White matter hyperintensities on MRI in dementia with Lewy bodies, Parkinson's disease with dementia, and Alzheimer's disease

Visual hallucinations (VHs) are common in dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD), while auditory hallucinations are rare. To neurophysiologically investigate the pathophysiology of VHs in these disorders, we studied event-related potentials (ERPs) of DLB, PDD, and Alzheimer's disease (AD) patients. We compared visual and auditory ERP latencies among PDD patients with and without VHs (PDD-H: 11, PDD-N: 6), DLB patients (24), and AD patients (21). To elicit visual and auditory ERPs, a facial discrimination paradigm and a conventional auditory odd-ball paradigm, respectively, were used. The mean visual P3 latencies in the PDD-H and DLB groups were significantly longer than that in the AD group, while the mean auditory P3 latencies in all four patient groups were comparable. The mean visual P2 latencies in the PDD-N, PDD-H, and DLB groups were significantly longer than that in the control group. Our findings suggest that visual cognitive functions are selectively impaired in hallucinatory patients with DLB and PDD. VHs may be associated in part with predominant visual cognitive impairments attributable to PDD and DLB pathologies. Our findings also suggest that the impairments occur at the early stage of facial information processing.

To study the use of transcranial sonography (TCS) in discriminating between patients with dementia with Lewy bodies (DLB) and Parkinson's disease with dementia (PDD). Fourteen patients with DLB, 31 with PDD and 73 with PD without dementia (PDnD) were studied with TCS. All assessable patients with DLB, 97% with PDD, and 94% with PDnD showed at least unilateral hyperechogenicity of substantia nigra (SN). However, bilateral marked SN hyperechogenicity was present in 80% of DLB patients but only in one third of PDD and PDnD patients, and was associated with younger age at disease onset in PD but not in DLB. An asymmetry index > or = 1.15 of bilateral SN echogenic sizes, estimated by division of larger size by smaller size, was found in 69% of PDD patients but only 20% of DLB patients. Combination of SN echogenic sizes, asymmetry indices and onset age discriminated PDD from DLB with a sensitivity of 96%, a specificity of 80% and a positive predictive value of 93%. TCS of brainstem raphe, thalami, lenticular nuclei, caudate nuclei and ventricle widths did not discriminate between DLB and PDD. Compared with PDnD patients, DLB and PDD patients exhibited significantly larger widths of third ventricle and of frontal horns. In PDD patients, scores on the Unified Parkinson's Disease Rating Scale correlated with widths of third ventricle and of frontal horns. SN hyperechogenicity is typical for PDD and DLB. However, size, asymmetry and relation of SN hyperechogenicity to age at disease onset discriminate PDD from DLB.

We compared the clinical and neuropsychological pattern of dementia with Lewy bodies (DLB) to Alzheimer's disease (AD) and Parkinson's disease with dementia (PD-d). Sixteen patients clinically diagnosed with DLB were compared with two groups of patients with PD-d (n = 15) and AD (n = 16) matched for level of dementia. Isolated cognitive impairment was the most common form of presentation in AD (93.8%) and DLB (31.3%) groups, while parkinsonism was in 100% of PD-d subjects. Psychoses associated with cognitive impairment at the beginning of the disease were more frequent in DLB patients (31.3%) than in AD (6.3%) and PD-d (0%) groups. There were no significant differences in Unified Parkinson Disease Rating Scale motor-subscale scores between DLB and PD-d patients. DLB and PD-d patients performed significantly worse on attentional functions and better on memory tests than AD. DLB patients also showed lower scores than AD subjects on visual memory, visuoperceptive, and visuoconstructive tests. No significant differences were found between PD-d group and DLB subjects on any neuropsychological test. We were unable to find any differences in cognitive tasks between PD-d and DLB subjects. Clinical features and neuropsychological deficiencies of DLB (attentional, visuoperceptive, and visuoconstructive deficits) and PD (attentional deficits) compared to AD (amnesic syndrome) can contribute to accurate identification of these entities and to the understanding of the neuropathological and neurochemical substrate underlying these diseases.

