Motor and cognitive function in Lewy body dementia: comparison with Alzheimer''s and Parkinson''s diseases.

OBJECTIVE: Motor and cognitive function were compared in patients with Lewy body dementia, Parkinson's disease, or Alzheimer's disease, to identify features that may be clinically useful in differentiating Lewy body dementia from Alzheimer's disease and Parkinson's disease. METHODS: A range of neuropsychological function and extrapyrimidal signs (EPS) was assessed in 16 patients with Lewy body dementia, 15 with Parkinson's disease, 25 with Alzheimer's disease, and 22 control subjects. RESULTS: The severity of total motor disability scores increased in the following order: controls approximately = Alzheimer's disease << Parkinson's disease < Lewy body dementia. Compared with patients with Parkinson's disease, patients with Lewy body dementia had greater scores for rigidity and deficits in the finger tapping test, but rest tremor and left/right asymmetry in EPS were more evident in Parkinson's disease. Patients with Lewy body dementia were also less likely to present with left/right asymmetry in EPS at the onset of their parkinsonism. "Sensitivity" to neuroleptic drugs was noted in 33% of patients with Lewy body dementia. Alzheimer's disease and Lewy body dementia groups had greater severity of dementia compared with the Parkinson's disease group and controls. Neuropsychological evaluation disclosed severe but similar degrees of impaired performances in tests of attention (digit span), frontal lobe function (verbal fluency, category, and Nelson card sort test) and motor sequencing in both Lewy body dementia and Alzheimer's disease groups, than Parkinson's disease and controls. In the clock face test, improved performance was noted in the "copy" compared to "draw" part of the test in controls, patients with Alzheimer's disease, and those with Parkinson's disease, but not in the patients with Lewy body dementia, who achieved equally poor scores in both parts of the test. CONCLUSIONS: EPS in Lewy body dementia resemble those seen in idiopathic Parkinson's disease, although less rest tremor and left/right asymmetry but more severe rigidity favours a diagnosis of Lewy body dementia. The unique profile of patients with Lewy body dementia seen in the clock face test suggests that this simple and easy to administer test may be useful in the clinical setting to differentiate Lewy body dementia and Alzheimer's disease.     

Diffuse Lewy body disease: clinical features in nine cases without coexistent Alzheimer's disease.

OBJECTIVE--To further elucidate the relation between diffuse Lewy body disease and Parkinson's disease. METHODS AND RESULTS--The clinical features of nine cases of pure diffuse Lewy body disease without pathological evidence of coexisting Alzheimer's neuritic pathology were reported. All patients were aged less than 70 years at onset (mean 62 years). Five patients presented with clinical features, which included assymetric resting tremor had levodopa responsiveness, which were initially indistinguishable from idiopathic Parkinson's disease. All five patients later became demented (mean of three years after presentation). Two further patients presented with parkinsonism and dementia and two patients presented with dementia and developed parkinsonism at a later stage. Hallucinations appeared 2.5-9 years after the onset of symptoms in six patients and were a presenting feature in one patient. All patients met the pathological criteria of idiopathic Parkinson's disease, with respect to the midbrain changes, in addition to having diffuse cortical Lewy bodies. CONCLUSIONS--Diffuse Lewy body disease may present a parkinsonism, dementia, or both depending on whether the Lewy body pathology begins in the midbrain, the cortex, or both together. When it begins in the midbrain, diffuse Lewy body disease is indistinguishable initially from idiopathic Parkinson's disease. Diffuse Lewy body disease may be a common cause of dementia complicating Parkinson's disease.     

