Progressive supranuclear palsy with Lewy bodies

Summary An autopsy case is reported which revealed not only clinical and neuropathological features of progressive supranuclear palsy, but also the presence of large numbers of Lewy bodies in the brain stem nuclei and cerebral cortex. This case seems to be progressive supranuclear palsy with Lewy bodies distributed as in Parkinson's disease. Such case has not been previously reported.after July 1988 as address above     

Dementia with Lewy bodies

Advanced Parkinson's disease (PD) is frequently associated with dementia. The pathogenesis of this dementia is complex, related to deficiency of several biogenic amines and cortical Lewy body deposition, as well as co-existent age-related brain changes, both of the Alzheimer type and vascular. However, degeneration of the cholinergic neurons in the nucleus basalis of Meynert may have an important contribution to the cognitive decline. The dementia of PD has a grave effect on the quality of life of the patients and their caregivers, as well as a negative effect on their survival. The treatment of dementia associated with PD with cholinesterase inhibitors produced gratifying (although limited) results. Future studies should define the exact role of these agents in the treatment of the dementia of PD. Another major problem presented by demented PD patients is the occurrence of delusions and hallucinations, which make the life of patients and caregivers miserable. Classical neuroleptics are of course contra-indicated in these patients but recent data increase concern about the safety of novel derivatives, leaving a void in the pharmacological armamentarium available when these manifestations appear.     

Dementias with Lewy bodies

Dementias with Lewy bodies are no rare cause of cognitive and motor impairments in old age. Neuropathologically, they must be distinguished into diffuse Lewy body disease resp. dementia with Lewy bodies, Parkinson's disease with concomitant Alzheimer's pathology, and the Lewy body variant of Alzheimer's disease according to extent and concomitant pathology. The most reliable diagnostic features of dementia with Lewy bodies are fluctuating disturbances of cognition and consciousness, visual disorders (hallucinations, visuoperceptive and visuoconstructive impairments), and early extrapyramidal signs of the hypokinetic-rigid type with a propensity to frequent falls. The pertinent diagnostic criteria are the consensus criteria according to McKeith et al. Additional contributions are to be expected by functional neuroimaging (SPECT, PET) and CSF examination (homovanillic acid). However, even assuming the most favorable conditions a diagnostic accuracy of 85 % is presently hard to achieve. Particularly, as is demonstrated using a case example, reliable antemortem diagnosis of Lewy body variant of Alzheimer's disease is hardly possible. Clinically, this group of diseases is important, since increased neuroleptic sensitivity must be taken into account and modern central cholinergic agents seem to be a promising therapeutic option.     

Dementia with Lewy bodies

The objective was to summarize recent findings about the clinical features, diagnosis and investigation of dementia with Lewy (DLB) bodies, together with its neuropathology, neurochemistry and genetics. Dementia with Lewy bodies (DLB) is a primary, neurodegenerative dementia sharing clinical and pathological characteristics with both Parkinson's disease (PD) and Alzheimer's disease (AD). Antiubiquitin immunocytochemical staining, developed in the early 1990s, allowed the frequency and distribution of cortical LBs to be defined. More recently, alpha-synuclein antibodies have revealed extensive neuritic pathology in DLB demonstrating a neurobiological link with other "synucleinopathies" including PD and multiple system atrophy (MSA). The most significant correlates of cognitive failure in DLB appear to be with cortical LB and Lewy neurites (LNs) rather than Alzheimer type pathology. Clinical diagnostic criteria for DLB, published in 1996, have been subjected to several validation studies against autopsy findings. These conclude that although diagnostic specificity is high (range 79- 100%, mean 92%), sensitivity is lower (range 0- 83 %, mean, 49%). Improved methods of case detection are therefore required. Fluctuating impairments in attention, visual recognition and construction are more indicative of DLB than AD. Relative preservation of medial temporal lobe volume on structural MRI and the use of SPECT tracers for regional blood flow and the dopamine transporter are the most reliable current biomarkers for DLB. There are no genetic or CSF tests recommended for the diagnosis of DLB at present. Between 15 and 20% of all elderly demented cases reaching autopsy have DLB, making it the most common cause of degenerative dementia after AD. Exquisite, not infrequently fatal, sensitivity to neuroleptic drugs and encouraging reports of the effects of cholinesterase inhibitors on cognitive, psychiatric and neurological features, mean that an accurate diagnosis of DLB is more than merely of academic interest. Dementia developing late in the course of PD shares many of the same clinical and pathological characteristics.     

