Core Features Of Dementia With Lewy Bodies Research Articles

Development and Validation of a Screening Questionnaire for Dementia With Lewy Bodies (DLB): the DLB Screening Questionnaire (DLBSQ).

Although dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia, its clinical prevalence is low. We developed a short and easy-to-complete DLB screening questionnaire (DLBSQ) to raise diagnostic sensitivity in routine clinical settings. A total of 501 participants were retrospectively enrolled, including 71 controls, 184 patients without DLB, and 246 patients with probable DLB. All patients underwent clinical evaluation, including core features of DLB, the DLBSQ, brain magnetic resonance imaging, and detailed neuropsychological assessments. The diagnostic performance of the DLBSQ for probable DLB was investigated using a receiver operating characteristic curve analysis. Total DLBSQ score was associated with visuospatial and frontal/executive dysfunction and the diagnosis of probable DLB. The area under the receiver operating characteristic curve for total DLBSQ score was 0.727. Youden's method revealed an optimal cutoff value of 3. The sensitivity and specificity of the DLBSQ were 68.7% and 62.4%, respectively. Its discriminating performance improved when cognitive test profiles were additionally considered (area under the curve: 0.822, sensitivity: 80.6%, and specificity: 70.4%). The DLBSQ might be a useful screening tool for DLB in routine clinical practice with good sensitivity and specificity.

Optimizing cCOG, a web‐based tool, to detect dementia with Lewy Bodies.

AbstractBackgroundDiagnosing dementia with Lewy bodies (DLB) is challenging due to overlapping clinical and cognitive presentation with Alzheimer’s disease (AD). Web‐based cognitive and clinical assessments could aid by providing remote and easily accessible diagnostic tools. In this study, we adapted a web‐based cognitive test tool, cCOG, by adding a visuospatial test and a brief clinical survey and assessed its ability to differentiate between DLB and AD.MethodWe included 110 patients (67±7 years, 44% female, MMSE 26±4; n = 30 DLB, n = 32 AD dementia and n = 48 controls with subjective cognitive decline (SCD)). All completed cCOG, comprising six cognitive subtasks assessing memory functioning, reaction time, executive functioning, a visuospatial task, and a brief survey addressing seven self‐reported DLB core features and suggestive autonomic features. First, we compared cCOG cognitive tasks to traditional neuropsychological tasks for all diagnostic groups and clinical questions to validated assessments of clinical features in DLB only. Then, we studied the performance of cCOG cognitive tasks and clinical questions, separately and combined, in differentiating diagnostic groups.ResultcCOG cognitive tasks and clinical survey had moderate to strong correlations to standard neuropsychological testing (.61≤ rs ≤ .77) and to validated assessments of clinical features (.41≤ rs ≤ .65), except for fluctuations and REM‐sleep behavior disorder (RBD) (rs= .32 and rs= .10). cCOG cognitive tasks only, resulted in a diagnostic accuracy of 0.70 [95% CI 0.61‐0.78]. Full cCOG, including both cognitive tasks and brief survey had a diagnostic accuracy of 0.82 [95% CI 0.73‐0.89], with good discrimination of DLB versus AD/controls (acc 0.90 [0.83‐0.95]) and DLB versus AD (acc 0.87 [0.76‐0.95]).ConclusionWe illustrated that cCOG aids in distinguishing DLB and AD patients by using remote assessment of cognition and clinical features. Our findings pave the way to a funneled, harmonized diagnostic process among memory clinics and eventually to a more timely and accurate diagnosis of DLB and AD.

Prevalence and Associated Factors of Visual Hallucinations in Patients with Vascular Cognitive Impairment.