Neuropathological substrates of psychiatric symptoms in prospectively studied patients with autopsy-confirmed dementia with lewy bodies

OBJECTIVE: This investigation was undertaken to clarify the neuropathological substrates of key psychiatric symptoms in dementia with Lewy bodies. METHOD: The authors studied 112 autopsy-confirmed cases of dementia with Lewy bodies in patients who had had annual standardized clinical evaluations until their death. The relationships of persistent psychiatric symptoms (visual hallucinations, delusions, depression) to plaques (Consortium to Establish a Registry for Alzheimer's Disease protocol), tangles (Braak staging), and Lewy bodies (consensus Lewy body staging) were evaluated. In addition, symptom frequency and persistent symptoms were compared in the patients with Lewy body dementia and 90 patients with autopsy-confirmed Alzheimer's disease studied prospectively during life. RESULTS: The main neuropathological correlate of persistent visual hallucinations was the presence of less severe tangle pathology, but there was no significant association between tangle pathology and persistent delusions. Lewy body staging was associated with the presence of persistent visual hallucinations and persistent delusions. All baseline psychiatric features were significantly more frequent in dementia with Lewy bodies than in Alzheimer's disease, as were persistent visual hallucinations, but patients who had dementia with Lewy bodies and severe tangle pathology had a clinical symptom profile more similar to that of Alzheimer's disease patients and were less likely to have neocortical Lewy bodies. CONCLUSIONS: The modest proportion of patients with Lewy body dementia and more severe tangle pathology resembled Alzheimer's disease patients clinically. Unlike Alzheimer's disease, dementia with Lewy bodies showed a significant inverse association between tangle burden and psychosis.     

Anosmia is very common in the Lewy body variant of Alzheimer's disease

BACKGROUND: Olfactory abnormalities are reported in Alzheimer's disease and Parkinson's disease. Anosmia appears to be common in dementia with Lewy bodies but not in pure Alzheimer's disease. OBJECTIVE: To determine whether anosmia improves discrimination between the Lewy body variant (LBV) of Alzheimer's disease and "pure" Alzheimer's disease. METHODS: 106 cases of necropsy confirmed pure Alzheimer's disease (n = 89) or LBV (n = 17) were reviewed. All had received butanol odour threshold testing. Anosmia was defined as a score < or = 1.0 on a 0-9 point scale. Logistic regression analysis was used to model potential predictors (for example, parkinsonism, smoking, hallucinations) of neuropathological diagnosis and anosmia. RESULTS: LBV cases had an increased prevalence of anosmia (65%) compared with Alzheimer's disease (23%; odds ratio (OR) = 6.3, p = 0.00045), or normal elderly people (6.7%). Within the dementia cases, the negative predictive value (92%) and specificity (78%) of anosmia were both good; sensitivity for detecting LBV was 65%, but the positive predictive value (PPV) was only 35%. Logistic regression models showed anosmia (OR = 5.4, p = 0.005) and visual hallucinations (OR = 7.3, p = 0.007) were strong independent predictors of Lewy body pathology. When anosmia was added as a core feature to consensus diagnostic criteria for probable Lewy body dementia, five additional cases of LBV were detected (29% increased sensitivity), but with four additional false positives (1% increased discrimination, 4% decreased specificity, 33% decreased PPV). CONCLUSIONS: Anosmia is very common in LBV. Adding anosmia as a core feature improved sensitivity for detecting LBV, but did not improve discrimination between Alzheimer's disease and LBV owing to a concomitant increase in false positives.     

Frontal cortical synaptophysin in Lewy body diseases: relation to Alzheimer's disease and dementia

OBJECTIVES—Dementia in Alzheimer's diseasecorrelates closely with loss of neocortical synapses. Similar synapticloss has been shown in patients whose Alzheimer's disease is alsoassociated with neocortical and brain stem Lewy bodies. The aim was todetermine if dementia in Lewy body disease was associated withdiminished concentrations of midfrontal cortex synaptophysin.
METHODS—An immunobinding assay was used to measuresynaptophysin in postmortem samples of midfrontal cortex from 89 patients with Alzheimer's disease (ages 59-100, mean 79), 22 withcombined Lewy body disease and Alzheimer's disease (ages69-103, mean 79), 15demented patients with "pure" Lewy bodydisease (ages 57-80, mean 74), nine with neocortical and brainstem Lewy bodies who had Parkinson's disease but were notdemented (ages 68-85, mean 79), and 20 neurologically normal controls(ages 58-89, mean 75). The diagnosis was confirmed in all cases bydetailed neuropathological examination of the contralateral hemibrain.Seven of the patients in the pure Lewy body disease with dementia grouphad initially presented with parkinsonism and eight with dementia.
RESULTS—Synaptophysin concentrations (arbitraryunits (AU)/µg) in patients with Alzheimer's disease (mean 79 (SD28)) or combined Lewy body disease and Alzheimer'sdisease (mean 83 (SD 33)) were significantly lower than in controls(mean 115 (SD 29)) (p=0.002). Synaptophysin concentrations in dementedpatients with pure Lewy body disease (mean 106 SD 39) andpatients with Lewy body disease who were not demented(mean 101 (SD 18)) did not differ significantly from control values orfrom each other.
CONCLUSION—Loss of midfrontal cortex synapsesprobably contributes to dementia in Lewy body disease whenAlzheimer's disease is also present but not to the dementia ofpure Lewy body disease.

