Familial dementia with Lewy bodies (DLB).

We report a rare familial case of dementia with Lewy bodies (DLB). The patient was a man who died at the age of 51. His parents were first cousins. Among three siblings, two were diagnosed as probable cases of DLB, and one was a possible case, according to the clinical diagnostic criteria of the consortium on DLB. Following the patient's autopsy, he was found to have had DLB without neurofibrillary tangles or senile plaques (pure form of diffuse Lewy body disease). His other siblings have been followed for more than ten years. Although these patients with familial DLB displayed clinical variability, all three siblings showed progressive dementia of early onset and progressive language disorder with paraphasia and difficulty in finding words. Psychotic features were also seen in the three siblings. The patient's sister showed compulsive behavior, and the other two siblings showed symptoms of parkinsonism. Neuropathologically, in addition to the usual neuropathology of DLB, the autopsy findings showed numerous small spheroids in the stratum pyramidale from the subiculum to CA1 of the hippocampus. Significant neuronal loss in CA2-3 of the hippocampus was detected. Axonal flow disturbance may be involved in the hippocampal formations of this incidence of familial DLB.     

Fall-related injuries in dementia with Lewy bodies (DLB) and Alzheimer's disease

Repeated falls are reported as one of the clinical characteristics in dementia with Lewy bodies (DLB). We examined the incidence of fall-related injuries in 561 dementia patients with various clinical diagnoses, including DLB and Alzheimer's disease (AD), in a ward established for dementia research. The incidence of fall-related injuries was significantly higher in DLB patients (10.7%) than in AD patients (1.1%) (P < 0.001). The high incidence in those patients with DLB cannot be attributed to Parkinsonism because none of the DLB patients with injuries showed extrapyramidal sign. Our observations suggest that patients with a clinical diagnosis of DLB have a high risk of fall-related injuries, even though they do not show Parkinsonism. An appropriate clinical discrimination between DLB and AD is recommended to manage and prevent fall-related injuries.     

Visual hallucinations and altered visual information processing in Parkinson disease and dementia with Lewy bodies

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. © 2010 Movement Disorder Society     

Depression associated with dementia with Lewy bodies (DLB) and the effect of somatotherapy

Background: Dementia with Lewy bodies (DLB) is a common type of dementia. It is difficult to make an initial diagnosis of DLB because of a variety of early symptoms, including psychosis‐like and depressive states. In this study, we examined the characteristic depressive symptoms of the prestage of DLB and the efficacy and safety of somatotherapy for depression accompanying DLB. Methods: Subjects in the study were 167 consecutive clinical cases aged 50 years or more, hospitalized at Tsukuba University Hospital from December 2002 to September 2007. At the time of admission, patients were diagnosed with certain types of mood disorders according to the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition Text Revision. For each subject, a series of neuropsychological tests, along with a standard psychiatric and neurological assessment and biological examinations, were conducted. Using the data from these exams, we diagnosed probable and possible DLB according to the criteria for dementia with Lewy bodies established by McKeith et al. 1 We compared patients' depressive symptoms according to the Hamilton Depression Scale, and distinguished between patients with depression associated with DLB and those with other mood disorders. 2 We also examined the efficacy and safety of somatotherapy (electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS)) for patients with drug therapy–resistant depression associated with DLB. Results: 1 The characteristic symptoms of patients with DLB were classified into two groups: psychotic and non‐psychotic. The former consisted of patients with states such as delusion and agitation, and the latter included patients exhibiting psychomotor retardation, loss of insight and hypochondriasis. 2 Eight DLB patients with therapy‐resistant depression underwent ECT. After ECT, significant improvement was observed, with no remarkable safety hazards. Six patients with drug therapy–resistant DLB underwent TMS. TMS appears to be an effective, safe remedy for this kind of patient. Conclusions: ? A total of 13.8% of patients came to be re‐diagnosed as having DLB as a consequence of a thorough examination after admission. ? Patients with depression associated with DLB were classified into psychotic and non‐psychotic clusters. ? ECT and TMS are effective and safe therapeutic tools for drug therapy–resistant depression observed in DLB patients.     

The relationship between hallucinations and FDG-PET in dementia with Lewy bodies

Visual hallucinations are common in dementia with Lewy bodies (DLB), although their etiology is unclear. This study aimed to investigate the relationship between severity and frequency of hallucinations and regional brain glucose metabolism. We performed brain FDG-PET scanning on 28 subjects with DLB (mean age 76). The neuropsychiatric index (NPI) was used to assess frequency and severity of hallucinations. We used the SPM package to investigate voxelwise correlations between NPI hallucination score (severity x frequency) and FDG uptake relative to the cerebellum. There was a bilateral medial occipital region where reduced FDG was associated with increased hallucination severity and frequency. We conclude that the reduced occipital metabolism frequently seen in DLB is associated with frequency and severity of visual hallucinations. Further studies are required to investigate whether this is the result of deficits in top-down or bottom-up visual processing pathways.     