Visual hallucinations (VHs) are striking features for dementia, especially dementia with Lewy bodies (DLB). We aimed to study the frequency and associated factors of VH in vascular cognitive impairment (VCI) and investigate the feasibility of clinically diagnosing the mixed pathology of VCI with DLB. This is a multicentre registration study. A consecutive series of VCI patients with and without dementia were enrolled. Frequency of VH and associated factors, including age, gender, education, disease severity, DLB clinical features, vascular risk factors, cognitive function, and neuropsychiatric symptoms, were compared between VCI with VH (VH+) and without VH (VH−). Among the 1281 patients analysed, 155 (12.1%) had VH. The VH+ group was older (t = 5.07; p < 0.001), was more likely to be female (χ2 = 13.46; p < 0.001), and has a higher clinical dementia rating (χ2 = 70.51; p < 0.001). After adjusting for age, gender, and disease severity, the VH+ group had poorer cognition and more severe neuropsychiatric symptoms. The VH+ group was more associated with DLB features in fluctuating cognition (OR = 2.48; p < 0.001), parkinsonism (OR = 1.85; p = 0.001), rapid eye movement (REM) behavioral disorder (OR = 4.56; p < 0.001), and ≧2 DLB core features (OR = 26.01; p < 0.001). VCI patients with VH tend to have more severe dementia, neuropsychiatric symptoms, and poorer cognitive function. Additionally, highly associated with clinical DLB features in VCI with VH raised the possibility of mixed pathology with DLB in this group. More than two core features in VCI might help in diagnosing a mixed pathology with DLB.

Cognitive Decline in Mild Cognitive Impairment With Lewy Bodies or Alzheimer Disease: A Prospective Cohort Study

ObjectiveWe explored whether the mild cognitive impairment (MCI) stages of dementia with Lewy bodies (DLB) and Alzheimer disease (AD) differ in their cognitive profiles, and longitudinal progression. DesignA prospective, longitudinal design was utilized with annual follow-up (Max 5 years, Mean 1.9, standard deviation 1.1) after diagnosis. Participants underwent repeated cognitive testing, and review of their clinical diagnosis and symptoms, including evaluation of core features of DLB. SettingThis was an observational study of independently living individuals, recruited from local healthcare trusts in North East England, UK. ParticipantsAn MCI cohort (n = 76) aged ≥60 years was utilized, differentially diagnosed with MCI due to AD (MCI-AD), or possible/probable MCI with Lewy bodies (MCI-LB). MeasurementsA comprehensive clinical and neuropsychological testing battery was administered, including ACE-R, trailmaking tests, FAS verbal fluency, and computerized battery of attention and perception tasks. ResultsProbable MCI-LB presented with less impaired recognition memory than MCI-AD, greater initial impairments in verbal fluency and perception of line orientation, and thereafter demonstrated an expedited decline in visuo-constructional functions in the ACE-R compared to MCI-AD. No clear diagnostic group differences were found in deterioration speeds for global cognition, language, overall memory, attention or other executive functions. ConclusionThese findings provide further evidence for differences in severity and decline of visuospatial dysfunctions in DLB compared with AD; further exploration is required to clarify when and how differences in attention, executive, and memory functions emerge, as well as speed of decline to dementia.

Clinical features of Lewy body dementia: insights into diagnosis and pathophysiology.

The recent revision of the consensus diagnostic criteria for dementia with Lewy bodies (DLB) incorporates an expansive set of core and supportive clinical features. However, the relationship between all features and optimal methods for their assessment has yet to be assessed within a single cohort. This has the potential to yield novel pathological insights and streamline diagnostic algorithms. Twenty-seven prospectively recruited probable DLB patients and 25 age-matched controls were assessed and core and supportive features scored using a unique combination of established clinical and research instruments. Prevalence of all features was reported and diagnostic methods were evaluated. An exploratory factor analysis was performed to uncover latent associations. Six independent factors were identified accounting for 81% of the diagnostic variance across all core and supportive clinical features. Within these factors, pathologically plausible relationships were highlighted between hallucinations, cognitive fluctuations, and excessive daytime somnolence; between REM sleep behaviour disorder (RBD) and postural hypotension as well as between Parkinsonism and urinary disturbance. 'Prodromal' DLB symptoms were represented in the remaining three factors. The UPDRS and RBD screening questionnaire were evaluated for their suitability for detecting DLB core features and a novel DLB-Parkinsonism scale is proposed to help standardize diagnosis (AUC = 0.94; 95% CI 0.81-1.00). Clusters of specific core and supportive DLB features are identified, which together with the evaluated screening instruments evaluated, may inform improved strategies to diagnose DLB in clinical and research settings.

