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Background

The clinical delineation of Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) remains unclear.

Objective

To compare the neuropsychological profiles of patients with clinically diagnosed Dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).

Methods

We first compared measures of memory, orientation, language, executive, visual perception and visual construction function between persons with DLB and AD in two Caribbean Hispanic cohorts, including a family dataset (DLB =89; AD: n=118) and an epidemiologic dataset (DLB: n=70; AD: n=157). DLB in the family sample was further divided into i) families with two or more affected family members (DLB), or ii) one affected family member (DLB). To determine whether observed differences in cognitive profiles were driven by heritable factors, we then repeated the analyses in the epidemiologic cohort excluding all familial cases. We applied general linear models adjusting for age, sex, education, disease duration, and APOE-ε4 genotype.

Results

Persons with DLB were in both cohorts more severely impaired in orientation, visual construction and non verbal reasoning after controlling for potential confounders. Persons with 2 or more DLB cases per family had the most severe impairment in episodic and semantic memory, followed by those with one DLB case per family, then by those with AD. When familial AD and DLB cases were excluded from the analysis in the epidemiologic cohort, the differences between the AD and DLB groups persisted but were attenuated.

Conclusions

Compared to persons with AD, persons with DLB are more severely impaired in various cognitive domains, particularly orientation, visual perception and visual construction. The difference appears strong in familial rather than sporadic DLB. Whether this divergence in cognitive functions is caused by gene-gene or gene-environmental interactions remains unclear.

Dementia with Lewy bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD), and is clinically characterized by the progressive cognitive decline with fluctuations in cognition and alertness, recurrent visual hallucinations and Parkinsonism. Once these characteristic symptoms of DLB emerge, discriminating it from AD is relatively easy. However, in the early disease stages, the clinical symptoms of various types of dementias largely overlap and it is difficult to distinguish DLB from other neurodegenerative dementias based on clinical manifestations alone. To increase the accuracy of antemortem diagnosis of DLB, the latest diagnostic criteria incorporate findings from 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy, or from neuroimaging such as computed tomography (CT), magnetic resonance imaging (MRI), single photon emission computed tomography (SPECT), and positron emission tomography (PET). In the present guidelines, decreased dopamine transporter uptake revealed by SPECT or PET receives the greatest importance among various neuroimaging findings and is listed as one of the suggestive features. Supportive features that commonly present but are not proven to have diagnostic specificity include relatively-preserved medial-temporal-lobe structures, occipital hypoperfusion, and abnormal MIBG myocardial scintigraphy. In this paper, we review the major findings on various neuroimaging modalities and discuss the clinical usefulness of them for the diagnosis of DLB. Although there is not enough evidence to reach the conclusion, considering the accessibility in clinical practice, in our personal views, we recommend the use of brain-perfusion SPECT and MIBG myocardial scintigraphy to improve the diagnosis of DLB.

The mild cognitive impairment (MCI) stage of dementia with Lewy bodies (MCI-DLB) has not yet been defined, but is likely to differ in the MCI stage of Alzheimer’s disease (MCI-AD). To determine whether clinical features distinguish MCI-DLB and MCI-AD, 9 cases of neuropathologically confirmed MCI-DLB and 12 cases of MCI-AD were compared. No significant differences were found between MCI-DLB and MCI-AD cases in age at death, gender, ApoE status, education, time followed while clinically normal, or duration of MCI. MCI-DLB and MCI-AD cases differed clinically in the expression of Parkinsonism (P = 0.012), provoked hallucinations or delirium (P = 0.042), or the presence of any of these noncognitive symptoms of DLB (P < 0.0001). Letter fluency (P = 0.007) was significantly lower and Wechsler Logical Memory I (P = 0.019) was significantly higher in MCI-DLB compared to MCI-AD cases. These data demonstrate the feasibility of differentiating underlying pathologic processes responsible for cognitive decline in the preclinical disease state and suggest that further refinement in diagnostic criteria may allow more accurate early detection of prodromal DLB and AD.

Objectives

Dementia with Lewy bodies (DLB) accounts for 10%–15% of dementia cases at autopsy and has distinct clinical features associated with earlier institutionalisation and a higher level of carer distress than are seen in Alzheimer's disease (AD). At present, there is on-going debate as to whether DLB is associated with a more rapid cognitive decline than AD. An understanding of the rate of decline of cognitive and non-cognitive symptoms in DLB may help patients and carers to plan for the future.

