Criteria For Dementia With Lewy Bodies Research Articles

Diagnostic value of CSF chromogranin A to discriminate between Alzheimer's disease and dementia with Lewy bodies.

Chromogranin A (CgA) seems to be involved in the pathophysiology of different neurodegenerative pathologies such as Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB). CgA is present in the aggregates of amyloid plaques and in Lewy bodies but CgA also has a function in neuroinflammatory processes via microglia. Our objective was to determine if there is a difference in the CgA concentration in the cerebrospinal fluid (CSF) of AD and DLB patients and whether the CgA concentration can discriminate between the two diseases. Using the previously described AlphaLewyMA cohort, we included 117 patients with a CSF CgA assay: 15 control subjects (CS group), 64 DLB patients, 17 AD patients and 21 patients with both AD and probable DLB criteria (AD/DLB group). CgA concentration was assessed using the MSD platform. CSF CgA was increased in the AD and AD/DLB groups compared with the DLB group (p = 0.0006 between AD and DLB, p = 0.0013 between AD/DLB and DLB). No significant difference in CgA concentration was found between DLB and CS. ROC curve analysis showed an area under the curve of 0.791 between AD and DLB. CgA concentrations were correlated with t-Tau and P-Tau regardless of the pathology (for Tau: p = 0.022 for AD; p < 0.0001 for DLB; p = 0.004 for AD/DLB; for P-Tau: p = 0.032 for AD; p < 0.0001 for DLB; p = 0.0009 for AD/DLB). Aβ42 was positively correlated with CgA in the DLB group but not in the AD and AD/DLB groups (for DLB: p < 0.0001; for AD: p = 0.57; for AD/DLB: p = 0.58). CSF CgA concentrations are increased in AD but not in DLB and correlate with P-Tau and Tau whatever the disease. These results suggest a link between tauopathy/neurodegeneration and CgA.

123I‐Ioflupane SPECT Striatal Binding Ratio Predicts Progression of Parkinsonism in a Dementia with Lewy Bodies Cohort

AbstractBackgroundThe criteria for diagnosis of dementia with Lewy bodies (DLB) remain predominantly clinical. However, use of striatal dopamine transporter visualization is suggested as an “indicative” biomarker for DLB under the most recent published DLB criteria (McKeith, Neurology, 2017). The objective of this study is to determine if 123I‐ioflupane SPECT (DaTscan) striatal binding ratio (SBR) correlates with parkinsonian symptoms measured on the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale Part III (MDS‐UPDRS‐III) in patients with either probable DLB or high‐likelihood DLB individuals with mild cognitive impairment (MCI). A secondary aim of this study is to determine if DaTscan SBR measured at baseline can predict progression of parkinsonian symptoms over 2 years in this study population.MethodsThis is a retrospective cohort study using the U.S. Dementia with Lewy Bodies Consortium (DLBC) dataset (U01 NS100610). The sample group included in this study are individuals with either probable DLB (McKeith, Neurology, 2017) or MCI‐LB (McKeith, 2020). Each participant had a baseline DaTscan analyzed with DaTQUANT software and physical examination scored with MDS‐UPDRS‐III. Participants without these data were excluded. Mixed effect models were fit with UPDRS score as the dependent variable and SBR z‐score as the primary independent variable. Data were adjusted for age, gender, diagnosis, and dopaminergic medication at time of examination.ResultsAn analysis between 53 participants’ baseline MDS‐UPDRS‐III and SBR z‐scores revealed a moderate negative correlation, indicating SBR is a significant predictor of baseline MDS‐UPDRS‐III score. An analysis between 23 participants’ baseline SBR z‐scores and 24‐month MDS‐UPDRS‐III revealed a moderate negative correlation, indicating that baseline SBR is a significant predictor of 24‐month MDS‐UPDRS‐III scores.ConclusionThese data reveal a significant relationship between DaTscan SBR and motor examination in DLB. Additionally, there is a significant relationship between baseline SBR and progression of parkinsonian features. We conclude that in DLB, DaTscan at time of diagnosis could be used to confirm underlying dopamine deficiency in the context of clinical parkinsonism and predict progression of parkinsonian symptoms in DLB. This could aid in guiding therapies and prognostication of symptom progression.