     

Psychiatric morbidity in dementia with Lewy bodies: a prospective clinical and neuropathological comparative study with Alzheimer's disease.

OBJECTIVE: The literature reports considerable variation in the rates of psychiatric morbidity for patients with dementia with Lewy bodies. The authors intended to clarify the frequency of psychiatric morbidity in dementia with Lewy bodies and how it differs from probable Alzheimer's disease. METHOD: The study incorporated two groups--a clinical case register cohort (98 with dementia with Lewy bodies; 92 with Alzheimer's disease) and 80 (40 with dementia with Lewy bodies: 40 with Alzheimer's disease) prospectively studied, neuropathologically confirmed cases. Diagnoses were made by using the McKeith et al. consensus criteria for dementia with Lewy bodies and the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease. Neuropathological diagnoses were made by using the consensus criteria for dementia with Lewy bodies and the Mirra et al. protocol for Alzheimer's disease. RESULTS: The occurrence of psychiatric symptoms was reported over 1 month. Hallucinations, depression, delusions, and delusional misidentification were all significantly higher for patients with dementia with Lewy bodies. The differences in frequency between dementia with Lewy bodies and Alzheimer's disease for auditory and visual hallucinations were especially pronounced for patients with mild cognitive impairment. The presence of psychiatric symptoms at presentation was a better discriminator between dementia with Lewy bodies and Alzheimer's disease than occurrence over the course of dementia. CONCLUSIONS: Delusional misidentification and hallucinations in the early stages of dementia may improve differentiation between patients with dementia with Lewy bodies and those with Alzheimer's disease and have important treatment implications.     

Anosmia in dementia is associated with Lewy bodies rather than Alzheimer's pathology

OBJECTIVES: To assess olfactory function of patients with dementia. Odour detection ability is impaired in clinical Parkinson's disease. Evidence of impaired detection in patients with clinically diagnosed Alzheimer's disease is inconsistent. No studies of olfaction have been neuropathologically validated. METHODS: The olfactory function of 92 patients with dementia and 94 controls was assessed using a simple bedside test as part of the Oxford Project To Investigate Memory and Ageing (OPTIMA). Neuropathological assessment was made of cortical Lewy bodies and substantia nigra (SN) cell counts and of Alzheimer's disease in all 92 patients, 22 of whom had SN Lewy bodies and 43 of whom had only Alzheimer's disease. RESULTS: Patients with Lewy bodies were more likely to be anosmic than those with Alzheimer's disease or controls. Patients with Alzheimer's disease were not more likely to be anosmic than controls. Nor was anosmia associated with degree of neurofibrillary tangles, as assessed by Braak stage. Among subjects with Lewy bodies, overall cortical Lewy body scores and Lewy body density in the cingulate were higher in those who were anosmic. Consensus clinical criteria for dementia with Lewy bodies had a sensitivity of 64% and specificity of 89%. In the absence of definite Alzheimer's disease, the criteria had sensitivity of 100%. In patients with definite Alzheimer's disease, anosmia was slightly more sensitive (55%) than the consensus criteria (33%). However, the addition of anosmia to the consensus criteria did not improve their overall performance. CONCLUSION: Dementia with Lewy bodies is associated with impaired odour detection. Misdiagnosis may have accounted for some previous reports of impaired odour detection in Alzheimer's disease. Simple but more sensitive tests of anosmia are required if they are to be clinically useful in identifying patients with dementia with Lewy bodies.     