Gender differences in Parkinson's disease with dementia and dementia with Lewy bodies

EEG abnormalities have been reported for both dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). Although it has been suggested that variations in mean EEG frequency are greater in the former, the existence of meaningful differences remains controversial. No evidence is as yet available for Parkinson's disease with dementia (PDD). The aim of this study was to evaluate whether EEG abnormalities can discriminate between DLB, AD and PDD in the earliest stages of dementia and to do this 50 DLB, 50 AD and 40 PDD patients with slight cognitive impairment at first visit (MMSE > or = 20) were studied. To improve clinical diagnostic accuracy, special emphasis was placed on identifying cognitive fluctuations and REM-sleep behaviour disorder. EEG variability was assessed by mean frequency analysis and compressed spectral arrays (CSA) in order to detect changes over time from different scalp derivations. Patients' initial diagnoses were revised at a 2-year follow-up visit with neuroimaging evaluation. Initial diagnoses were confirmed in 36 DLB, 40 AD and 35 PDD patients. The most relevant group differences were observed between the AD and DLB patients in EEGs from posterior derivations (P<0.001). Dominant frequencies were 8.3 +/- 0.6 Hz for the AD group and 7.4 +/- 1.6 Hz for the DLB group, in which most of the patients (88%) exhibited a frequency band of 5.6-7.9 Hz. Dominant frequency variability also differed between the AD (1.1 +/- 0.4 Hz) and DLB groups (1.8 +/- 1.2 Hz, P<0.001). Of note, less than a half (46%) of the patients with PDD exhibited the EEG abnormalities seen in those with DLB. Graded according to the presence of alpha activity, five different patterns were identified on EEG CSA from posterior derivations. A pattern with dominant alpha bands was observed in patients with AD alone while, in those with DLB and PDD, the degree to which residual alpha and 5.6-7.9 bands appeared was related to the presence and severity of cognitive fluctuations. At follow-up, EEG abnormalities from posterior leads were seen in all subjects with DLB and in three-quarters of those with PDD. Of interest, in four patients initially labelled as having AD, in whom the occurrence of fluctuations and/or REM-sleep behaviour disorder during the 2-year follow-up had made the diagnosis of AD questionable, the initial EEG was characterized by the features observed in the DLB group. If revised consensus criteria for DLB diagnosis are properly applied (i.e. emphasizing the diagnostic weight of fluctuations and REM sleep behaviour disorder), EEG recording may act to support discrimination between AD and DLB at the earliest stages of dementia, since characteristic abnormalities may even precede the appearance of distinctive clinical features.

Objective To investigate the clinical features in patients with Parkinson disease with dementia (PDD) and dementia with lewy bodies (DLB), in order to provide evidence for clinical diagnosis. Methods 36 patients with DLB and 24 patients with PDD were collected in department of neurology of our hospital from March 2015 to December 2017. The severity of motor symptoms, cognitive function, and mental behavior symptoms were compared between the two groups. Results The course of disease in DLB group was significantly shorter than that in PDD group [(2.13±1.98)d vs.(5.65±3.59)d]. The scores of UPDRSⅢ and tremor in DLB group were lower than those in PDD group [(26.73±11.61) vs.(37.16±13.73), (2.59±1.83) vs.(5.15±3.59)], but the score of posture and gait disorder in DLB group was higher than that in PDD group [(9.16±1.64) vs.(6.35±2.48)] (P<0.05). The scores of MMSE, MoCA, and CDT in DLB group were lower than those in PDD group (P<0.05). The rates of illusion and emotional instability in DLB group were higher than those in PDD group, the rates of apathy, depression, anxiety, and sleep disorders in DLB group were lower than those in PDD group (P<0.05). Conclusion Cognitive impairment is more progressive in DLB patients compared with PDD patients. Hallucinations and emotional instability are more common in DLB patients, but depression, anxiety, and sleep disorders are more common in PDD patients. Key words: Dementia with lewy bodies; Parkinson disease with dementia; Clinical features

Cerebrospinal Fluid Biomarkers in Parkinson's Disease with Dementia and Dementia with Lewy Bodies

To examine the occurrence of fluctuating cognition (FC) in a group of patients with Parkinson's disease with dementia (PDD), and to determine whether the presence of FC in PDD is associated with a pattern of cognitive and behavioural disturbances similar to the one shown by patients affected by dementia with Lewy bodies (DLB), a cluster analysis was carried out on the scores obtained by 27 PDD patients on the Clinician Assessment of Fluctuation Scale (CAF). The analysis separated the PDD patients into two subgroups, called PDD non-fluctuators (PDDNF; CAF <or= 2) and PDD fluctuators (PDDF; CAF > 2). The two groups underwent a cognitive and behavioural evaluation. Their scores were compared with those obtained by DLB and Alzheimer's disease (AD) patients. When exploring the cognitive performance of the patients with the Dementia Rating Scale-2 (DRS-2), PDDF had a similar pattern of impairments compared to DLB, which involved prevalently the attention and initiation/perseveration domains, and which was significantly more pronounced compared to that shown by PDDNF. The main behavioural finding of the study was the similar incidence of visual hallucinations in the PDDF and DLB groups, which was significantly higher compared to PDDNF and AD. Our results confirmed the hypothesis that subgroups with different cognitive profiles exist within PDD and that the occurrence of FC is the clinical variable associated with a DLB pattern of impairment in PDD. In conclusion, our study suggests that when FC occurs in PDD this syndrome becomes clinically undistinguishable from DLB.