Design

In this cohort study, the authors compared 100 AD and 58 DLB subjects at baseline and at 12-month follow-up on cognitive and neuropsychiatric measures.

Setting

Patients were recruited from 40 European centres.

Participants

Subjects with mild–moderate dementia. Diagnosis of DLB or AD required agreement between consensus panel clinical diagnosis and visual rating of 123I-FP-CIT (dopamine transporter) single photon emission computed tomography neuroimaging.

Outcome measures

The Cambridge Cognitive Examination including Mini-Mental State Examination and Neuropsychiatric Inventory (NPI).

Results

The AD and DLB groups did not differ at baseline in terms of age, gender, Clinical Dementia Rating score and use of cholinesterase inhibitors or memantine. NPI and NPI carer distress scores were statistically significantly higher for DLB subjects at baseline and at follow-up, and there were no differences between AD and DLB in cognitive scores at baseline or at follow-up. There was no significant difference in rate of progression of any of the variables analysed.

Conclusions

DLB subjects had more neuropsychiatric features at baseline and at follow-up than AD, but the authors did not find any statistically significant difference in rate of progression between the mild–moderate AD and DLB groups on cognitive or neuropsychiatric measures over a 12-month follow-up period.

Article summary

Article focus

Dementia with Lewy bodies (DLB) has distinct neuropsychiatric features.

At present, we do not know whether the poorer prognosis of DLB is due to a more rapid cognitive decline compared with Alzheimer's disease (AD).

Key messages

In this fairly large cohort of patients with DLB and AD, while there was no difference in level of cognitive impairment (Cambridge Cognitive Examination (CAMCOG) score) at baseline and at 12-month follow-up, DLB patients had significantly higher Neuropsychiatric Inventory (NPI) and NPI carer distress scores both at baseline and at 12-month follow-up.

Therefore, the worse prognosis of DLB is likely to be mediated by neuropsychiatric or other symptoms and not only by cognitive decline.

Strengths and limitations of this study

Inclusion of high number of subjects from 40 European clinical centres.

Well-characterised cases with both consensus panel clinical diagnosis (three clinical experts) and dopaminergic transporter single photon emission computed tomography imaging.

No autopsy data were available and therefore it is possible that more rapid cognitive decline may be present in pure DLB.

Only 1 year of follow-up.

There was higher attrition rate (no-follow-up assessment) in the DLB group, and DLB patients that did not return for follow-up were more impaired than AD patients.

Background and Purpose

It is particularly difficult to differentiate dementia with Lewy bodies (DLB) from the related dementias of Alzheimer's disease (AD) and Parkinson's disease dementia (PDD). Few studies have been designed to comparatively analyze detailed neuropsychological assessments of DLB patients and patients with AD and PDD.

Methods

Three groups of patients participated in this study: 10 with DLB, 76 with AD, and 17 with PDD, who had been diagnosed as probable DLB, AD, and PDD, respectively, according to the clinical criteria of the consortium on DLB, National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorder Association, and the clinical diagnostic criteria for PDD. All patients were evaluated by careful neurological examination with detailed neuropsychological testing.

Results

Significant differences among the three groups were found for attention, memory, and executive function, which included tasks of backward digit span, three-word recall, verbal delayed recall, and the Stroop test. Post hoc analysis revealed that the deficiencies of attention on the digit span task were greater in the DLB group than in the AD and PDD groups. The scores for episodic verbal memory tasks were significantly lower in the DLB and AD groups than in the PDD group. The performance in frontal executive function, as indicated by the Stroop test, was significantly worse in the DLB and PDD groups than in the AD group.

Conclusions

The results of the present study show that the pattern of cognitive dysfunction, in terms of attention, episodic memory, and executive functions, differ between patients with DLB and patients with AD and PDD.

Background

Attentional dysfunction is believed to be a prominent and distinguishing neuropsychological feature of dementia with Lewy bodies (DLB); yet, the specific nature of the attentional deficit and factors that can potentially influence attentional processing in DLB have not been fully defined.

Aims

To clarify the nature of the attentional deficit in early‐stage DLB relative to patients with early‐stage dementia of the Alzheimer's type (DAT) and elderly controls, and examine the effect of task complexity and type of cognitive load on attentional processing in DLB.