Associations between neuropsychiatric symptoms, pathology in neuropathological cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies

AbstractBackgroundNeuropsychiatric symptoms (NPS) are frequent in Alzheimer’s Disease dementia (ADD) but a higher NPS burden is found in dementia with Lewy bodies (DLB). Lewy body (LB) pathology frequently co‐occurs with AD pathology and may not meet neuropathological criteria for DLB (ADLB). Previous studies have shown that both ADLB and DLB cases have faster cognitive and/or functional decline compared to AD. However, the differences in NPS severity over disease course and survival in these pathologic subgroups is not well understood.MethodCases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with a final neuropathologic diagnosis of DLB (±AD co‐pathology; n = 65), ADLB (n = 89), AD (without LB) (n = 140), and controls (no neuropathological diagnosis) (n = 82) were included. Total NPI‐Q (scores ranging from 0‐36) at time of enrollment and within 2.5 years of death were calculated for all groups. Statistical analysis utilizing ANCOVA (adjusting for age, sex, baseline MMSE and cognitive symptom duration) with pairwise comparisons, and Kaplan‐Meier curves were completed.ResultAge at onset of cognitive symptoms was not different between pathology groups. NPI‐Q scores at enrollment were highest in ADLB (7.33 ± 4.85), and higher (p&lt;0.001) than DLB (5.10 ± 3.37), AD (4.54 ± 3.63) and controls (1.78 ± 1.70). At final evaluation, NPI‐Q scores were highest in DLB (10.04 ± 6.28), followed by ADLB (8.0 ± 4.), and ADD (7.61 ± 5.05) when compared to controls (2.78 ± 3.97) (all p&lt;0.001). DLB and AD demonstrated significant increases in NPI‐Q severity during follow up (p &lt; 0.001). AD had longer survival time (5.8 years) compared to ADLB (4.0 years) and DLB (3.9 years). Subjects with NPS had a shorter median survival time (3.4 years) compared to subjects without NPS (6.5 years; p = 0.002).ConclusionA higher NPS burden and shorter survival is seen in both DLB and ADLB, as compared with AD. This suggests that diffuse neocortical LB pathology is not the major driver of either NPS or survival.

Plasma p‐tau181 levels in Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB)

AbstractBackgroundThe fundamental pathological process in AD involves amyloid(Aβ) deposition and Tau hyperphosphorylation (ptau). Plasma ptau has been proven as more accessible and less invasive biomarker than CSF for the assessment of AD pathological features. DLB is another common cause of dementia in the elderly and has overlapping features with AD. Thus, the detection of Alzheimer’s biomarkers might be useful for distinguishing the underlying pathology of AD from other concurrent pathologic processes. In this study, we compared the plasma levels of p‐tau181 in patients with clinically diagnosed DLB and AD.MethodWe examined EDTA plasma samples of patients assessed at the UBC Hospital Clinic for AD. The cohort was clinically characterized as control (n = 89) if no significant cognitive impairment was found, AD (n = 195) if they fulfill the NIA‐AA criteria (McKhann 2011), and DLB (n = 39) if they fulfill the consensus criteria for DLB (McKeith 2005; McKeith 2017). The samples were analyzed by a p‐tau181‐specific Simoa assay.ResultThe mean age of the cohort is 69.2 ± 10.3 with the control 63.4 ± 8.7, AD 70.1 ±9.9 and DLB 77.8 ± 8. There are 74.2% females in the controls, 52.8% in AD, and 35.9% in DLB.).The patients with DLB were older than the cases of AD and controls (p&lt;0.001) and there was no significant effect of age on plasma ptau‐181 concentrations (p = 0.65). There were more females in the controls and AD groups compared to DLB (p&lt;0.001), however, there was no significant correlation between sex and plasma ptau‐181 (p = 0.24). While the plasma p‐tau181 concentrations of cases with AD (74.1 ± 35.6 pg/ml) were slightly higher than DLB (73.2 ± 44.4 pg/ml), they were not significantly different. However, they were significantly higher than the control group (26.5 ± 23 pg/ml) (p &lt; 0.001).ConclusionIn current study, plasma p‐tau181 levels did not differentiate the DLB group from the AD, but both groups were significantly higher than controls. This suggests that DLB often have co‐existing AD pathology, making their p‐tau measurements like the AD group. Further studies with autopsy‐defined samples will be needed to clarify the role of plasma p‐tau181 in DLB.

Associations between neuropsychiatric symptoms, pathology, and survival in an autopsy-confirmed cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies (S39.008)

Associations between neuropsychiatric symptoms, pathology, and survival in an autopsy-confirmed cohorts of Alzheimer’s disease, Alzheimer’s disease with Lewy bodies and Dementia with Lewy bodies (S39.008)

Identifying mixed Lewy body and Alzheimer’s disease pathologies using functional neuroimaging (P6-12.002)

