Comparison of clinical features between dementia with lewy bodies and Parkinson disease with dementia

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.

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.

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.

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.

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.

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.

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.

Sirs: Dementia with Lewy bodies (DLB) is clinically characterized by fluctuating cognitive impairment, visual hallucinations and parkinsonism [4]. It is the second most common neurodegenerative disease that causes dementia after Alzheimer’s disease (AD). One of the most distinct pathologic features in the brains of DLB patients is the prominent loss of nigrostriatal dopaminergic neurons similar to that in the brains of Parkinson’s disease (PD) patients. The previous SPECT and PET studies have shown that the assessment of nigrostriatal dopaminergic functions is useful in distinguishing between DLB and AD patients [2, 6]. In the present study, we measured the CSF levels of homovanillic acid (HVA), a major dopamine metabolite, in DLB and AD patients. We report here that the assessment of CSF HVA levels is also a possible marker for distinguishing DLB patients from AD patients. Although Weiner et al. [7] previously reported that CSF HVA levels in DLB patients were lower than those in AD patients, the number of samples was small (DLB, n = 8) and they did not show the normal control levels of CSF HVA. Sixty-five patients with PD without dementia (32 men and 33 women, 74.5 ± 5.6 years, mean ± SD), 14 patients with DLB (8 men and 6 women, 74.0 ± 7.8 years), 53 patients with AD (23 men and 30 women, 77.1 ± 6.8 years) and 34 normal control subjects (16 men and 18 women, 76.9 ± 6.4 years) were examined. There were no significant differences in age and gender among the four groups. The clinical diagnosis of DLB was based on the criteria of the consortium on DLB international workshop [4]. All the patients with DLB had at least two of the three core features of DLB (fluctuating cognition, recurrent visual hallucinations, and spontaneous parkinsonism). CT or MRI of the heads of these patients showed no focal brain lesions, including those of cerebrovascular disease. Thus, they were diagnosed as having probable DLB. The clinical diagnosis of AD was based on the NINCDS-ADRDA criteria [5]. The mean Mini-Mental State Examination (MMSE) scores (mean ± SD) were 15.1 ± 5.4 (5 to 23) in the DLB group and 16.1 ± 5.1 (0 to 23) in the AD group. The difference in MMSE scores between the two groups was not significant. The mean Hoehn and Yahr scores were 2.08 ± 0.56 in the PD group and 2.13 ± 0.64 in the DLB group. All the AD patients had no apparent extrapyramidal signs and could walk unassisted. After informed consent was obtained, CSF samples were collected from the patients by lumbar puncture. None of the patients took any antiparkinsonian drugs, neuroleptics, or antidepressants when the lumbar puncture was performed. Three milliliters of CSF was used for routine examination, and an additional 2 ml was stored at –70 °C until analysis. The CSF HVA levels were measured by injection of 80 μl of CSF into a high-performance liquid chromatography (HPLC) system equipped with 16 electrochemical sensors (CEAS Model 5500, ESA, Bedford, MA, USA). The mean CSF HVA values were compared by ANOVA with post hoc Scheffe’s analyses. The study protocol was reviewed and approved by the ethics committee of Tokyo Metropolitan Geriatric Hospital. CSF HVA levels were 37.1 ± 14.4 ng/ml in the control group, 14.5 ± 7.3 ng/ml in the PD group, 10.9 ± 9.0 ng/ml in the DLB group and 22.0 ± 10.9 ng/ml in the AD group (Fig. 1). CSF HVA levels were lower in the PD, DLB and AD groups than in the control subjects (p< 0.001, ANOVA). CSF HVA levels in the DLB and PD groups were much lower than those in the AD group (p< 0.01, ANOVA). The difference in CSF HVA levels between the PD and DLB groups was not significant. The cutoff value of 12.6 ng/ml could distinguish the DLB patients from the AD patients with a sensitivity of 78.6 % and a specificity of 79.2 %. We demonstrated a prominent reduction in CSF HVA levels in DLB patients. This finding is compatible with the pathological features that nigrostriatal dopaminergic neurons are severely degenerated in the DLB brain. As previously reported, CSF HVA levels were also lower in AD patients than in the control subjects [1]. However, CSF HVA levels in DLB patients were much lower than those in AD patients. The analysis of CSF HVA levels may be useful in distinguishing DLB patients from AD patients. Recently, we have shown that CSF Aβ42 levels are decreased and CSF tau levels are normal in DLB patients [3]. Although our results should be confirmed by postmortem examination, decreased As42, normal tau and decreased HVA levels may be the characteristic CSF features of DLB. LETTER TO THE EDITORS

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

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

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

Background: The relation between dementia with Lewy bodies (DLB) and Parkinson’s disease with dementia (PDD) is unknown. Objectives: To compare the cognitive profiles of patients with DLB and PDD, and...

Resting-state electroencephalographic rhythms depend on sex in patients with dementia due to Parkinson's and Lewy Body diseases: An exploratory study.

Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB) overlap in phenomenology and neurochemical deficits. We hypothesised they would not differ in their response to the cholinesterase inhibitor donepezil. We recruited 70 subjects, 30 DLB and 40 PDD, in an open label study to compare the efficacy of donepezil in these two patient groups. They were assessed at baseline, 4, 12 and 20 weeks. The main outcome measures were the Mini-Mental State Examination (MMSE), Neuropsychiatric Inventory (NPI) and motor sub-section of the Unified Parkinson's Disease Rating Scale (UPDRS III). PDD patients were younger than DLB and had more severe parkinsonism at baseline. The groups were similar on all other variables of interest. By 20 weeks the mean MMSE score increased by 3.9 points in the DLB group and by 3.2 points in PDD. The mean NPI score reduced by 14.6 points for DLB and 12.0 points for PDD. These treatment effects were all significant compared to baseline (p < 0.001) but there were no significant between-group treatment differences (MMSE p = 0.56, NPI p = 0.39). UPDRS III motor scores did not change significantly from baseline values in either group. Although adverse effects were common (69%) they were usually mild and 64 patients (91%) completed the study. The four patients who did withdraw with adverse effects all had a PDD diagnosis. Donepezil produced similar improvements in cognition and behaviour in DLB and PDD. This supports the hypothesis that the two disorders are closely related clinically and neurobiologically. Larger scale, placebo controlled clinical trials are needed to provide an evidence base to guide the clinical use of cholinesterase inhibitors in Lewy body disease.

There is controversy regarding whether Dementia with Lewy Bodies (DLB) and Parkinson's disease with dementia (PDD) may or not be different manifestations of the same disorder. The purpose of the present study was to investigate possible correlations between brain structure and neuropsychological functions in clinically diagnosed patients with DLB and PDD. The study sample consisted of 12 consecutively referred DLB patients, 16 PDD patients, and 16 healthy control subjects recruited from an outpatient setting, who underwent MRI and neuropsychological assessment. Voxel-based morphometry results showed that DLB patients had greater gray matter atrophy in the right superior frontal gyrus, the right premotor area and the right inferior frontal lobe compared to PDD. Furthermore, the anterior cingulate and prefrontal volume correlated with performance on the Continuous Performance Test while the right hippocampus and amygdala volume correlated with Visual Memory Test in the DLB group. In conclusion, DLB patients had more fronto-temporal gray matter atrophy than PDD patients and these reductions correlated with neuropsychological impairment.