Deep-learning-based imaging-classification\xa0identified cingulate island sign in dementia with Lewy bodies

The differentiation of dementia with Lewy bodies (DLB) from Alzheimer’s disease (AD) using brain perfusion single photon emission tomography is important but is challenging because these conditions exhibit typical features. The cingulate island sign (CIS) is the most recently identified specific feature of DLB for a differential diagnosis. The current study aimed to examine the usefulness of deep-learning-based imaging classification for the diagnoses of DLB and AD. Furthermore, we investigated whether CIS was emphasized by a deep convolutional neural network (CNN) during differentiation. Brain perfusion single photon emission tomography images from 80 patients, each with DLB and AD, and 80 individuals with normal cognition (NL) were used for training and 20 each for final testing. The CNN was trained on brain surface perfusion images. Gradient-weighted class activation mapping (Grad-CAM) was applied to the CNN to visualize the features that was emphasized by the trained CNN. The binary classifications between DLB and NL, DLB and AD, and AD and NL were 93.1%, 89.3%, and 92.4% accurate, respectively. The CIS ratios closely correlated with the output scores before softmax for DLB–AD discrimination (DLB/AD scores). The Grad-CAM highlighted CIS in the DLB discrimination. Visualization of learning process by guided Grad-CAM revealed that CIS became more focused by the CNN as the training progressed. The DLB/AD score was significantly associated with the three core features of DLB. Deep-learning-based imaging classification was useful for an objective and accurate differentiation of DLB from AD and for predicting clinical features of DLB. The CIS was identified as a specific feature during DLB classification. The visualization of specific features and learning processes could be critical in deep learning to discover new imaging features.

REM Sleep Behavior Disorder (RBD) in Dementia with Lewy Bodies (DLB).

Rapid eye movement sleep behavior disorder (RBD) is a parasomnia, with abnormal dream-enacting behavior during the rapid eye movement (REM) sleep. RBD is either idiopathic or secondary to other neurologic disorders and medications. Dementia with Lewy bodies (DLB) is the third most common cause of dementia, and the typical clinical presentation is rapidly progressive cognitive impairment. RBD is one of the core features of DLB and may occur either in advance or simultaneously with the onset of DLB. The association between RBD with DLB is widely studied. Evidences suggest that both DLB and RBD are possibly caused by the shared underlying synucleinopathy. This review article discusses history, clinical manifestations, possible pathophysiologies, and treatment of DLB and RBD and provides the latest updates.

Color Vision Impairment Differentiates Alzheimer Dementia From Dementia With Lewy Bodies.

Dementia with Lewy bodies (DLB) is frequently misdiagnosed for Alzheimer dementia (AD), especially in its earlier stages. We characterized color vision impairment (CVI) in patients with DLB versus patients with AD to determine its usefulness in improving accuracy of early diagnosis. We retrospectively reviewed charts of patients with AD, DLB, and patients with mild cognitive impairment suspected to be in the prodromal phase of DLB (pro-DLB) or prodromal phase of AD (pro-AD). All patients underwent an online 15-hue color vision arrangement test. Fifty-two patients were included in this study with a median age of 77 years, of which 44% were female. No significant differences in gender, age, or Montreal Cognitive Assessment existed among patients with AD (n = 15), pro-AD (n = 5), pro-DLB (n = 8), and DLB (n = 24). Of the 52 patients, 4 (2 AD, 1 DLB, and 1 pro-AD) had CVI history from a young age and were excluded from final analyses. New-onset CVI prevalence differed significantly based on diagnosis: patients with pro-AD (20%), patients with AD (15%), patients with pro-DLB (38%), and patients with DLB (78%, P < .001). In a stepwise multivariate logistic regression analysis to determine factors associated with CVI, "diagnosis type" as a binary variable (DLB or pro-DLB vs AD or pro-AD) was the only variable retained in the model (odds ratio = 9.8 [95% CI: 2.3-42.1], P < .001). Color vision impairment in patients with DLB showed a prevalence similar to the core features of DLB (∼80%) and can be supportive to a diagnosis of DLB versus AD. Pending prospective confirmation of our findings, simple online color vision testing could be incorporated into multivariate diagnostic tools to possibly improve accuracy of early diagnosis of DLB.

