rivastigmine for 12 months, the MoCA scores of patients in the Rivastigmine treatment group were significantly higher than those of the control group (p = 0.002). The number of falls per person and the incidence of falls of patients in Rivastigmine treatment group were significantly lower than those in the placebo group (p < 0.01). Conclusion: This study suggests that the degree of cognitive impairment is closely associated with the incidence of falls, and the cholinesterase inhibitor Rivastigmine can delay the deterioration of cognitive function and lower the incidence of falls in PD patients.