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people, accounting for 10% to 15% of all cases, it occupies part of a spectrum that includes Parkinson's disease and primary autonomic failure. All these diseases share a neuritic pathology based upon abnormal aggregation of the synaptic protein α-synuciein. It is important to identify DLB patients accurately because they have specific symptoms, impairments, and functional disabilities thai differ from other common dementia syndromes such as Alzheimer's disease, vascular cognitive impairment, and frontotemporal dementia. Clinical diagnostic criteria for DLB have been validated against autopsy, but fail to detect a substantial minority of cases with atypical presentations that are often due to the presence of mixed pathology. DLB patients frequently have severe neuroleptic sensitivity reactions, which are associated with significantly increased morbidity and mortality. Cholinesterase inhibitor treatment is usually well tolerated and substantially improves cognitive and neuropsychiatrie symptoms. Although virtually unrecognized 20 years ago, DLB could within this decade become one of the most treatable neurodegenerative disorders of late life.     

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second commonest cause of neurodegenerative dementia in older people. It is part of the range of clinical presentations that share a neuritic pathology based on abnormal aggregation of the synaptic protein alpha-synuclein. DLB has many of the clinical and pathological characteristics of the dementia that occurs during the course of Parkinson's disease. Here we review the current state of scientific knowledge on DLB. Accurate identification of patients is important because they have specific symptoms, impairments, and functional disabilities that differ from those of other common types of dementia. Severe neuroleptic sensitivity reactions are associated with significantly increased morbidity and mortality. Treatment with cholinesterase inhibitors is well tolerated by most patients and substantially improves cognitive and neuropsychiatric symptoms. Clear guidance on the management of DLB is urgently needed. Virtually unrecognised 20 years ago, DLB could within this decade be one of the most treatable neurodegenerative disorders of late life.     

Dementia with Lewy bodies

The advent of new immunostains have improved the ability to detect limbic and cortical Lewy bodies, and it is evident that dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia, after Alzheimer's disease (AD). Distinguishing DLB from AD has important implications for treatment, in terms of substances that may worsen symptoms and those that may improve them. Neurocognitive patterns, psychiatric features, extrapyramidal signs, and sleep disturbance are helpful in differentiating DLB from AD early in the disease course. Differences in the severity of cholinergic depletion and type/distribution of neuropathology contribute to these clinical differences.     

Dementia with Lewy bodies

Synucleinopathies, with and without dementia, encompass a wide range of diseases including Parkinson's disease, multiple system atrophy, rapid eye movement (REM) sleep behavior disorder, and dementia with Lewy bodies (DLB). DLB is a neurodegenerative disorder resulting in slowly progressive and unrelenting dementia until death. Prevalence studies suggest that it is the second most common dementing illness in the elderly. The neuropathologic findings of DLB show a wide anatomic range. Lewy bodies and Lewy-related pathology are found from the brain stem to the cortex and, in many cases, associated with concurrent Alzheimer's disease pathology. A recent international consortium on DLB has resulted in revised criteria for the clinical and pathological diagnosis of DLB incorporating new information about the core clinical features and improved methods for their assessment. The presentation of DLB is typically one of cortical and subcortical cognitive impairments, with worse visuospatial and executive dysfunction than Alzheimer's disease. There may be relative sparing of memory especially in the early stages. Core clinical features of DLB include fluctuating attention, recurrent visual hallucinations, and parkinsonism. Suggestive features include REM sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in the basal ganglia on functional neuroimaging. Additional supportive features that commonly occur in DLB, but with lower specificity, include repeated falls and syncope, transient, unexplained loss of consciousness, severe autonomic dysfunction, hallucinations in other modalities, systematized delusions, depression, relative preservation of medial temporal lobe structures on structural neuroimaging, reduced occipital activity on functional neuroimaging, prominent slow wave activity on electroencephalogram, and low uptake myocardial scintigraphy. Management of DLB includes pharmacological and nonpharmacological interventions for its cognitive, neuropsychiatric, motor, and sleep disturbances.     