COLOR VISION IMPAIRMENT IN DEMENTIA WITH LEWY BODIES: A NOVEL AND HIGHLY SPECIFIC DISTINGUISHING FEATURE FROM ALZHEIMER DEMENTIA

Dementia with Lewy Bodies (DLB) is frequently misdiagnosed for Alzheimer dementia (AD), especially in its earlier stages. Identification of clinical features that lend to accurate and earlier diagnosis remains paramount. We characterized the prevalence of color vision impairment (CVI) in DLB vs. AD patients and investigated how CVI is associated with other features of DLB. We retrospectively reviewed charts of patients with AD, DLB, and patients with mild cognitive impairment suspected to be in the prodromal phase of DLB (pro-DLB) or AD (pro-AD). All patients underwent an online 15-hue color vision arrangement test as part of the clinical assessment. The median age of the 47 included patients was 76 years and 47% were female. No significant differences in age or gender existed between patients with AD (n=14 patients) and pro-AD (n=6) versus pro-DLB (n=7) and DLB patients (n=20). Three patients (2 AD, 1 DLB) had CVI history from young age. New-onset CVI prevalence was: pro-AD patients (0%), AD patients (8%), pro-DLB patients (29%), and DLB patients (79%). CVI type was as follows: AD (1 protanopia), pro-DLB (2 deutanopia), DLB (10 protanopia, 3 deutanopia, and 2 tritanopia). The clinical signs and symptoms of patients with DLB were analyzed to evaluate factors associated with color vision impairment. In the 20 DLB patients, the symptom prevalence was: visual hallucinations (90%), tremor (80%), REM-behavior disorder (75%), postural instability (65%), bradykinesia (55%), rigidity (55%), and autonomic instability (50%). Normal mixtures iterative clustering analysis identified two DLB patient groups. While Cluster1 (n=10) and Cluster2 (n=8) had similar total number of Parkinsonian symptoms (2.4 vs. 2.0) and autonomic instability (50% vs. 38%), compared to Cluster2, Cluster1 patients were more likely to have CVI (100% vs. 50%), lower MOCA scores (14 vs. 19), lower visuospatial scores (1.4 vs. 2.5), and REM behavior disturbances (100% vs. 38%). Color vision impairment in DLB patients showed prevalence similar to the core features of DLB (∼80%) and was highly specific for DLB versus AD. Further larger scale investigation will determine if incorporation of color vision tests improve the accuracy of earlier diagnosis of DLB.

Long-Term Cognitive Decline in Dementia with Lewy Bodies in a Large Multicenter, International Cohort.

The aim of this study was to describe the rate and clinical predictors of cognitive decline in dementia with Lewy bodies (DLB), and compare the findings with Alzheimer's disease (AD) and Parkinson's disease dementia (PDD) patients. Longitudinal scores for the Mini-Mental State Examination (MMSE) in 1,290 patients (835 DLB, 198 PDD, and 257 AD) were available from 18 centers with up to three years longitudinal data. Linear mixed effects analyses with appropriate covariates were used to model MMSE decline over time. Several subgroup analyses were performed, defined by anti-dementia medication use, baseline MMSE score, and DLB core features. The mean annual decline in MMSE score was 2.1 points in DLB, compared to 1.6 in AD (p = 0.07 compared to DLB) and 1.8 in PDD (p = 0.19). Rates of decline were significantly higher in DLB compared to AD and PDD when baseline MMSE score was included as a covariate, and when only those DLB patients with an abnormal dopamine transporter SPECT scan were included. Decline was not predicted by sex, baseline MMSE score, or presence of specific DLB core features. The average annual decline in MMSE score in DLB is approximately two points. Although in the overall analyses there were no differences in the rate of decline between the three neurodegenerative disorders, there were indications of a more rapid decline in DLB than in AD and PDD. Further studies are needed to understand the predictors and mechanisms of cognitive decline in DLB.