Methods

Attentional impairment and fluctuating attention were investigated in three groups of subjects—patients with clinical features of early probable DLB (n = 20), a group with early probable DAT (n = 19) and healthy elderly controls (n = 20)—using an experimental computerised reaction time paradigm.

Results

Patients with DLB showed greater attentional impairment and fluctuations in attention relative to patients with DAT and elderly controls. The attentional deficit was generalised in nature but increased in magnitude as greater demands were placed on attentional selectivity. Attentional deficits in DLB were most pronounced under task conditions that required more active recruitment of executive control and visuospatial cognitive processes.

Conclusions

Attentional deficits in DLB are widespread and encompass all aspects of attentional function. Deficits in higher cortical function influence the degree of attentional impairment and fluctuating attention, suggesting that attentional processing in DLB is mediated by interacting cortical and subcortical mechanisms. These findings serve to clarify the nature of the attentional deficit in DLB and have potentially important ramifications for our understanding of the neurocognitive underpinnings of fluctuations.

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.

Objective:

To determine whether adding REM sleep behavior disorder (RBD) to the dementia with Lewy bodies (DLB) diagnostic criteria improves classification accuracy of autopsy-confirmed DLB.

Methods:

We followed 234 consecutive patients with dementia until autopsy with a mean of 4 annual visits. Clinical diagnoses included DLB, Alzheimer disease (AD), corticobasal syndrome, and frontotemporal dementia. Pathologic diagnoses used the 2005 DLB consensus criteria and included no/low likelihood DLB (non-DLB; n = 136) and intermediate/high likelihood DLB (DLB; n = 98). Regression modeling and sensitivity/specificity analyses were used to evaluate the diagnostic role of RBD.

Results:

Each of the 3 core features increased the odds of autopsy-confirmed DLB up to 2-fold, and RBD increased the odds by 6-fold. When clinically probable DLB reflected dementia and 2 or more of the 3 core features, sensitivity was 85%, and specificity was 73%. When RBD was added and clinically probable DLB reflected 2 or more of 4 features, sensitivity improved to 88%. When dementia and RBD were also designated as probable DLB, sensitivity increased to 90% while specificity remained at 73%. The VH, parkinsonism, RBD model lowered sensitivity to 83%, but improved specificity to 85%.

Conclusions:

Inclusion of RBD as a core clinical feature improves the diagnostic accuracy of autopsy-confirmed DLB.

Aim

Little is known about the concordance rate in twins for dementia with Lewy bodies (DLB). The rate of agreement between clinical and pathological diagnoses for DLB is typically low, necessitating confirmation of the diagnosis neuropathologically.

Methods

Participants were 17 twin pairs enrolled in the Duke Twins Study of Memory in Aging in which at least one member of the pair had an autopsy confirmed diagnosis of DLB, Alzheimer's disease (AD) with Lewy bodies, or fronto-temporal dementia with Lewy bodies. We assessed characteristics of those with dementia and examined rates of concordance for pathological confirmed dementia.

Results

Four monozygotic twin pairs had a proband with neuropathologically confirmed pure DLB; all remained discordant for dementia for periods up to 16 years or more. Five of 13 pairs in which the proband had AD plus DLB were concordant for dementia, but only one pair was concordant for AD plus DLB, while the cotwins in the other four pairs had other types of dementia.

Conclusions

The present study indicates that even among twins, a diagnosis of DLB in one twin does not predict the same diagnosis in the other twin. Neuropathological discordance in type of dementia among monozygotic pairs hints at environmental or epigenetic factors playing a role in Lewy body pathology.

Objectives: To determine whether dementia with Lewy bodies (DLB) and Alzheimer's disease (AD) can be differentiated on the basis of qualitative performance characteristics during neuropsychological evaluation.

Methods: Forty one patients with clinically defined DLB were matched with 26 patients with AD for age, illness duration, nature and severity of cognitive deficits, and regional blood flow distribution on SPECT. The presence or absence of a set of qualitative performance characteristics, observed and recorded during the patients' initial cognitive evaluation, was identified by retrospective analysis of patients' records and the groups compared.

Results: Inattention, visual distractibility, impairments in establishing and shifting mental set, incoherence, confabulatory responses, perseveration, and intrusions were significantly more common in DLB than AD. Intrusions were particularly common in DLB, occurring in 78% of the group. They included externally cued intrusions arising from the visual environment, a feature never seen in AD. In a stepwise logistic regression analysis impaired mental set shifting, perseveration, and the presence of intrusions correctly classified 79% of patients.