One year follow-up of parkinsonism in dementia with Lewy bodies

The progression of parkinsonism over 1 year was evaluated in a prospective cohort of patients (n = 338), suffering from dementia with Lewy bodies (DLB), Alzheimer's disease (AD) or vascular dementia (VaD). Parkinsonism was assessed using the modified Unified Parkinson's Disease Rating Scale. Significant parkinsonism was significantly commoner in DLB sufferers (71%) than amongst patients with AD (7%) or VaD (10%). DLB patients with established parkinsonism had an annual increase in severity of 9%, but progression was more rapid (49% in 1 year) in patients with early parkinsonism. Parkinsonism was frequent at all severities in DLB patients, but usually only present in other dementias when MMSE <10.     

Parkinson disease neuropathology: later-developing dementia and loss of the levodopa response.

OBJECTIVE: To investigate the neuropathologic substrate for dementia occurring late in Parkinson disease (PD). DESIGN: We identified 13 patients with a clinical diagnosis of PD who experienced dementia at least 4 years after parkinsonism onset (mean, 10.5 years) and subsequently underwent postmortem examination. Despite levodopa therapy, 9 patients later became severely impaired and nonambulatory, requiring total or near-total care; this included 4 patients treated with 1200 mg/d or more of levodopa (with carbidopa), which was consistent with loss of the levodopa response. These 13 patients were compared with 9 patients clinically diagnosed as having PD, but without dementia, who had undergone autopsies. RESULTS: Twelve of 13 PD patients with dementia had findings of diffuse or transitional Lewy body disease as the primary pathologic substrate for dementia; 1 had progressive supranuclear palsy. This pathology also apparently accounted for the levodopa refractory state. Among the 12 PD patients with dementia, mean and median Lewy body counts were increased nearly 10-fold in neocortex and limbic areas compared with PD patients without dementia (P< or =.002). Alzheimer pathology was modest. Only one patient met the criteria defined by the National Institute on Aging and the Reagan Institute Working Group on the Diagnostic Criteria for the Neuropathologic Assessment of Alzheimer's Disease for "intermediate probability of Alzheimer's disease." There were, however, significant correlations between neocortical Lewy body counts and senile plaques as well as neurofibrillary tangles. Senile plaque counts did not significantly correlate with tangle counts in any of the analyzed nuclei. Arteriolar disease may have contributed to the clinical picture in 2 patients. CONCLUSIONS: Diffuse or transitional Lewy body disease is the primary pathologic substrate for dementia developing later in PD. This same pathologic substrate seemed to account for end-stage, levodopa refractory parkinsonism. The occurrence of Alzheimer pathology was modest, but was highly correlated with Lewy body pathology, suggesting common origins or one triggering the other.     

Predicting lewy body pathology in a community-based sample with clinical diagnosis of Alzheimer's disease

Accurate antemortem prediction of Lewy body pathology in patients with dementia is problematic. This study generates a model that better predicts Lewy body pathology in community-based patients with clinical Alzheimer's disease. Lewy body pathology was detected in 80 of 152 participants (52.6%) with an initial diagnosis of probable Alzheimer's disease. In a stepwise logistic regression model, female gender, lower education, being married, bradykinesia, hallucinations, and absence of irritability predicted the greatest likelihood of Lewy body pathology. The predictive model correctly diagnosed Lewy body pathology with an estimated sensitivity of 75%, specificity of 68%, and accuracy of 72%; the area under the receiver operating characteristic curve was 0.75. In a community-based autopsy sample, this predictive model confirmed parkinsonism and hallucinations as important predictors of Lewy body pathology in patients with clinical Alzheimer's disease. The model also identified other demographic and clinical characteristics that might enhance the prediction of Lewy body pathology.     