<h3>Objective:</h3> To distinguish between Alzheimer’s disease, Lewy body dementia and Parkinson’s disease using functional neuroimaging. <h3>Background:</h3> Lewy body dementia (LBD) and Alzheimer’s disease (AD) are the two most common neurodegenerative causes of dementia. Autopsy studies report many cases with these clinical diagnoses having mixed pathology with alpha-synuclein, tau and amyloid proteinopathies. There is limited research in trying to distinguish these potential mixed pathology conditions prior to death. <h3>Design/Methods:</h3> 43 subjects were recruited from Ohio State University Memory Disorder and Movement Clinics. Subjects were diagnosed based on standard clinical criteria for DLB, PD and AD by fellowship trained cognitive and movement disorders faculty. Cognitive testing performed included MMSE and SAGE. We used neuroimaging methods including FDG PET, amyloid PET, and DaTscan SPECT to evaluate subjects diagnosed with dementia with Lewy bodies (DLB), AD and PD to investigate how often potential mixed pathologies could be present. The neuroimaging evaluations were blinded to clinical diagnosis. <h3>Results:</h3> 28 subjects with clinical diagnosis of Lewy body disease (15 DLB and 13 PD) and 15 subjects with clinical diagnosis AD were compared. The Lewy body subjects were 69.5 ± 7.2 years old, MMSE 26.6 ± 4, and SAGE 18.4 ± 4.7. AD subjects were 68.4 ± 9.3 years old, MMSE 16.3 ± 6.4, and SAGE 7.4 ± 6.1. 5 subjects (33%) of the clinical AD cases showed abnormal DAT scan uptake, 3 subjects (20%) of the clinical AD cases were negative for amyloid with normal DaTscan uptake, 3 subjects (20%) of the clinical DLB cases showed mixed LBD and AD features, 2 subjects (13%) of the clinical DLB cases were positive for amyloid with normal DaTscan uptake, and 1 (8%) subject with clinical PD had normal DAT scan. <h3>Conclusions:</h3> Based on functional neuroimaging, 26% of clinically diagnosed AD or DLB subjects had evidence of potential mixed pathologies and 25% were misdiagnosed. <b>Disclosure:</b> Dr. Bouchachi has nothing to disclose. Ms. Truelove has nothing to disclose. Ms. Rawson has nothing to disclose. Mrs. Icenhour has nothing to disclose. Michael Knopp has nothing to disclose. Prof. Wright has a non-compensated relationship as a Board of Directors Member with American Board of Science in Nuclear Medicine that is relevant to AAN interests or activities. Dr. Scharre has received personal compensation in the range of $10,000-$49,999 for serving as a Consultant for BrainTest, Inc. Dr. Scharre has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Vascular Scientific. Dr. Scharre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Acadia. Dr. Scharre has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Biogen. Dr. Scharre has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Acadia. Dr. Scharre has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Biogen. Dr. Scharre has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Hickman &amp; Lowder Co.. The institution of Dr. Scharre has received research support from InSightec. The institution of Dr. Scharre has received research support from Alzheimer’s Therapeutic Research Institute (ATRI). The institution of Dr. Scharre has received research support from Eisai. The institution of Dr. Scharre has received research support from vTv Therapeutics. The institution of Dr. Scharre has received research support from National Institute of Health. The institution of Dr. Scharre has received research support from Eli Lilly. The institution of Dr. Scharre has received research support from Johns Hopkins. The institution of Dr. Scharre has received research support from Biogen. The institution of Dr. Scharre has received research support from Roche. The institution of Dr. Scharre has received research support from AZ Therapies. The institution of Dr. Scharre has received research support from Biohaven. The institution of Dr. Scharre has received research support from Novartis. The institution of Dr. Scharre has received research support from Avanir. The institution of Dr. Scharre has received research support from PrecisionMed, Inc. Dr. Scharre has received intellectual property interests from a discovery or technology relating to health care. Dr. Scharre has received intellectual property interests from a discovery or technology relating to health care.

Electroconvulsive therapy improves psychotic symptoms in patients with dementia with Lewy bodies.

The aim of this study was to examine the efficacy and safety of electroconvulsive therapy (ECT) for psychotic symptoms of dementia with Lewy bodies (DLB), and also to determine its use as an adaptive criterion. Eight patients aged 66-83years old (mean 75.4±5.9years) diagnosed with probable DLB based on the criteria for DLB and who received ECT between September 2013 and December 2019 at Aichi Medical University were enrolled. The efficacy and safety of ECT were retrospectively examined. Psychotic symptoms were evaluated using the Brief Psychiatric Rating Scale (BPRS), while parkinsonism was evaluated based on Hoehn-Yahr (HY) stage, with both scores analyzed and comparedstatistically between before and after ECT. Additionally, a follow-up survey after undergoing ECT was performed. Two incidents occurred during ECT sessions, arrhythmia in one patient and respiratory arrest in another, both of whom quickly recovered. Following ECT, a significant improvement in BPRS score was noted (p<0.018, Wilcoxon signed rank test), whereas no significant difference was seen in regard to HY stage (p=0.059). Follow-up survey findings obtained after ECT (mean observation period 15.9±16.7months), showed that all eight patients were alive and none had a relapse of psychotic symptoms. The present results suggest that ECT for patients with mild to moderate DLB and drug therapy-resistant psychotic symptoms is safe, well tolerated and effective. We consider it worth considering as a DLB therapeutic option.