Conclusion: It is possible to differentiate DLB and AD on the basis of qualitative features of performance. As many features are amenable to detection at clinical interview, they ought to contribute to clinicians' diagnostic armoury, leading to improved clinical recognition of DLB.

The authors report a case of a 64-year-old male with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLB) pathology at autopsy who did not manifest the core symptoms of DLB until very late in his clinical course. His initial presentation of early executive and language dysfunction suggested a cortical dementia similar to frontotemporal lobar degeneration (FTLD). Core symptoms of DLB including dementia, hallucination, and parkinsonian symptoms were not apparent until late in the course of his illness. Autopsy revealed both brainstem and cortical Lewy bodies and AD pathology. Family history revealed 7 relatives with a history of dementia including 4 with possible or probable DLB. This case is unique because of the FTLD-like presentation, positive family history of dementia, and autopsy confirmation of DLB.

The diagnosis of dementia with Lewy bodies (DLB) is difficult if one relies solely on clinical features. Current International Consensus Criteria for DLB have high specificity but a significant percentage of patients might be misdiagnosed. Reasons for clinical uncertainty regard the presence of concomitant motor signs in patients with Alzheimer’s disease as well as the observation that cognitive abnormalities in DLB might develop with memory impairment without significant parkinsonism. This has clinical relevance as DLB patients may be particularly sensitive to antipsychotics and even the effectiveness of atypical neuroleptics such as quetiapine for the treatment of agitation and hallucinations has been questioned by double-blind, placebo-controlled, randomized studies. By contrast, acetyl-cholinesterase inhibitors such as rivastigmine have shown benefit not only on cognitive but also on psychiatric symptoms. Recent evidence shows that striatal dopamine transporter binding of 123I-ioflupane SPECT is reduced in DLB and this is consistent with a significant loss of nigral dopamine neurons in this disorder. Several studies have demonstrated the diagnostic accuracy of 123I-ioflupane in the differential diagnosis of parkinsonism. Given the availability of SPECT, this investigation represents a useful marker to support clinical diagnosis and can help establishing appropriate treatment for this disorder.

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.

Objective. The authors investigated the validity of the designation “familial dementia with Lewy bodies (DLB)” by evaluating the clinical, neuropathological, and genetic characteristics of previously reported families exhibiting both familial parkinsonism and dementia.

Methods. Several families, including multiple individuals with parkinsonism as well as prominent dementia, were identified through a literature search. Selected families had at least one member with dementia with autopsy evidence of neocortical and/or limbic Lewy-body (LB) pathology. Clinical and neuropathological evidence from reports of families with prominent dementia as well as parkinsonism was reviewed to further define familial DLB.

Results. All selected families had at least one affected individual with dementia and autopsy-proven DLB. Therefore, these families might be considered examples of familial DLB. Individuals in the first six families typically presented with parkinsonian features, whereas cognitive decline did not appear until years later. In contrast, in the other six families, affected individuals typically presented with cognitive decline, and parkinsonism developed later.

Conclusions. Families exist in which one or more persons meet both clinical and neuropathological criteria for DLB. They differ as to whether the signs of parkinsonism precede or follow signs of dementia. It remains to be determined whether this clinical distinction is biologically important. Susceptibility to developing LB pathology may be determined by the interaction between genetic predisposition and environmental risk factors.

Background:

Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).

Objectives:

To determine whether amyloid deposition, as assessed by PET imaging with the β-amyloid–binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.

Methods:

Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.

Results:

Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.

Conclusions:

Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that β-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

GLOSSARY

= Automated Anatomic Labeling;

= Alzheimer disease;

= Alzheimer’s Disease Research Center;

= American version of the National Adult Reading Test;

= analysis of covariance;

= Blessed Dementia Scale;

= cerebral amyloid angiopathy;

= Clinical Dementia Rating;

= Clinical Dementia Rating Sum of Boxes;

= dementia with Lewy bodies;

= distribution volume ratio;

= Cued Selective Reminding Test;

= Free Selective Reminding Test;

= Hoehn and Yahr;

= Massachusetts General Hospital;

= Mini-Mental State Examination;

= normal control;

= neurofibrillary tangle;

= Neuropsychiatric Inventory Questionnaire;

= not significant;

= Parkinson disease;

= Parkinson disease dementia;

= Pittsburgh Compound B;

= region of interest;

= Statistical Parametric Mapping;

= UK Parkinson’s Disease Society Brain Bank Research Center;

= United Parkinson’s Disease Rating Scale;

= Wechsler Adult Intelligence Scale–Revised.