Abnormal daytime sleepiness in dementia with Lewy bodies compared to Alzheimer's disease using the Multiple Sleep Latency Test.

IntroductionExcessive daytime sleepiness is a commonly reported problem in dementia with Lewy bodies (DLB). We examined the relationship between nighttime sleep continuity and the propensity to fall asleep during the day in clinically probable DLB compared to Alzheimer’s disease (AD) dementia.MethodsA full-night polysomnography was carried out in 61 participants with DLB and 26 with AD dementia. Among this group, 32 participants with DLB and 18 with AD dementia underwent a daytime Multiple Sleep Latency Test (MSLT). Neuropathologic examinations of 20 participants with DLB were carried out.ResultsAlthough nighttime sleep efficiency did not differentiate diagnostic groups, the mean MSLT initial sleep latency was significantly shorter in participants with DLB than in those with AD dementia (mean 6.4 ± 5 minutes vs 11 ± 5 minutes, P <0.01). In the DLB group, 81% fell asleep within 10 minutes compared to 39% of the AD dementia group (P <0.01), and 56% in the DLB group fell asleep within 5 minutes compared to 17% in the AD dementia group (P <0.01). Daytime sleepiness in AD dementia was associated with greater dementia severity, but mean MSLT latency in DLB was not related to dementia severity, sleep efficiency the night before, or to visual hallucinations, fluctuations, parkinsonism or rapid eye movement sleep behavior disorder. These data suggest that abnormal daytime sleepiness is a unique feature of DLB that does not depend on nighttime sleep fragmentation or the presence of the four cardinal DLB features. Of the 20 DLB participants who underwent autopsy, those with transitional Lewy body disease (brainstem and limbic) did not differ from those with added cortical pathology (diffuse Lewy body disease) in dementia severity, DLB core features or sleep variables.ConclusionsDaytime sleepiness is more likely to occur in persons with DLB than in those with AD dementia. Daytime sleepiness in DLB may be attributed to disrupted brainstem and limbic sleep–wake physiology, and further work is needed to better understand the underlying mechanisms.

Clinical features of dementia with lewy bodies in 35 Chinese patients.

ObjectiveTo investigate the clinical features of dementia with Lewy bodies (DLB) in a Chinese population.MethodsComputer-based online searches through China Biology Medicine disc and China National Knowledge Infrastructure were performed to collect case reports of DLB published between 1980 and 2012. Clinical characteristics were analyzed.ResultsA total of 18 studies comprising 35 patients (26 males and 9 females) were included. The mean age at onset was 67.2 ± 9.8 years. Onset was characterized by memory impairment and accounted for 58.8% of all cases, followed by parkinsonism (11.8%), visual hallucinations (8.8%), and compulsive personality disorder (2.9%). The other patients (17.6%) presented two of the three core features of DLB at onset. With disease progression, parkinsonism was reported in 100% of cases, followed by visual hallucinations (97.1%), psychiatric symptoms (85.7%), severe neuroleptic sensitivity (81.8%), fluctuating cognition (68.6%), repeated falls (40.0%), sleep disorders (22.9%), and transient loss of consciousness (17.1%). 26 patients who were subjected to Mini-Mental State Examination scored ≤ 24. 10 patients presented relative preservation of hippocampus and medial temporal lobe structures on CT/MRI scan. Occipital hypometabolism occurred in 2 of 3 patients who underwent SPECT/PET perfusion scan. 12 patients showed an increasing of slow frequency activity on EEG, prominently in frontal and temporal lobes.ConclusionsDLB often strikes elderly individuals. Its clinical core features are dementia, fluctuating cognition, recurrent visual hallucinations and spontaneous features of parkinsonism. Neuropsychological, neuroimaging and EEG examinations may improve the diagnostic accuracy and discriminate DLB from other dementias.