Evolution of core features in Lewy body disease pathologic subtypes

AbstractBackgroundNeocortical tau can be present in over half of patients with Lewy body disease at autopsy, and may influence the timing of when a diagnosis of Dementia with Lewy bodies (DLB) can be made. We examined whether the core features, onset age and latency of probable DLB diagnosis differ by pathological subgroups.MethodAll patients (n=176) met clinical criteria for probable DLB, underwent autopsy and were classified as transitional or diffuse Lewy body disease (TLBD, DLBD). The TLBD and DLBD groups were further subdivided based on the absence of neocortical tangles represented by a low (L) Braak NFT stage of 0‐III or by the presence of neocortical tangles represented by a high (H) Braak NFT stage of IV‐VI. Onset age and latency from cognitive symptom onset to probable DLB were compared for TLBD‐L (n=30), DLBD‐L (n=47), DLBD‐H (n=78) and TLBD‐H (n=21).ResultThe TLBD‐H group met criteria for DLB at an older age (median 76 years) compared to TLBD‐L, DLBD‐L or DLBD‐H groups (median age 70 years, p&lt;0.001). The latency to probable DLB from cognitive onset was shortest for TLBD‐L and DLBD‐L (median &lt; 1 year), which was shorter than DLBD‐H (median 2 years; p=0.016), each of which were shorter than TLBD‐H (median 7.3 years; p&lt;0.001). RBD was more common in men (79% men vs. 40% women, p&lt;0.001) and in patients without neocortical tangles (86% vs. 57%, p&lt;0.001). Patients with RBD met criteria for probable DLB at a younger age than those without a history of RBD (median 69 years vs. 76 years, p&lt;0.001). Men had a shorter latency to probable DLB than women (median 1.0 year vs. 2.8 years, p&lt;0.01), but this was related to RBD status that was more common in men.ConclusionPresence of RBD in both sexes led to a younger onset age and shorter latency to diagnosis of probable DLB. Patients with more widespread tau relative to α‐synuclein pathology (TLBD‐H) were older when probable DLB was diagnosed compared to those with so‐called pure Lewy body disease (TLBD‐L, DLBD‐L) or those with diffuse α‐synuclein and tau pathology (DLBD‐H).

Identifying mixed Lewy body and Alzheimer’s disease pathologies using functional neuroimaging

AbstractBackgroundLewy body dementia (LBD) and Alzheimer’s disease (AD) are the two most common neurodegenerative causes of dementia. Autopsy studies report many cases with these clinical diagnoses having mixed pathology with alpha‐synuclein, tau and amyloid proteinopathies. There is limited research in trying to distinguish these potential mixed pathology conditions prior to death. We used functional neuroimaging methods including FDG PET, amyloid PET, and DaTscan SPECT to evaluate clinically diagnosed subjects with dementia with Lewy bodies (DLB), AD and PD to investigate how often potential mixed pathologies could be present.MethodEighteensubjects (all Caucasian, male/female ratio 15:3) so far were recruited from Ohio State University Memory Disorder and Movement Disorder Clinics in this currently enrolling study. Subjects were diagnosed based on standard clinical criteria for DLB, PD and AD by fellowship trained cognitive and movement disorders faculty. Cognitive testing including Mini‐Mental State Examination (MMSE) and Self‐Administered Gerocognitive Examination (SAGE) were performed. Neuroimaging evaluations performed by neuroradiology faculty were blinded to clinical diagnosis.ResultNine subjects with clinical diagnosis of Lewy body disease (5 DLB and 4 PD) and nine subjects with clinical diagnosis AD were compared. The Lewy body subjects were 71.3 ± 7.4 years old, MMSE 22.3 ± 5.4, and SAGE 9.7 ± 4.8. AD subjects were 67.1 ± 9.6 years old, MMSE 18.6 ± 5.2, and SAGE 9.0 ± 5.2. One subject (11%) of the clinical AD cases showed mixed LBD and AD features, one subject (11%) of the clinical AD cases was negative for amyloid with normal DaTscan uptake, two subjects (40%) of the clinical DLB cases showed mixed LBD and AD features, one subject (20%) of the clinical DLB cases was positive for amyloid with normal DaTscan uptake, and all four subjects with clinical PD showed neuroimaging findings consistent with PD.ConclusionBased on functional neuroimaging, 21% of clinically diagnosed AD or DLB subjects had evidence of potential mixed pathologies and 14% were misdiagnosed. Although the sample size is small, functional neuroimaging studies revealed possibly incomplete or incorrect diagnoses in about one third of subjects clinically diagnosed by subspecialists using standard clinical diagnostic criteria. Larger studies are required to confirm these findings.