Visual hallucinations (VH) occur commonly in Parkinson's disease (PD) and dementia with Lewy bodies (DLB) but are reported much less frequently in other neurodegenerative causes of parkinsonism, such as progressive supranuclear palsy, multiple system atrophy and corticobasal degeneration syndrome. This clinical sign may be helpful when considering the differential diagnosis of patients with parkinsonism. The observation that VH may be specific to Lewy body pathology probably reflects a greater vulnerability of the visual systems to PD and DLB neurodegeneration compared with other diseases. Topographic differences in pathology are probably the major factor producing VH in Lewy body diseases, rather than neurophysiological changes that are specific to α-synuclein protein accumulation. VH correlate with pathology in the limbic system and more specifically the amygdale that is frequently affected in PD and DLB but relatively preserved in other forms of parkinsonism often misdiagnosed as PD. In this review, the published frequencies of VH in these different conditions are compared to put into context the notion of VH as a clinical clue to underlying Lewy body pathology.

The objective is to study β-amyloid (Aβ) deposition in dementia with Lewy bodies (DLB) with Alzheimer’s disease (AD) pathology (DLB/AD). The size frequency distributions of the Aβ deposits were studied and fitted by log-normal and power-law models. Patients were ten clinically and pathologically diagnosed DLB/AD cases. Size distributions had a single peak and were positively skewed and similar to those described in AD and Down’s syndrome. Size distributions had smaller means in DLB/AD than in AD. Log-normal and power-law models were fitted to the size distributions of the classic and diffuse deposits, respectively. Size distributions of Aβ deposits were similar in DLB/AD and AD. Size distributions of the diffuse deposits were fitted by a power-law model suggesting that aggregation/disaggregation of Aβ was the predominant factor, whereas the classic deposits were fitted by a log-normal distribution suggesting that surface diffusion was important in the pathogenesis of the classic deposits.

Parkinson's Disease (PD), multiple system atrophy (MSA) and dementia with Lewy Bodies (DLB) share α-synuclein immunoreactivity 1. These “synucleinopathies” have overlapping signs and symptoms, but less is known about similarities and differences in their cognitive and neuropsychiatric profiles. We compared the cognitive and neuropsychiatric profiles of individuals with PD, MSA and DLB. Overall, the DLB group showed the most cognitive impairment, the MSA group demonstrated milder impairment and the PD group was the least cognitively impaired. The DLB and MSA groups showed worse executive function and visuospatial skills than PD, while DLB showed impaired memory relative to both PD and MSA. On the neuropsychiatric screening, all groups endorsed depression and anxiety; the DLB group alone endorsed delusions and disinhibition. Consistent with their greater level of cognitive and neuropsychiatric impairment, the DLB group showed the greatest amount of functional impairment on a measure of instrumental ADLs (FAQ). We found that MSA subjects had cognitive difficulties that fell between the mild deficits of the PD group and the more severe deficits of the DLB group. PD, MSA and DLB groups have similar neuropsychiatric profiles of increased depression and anxiety. Similar underlying α-synuclein pathology may contribute to these shared features.

OBJECTIVE: To review clinical features of dementia with Lewy bodies (DLB) and to guide family physicians in pharmacologic management, including medications to avoid. QUALITY OF EVIDENCE A MEDLINE: search of literature from 1995 to 2002 used the MeSH terms dementia with Lewy bodies/diagnosis, dementia with Lewy bodies/therapy, and antipsychotics/dementia with Lewy bodies. Level II and III evidence was available for diagnosis and treatment of DLB. One randomized controlled trial of rivastigmine was reviewed and appraised. MAIN MESSAGE: Dementia with Lewy bodies is common. Diagnosis can be made by family physicians using clinical criteria including presence of dementia with marked fluctuation in performance, hallucinations, and the onset of parkinsonism. Cholinesterase inhibitors should be considered for neuropsychiatric symptoms. Levodopa-carbidopa combinations should be considered for treatment of parkinsonism. Neuroleptics should be used with caution because of the risk of serious sensitivity reactions. If they are needed, atypical agents could be safer. CONCLUSION: Recognition and diagnosis of DLB is important to optimize pharmacologic management and to minimize risk of adverse reactions to neuroleptics.