Steroid-responsive encephalopathy subsequently associated with Alzheimer's disease pathology: a case series

Background: Steroid-responsive encephalopathies can be considered vasculitic or non-vasculitic. Clinicopathological studies of non-vasculitic steroid-responsive encephalopathy are unusual, but can explain the range of diagnoses consistent with a steroid-responsive presentation in life. Objective: To extend the range of clinical features and pathological findings consistent with steroid-responsive encephalopathy. Design, methods, and patients: A clinicopathological case series of four patients (two women, ages 54-71 years) with steroid-responsive encephalopathy followed at this institution until the time of death. Results: Clinical features were suggestive of Creutzfeld-Jakob disease (CJD), dementia with Lewy bodies (DLB), and parkinsonism, but pathological examination revealed only Alzheimer's disease-related findings without evidence of Lewy bodies or prion disease in all cases. All patients demonstrated marked, sustained improvement following steroid treatment, based on clinical, magnetic resonance imaging, and/or electroencephalogram studies. Alzheimer's disease was not diagnosed in life due to the atypical clinical features, lack of hippocampal atrophy on brain imaging, and a dramatic symptomatic response to steroids. Conclusions: Steroid-responsive encephalopathy is the clinical presentation of some patients with Alzheimer's disease-related pathology at autopsy, and can be consistent with the clinical diagnoses of parkinsonism, DLB, or CJD disease in life.     

Clinical parkinsonism in dementia patients with substantia nigra Lewy bodies

Summary. In a retrospective clinicopathological study, we examined the substantia nigra (SN) of 48 dementia patients with SN Lewy bodies (LBs) to determine if the severity of degeneration correlated with either the occurrence of signs of parkinsonism at dementia presentation or with the frequency of treatment for parkinsonism during the disease course. The SN specimens were graded for microscopic degeneration using a semi-quantitative five-tiered scale. Whereas no correlation was found between the grade of degeneration and occurrence of signs at presentation (r = −0.16, p = 0.18), with 16 of 38 patients having had signs reported, a more severe grade was statistically correlated with an increased frequency of treatment during the course (r = 0.41, p = 0.004), with ten of 41 patients having been treated for parkinsonism. Contrary to our expectations, we found that fewer than half of the patients with the two most severe grades of degeneration presented with signs of parkinsonism or were ever treated for parkinsonism. Received June 8, 1998; accepted July 9, 1998     

Prevalence of essential tremor in patients with Parkinson's disease vs. Parkinson-plus syndromes.

Clinical literature suggests an association between essential tremor (ET) and Parkinson's disease (PD), and recent pathological studies describe Lewy bodies in some ET patients. If some ET were an expression of Lewy body disease, one could hypothesize that ET patients who develop parkinsonism would more likely develop PD (a Lewy body disease) than non-Lewy body forms of parkinsonism. The objective was to compare the proportions of patients with PD vs. Parkinson-plus syndromes who had diagnoses of ET. Retrospective chart review at the Neurological Institute (NI) of New York. A larger proportion of the 210 PD than 210 Parkinson-plus syndrome patients had kinetic tremor on examination (119 [56.7%] vs. 70 [33.3%], P < 0.001). Patients with PD were more likely to have a prior diagnosis of ET than were patients with Parkinson-plus syndromes (7.1% vs. 2.4%, OR 3.16, 95% CI 1.13-8.85, P = 0.02) and more likely to have a diagnosis of ET assigned by an NI neurologist (5.3% vs. 0.0%, OR 12.85, 95% CI 1.66-99.8, P = 0.001). Patients with PD were three to thirteen times more likely to have diagnoses of ET than were patients with Parkinson-plus syndromes. These data further confirm the link between ET and PD, and possibly, between ET and Lewy body disease.     

Heterogeneous factors in dementia with Parkinson's disease: IMP-SPECT study

BACKGROUND: Nature of the dementing process in Parkinson's disease, and particularly its relationship with Alzheimer's disease, diffuse Lewy body disease or frontal dementia remains controversial. OBJECTIVE: We hypothesize that origins of dementia in Parkinson's disease are heterogeneous, so we compared cortical regional cerebral blood flow (rCBF) between Parkinson's disease patients with and without dementia. PATIENTS: Forty consecutive patients with Hoehn-Yahr stage III or IV Parkinson's disease were used (13 patients had dementia (PDD group), and 27 patients had no dementia (PDND group)). RESULTS: There were significant rCBF reductions in the left parietal association cortex and left frontal association cortex in PDD. Multiple logistic regression analysis demonstrated that only rCBF of the left frontal association cortex was significant. PDD patients were divided into three groups according to rCBF patterns: frontal hypoperfusion group, Alzheimer's disease-like group, and diffuse Lewy body disease-like group. CONCLUSIONS: Controversial study results involving PDD patients may be mainly due to heterogeneity in dementing processes in Parkinson's disease.     