Lewy Body Dementias: A Coin with Two Sides?

Lewy body dementias (LBDs) consist of dementia with Lewy bodies (DLB) and Parkinson’s disease dementia (PDD), which are clinically similar syndromes that share neuropathological findings with widespread cortical Lewy body deposition, often with a variable degree of concomitant Alzheimer pathology. The objective of this article is to provide an overview of the neuropathological and clinical features, current diagnostic criteria, biomarkers, and management of LBD. Literature research was performed using the PubMed database, and the most pertinent articles were read and are discussed in this paper. The diagnostic criteria for DLB have recently been updated, with the addition of indicative and supportive biomarker information. The time interval of dementia onset relative to parkinsonism remains the major distinction between DLB and PDD, underpinning controversy about whether they are the same illness in a different spectrum of the disease or two separate neurodegenerative disorders. The treatment for LBD is only symptomatic, but the expected progression and prognosis differ between the two entities. Diagnosis in prodromal stages should be of the utmost importance, because implementing early treatment might change the course of the illness if disease-modifying therapies are developed in the future. Thus, the identification of novel biomarkers constitutes an area of active research, with a special focus on α-synuclein markers.

Severe hyposmia distinguishes neuropathologically confirmed dementia with Lewy bodies from Alzheimer's disease dementia.

Many subjects with neuropathologically-confirmed dementia with Lewy bodies (DLB) are never diagnosed during life, instead being categorized as Alzheimer’s disease dementia (ADD) or unspecified dementia. Unrecognized DLB therefore is a critical impediment to clinical studies and treatment trials of both ADD and DLB. There are studies that suggest that olfactory function tests may be able to distinguish DLB from ADD, but few of these had neuropathological confirmation of diagnosis. We compared University of Pennsylvania Smell Identification Test (UPSIT) results in 257 subjects that went on to autopsy and neuropathological examination. Consensus clinicopathological diagnostic criteria were used to define ADD and DLB, as well as Parkinson’s disease with dementia (PDD), with (PDD+AD) or without (PDD-AD) concurrent AD; a group with ADD and Lewy body disease (LBD) not meeting criteria for DLB (ADLB) and a clinically normal control group were also included. The subjects with DLB, PDD+AD and PDD-AD all had lower (one-way ANOVA p < 0.0001, pairwise Bonferroni p < 0.05) first and mean UPSIT scores than the ADD, ADLB or control groups. For DLB subjects with first and mean UPSIT scores less than 20 and 17, respectively, Firth logistic regression analysis, adjusted for age, gender and mean MMSE score, conferred statistically significant odds ratios of 17.5 and 18.0 for the diagnosis, vs ADD. For other group comparisons (PDD+AD and PDD-AD vs ADD) and UPSIT cutoffs of 17, the same analyses resulted in odds ratios ranging from 16.3 to 31.6 (p < 0.0001). To our knowledge, this is the largest study to date comparing olfactory function in subjects with neuropathologically-confirmed LBD and ADD. Olfactory function testing may be a convenient and inexpensive strategy for enriching dementia studies or clinical trials with DLB subjects, or conversely, reducing the inclusion of DLB subjects in ADD studies or trials.

A visual rating scale for cingulate island sign on 18F-FDG-PET to differentiate dementia with Lewy bodies and Alzheimer's disease

Valid diagnosis of dementia with Lewy bodies (DLB) is essential to establish appropriate treatment and care. However, the diagnostic accuracy is complicated by clinical and pathological overlap with Alzheimer's disease (AD). Cingulate island sign (CIS), defined as sparing of posterior cingulate cortex (PCC) relative to precuneus and cuneus on 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET), is included in the revised diagnostic DLB criteria. There are no guidelines for the visual grading of CIS, although visual rating is a fast-applicable method in a clinical setting.The objective was to develop a robust visual CIS scale and evaluate the performance in differentiating DLB with and without amyloid beta pathology (Aβ+/−), and AD.18F-FDG-PET scans from 35 DLB patients, 36 AD patients, and 23 healthy controls were rated according to a visual CIS scale based on specific reading criteria. The visual CIS scale was validated against a quantitative CIS ratio derived from a region of interest analysis of PCC, precuneus, and cuneus.DLB patients had a significantly higher visual CIS score compared to AD patients, and controls.A cut-off visual CIS score of 4 significantly differentiated DLB Aβ− patients from DLB Aβ+ patients.In conclusion, the visual CIS scale is clinically useful to differentiate DLB from AD. The degree of CIS may be related to Aβ pathology in DLB patients.