Background

Extrapyramidal motor symptoms precede dementia in Parkinson disease (PDD) by many years, whereas dementia occurs early in dementia with Lewy bodies (DLB). Despite this clinical distinction, the neuropsychological and neuropathologic features of these conditions overlap. In addition to widespread distribution of Lewy bodies, both diseases have variable burdens of neuritic plaques and neurofibrillary tangles characteristic of Alzheimer disease (AD).

Objectives

To determine whether amyloid deposition, as assessed by PET imaging with the β-amyloid–binding compound Pittsburgh Compound B (PiB), can distinguish DLB from PDD, and to assess whether regional patterns of amyloid deposition correlate with specific motor or cognitive features.

Methods

Eight DLB, 7 PDD, 11 Parkinson disease (PD), 15 AD, and 37 normal control (NC) subjects underwent PiB-PET imaging and neuropsychological assessment. Amyloid burden was quantified using the PiB distribution volume ratio.

Results

Cortical amyloid burden was higher in the DLB group than in the PDD group, comparable to the AD group. Amyloid deposition in the PDD group was low, comparable to the PD and NC groups. Relative to global cortical retention, occipital PiB retention was lower in the AD group than in the other groups. For the DLB, PDD, and PD groups, amyloid deposition in the parietal (lateral and precuneus)/posterior cingulate region was related to visuospatial impairment. Striatal PiB retention in the DLB and PDD groups was associated with less impaired motor function.

Conclusions

Global cortical amyloid burden is high in dementia with Lewy bodies (DLB) but low in Parkinson disease dementia. These data suggest that β-amyloid may contribute selectively to the cognitive impairment of DLB and may contribute to the timing of dementia relative to the motor signs of parkinsonism.

Objectives: To document and illustrate qualitative features of fluctuating cognition as described by care givers of patients with probable dementia with Lewy bodies (DLB) and Alzheimer's disease (AD). To determine whether the quality of the fluctuations differs between DLB and AD. To examine the clinical utility of two recently developed rating scales.

Methods: Care givers of 13 patients with early probable DLB and 12 patients with early probable AD were interviewed using the Clinician Assessment of Fluctuation and the One Day Fluctuation Assessment Scale, both developed recently. Descriptions of fluctuating cognition were recorded verbatim, analysed, and rated.

Results: Descriptions of fluctuating cognition in DLB had a spontaneous, periodic, transient quality, which appeared to reflect an interruption in the ongoing flow of awareness or attention that impacted on functional abilities. Descriptions of fluctuations in AD frequently highlighted episodes of memory failure, or a more enduring state shift in the form of "good" and "bad" days, typically occurring in response to the cognitive demands of the immediate environment. These qualitative differences could be detected reliably by independent raters, but were not always captured in standard severity scores.

Conclusion: Fluctuations occuring in DLB have particular characteristics that are distinguishable from fluctuations occurring in AD. Interpretation and application of the fluctuation criterion continues to limit the diagnostic sensitivity of the consensus criteria for DLB. Findings suggest that explicit documentation and a wider appreciation of these distinctions could improve the reliability with which less experienced clinicians identify this core diagnostic feature in the clinical setting.

Background:

Recent studies raised questions about the severity of cognitive impairment associated with dementia with Lewy bodies (DLB). However, there have been few analyses of large, multicenter data registries for clinical–pathologic correlation.

Methods:

We evaluated data from the National Alzheimer's Coordinating Center registry (n = 5,813 cases meeting initial inclusion criteria) and the University of Kentucky Alzheimer's Disease Center autopsy series (n = 527) to compare quantitatively the severity of cognitive impairment associated with DLB pathology vs Alzheimer disease (AD) and AD+DLB pathologies.

Results:

Mini-Mental State Examination (MMSE) scores showed that persons with pure DLB had cognitive impairment of relatively moderate severity (final MMSE score 15.6 ± 8.7) compared to patients with pure AD and AD+DLB (final MMSE score 10.7 ± 8.6 and 10.6 ± 8.6). Persons with pure DLB pathology from both data sets had more years of formal education and were more likely to be male. Differences in final MMSE scores were significant (p < 0.01) between pure DLB and both AD+DLB and pure AD even after correction for education level, gender, and MMSE–death interval. Even in cases with extensive neocortical LBs, the degree of cognitive impairment was most strongly related to the amount of concomitant AD-type neurofibrillary pathology.