Striatal Dopamine Transporter Binding Does Not Correlate with Clinical Severity in Dementia with Lewy Bodies

Patients who have dementia with Lewy bodies (DLB) show both clinical and histopathologic overlap with Alzheimer disease patients and Parkinson disease patients. In this study, we correlated the core features of DLB (dementia, parkinsonism, hallucinations, and fluctuations) with striatal dopamine transporter (DAT) availability as assessed with SPECT and (123)I-N-(3-iodoprop-2E-enyl)-2-β-carbomethoxy-3β-(4-methylphenyl) nortropane ((123)I-PE2I) in patients with newly diagnosed DLB. Two hundred eighty-eight patients were consecutively included in the study as they were referred for diagnostic SPECT scanning of DAT with (123)I-PE2I. Of those patients, 51 had, on the basis of clinical guideline criteria, a probable-DLB diagnosis at follow-up 16 ± 11.6 mo later. Before or on the day of the SPECT scan, DLB patients had a routine neurologic examination including Hoehn and Yahr grading and were cognitively evaluated with the Mini Mental State Examination. There was no correlation between Mini Mental State Examination, Hoehn and Yahr score, fluctuations or hallucinations, and striatal DAT availability as measured with (123)I-PE2I and SPECT. In patients with newly diagnosed DLB, symptoms are not associated with a reduction in striatal DAT despite its firm involvement in DLB pathology.

Glucose hypometabolism in primary visual cortex is commonly associated with clinical features of dementia with Lewy bodies regardless of cognitive conditions

Although metabolic reduction in the primary visual cortex on [(18) F]-fluoro-d-glucose (FDG) positron emission tomographic (PET) scans is the hallmark of dementia with Lewy bodies (DLB) for differential diagnosis from Alzheimer's disease, the clinical significance of the metabolic pattern in patients without dementia remains unknown. The purpose of this study was to investigate the clinical profiles of patients without dementia with the metabolic pattern and its relevance to DLB. Of 145 individuals who underwent (18) F-FDG PET, 25 patients with glucose hypometabolism in the primary visual cortex were identified based on three-dimensional stereotactic surface projection images through comparison with a normative database. The frequency of core and suggestive clinical features of DLB was compared between the groups with and without the metabolic pattern. Of 25 patients with glucose hypometabolism in the primary visual cortex, 12 exhibited more than two core features of DLB (probable DLB group) and 6 had rapid eye movement sleep behavior disorder (possible DLB group). Three patients exhibited memory loss without any core or suggestive features but with reduced cardiac iodine-123 metaiodobenzylguanidine uptake. Ten of these 21 patients exhibited no dementia. The proportion of individuals in the probable and possible DLB groups was significantly higher in the group with glucose hypometabolism in the primary visual cortex. Glucose hypometabolism in the primary visual cortex is commonly associated with the clinical features of DLB regardless of cognitive conditions. Continued follow-up of these patients without dementia with the metabolic pattern is warranted to determine if they represent the prodromal state of DLB.

Familial aggregation of dementia with lewy bodies

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.

P3-060: Cerebrospinal fluid markers in dementia with Lewy bodies (DLB) in comparison with Alzheimer′s disease (AD)