Dementia with Lewy bodies

OBJECTIVE: The aim of this paper is to summarise recent clinical and research findings with regard to dementia with Lewy bodies (DLB). METHOD: A literature review (Medline) was carried out, as well as a review of reports of recent DLB symposia of international meetings and of other relevant papers and data known to the authors. RESULTS: Dementia with Lewy bodies, as the disorder should be known, is the second commonest form of degenerative dementia, accounting for up to 20% cases in the elderly. It is characterised by fluctuating cognitive impairment, spontaneous parkinsonism and recurrent visual hallucinations. Consensus clinical and neuropathological criteria have been published. The clinical criteria have been shown to have high specificity, but may still lack sensitivity. Recognition of DLB is clinically important in view of the high incidence (60%) of adverse and life-threatening reaction to antipsychotics, the difference in prognosis and, possibly, the differential treatment response to cholinergic therapy. Neuroimaging changes have not been well described in DLB but some show promise as potential markers to differentiate DLB from AD. These include relative preservation of temporal lobe structures on magnetic resonance imaging and loss of pre- and postsynaptic dopaminergic markers on single photon emission tomography. CONCLUSIONS: Dementia with Lewy bodies is a common cause of cognitive impairment in late life which appears to be clinically and neuropathologically distinct from AD. All clinicians should be aware of the typical triad of clinical features (fluctuating cognitive impairment, visual hallucinations and parkinsonism) which characterise the disorder and either avoid antipsychotics or prescribe them with extreme caution in such patients. Further research is likely to result in advances in diagnostic methods and therapeutics in the near future.     

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most frequent cause of primary degenerative dementias, following Alzheimer's disease (AD). The nosologic situation of this disease has fragile limits. There is controversy as to whether Parkinson's disease (PD) and DLB are two different entities or whether they make up part of the same spectrum. The terms diffuse Lewy bodies disease and the variant of Lewy bodies in senile dementia or AD have been used to describe pathologic changes with clinical manifestations of dementia and parkinsonism. At present, DLB should be understood as an entity with the essential feature being the presence of Lewy bodies in the brain stem and cerebral cortex. From the point of view of clinical examination, DLB is characterized by the presence of subcortical or progressive cortical dementia, at times without severe memory disorders, with great fluctuations and well detailed recurrent visual hallucinations. These cognitive alterations are associated with parkinsonism. Other frequent disorders are falls, syncopes, transitory alterations in consciousness, great sensitivity to neuroleptic drugs and visual illusions with pseudoperception. The correct diagnosis of this entity is important to administer adequate treatment, to avoid classical neuroleptic drugs and to establish precise prognosis. From a therapeutic point of view, cholinesterase inhibitors show some efficacy in the treatment of cognitive alterations.     

Dementia with Lewy bodies]

"Dementia with Lewy bodies (DLB)" was proposed at the first international workshop in 1995. It has received much attention since we had proposed "Lewy body disease" in 1980 and "diffuse Lewy body disease" in 1984. In the CDLB guidelines, which were reported in 1996, the clinical and pathological diagnostic criteria for DLB were shown for the first time. At present, DLB as well as Alzheimer's disease (AD) and vascular dementia (VD) are known as the three major dementing illnesses. The second international workshop was held in 1998, and the third in 2003. One of the authors, K. Kosaka, presented a paper on DLB at each international workshop, based on series of our papers which we had reported since 1976. The revised CDLB guidelines will be reported soon. In addition, the fourth international workshop on DLB will be held by Kosaka in Yokohama in 2007. In this article, we review the history, the clinical, therapeutic, neuropathological, neurochemical and molecular biological issues, based on our previous papers and other important reports on DLB.     

Hallervorden-Spatz disease with Lewy bodies

At the age of 6 years a patient developed disorders of character, intellectual deterioration, tremor, falls and epileptic seizures. This was followed by extrapyramidal and pyramidal disorders with a fatal outcome at age 21. There was no family history. Histopathology showed evidence of Hallervorden-Spatz disease, remarkable by the diffusion of spheroids into the central nervous system gray matter and by the presence of innumerable Lewy bodies in the substantia nigra and locus coeruleus. Similar findings have been reported in only 3 other cases of typical Hallervorden-Spatz disease. They suggest a preferential affection of monoaminergic neurons.     

Treatment of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is known for its partial resistance and hypersensitivity to some treatments, but DLB is treatable with cholinesterase inhibitors, sometimes better than in Alzheimer's disease. Cholinesterase inhibitors have a symptomatic effect on cognition and behavior. Nevertheless, new antipsychotics are sometimes also useful to manage psychotic symptoms. Although DLB patients respond less well to levodopa than patients with Parkinson's disease, 75 percent of DLB patients improve with levodopa, which is the best-tolerated dopaminergic agent. Nonpharmacological strategies include speech therapy, physiotherapy, psychotherapy, and educational support groups for care givers.     

Neuroimaging of dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is a relative newcomer to the field of late-life dementia. Although a diversity of imaging methodologies is now available for the study of dementia, these have been applied most often to Alzheimer's disease (AD). Studies on DLB, although fewer, have yielded fascinating and important insights into the underlying pathophysiology of this condition and allowed clinical differentiation of DLB from other dementias. Imaging research on DLB has had significant ramifications in terms of raising the profile of DLB and helping define it as a distinctive and separate disease entity from AD.