Conclusions:

Dementia with Lewy bodies can constitute a debilitating disease with associated psychiatric, motoric, and autonomic dysfunction. However, neocortical Lewy bodies are not a substrate for severe global cognitive impairment as assessed by the Mini-Mental State Examination. Instead, neocortical Lewy bodies appear to constitute or reflect an additive disease process, requiring Alzheimer disease or other concomitant brain diseases to induce severe global cognitive deterioration.

GLOSSARY

= Alzheimer disease;

= AD Center;

= Consortium to Establish a Registry for Alzheimer's Disease;

= dementia with Lewy bodies;

= Lewy bodies;

= Mini-Mental State Examination;

= National Alzheimer's Coordinating Center;

= neurofibrillary;

= National Institute of Aging-Reagan Institute;

= University of Kentucky Alzheimer's Disease Center.

Objective:

To identify the patterns of diffusivity changes in patients with dementia with Lewy bodies (DLB) and Alzheimer disease (AD) and to determine whether diffusion tensor MRI (DTI) is complementary to structural MRI in depicting the tissue abnormalities characteristic of DLB and AD.

Methods:

We studied clinically diagnosed age-, gender-, and education-matched subjects with DLB (n = 30), subjects with AD (n = 30), and cognitively normal (CN) subjects (n = 60) in a case-control study. DTI was performed at 3T with a fluid-attenuated inversion recovery–based DTI sequence that enabled cortical diffusion measurements. Mean diffusivity (MD) and gray matter (GM) density were measured from segmented cortical regions. Tract-based diffusivity was measured using color-coded fractional anisotropy (FA) maps.

Results:

Patients with DLB were characterized by elevated MD in the amygdala and decreased FA in the inferior longitudinal fasciculus (ILF). ILF diffusivity was associated with the presence of visual hallucinations (p = 0.007), and amygdala diffusivity was associated with Unified Parkinson's Disease Rating Scale (r = 0.50; p = 0.005) in DLB. In contrast, patients with AD were characterized by elevated MD in the medial temporal, temporal, and parietal lobe association cortices and decreased FA in the fornix, cingulum, and ILF. Amygdala diffusivity was complementary to GM density in discriminating DLB from CN; hippocampal and parahippocampal diffusivity was complementary to GM density in discriminating AD from CN.

Conclusion:

Increased amygdalar diffusivity in the absence of tissue loss in dementia with Lewy bodies (DLB) may be related to microvacuolation, a common pathology associated with Lewy body disease in the amygdala. Diffusivity measurements were complementary to structural MRI, demonstrating that measures of diffusivity on diffusion tensor MRI are valuable tools for characterizing the tissue abnormalities characteristic of Alzheimer disease and DLB.

GLOSSARY

= Alzheimer disease;

= cognitively normal;

= dementia with Lewy bodies;

= diffusion tensor MRI;

= fractional anisotropy;

= false discovery rate;

= fluid-attenuated inversion recovery;

= gray matter;

= inferior longitudinal fasciculus;

= Lewy body;

= mean diffusivity;

= REM sleep behavior disorder;

= region of interest;

= superior longitudinal fasciculus;

= echo time;

= inversion time;

= repetition time;

= Unified Parkinson's Disease Rating Scale;

= white matter.

Dementia with Lewy Bodies (DLB) is often characterized by pronounced impairment in visuospatial skills, attention, and executive functions. However, the strength of the phenotypic expression of DLB varies and may be weaker in patients with extensive concomitant Alzheimer’s disease (AD). To determine whether strength of the DLB clinical phenotype impacts cognitive decline, visuospatial and language tests were retrospectively used to predict two-year rate of global cognitive decline in 22 autopsy-confirmed DLB patients (21 with concomitant AD) and 44 autopsy-confirmed “pure” AD patients. Generalized Estimating Equations (GEE) revealed a significant interaction such that poor baseline performances on tests of visuospatial skills were strongly associated with a rapid rate of cognitive decline in DLB but not AD (p < .001). No effect of confrontation naming was found. DLB patients with poor visuospatial skills had fewer neurofibrillary tangles and were more likely to experience visual hallucinations than those with better visuospatial skills. These results suggest that the severity of visuospatial deficits in DLB may identify those facing a particularly malignant disease course and may designate individuals whose clinical syndrome is impacted more by Lewy body formation than AD pathology.

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.