AD and DLB present with similar clinical features and biological markers to differentiate both disorders are still lacking. Pathologically, most cases with pure DLB exhibit a diffuse plaque-only pathology with rare or absent neocortical neurofibrillary tangles, as opposed to the wide cortical neurofibrillary-tau involvement in AD. We analyzed CSF markers chosen as to reflect some of these underlying pathological differences. CSF samples of 33 cases with probable AD (NINCDS-ADRA criteria) without parkinsonism, 25 cases will all the core features of DLB (Consortium criteria) and 46 age-matched controls were analyzed. Total tau, Ab1–42 amyloid, IL-1b and IL-6 levels were measured by sandwich ELISA using commercially available kits (Innogenetics NV, Belgium and Diaclone Research, France). Tau protein: AD cases had significantly higher levels (500 ± 399 pg/ml, mean ± SD) than DLB cases (213 ± 243) and controls (200 ± 243) (p< 0.0001). There were no differences between DLB and control groups. The most efficient cutoff point (250 pg/ml) provided a 76% specificity to distinguish AD and DLB cases. b-amyloid: AD (348 ± 309 pg/ml) and DLB cases (320 ± 233) had lower b-amyloid levels than controls (462 ± 352) but the differences did not reach statistical significance. The combination of tau/ b-amyloid levels provided the best value to differenciate AD vs controls (cut-off point 0.5, sensitivity 82,5%, specificity 75%) but was worse than tau values alone to discriminate between AD and DLB. Interleukine 1b: IL-1b levels in the three groups were within the lowest values of the standard curve. There were no significant differences among AD (2.17 ± 3.00 pgr/ml), DLB (2.60 ± 2.97) cases and controls (2.02 ± 3.28). Interleukine 6: AD (7.14 ± 5.74 pgr/ml) and DLB (6.14 ± 5.00) cases showed slightly higher IL-6 levels than controls (4.96 ± 4.72) but the differences among the three groups were not significant. Tau levels in CSF may contribute to the clinical distinction between AD and DLB. b-amyloid CSF levels are similar in AD and DLB cases and tend to be lower than in controls. Interleukine CSF concentrations do not distinguish between both dementia disord.

S1-04-04: Dementia with Lewy bodies

Dementia with Lewy Bodies (DLB) is a common cause of dementia in older people but is still associated by many clinicians with uncertainty about diagnosis and mangement . Accurate clinical diagnosis of DLB is justified by the specific functional disabilities, care needs and responses to pharmacological treatments of this group compared with other dementias. To review recent guidelines about the clinical and pathological diagnosis of DLB. The DLB International Consortium published revised methods for diagnosis and management in December 2005. No major amendments to the three core features of DLB are proposed, but better methods for measurement of symptom severity are recommended. A new category of features “suggestive” of DLB is described comprising, REM sleep behaviour disorder (RBD), severe neuroleptic sensitivity, and abnormal dopamine transporter neuro–imaging imaging. If one or more of these suggestive features is present, in addition to one or more core features, a diagnosis of probable DLB is made. Possible DLB can be diagnosed if one or more is present in a patient with dementia even in the absence of any core features. The revised criteria are also more explicit about the importance to be attached to clinical and radiological evidence of cerebrovascular disease since pathological and imaging studies suggest that white matter lesions (periventricular and deep white matter), microvascular changes and lacunes may frequently be present. For the purposes of assessing Lewy–related pathology, the latest recommendation is to use alpha–synuclein immunohistochemistry and a semi–quantitative grading of lesion density rather than the counting methods previously proposed. The pattern of regional involvement is more important than total LB count. The guidelines have also been modified to address the issue of concomitant Alzheimer type pathology to take account of the pathoplastic effect that this has upon the clinical presentation. Finally a patient management outline is offered including behavioural and pharmacological components and acknowledging that in the absence of substantial RCT evidence the recommendations are largely based upon expert opinion. New diagnostic criteria and management guidelines for DLB are now available for clinical use and further research and evaluation should be widely disemminated.

Dementia with Lewy bodies

Dementia with Lewy bodies (DLB) is the second most common cause of neurodegenerative dementia in older people, accounting for 10–15% of all cases. It occupies part of a spectrum that includes Parkinson's disease and primary autonomic failure, all of which share a neuritic pathology based upon abnormal aggregation of the synaptic protein alpha-synuclein. It is important to identify DLB patients accurately because they have specific symptoms, impairments and functional disabilities that differ from those of other common dementia syndromes, including 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. Newly developed rating scales for the core features of DLB (fluctuation, visual hallucinations and parkinsonism) should improve clinical diagnostic accuracy, as should the use of structural and functional neuroimaging. 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 neuropsychiatric symptoms. Virtually unrecognized 20 years ago, DLB could within this decade be one of the most treatable neurodegenerative disorders of late life.

