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1.  Familial Aggregation of Dementia With Lewy Bodies 
Archives of Neurology  2011;68(1):90-93.
Background
Familial aggregation of dementia with Lewy bodies (DLB) remains unclear.
Objectives
To determine the degree of family aggregation of DLB by comparing DLB risk between siblings of probands with clinically diagnosed DLB and siblings of probands with clinically diagnosed Alzheimer disease in a cohort of Caribbean Hispanic families and to explore the degree of aggregation of specific clinical manifestations (ie, cognitive fluctuations, visual hallucinations, and parkinsonism) in DLB.
Design
Familial cohort study.
Setting
Academic research.
Patients
We separately compared risks of possible DLB, probable DLB, and clinical core features of DLB (cognitive fluctuations, visual hallucinations, and parkinsonism) between siblings of probands with clinically diagnosed DLB (n=344) and siblings of probands with clinically diagnosed Alzheimer disease (n=280) in 214 Caribbean Hispanic families with extended neurologic and neuropsychological assessment.
Main Outcome Measures
We applied general estimating equations to adjust for clustering within families. In these models, age and proband disease status were independent variables, and disease status of siblings was the measure of disease risk and the dependent variable.
Results
Compared with siblings of probands having clinically diagnosed Alzheimer disease, siblings of probands having clinically diagnosed DLB had higher risks of probable DLB (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.04–5.04) and visual hallucinations (2.32; 1.16–4.64). They also had increased risks of possible DLB (OR, 1.51; 95% CI, 0.97–2.34) and cognitive fluctuations (1.55; 0.95–2.53).
Conclusions
Dementia with Lewy bodies and core features of DLB aggregate in families. Compared with siblings of probands having clinically diagnosed AD, siblings of probands having clinically diagnosed DLB are at increased risks of DLB and visual hallucinations. These findings are an important step in elucidating the genetic risk factors underlying DLB and in delineating DLB from other neurodegenerative diseases, such as Alzheimer disease.
doi:10.1001/archneurol.2010.319
PMCID: PMC3268781  PMID: 21220678
2.  Comparison of Clinical Manifestation in Familial Alzheimer's disease and Dementia with Lewy Bodies 
Archives of neurology  2008;65(12):1634-1639.
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.
doi:10.1001/archneur.65.12.1634
PMCID: PMC2633487  PMID: 19064751
3.  Imaging Improves Diagnosis of Dementia with Lewy Bodies 
Psychiatry Investigation  2009;6(4):233-240.
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.
doi:10.4306/pi.2009.6.4.233
PMCID: PMC2808791  PMID: 20140120
Dementia; Dementia with Lewy bodies; Magnetic resonance imaging; Single photon emission computed tomography; Positron emission tomography; 123I-metaiodobenzylguanidine myocardial scintigraphy
4.  Comparison of cognitive decline between dementia with Lewy bodies and Alzheimer's disease: a cohort study 
BMJ Open  2012;2(1):e000380.
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.
doi:10.1136/bmjopen-2011-000380
PMCID: PMC3330257  PMID: 22318660
5.  Dementia with Lewy Bodies versus Alzheimer's Disease and Parkinson's Disease Dementia: A Comparison of Cognitive Profiles 
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.
doi:10.3988/jcn.2011.7.1.19
PMCID: PMC3079155  PMID: 21519522
dementia with lewy bodies; Alzheimer's disease; Parkinson's disease dementia; cognition; neuropsychology
6.  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.
doi:10.1136/jnnp.74.9.1215
PMCID: PMC1738667  PMID: 12933921
7.  Inclusion of RBD improves the diagnostic classification of dementia with Lewy bodies 
Neurology  2011;77(9):875-882.
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.
doi:10.1212/WNL.0b013e31822c9148
PMCID: PMC3162640  PMID: 21849645
8.  Dementia with Lewy bodies and Alzheimer disease 
Neurology  2010;74(22):1814-1821.
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.
doi:10.1212/WNL.0b013e3181e0f7cf
PMCID: PMC2882217  PMID: 20513818
9.  Fluctuating cognition in dementia with Lewy bodies and Alzheimer's disease is qualitatively distinct 
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.
doi:10.1136/jnnp.2002.002576
PMCID: PMC1738966  PMID: 14966152
10.  Higher cortical deficits influence attentional processing in dementia with Lewy bodies, relative to patients with dementia of the Alzheimer's type and controls 
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.
doi:10.1136/jnnp.2006.090183
PMCID: PMC2077555  PMID: 16772356
11.  Visuospatial Deficits Predict Rate of Cognitive Decline in Autopsy-Verified Dementia with Lewy Bodies 
Neuropsychology  2008;22(6):729-737.