Performance on the dementia rating scale in Parkinson's disease with dementia and dementia with Lewy bodies: comparison with progressive supranuclear palsy and Alzheimer's disease

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 compare those with the performance of patients with a subcortical dementia (progressive supranuclear palsy) and a cortical dementia (Alzheimer's disease). DESIGN: Survey of cognitive features. SETTING: General community in Rogaland county, Norway, and a university dementia and movement disorder research centre in the USA. PATIENTS: 60 patients with DLB, 35 with PDD, 49 with progressive supranuclear palsy, and 29 with Alzheimer's disease, diagnosed by either standardised clinical procedures and criteria (all PDD and Alzheimer cases and 76% of cases of progressive supranuclear palsy), or necropsy (all DLB cases and 24% of cases of progressive supranuclear palsy). Level of dementia severity was matched using the total score on the dementia rating scale adjusted for age and education. MAIN OUTCOME MEASURES: Dementia rating scale subscores corrected for age. RESULTS: No significant differences between the dementia rating scale subscores in the PDD and DLB groups were found in the severely demented patients; in patients with mild to moderate dementia the conceptualisation subscore was higher in PDD than in DLB (p = 0.03). Compared with Alzheimer's disease, PDD and DLB had higher memory subscores (p < 0.001) but lower initiation and perseveration (p = 0.008 and p=0.021) and construction subscores (p = 0.009 and p = 0.001). DLB patients had a lower conceptualisation subscore (p = 0.004). Compared with progressive supranuclear palsy, PDD and DLB patients had lower memory subscores (p < 0.001). CONCLUSIONS: The cognitive profiles of patients with DLB and PDD were similar, but they differed from those of patients with Alzheimer's disease and progressive supranuclear palsy. The cognitive pattern in DLB and PDD probably reflects the superimposition of subcortical deficits upon deficits typically associated with Alzheimer's disease.     

A pathological study of the association between Lewy body disease and Alzheimer''s disease.

The possibility of an association between Parkinson's disease and Alzheimer's disease has been examined by studying the age-specific prevalence of Lewy bodies in the substantia nigra in a group of 273 control cases without Parkinson's disease and 121 cases of Alzheimer's disease. The substantia nigra was also studied in 14 cases of Down's syndrome, 13 of which had cortical Alzheimer pathology. Twelve (7.8%) of the controls aged over 60 years showed nigral Lewy bodies. There was mild nerve cell degeneration and/or an extranigral distribution of Lewy bodies, suggestive of presymptomatic Parkinson's disease. Twenty five (22.5%) of the Alzheimer's disease cases over 60 years showed Lewy bodies, but only 14 (14.0%) of these had mild nigral cell loss consistent with presymptomatic Parkinson's disease. No case of Down's syndrome had Lewy bodies. Counts of tangles and plaques in hippocampus, frontal and temporal cortex were lower in cases of Alzheimer's disease with Lewy bodies compared with those without, but cortical choline acetyltransferase (ChAT) activities were similar. This suggests that Lewy body degeneration in the nucleus basalis of Meynert contributes to the deficit of cortical ChAT, but not to the cortical Alzheimer pathology. The relatively small difference in the prevalence of Lewy bodies between controls and Alzheimer's disease could be explained by the additive effects of Lewy body and tangle pathology causing dementia, rather than a greater than chance association between Parkinson's disease and Alzheimer's disease.     