Background The study is aimed at assessing the usefulness of 99m Tc-ECD SPECT in distinguishing patients with: Dementia with Lewy Bodies (DLB), Alzheimer's disease (AD) and Parkinson's disease with dementia (PD-D). Methods Fifty patients participated in the study: 13 patients with DLB (aged 74 ± 4 years), 19 patients with AD (aged 75 ± 7 years), 18 patients with PD-D (aged 72 ± 3 years) and 14 healthy individuals (aged 70 ± 6 years). A neuropsychological examination was conducted on all patients. Motor function of DLB and PD-D patients was assessed using the Hoehn-Yahr scale, Unified Parkinson's Disease Rating Scale and Schwab and England Activities of Daily Living Scale. 99m Tc-ECD SPECT was performed on all subjects. Statistical analysis of radiotracer uptake was performed for 16 regions of interest. To differentiate patients with DLB, PD-D and AD discriminate analysis was conducted. Results SPECT showed global hypoperfusion in all patient groups when compared to control group. In DLB perfusion was significantly lower within the left temporal region as compared to AD and within the right parietal region, left temporo-occipital junction and left thalamus as compared to PD-D. A significant decrease of perfusion in both thalami was found in PD-D in comparison to AD. Discriminate analysis allowed for the proper classification in 68% of all patients: PD-D was classified the most accurately (83%) and DLB with least precision (46%). Conclusions 99m Tc-ECD SPECT did not allow us to differentiate precisely among DLB, PD-D and AD. Overlapping neuropathological features of DLB, PD-D and AD may account for this pattern of perfusion.

IntroductionThe objective was to study whether α-synuclein oligomers are altered in the cerebrospinal fluid (CSF) of patients with dementia, including Parkinson disease with dementia (PDD), dementia with Lewy bodies (DLB), and Alzheimer disease (AD), compared with age-matched controls.MethodsIn total, 247 CSF samples were assessed in this study, including 71 patients with DLB, 30 patients with PDD, 48 patients with AD, and 98 healthy age-matched controls. Both total and oligomeric α-synuclein levels were evaluated by using well-established immunoassays.ResultsThe levels of α-synuclein oligomers in the CSF were increased in patients with PDD compared with the controls (P < 0.05), but not in patients with DLB compared with controls. Interestingly, the levels of α-synuclein oligomers in the CSF were also significantly higher in patients with PDD (P < 0.01) and DLB (P < 0.05) compared with patients with AD. The levels of CSF α-synuclein oligomers and the ratio of oligomeric/total-α-synuclein could distinguish DLB or PDD patients from AD patients, with areas under the curves (AUCs) of 0.64 and 0.75, respectively. In addition, total-α-synuclein alone could distinguish DLB or PDD patients from AD patients, with an AUC of 0.80.ConclusionsThe levels of α-synuclein oligomers were increased in the CSF from α-synucleinopathy patients with dementia compared with AD cases.

Structural and functional imaging study in dementia with Lewy bodies and Parkinson's disease dementia.

Parkinson disease (PD), Parkinson disease with dementia (PDD), and Dementia with Lewy bodies (DLB) differ clinically with regard to the presence and timing of dementia. In this postmortem study, we evaluated whether the burden and distribution pattern of amyloid-β (Aβ) pathology differs among these disease entities. We assessed Aβ phases and neuritic plaque scores in 133 patients fulfilling clinical diagnostic criteria for PD, PDD, and DLB, and determined the presence and load of Aβ pathology in 5 cortical and 4 subcortical regions in a subset of patients (n = 89) using a multispectral imaging system. Aβ phases and neuritic plaque scores were higher in DLB versus PDD (both p < 0.001) and in PDD vs PD patients (p = 0.020 and 0.022, respectively). Aβ pathology was more often observed in the entorhinal cortex, amygdala and putamen in DLB versus PDD patients; Aβ load was higher in both cortical and subcortical regions. PDD patients had more frequent Aβ pathology in temporal cortex and higher Aβ load in cortical regions and striatum versus PD patients. Our findings suggest that the load and extent of Aβ pathology may contribute to cognitive dysfunction in PDD and the early-stage severe dementia in DLB.