Prevalence and clinical features of dual diseases of Alzheimer's disease and dementia with Lewy bodies: A neuroimaging‐based study

AbstractBackgroundWhile dual diseases of Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are documented pathologically, few studies are available concerning the frequency of dual diseases.AimWe present our data of the frequency of AD, DLB and dual diseases based on neuroimaging, together with the frequency of Parkinson's disease (PD) without dementia.MethodsThis is a prospective cohort study (745 dementia and/or movement disorder referred patients; recruiting period, 3 years; prospectively follow‐up period, 2.0 ± 1.8 years; age 73.0 ± 6.3 years at the first visit; 360 men, 385 women; all underwent MRI scan). Patients met the published criteria at least once during a course of disease. We included both dopaminergic denervation in the striatum and noradrenergic denervation in the heart to the inclusion criteria of DLB and PD.ResultsAmong them, total 476 patients met the criteria as follows: 232 AD (48.7%), 91 DLB (19.1%), 29 dual diseases (6.1%), and 124 PD (26.1%). Patients with dual diseases were initially diagnosed as AD in 18, PD in 8, DLB in two, and Lewy body disease in one.ConclusionIn the cases presented, 6.1% of patients who visited dementia/movement disorder clinics showed duals diseases. It is therefore important to follow such patients, from the view point of disease progression and necessary care.

The role of molecular imaging in the frame of the revised dementia with Lewy body criteria

Recommendations about clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) have been recently refined by the DLB Consortium. Substantial new information has been incorporated with increased diagnostic weighting given to molecular imaging biomarkers. The present work attempted to present a comprehensive evaluation of the role of molecular imaging in the frame of the revised DLB criteria. To this end, we briefly review the molecular imaging tools in the fourth Consensus report of the DLB Consortium, highlighting several indicative and supportive surrogate markers, including I-123 brain dopamine transporter (DaT), I-123 mIBG cardiac norepinephrine transporter (NeT) and brain F-18 fluorodeoxyglucose (FDG) imaging, as the main way to increase accuracy of ante-mortem diagnosis of probable or possible DLB. Along with main neuropathological and clinical issues, we focus on the diagnostic performance and appropriate use of current available items included in the index by nuclear medicine physicians, namely a low DaT uptake, a low NeT expression in myocardial tissue, and reduced parieto-occipital metabolism on brain FDG-PET. Moreover, a critical summary of the current state of the art in pathological validation of other biomarkers including amyloid and tau-PET imaging is provided. DLB Consortium clearly states that clinical diagnosis in clinical routine is suboptimal and gives more weight to molecular imaging biomarkers to offer a more objective information. Along with DaT, mIBG and FDG techniques, brain PET with more specific radiotracers could open a new scenario for an accurate evaluation of biomarkers involved in DLB.

A case of treatable dementia with Lewy bodies remarkably improved by immunotherapy

We report a case of probable dementia with Lewy bodies (DLB) with several findings indicating autoimmune encephalitis (e.g. anti-thyroid antibodies in serum and oligoclonal band and anti-N-methyl-d-aspartic acid receptor antibodies in cerebrospinal fluid). The symptoms and the findings of ancillary tests such as Iodine-123-metaiodobenzylguanidine myocardial scintigraphy and 99mTechnetium-ethyl-cysteinate-dimer single photon emission computed tomography were improved after the pulse and oral steroid treatment. This case is thought the autoimmune encephalitis mimicking DLB. This experience indicated the importance of suspecting treatable DLB even when the findings of laboratory and radiological tests fulfill the diagnostic criteria of DLB.

Aripiprazole for the treatment of psychotic symptoms in patients with dementia with Lewy bodies: a case series.