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.
doi:10.1037/a0012949
PMCID: PMC2587484  PMID: 18999346
Dementia with Lewy bodies; cognitive decline; visuospatial skills; Alzheimer’s disease
12.  Dementia with Lewy bodies: a comparison of clinical diagnosis, FP‐CIT single photon emission computed tomography imaging and autopsy 
Background
Dementia with Lewy bodies (DLB) is a common form of dementia. The presence of Alzheimer's disease (AD) pathology modifies the clinical features of DLB, making it harder to distinguish DLB from AD clinically during life. Clinical diagnostic criteria for DLB applied at presentation can fail to identify up to 50% of cases. Our aim was to determine, in a series of patients with dementia in whom autopsy confirmation of diagnosis was available, whether functional imaging of the nigrostriatal pathway improves the accuracy of diagnosis compared with diagnosis by means of clinical criteria alone.
Methods
A single photon emission computed tomography (SPECT) scan was carried out with a dopaminergic presynaptic ligand [123I]‐2beta‐carbometoxy‐3beta‐(4‐iodophenyl)‐N‐(3‐fluoropropyl) nortropane (FP‐CIT; ioflupane) on a group of patients with a clinical diagnosis of DLB or other dementia. An abnormal scan was defined as one in which right and left posterior putamen binding, measured semiquantitatively, was more than 2 SDs below the mean of the controls.
Results
Over a 10 year period it was possible to collect 20 patients who had been followed from the time of first assessment and time of scan through to death and subsequent detailed neuropathological autopsy. Eight patients fulfilled neuropathological diagnostic criteria for DLB. Nine patients had AD, mostly with coexisting cerebrovascular disease. Three patients had other diagnoses. The sensitivity of an initial clinical diagnosis of DLB was 75% and specificity was 42%. The sensitivity of the FP‐CIT scan for the diagnosis of DLB was 88% and specificity was 100%.
Conclusion
FP‐CIT SPECT scans substantially enhanced the accuracy of diagnosis of DLB by comparison with clinical criteria alone.
doi:10.1136/jnnp.2006.110122
PMCID: PMC2117602  PMID: 17353255
13.  Positive FP-CIT SPECT (DaTSCAN) in Clinical Alzheimer's Disease – An Unexpected Finding? 
Clinically, Alzheimer's disease (AD) is by far the most common cause of dementia. Criteria for the diagnosis of dementia with Lewy bodies (DLB) are highly specific but not at all sensitive, which is reflected by the higher number of DLB cases detected histopathologically at autopsy. Imaging of dopamine transporter with FP-CIT SPECT is one possibility to increase sensitivity. Pathological confirmation was also included in the revised consensus criteria for the diagnosis of DLB. However, in the absence of parkinsonism, one of the core features, a clinical diagnosis of AD is more likely. The role of FP-CIT SPECT in DLB diagnosis remains to be clarified. Based on our 3 case reports and a review of the literature, the utility of this imaging method in the differential diagnosis of AD and DLB is highlighted.
doi:10.1159/000330470
PMCID: PMC3235939  PMID: 22545039
Alzheimer's disease; Dementia; Dopamine; Lewy bodies; FP-CIT SPECT
14.  Relative preservation of MMSE scores in autopsy-proven dementia with Lewy bodies 
Neurology  2009;73(14):1127-1133.
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.
doi:10.1212/WNL.0b013e3181bacf9e
PMCID: PMC2764396  PMID: 19805729
15.  Semantic memory is impaired in both dementia with Lewy bodies and dementia of Alzheimer's type: a comparative neuropsychological study and literature review 
OBJECTIVE—To test the hypothesis that semantic impairment is present in both patients with dementia with Lewy bodies (DLB) and those with dementia of Alzheimer's type (DAT).
METHODS—A comprehensive battery of neuropsychological tasks designed to assess semantic memory, visuoperceptual function, verbal fluency, and recognition memory was given to groups of patients with DLB (n=10), DAT (n=10) matched pairwise for age and mini mental state examination (MMSE), and age matched normal controls (n=15).
RESULTS—Both DLB and DAT groups exhibited impaired performance across the range of tasks designed to assess semantic memory. Whereas patients with DAT showed equivalent comprehension of written words and picture stimuli, patients with DLB demonstrated more severe semantic deficits for pictures than words. As in previous studies, patients with DLB but not those with DAT were found to have impaired visuoperceptual functioning. Letter and category fluency were equally reduced for the patients with DLB whereas performance on letter fluency was significantly better in the DAT group. Recognition memory for faces and words was impaired in both groups.
CONCLUSIONS—Semantic impairment is not limited to patients with DAT. Patients with DLB exhibit particular problems when required to access meaning from pictures that is most likely to arise from a combination of semantic and visuoperceptual impairments.