Objective: We studied autonomic disturbance in patients with dementia with Lewy bodies (DLB), Parkinson disease with dementia (PDD), Alzheimer disease (AD), to determine whether autonomic function tests can be used to distinguish these disorders. Methods: Autonomic function was tested in 56 patients with DLB, 37 patients with PDD, and 59 patients with AD by using the sympathetic skin response, coefficient of variation in R-R interval, the head-up tilt test, serum norepinephrine concentration, and 123I-meta-iodobenzylguanidine cardiac scintigraphy. Symptoms of autonomic dysfunction, such as constipation, urinary symptoms, and orthostatic hypotension, were also noted. Results: The groups did not differ on baseline characteristics other than those associated with Parkinsonism and dementia. All patients with DLB and PDD had some dysautonomia, whereas rates were much lower for patients with AD (19%). Significantly more DLB and PDD patients than AD patients showed abnormalities on autonomic function tests. Conclusions: Autonomic function tests might be quite useful to distinguish DLB and PDD from AD.

IntroductionWhether dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) should be considered as one entity or two distinct conditions is a matter of controversy. The aim of this study was to compare the characteristics of DLB and PDD patients using data from the Swedish Dementia Quality Registry (SveDem).MethodsSveDem is a national Web-based quality registry initiated to improve the quality of diagnostic workup, treatment, and care of patients with dementia across Sweden. Patients with newly diagnosed dementia of various types were registered in SveDem during the years 2007–2011. The current cross-sectional report is based on DLB (n = 487) and PDD (n = 297) patients. Demographic characteristics, diagnostic workup, Mini-Mental State Examination (MMSE) score, and medications were compared between DLB and PDD groups.ResultsNo gender differences were observed between the two study groups (P = 0.706). PDD patients were significantly younger than DLB patients at the time of diagnosis (74.8 versus 76.8 years, respectively; P < 0.001). A significantly higher prevalence of patients with MMSE score ≤24 were found in the PDD group (75.2% versus 67.6%; P = 0.030). The mean number of performed diagnostic modalities was significantly higher in the DLB group (4.9 ± 1.7) than in the PDD group (4.1 ± 1.6; P < 0.001). DLB patients were more likely than PDD patients to be treated with cholinesterase inhibitors (odds ratio = 2.5, 95% confidence interval = 1.8–3.5), whereas the use of memantine, antidepressants, and antipsychotics did not differ between the groups.ConclusionThis study demonstrates several differences in the dementia work-up between DLB and PDD. The onset of dementia was significantly earlier in PDD, while treatment with cholinesterase inhibitors was more common in DLB patients. Severe cognitive impairment (MMSE score ≤24) was more frequent in the PDD group, whereas more diagnostic tests were used to confirm a DLB diagnosis. Some similarities also were found, such as gender distribution and use of memantine, antidepressants, and antipsychotics drugs. Further follow-up cost-effectiveness studies are needed to provide more evidence for workup and treatment guidelines of DLB and PDD.

This study compared verbal learning and memory in patients with autopsy-confirmed dementia with Lewy bodies (DLB) and patients with Parkinson's disease with dementia (PDD). A total of 24 DLB patients, 24 PDD patients, and 24 normal comparison participants were administered the California Verbal Learning Test. The three groups were matched on demographic variables, and the two patient groups were matched on the Mattis Dementia Rating Scale. The results indicated that DLB patients recalled less information than PDD patients on all but one recall measure and displayed a more rapid rate of forgetting. In contrast, the PDD patients committed a greater percentage of perseveration errors than the DLB patients. The two groups did not differ in the percentage of recall intrusion errors or any measures of recognition. A discriminant function analysis (DFA) using short-delay cued recall, percentage of perseveration errors, and List B recall differentiated the DLB and PDD groups with 81.3% accuracy. The application of the DFA algorithm to another sample of 42 PDD patients resulted in a 78.6% correct classification rate. The results suggest that, despite equivalent levels of general cognitive impairment, patients with DLB or PDD exhibit a different pattern of verbal learning and memory deficits.