PurposeThe core features of dementia with Lewy bodies (DLB) are cognitive fluctuations, visual hallucinations, and parkinsonian symptoms. Although there have been several reports on the efficacy of treatments for psychotic symptoms in patients with DLB, little is known regarding the treatment effects of aripiprazole. The aim of this study was to evaluate the efficacy and safety of aripiprazole for the treatment of psychotic symptoms in patients with DLB.Patients and methodsWe employed a 10-week, open-label study design with 11 patients who met the criteria for DLB. The patients had previously experienced persistent or intermittent delusions, hallucinations, or both for at least 1 month. Aripiprazole was initiated at a low dose (3 or 6 mg/day) and titrated to higher doses at 2-week intervals or more rapidly, as needed. The Neuropsychiatric Inventory (NPI), Brief Psychiatric Rating Scale (BPRS), and Clinical Global Impression-Severity (CGI-S) were administered at baseline and 1, 2, 4, 8, and 10 weeks later. The Simpson–Angus Scale (SAS), Clinical Dementia Rating (CDR), and Mini-Mental State Examination (MMSE) Scale were evaluated at baseline and at week 10. The NPI, CGI-S, and BPRS scores were compared between the baseline and each assessment point and between each assessment point and the one before assessment point. The SAS, CDR, and MMSE scores were compared between the baseline and the end point.ResultsThe mean NPI and BPRS scores improved until the fourth week; they significantly decreased at each assessment point compared to the previous one. Afterward, improvements slowed and continued without significant decrease. The median SAS scores significantly decreased at the end point compared to the baseline (P<0.05). The median MMSE score was higher at the end point than at the baseline (P<0.05).ConclusionThis study showed that aripiprazole may be effective and well tolerated for the treatment of psychotic symptoms in patients with DLB.

Diffuse Lewy body disease manifesting as corticobasal syndrome: A rare form of Lewy body disease.

To describe clinical and pathologic characteristics of diffuse Lewy body disease (DLBD) manifesting as corticobasal syndrome (CBS). In 523 autopsy-confirmed cases of DLBD, we identified 11 patients diagnosed with CBS. For comparison, we studied 22 DLBD brains with antemortem presentation of dementia with Lewy bodies (DLB). Given previous studies suggesting the importance of pathology in peri-Rolandic cortices in CBS, we used digital pathology to count Lewy bodies and to quantify intracytoplasmic and neuritic α-synuclein and phospho-tau burden in the motor cortex. DLBD patients with antemortem features of CBS were significantly younger at disease onset and less likely to have REM sleep behavior disorder than DLBD cases who met clinical criteria for DLB during life. Patients with DLBD manifesting as CBS had more Lewy bodies in the motor cortex than DLBD manifesting as clinically probable DLB. Three cases had concomitant progressive supranuclear palsy and 4 cases had concomitant Alzheimer disease as probable correlates of CBS. The neuropathology underlying CBS is heterogeneous, including corticobasal degeneration, Alzheimer disease, and progressive supranuclear palsy. This study suggests that atypical variants of Lewy body disease with severe peri-Rolandic Lewy-related pathology can present clinically as CBS. Patients with DLBD who present as CBS tend to have an earlier age at onset and are less likely to have clinical features of DLB, such as dream enactment behavior during sleep, visual hallucinations, and levodopa-responsive parkinsonism. Future studies with biofluid or molecular imaging biomarkers for α-synuclein will permit better recognition of this uncommon pathologic substrate of CBS.

Psychotropic and anti-dementia treatment in elderly persons with clinical signs of dementia with Lewy bodies: a cross-sectional study in 40 nursing homes in Sweden

BackgroundElderly persons with a dementia diagnosis often suffer from different neuropsychiatric symptoms (NPS) such as delusions, hallucinations, depression, anxiety, irritability and agitation. Currently, the medical treatment for NPS consists mostly of psychotropic medication such as hypnotics/sedatives, anxiolytics and antipsychotics. In elderly persons with dementia, usage of antipsychotics is less appropriate because of the risk of side effects such as parkinsonism, rapid cognitive decline, cerebrovascular events and finally mortality. Furthermore, elderly persons with dementia with Lewy bodies (DLB) are often hypersensitive to antipsychotics with numerous serious adverse events such as somnolence, sedation, extra-pyramidal symptoms, delirium and increased mortality. The aim of this study was to investigate the usage of psychotropics with a focus on antipsychotics and anti-dementia medication (according to the Anatomical Therapeutic Chemical Classification System) in elderly persons with clinical signs of DLB living in dementia nursing homes (NHs) in Sweden.MethodsBetween 2012 and 2013, we applied a specially designed questionnaire that covered the clinical DLB features according to the consensus criteria of DLB. We also collected computerized medical lists from the Swedish National Medication Dispensing System from the same period. All dementia NHs (n = 40) in Malmö, the third largest city in Sweden, were covered. Of 650 eligible residents, 610 (94%) were included with 576 medical lists. The mean age was 86 years and 76% were women.ResultsTreatment with antipsychotics was seen in 22% of residents, hypnotics/sedatives in 41%, antidepressants in 50% and anxiolytics in 58%. We also found an increasing usage of antipsychotics from 25% to 43% in residents with the increasing number of DLB features. Anti-dementia medications were found in 45% of the elderly with a dementia diagnosis. However, residents with two or more DLB features had less anti-dementia medication (37%) than the rest of the dementia-diagnosed NH residents (62–69%).ConclusionsResidents with 2–4 DLB clinical features in Swedish NHs receive an unfavourable medical treatment with high antipsychotic usage and insufficient anti-dementia medication. These findings show the importance of identifying elderly persons with DLB features more effectively and improving the collaboration with nursing care to provide better medical prescription.