doi:10.1136/jnnp.70.2.149
PMCID: PMC1737202  PMID: 11160461
16.  Verbal Learning and Memory in Patients with Dementia with Lewy Bodies or Parkinson's Disease with Dementia 
This study compared verbal learning and memory in patients with autopsy-confirmed dementia with Lewy Bodies (DLB) and patients with Parkinson's disease with dementia (PDD). Twenty-four DLB patients, 24 PDD patients, and 24 normal comparison participants were administered the California Verbal Learning Test. The three groups were matched on demographic variables and the two patient groups were matched on the Mattis Dementia Rating Scale. The results indicated that DLB patients recalled less information than PDD patients on all but one recall measure and displayed a more rapid rate of forgetting. In contrast, the PDD patients committed a greater percent of perseveration errors than the DLB patients. The two groups did not differ in the percentage of recall intrusion errors or any measures of recognition. A discriminant function analysis (DFA) using short delay cued recall, percent perseveration errors, and list b recall, differentiated the DLB and PDD groups with 81.3% accuracy. The application of the DFA algorithm to another sample of 42 PDD patients resulted in a 78.6% correct classification rate. The results suggest that, despite equivalent levels of general cognitive impairment, patients with DLB or PDD exhibit a different pattern of verbal learning and memory deficits.
doi:10.1080/13803390802572401
PMCID: PMC2935683  PMID: 19221922
17.  EEG findings in dementia with Lewy bodies and Alzheimer's disease 
OBJECTIVES—To evaluate the role of the EEG in the diagnosis of dementia with Lewy bodies (DLB).
METHODS—Standard EEG recordings from 14 patients with DLB confirmed at postmortem were examined and were compared with the records from 11 patients with Alzheimer's disease confirmed at postmortem
RESULTS—Seventeen of the total of 19 records from the patients with DLB were abnormal. Thirteen showed loss of alpha activity as the dominant rhythm and half had slow wave transient activity in the temporal lobe areas. This slow wave transient activity correlated with a clinical history of loss of consciousness. The patients with Alzheimer's disease were less likely to show transient slow waves and tended to have less marked slowing of dominant rhythm.
CONCLUSIONS—The greater slowing of the EEG in DLB than in Alzheimer's disease may be related to a greater loss of choline acetyltransferase found in DLB. Temporal slow wave transients may be a useful diagnostic feature in DLB and may help to explain the transient disturbance of consciousness which is characteristic of the disorder.


PMCID: PMC1736269  PMID: 10084544
18.  Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake in dementia with Lewy bodies: comparison with Alzheimer's disease 
Cardiac 123I-meta-iodobenzylguanidine (MIBG) uptake was measured in 11 patients with dementia with Lewy bodies (DLB), 10 patients with Alzheimer's disease (AD), and 10 age matched control subjects. The severity of cognitive impairment and duration of symptoms in patients with DLB matched that in the patients with AD. The heart/mediastinum (H/M) ratio of MIBG uptake in the patients with AD was indistinguishable from that in the control subjects. However, the H/M ratio in all patients with DLB was significantly lower than that in the patients with AD and control subjects (p<0.001). These findings indicate that local myocardial sympathetic nerves are affected in DLB and that cardiac 123I-MIBG scintigraphy may provide a means of differentiating DLB from AD.


doi:10.1136/jnnp.70.6.781
PMCID: PMC1737405  PMID: 11385013
19.  Focal atrophy in Dementia with Lewy Bodies on MRI: a distinct pattern from Alzheimer's disease 
Brain : a journal of neurology  2007;130(Pt 3):708-719.
SUMMARY
Dementia with Lewy Bodies (DLB) is the second most common cause of degenerative dementia after Alzheimer's disease (AD). However, unlike in AD the patterns of cerebral atrophy associated with DLB have not been well established. The aim of this study was to identify a signature pattern of cerebral atrophy in DLB and to compare it to the pattern found in AD. Seventy-two patients that fulfilled clinical criteria for probable DLB were age and gender-matched to 72 patients with probable AD and 72 controls. Voxel-based morphometry (VBM) was used to assess patterns of grey matter atrophy in the DLB and AD groups, relative to controls, after correction for multiple comparisons (p<0.05). Study specific templates and prior probability maps were used to avoid normalization and segmentation bias. Region-of-interest (ROI) analyses were also performed comparing loss of the midbrain, substantia innominata (SI), temporoparietal cortex and hippocampus between the groups. The DLB group showed very little cortical involvement on VBM with regional grey matter loss observed primarily in the dorsal midbrain, SI and hypothalamus. In comparison, the AD group showed a widespread pattern of grey matter loss involving the temporoparietal association cortices and the medial temporal lobes. The SI and dorsal midbrain were involved in AD however they were not identified as a cluster of loss discrete from uninvolved surrounding areas, as observed in the DLB group. On direct comparison between the two groups, the AD group showed greater loss in the medial temporal lobe and inferior temporal regions than the DLB group. The ROI analysis showed reduced SI and midbrain grey matter in both the AD and DLB groups. The SI grey matter was reduced more in AD than DLB, yet the midbrain was reduced more in DLB than AD. The hippocampus and temporoparietal cortex showed significantly greater loss in the AD group compared to the DLB group. A pattern of relatively focused atrophy of the midbrain, hypothalamus and SI, with a relative sparing of the hippocampus and temporoparietal cortex, is therefore suggestive of DLB and may aid in the differentiation of DLB from AD. These findings support recent pathological studies showing an ascending pattern of Lewy Body progression from brainstem to basal areas of the brain. Damage to this network of structures in DLB may affect a number of different neurotransmitter systems which in turn may contribute to a number of the core clinical features of DLB.