The natural history of psychosis and depression in dementia with Lewy bodies and Alzheimer's disease: persistence and new cases over 1 year of follow-up

BACKGROUND: Few data are available regarding the natural course of psychiatric symptoms in dementia with Lewy bodies and Alzheimer's disease. To acquire this information is essential to inform differential diagnosis and treatment decisions. METHOD: The current study provides prospective data regarding a representative case-register cohort of patients with operationalized clinical diagnoses of dementia with Lewy bodies (N = 82) or Alzheimer's disease (N = 132), with verified accuracy of clinical diagnosis against postmortem examination. Psychosis (Columbia University Scale for Psychopathology in Alzheimer's Disease) and depression (Cornell Scale for Depression in Dementia) were assessed at baseline and annual follow-up. RESULTS: Visual hallucinations were significantly more likely to be persistent in patients suffering from dementia with Lewy bodies (chi2 = 19.1, df = 1, p < .0001). Although a number of other psychiatric symptoms were also more frequent at baseline in dementia with Lewy body patients, they were not significantly more likely to persist. Delusions and auditory hallucinations did, however, persist in more than 40% of patients across both diagnostic groups. Patients suffering from dementia with Lewy bodies were significantly more likely to develop new auditory hallucinations over the year of follow-up (chi2 = 14.4, df= 1, p < .0001). CONCLUSION: These results confirm that, although a number of psychiatric symptoms are common in dementia with Lewy bodies, it is only visual hallucinations that are significantly more persistent, with important treatment implications.     

Inconsistency between severe substantia nigra degeneration with Lewy bodies and clinical parkinsonism in dementia patients: a cliniconeuropathological study

 In a retrospective cliniconeuropathological study, we reviewed all the cases received in our dementia brain bank during a 4-year period to determine if all patients with severe substantia nigra (SN) degeneration and SN Lewy bodies (LBs) exhibited prominent signs of parkinsonism and were treated for parkinsonism during the disease course. The SN of 426 cases were graded for microscopic degeneration using a semiquantitative five-tiered scale, with grade 0 indicating normal and grade 4 the most severe degeneration. Twenty-nine cases with grade 3 (16) or grade 4 (13) SN degeneration with SN LBs and clinical records were identified. Ten had been treated for parkinsonism (6 grade 3, 4 grade 4) and 19 had not. Whereas most of the patients had exhibited signs of end-stage parkinsonism during their last year, 1 grade 3 and 2 grade 4 patients apparently never exhibited prominent signs of parkinsonism during the course of their dementia. No clear neuropathological differences were noted between these patients that did not have prominent signs and a control group of six patients with clinical Parkinson’s disease with dementia (parkinsonism onset at least 1 year before dementia onset). We conclude that in patients with dementia there is an inconsistent relationship between the expression of clinical parkinsonism during life and severe SN degeneration with LBs identified at necropsy. Received: 20 August 1998 / Revised: 2 February 1999, 14 August 1999 / Accepted: 6 September 1999     

Cortical Lewy body dementia: clinical features and classification.

Seven patients, aged 65-72 years, are described with dementia and cortical Lewy bodies. In one patient a Parkinsonian syndrome was followed by dementia and motor neuron disease. In the remaining six patients dementia was accompanied by dysphasia, dyspraxia and agnosia. One developed a Parkinsonian syndrome before the dementia, in three cases a Parkinsonian syndrome occurred later, and in two cases not at all. All patients showed Lewy bodies and cell loss in the substantia nigra, locus coeruleus and dorsal vagal nucleus, as in Parkinson's disease. The severity of cell loss in the nucleus basalis varied from mild to severe. Lewy bodies were also present in the parahippocampus and cerebral cortex, but Alzheimer-type pathology was mild or absent, and insufficient for a diagnosis of Alzheimer's disease. Patients with moderate or severe dementia, some with temporal or parietal features, may have cortical Lewy body disease, Alzheimer's disease, or a combination of the two. Cortical Lewy body disease may be associated with dementia in Parkinson's disease more often than realised, but is not necessarily associated with extensive Alzheimer pathology.     

Novel antibodies to synuclein show abundant striatal pathology in Lewy body diseases

Intracytoplasmic inclusions composed of alpha-synuclein (alpha-syn) are characteristic of neurodegenerative Lewy body disorders. Using novel monoclonal antibodies raised against altered alpha-syn, we uncovered an unprecedented and extensive burden of alpha-syn pathology in the striatum of Lewy body disorders. The highest density of striatal pathology was observed in patients with a combination of Alzheimer's disease and dementia with Lewy bodies or pure dementia with Lewy bodies, and these alpha-syn aggregates may contribute to the parkinsonism seen in these disorders.