Cerebrospinal fluid markers in dementia with lewy bodies compared with Alzheimer disease.

Most patients with dementia with Lewy bodies (DLB) exhibit diffuse plaque-only pathology with rare neocortical neurofibrillary tangles (NFTs), as opposed to the widespread cortical neurofibrillary-tau involvement in Alzheimer disease (AD). Another pathological difference is the astrocytic and microglial inflammatory responses, including release of interleukins (ILs), around the neuritic plaques and NFTs in AD brains that are absent or much lower in DLB. We analyzed cerebrospinal fluid (CSF) markers that reflect the pathological differences between AD and DLB. To determine CSF concentrations of tau, beta-amyloid, IL-1beta, and IL-6 as potential diagnostic clues to distinguish between AD and DLB. We measured total tau, beta-amyloid1-42, IL-1beta, and IL-6 levels in CSF samples of 33 patients with probable AD without parkinsonism, 25 patients with all the core features of DLB, and 46 age-matched controls. Patients with AD had significantly higher levels of tau protein than patients with DLB and controls (P<.001). The most efficient cutoff value provided 76% specificity to distinguish AD and DLB cases. Patients with AD and DLB had lower, but not significantly so, beta-amyloid levels than controls. The combination of tau and beta-amyloid levels provided the best sensitivity (84%) and specificity (79%) to differentiate AD vs controls but was worse than tau values alone in discriminating between AD and DLB. Beta-amyloid levels had the best correlation with disease progression in both AD and DLB (P =.01). There were no significant differences in IL-1beta levels among patients with AD, patients with DLB, and controls. Patients with AD and DLB showed slightly, but not significantly, higher IL-6 levels than controls. The tau levels in CSF may contribute to the clinical distinction between AD and DLB. Beta-amyloid CSF levels are similar in both dementia disorders and reflect disease progression better than tau levels. Interleukin CSF concentrations do not distinguish between AD and DLB.

A 6-Year Study of Cognition and Spatial Function in the Demented and Non-Demented Elderly: The Sydney Older Persons Study

Background: Spatial function has been suggested to be disproportionately worse in people with dementia with Lewy bodies (DLB) than other dementia groups, and poor performance on the Mini-Mental State Examination pentagon copying (PC) task has been proposed as adequate for assessing this. We aimed to establish the prevalence of poor PC in the non-demented elderly; determine the validity of the use of PC as a spatial function test, and determine if poor PC is more common in DLB than non-DLB dementias. Methods: In a population-based sample of 299 participants, 126 were rated as being cognitively normal (clinical rating scale [CDR] = 0), 95 mildly cognitively impaired (CDR = 0.5), and 78 met criteria for dementia, 19 of whom met criteria for probable DLB (pDLB) and 25 with none of the core features of DLB (non-DLB). The accuracy of PC performance was determined across CDR groups, and the relationship of PC to performance on a broad range of cognitive tests was evaluated. The dementia groups were compared cross-sectionally to determine differences in PC and other cognitive test performance, as well as 3 and 6 years earlier to determine cognitive differences at initial stages of cognitive decline. Results: Poor PC was common in the non-demented elderly (39% CDR = 0; 43% CDR = 0.5). In this non-demented group, PC was selectively related to tests of spatial function. Poor PC was not significantly different in the pDLB and non-DLB groups at any assessment time, however it became more prevalent as dementia severity increased. Memory function and verbal fluency were more impaired in the pDLB group in the early stages of the disorder. Comment: PC appears to be a good measure of spatial function in the elderly. However, in contrast to other findings of poor spatial skills in DLB when dementia is in the mild to moderate stages, poor PC performance has not been shown to be a good early marker of DLB and its clinical correlates are yet to be determined.