doi:10.1093/brain/awl388
PMCID: PMC2730778  PMID: 17267521
Dementia with Lewy Bodies; Alzheimer's disease; voxel-based morphometry; magnetic resonance imaging; neurotransmitter systems
20.  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.
doi:10.1136/jnnp.2006.104257
PMCID: PMC2117680  PMID: 17287240
21.  Neuropathology of Dementia with Lewy Bodies in Advanced Age: a comparison with Alzheimer Disease 
Neuroscience letters  2010;485(3):222-227.
Dementia with Lewy Bodies (DLB) is a common neurodegenerative disorder of the aging population characterized by α–synuclein accumulation in cortical and subcortical regions. Although neuropathology in advanced age has been investigated in dementias such as Alzheimer Disease (AD), severity of the neuropathology in the oldest old with DLB remains uncharacterized. For this purpose we compared characteristics of DLB cases divided into three age groups 70–79, 80–89 and ≥90 years (oldest old). Neuropathological indicators and levels of synaptophysin were assessed and correlated with clinical measurements of cognition and dementia severity. These studies showed that frequency and severity of DLB was lower in 80–89 and ≥90 year cases compared to 70–79 year old group but cognitive impairment did not vary with age. The extent of AD neuropathology correlated with dementia severity only in the 70–79 year group, while synaptophysin immunoreactivity more strongly associated with dementia severity in the older age group in both DLB and AD. Taken together these results suggest that the oldest old with DLB might represent a distinct group.
doi:10.1016/j.neulet.2010.09.016
PMCID: PMC2987680  PMID: 20849919
Cognition; Neuropsychological assessment
22.  Pentagon copying is more impaired in dementia with Lewy bodies than in Alzheimer's disease 
OBJECTIVES—In many cases the clinical differentiation of patients with dementia with Lewy bodies (DLB) from those with Alzheimer's disease (AD) has been difficult. Because many neuropsychological studies have reported greater visuospatial/constructional impairment in DLB than in AD, it was determined whether accuracy in copying the interlocking pentagons item on the mini mental state examination (MMSE) may be helpful in distinguishing patients with DLB from those with AD relatively early in the course of the dementia.
METHODS—All cases of neuropathologically proved DLB and AD in the Center for Alzheimer Disease and Related Disorders brain bank were retrospectively reviewed, and the first available MMSE for each was retrieved. Only patients with MMSE scores⩾13 were included, indicating mild to moderate dementia. The patients' copies of the interlocking pentagons were analyzed and graded as acceptable or unacceptable according to the original instructions for grading the MMSE.
RESULTS—Seventeen patients with DLB and 27 patients with AD were identified for whom MMSE with copies of the interlocking pentagons were available. Two patients with DLB (MMSEs 22 and 27) drew the pentagons acceptably, by contrast with 16 of the patients with AD (MMSEs 13-28). An unacceptable copy was associated with DLB with a sensitivity of 88% and a specificity of 59% (p=0.002).
CONCLUSIONS—For patients with MMSE scores⩾13, an inability to accurately copy the pentagons suggests that the diagnosis is more likely DLB than AD. The results confirm the work of others on visuospatial/constructional impairment in DLB and indicate that this feature may be helpful in its diagnosis.


doi:10.1136/jnnp.70.4.483
PMCID: PMC1737321  PMID: 11254771
23.  The role of 123I-ioflupane SPECT dopamine transporter imaging in the diagnosis and treatment of patients with dementia with Lewy bodies 
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.
PMCID: PMC2654798  PMID: 19300562
dementia with Lewy bodies; 123I-ioflupane-SPECT; dopamine transporter; parkinsonism; Alzheimer’s disease
24.  Imaging amyloid deposition in Lewy body diseases 
Neurology  2008;71(12):903-910.
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.
doi:10.1212/01.wnl.0000326146.60732.d6
PMCID: PMC2637553  PMID: 18794492
25.  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.
PMCID: PMC3181810  PMID: 22033743
Lewy body; dementia; Parkinson's disease; α-synuclein; diagnosis; treatment; cholinesterase inhibitor

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