Delusions and hallucinations in dementia with Lewy bodies: worsening with memantine

Three patients with probable dementia with Lewy bodies (DLB) experienced worsening delusions and visual hallucinations as a result of memantine therapy. Significant resolution occurred once treatment was discontinued. Caution is required when prescribing memantine to patients with possible DLB.     

Combined duloxetine and benzodiazepine-induced visual hallucinations in prodromal dementia with Lewy bodies

Objective

We describe a patient with prodromal dementia with Lewy bodies (DLB) presenting with drug-induced visual hallucinations (VHs).

Case report

A 78-year-old woman complained of daytime recurrent VHs characterized by seeing her face and arms covered in fur and viewing moustaches on her daughter's face. VHs started a few days after the beginning of a combination therapy with duloxetine and lorazepam and ceased within 24 h after their discontinuation. Nonamnestic mild cognitive impairment with profound visual perception deficits and very mild extrapyramidal signs, with abnormal brain DaTscan single photon emission tomography, were present. Three years later, cognitive and neurological follow-up assessments supported the diagnosis of DLB.

Conclusion

Perturbation of cerebral serotonergic tone induced by duloxetine, associated with reduced attentional control due to benzodiazepine use, may be the physiopathological substrate of transient VHs in prodromal DLB.     

Visual evoked potential abnormalities in dementia with Lewy bodies

ObjectivesVisuo-perceptual deficits and visual hallucinations (VHs) are common disturbances in patients with dementia with Lewy bodies (DLB) and those with Parkinson’s disease (PD). In particular, delays in visual evoked potential (VEP), reversed by l-dopa administration, have previously been observed in PD patients. Impairment in metabolic functions of dopaminergic amacrine cells within the inner plexiform layer of the retina has been largely documented and has been posited as the underlying cause of visual and retinal alterations in PD. The aims of the present study were to investigate the presence of VEP abnormalities in DLB patients, as compared to a PD control group, and to assess the presence of significant correlations between neurophysiological measures and clinical symptoms (i.e., presence of visuospatial deficits and/or visual hallucinations).MethodsFifteen DLB patients and fifteen matched PD patients underwent pattern reversal before and after l-dopa administration, and a short neuropsychological assessment.ResultsIn DLB patients, we observed delay of the P100 latency to foveal stimuli in both eyes compared to normative values. Compared to PD, DLB patients showed higher values of the P100 latency for foveal stimulation from the right eye prior to l-dopa administration (p = 0.018). No correlations between VEP alterations, visuo-spatial deficit and visual hallucinations were found.DiscussionOur findings demonstrated a longer P100 delay in DLB than in PD patients, especially along the right visual pathway. In contrast to previous studies, which focused on a dopaminergic pre-geniculate impairment of visual pathways, our evidence suggests that other mechanisms, possibly relying on thalamic involvement, which is known to be dysfunctional in DLB, can interfere with VEP abnormalities.     

Visual recognition memory differentiates dementia with Lewy bodies and Parkinson's disease dementia

Objective

To compare cognitive impairments in dementia with Lewy bodies (DLB) and Parkinson''s disease dementia (PDD), to discriminate between the two entities.

Methods

10 DLB and 12 PDD consecutive patients performed a neuropsychological battery designed to assess several cognitive domains: verbal and visual memory (Delayed Matching to Sample (DMS)‐48), language, gnosia, praxia and executive functions.

Results

DLB patients had poorer performances in orientation (p<0.05), Trail Making Test A (p<0.05) and reading of names of colours in the Stroop Test (p<0.05). Their scores were also lower in the visual object recognition memory test (DMS‐48), in both immediate (p<0.05) and delayed recognition (p<0.05). No differences were observed in the other tests.

Conclusion

Despite global similarities in cognitive performances between DLB and PDD patients, we observed important differences: in particular, DMS‐48, a test of visual object recognition memory and visual storage capacity, was poorer in DLB patients.Parkinson''s disease dementia (PDD) and dementia with Lewy bodies (DLB) share some common clinical features, such as extrapyramidal symptoms and neuropsychological impairment.^1,2,3 In practice, consensus guidelines recommend an arbitrary distinction between the two disorders based on a temporal sequence of 1 year between the presentation of extrapyramidal motor symptoms and the manifestation of dementia: PDD is diagnosed if dementia occurs belatedly in the context of well established Parkinson''s disease; DLB is diagnosed when motor and cognitive signs appear during the first year of evolution.⁴ A key question is whether this is a meaningful distinction between the two different clinical entities.Subtle clinical distinction in terms of cognitive pattern could prove useful for clinicians.In this study, we compared cognitive performances in a group of patients with a clinical diagnosis of “probable” DLB with those of PDD patients. As the clinical symptoms overlap, our aim was to determine possible differences in the cognitive abilities between DLB and PDD.