Accuracy of Clinical Diagnosis of Dementia with Lewy Bodies versus Neuropathology.

The first consensus criteria for dementia with Lewy bodies (DLB) published in 1996 were revised in 2005, partly because the original clinical criteria had suboptimal sensitivity. Few studies have assessed the accuracy of the 2005 criteria applied prospectively in newly diagnosed patients who have been followed longitudinally. To explore the correlation between clinical and pathological diagnoses in patients with DLB and Parkinson's disease with dementia (PDD). From a prospective referral cohort study with enriched recruitment of patients with DLB and PDD, we included the first 56 patients coming to autopsy. Patients had mild dementia at inclusion and were followed annually until death with standardized clinical assessments. Pathological assessment was performed blind to clinical information according to standardized protocols and consensus criteria for DLB. 20 patients received a pathological diagnosis of Lewy body disease; the corresponding clinical diagnoses were probable DLB (n = 11), PDD (n = 5), probable (n = 2) or possible (n = 2) Alzheimer's disease (AD). Of 14 patients with a clinical diagnosis of probable DLB, 11 had DLB/PDD and 3 had AD at pathology. One patient with clinically possible DLB fulfilled criteria for pathological AD. Sensitivity, specificity, positive predictive value, and negative predictive values for probable DLB were 73%, 93%, 79%, and 90%. Our findings suggest that the international clinical consensus criteria for DLB perform reasonably well. However, false positive and false negative diagnoses still occur, indicating that the criteria need to be improved, that biomarkers may be needed, and that neuropathological feedback is vital to improve accuracy.

Editors' Note

Editors' Note: In “Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials,” Drs. Figueroa and Wright reviewed published clinical trials on the effect of hyperbaric oxygen therapy (HBOT) on mild to moderate traumatic brain injury/persistent postconcussion syndrome (mTBI/PPCS) and concluded that HBOT has therapeutic effects on mTBI/PPCS symptoms and can alleviate posttraumatic stress disorder symptoms secondary to a brain injury. Challenging the review, Drs. Hampson and Holm critique the claim that oxygen content of arterial blood plasma (oxygen dissolved in plasma) during hyperbaric exposure correlates with treatment response. They point out that arterial blood plasma oxygen content was not measured in any of the studies reviewed and that the authors presumably estimated the arterial blood partial pressure of oxygen from the calculated alveolar PO2 using the alveolar gas equation and assumed that the participants had normal metabolism and pulmonary. They also suggest that the authors did not take into consideration the fact that the studies used different treatment times and numbers. Drs. Figueroa and Wright agree that PaO2 was not measured in the published studies but assumed that study participants had normal metabolism and pulmonary function since they were cleared to be placed inside a pressure vessel. They also address the difference in time to HBOT exposure and stress that pressurized air is a biologically active agent, rendering the conclusions of inactivity or placebo effect in HBOT/TBI studies questionable. In the study “Autopsy validation of 123I-FP-CIT dopaminergic neuroimaging for the diagnosis of DLB,” Thomas et al. showed that 123I-FP-CIT imaging in dementia is a valid and accurate biomarker for dementia with Lewy bodies (DLB) and that the high specificity compared with clinical diagnosis (20% higher) is clinically important. They also concluded that while an abnormal 123I-FP-CIT scan strongly supports Lewy body disease, a normal scan does not exclude DLB with minimal brainstem involvement. Commenting on the study, Professor Abe notes that there are some patients with cognitive and behavioral dysfunction, but without parkinsonism for years. In such situations, he says that he cannot diagnose patients with DLB. In response, Thomas et al. clarify that about 25% of patients with DLB do not show features of parkinsonism. This is recognized in the consensus criteria for DLB, which do not require parkinsonism for diagnosis. They emphasize that DLB can be recognized despite a normal dopaminergic scan if other characteristic symptoms of DLB are present. —Chafic Karam, MD, and Robert C. Griggs, MD Editors' Note: In “Hyperbaric oxygen: B-level evidence in mild traumatic brain injury clinical trials,” Drs. Figueroa and Wright reviewed published clinical trials on the effect of hyperbaric oxygen therapy (HBOT) on mild to moderate traumatic brain injury/persistent postconcussion syndrome (mTBI/PPCS) and concluded that HBOT has therapeutic effects on mTBI/PPCS symptoms and can alleviate posttraumatic stress disorder symptoms secondary to a brain injury.