Diagnosis Of Dementia With Lewy Bodies Research Articles

Dementia with Lewy bodies: Primary care PAs can make this difficult diagnosis.

Lewy body dementia is an umbrella term for dementia with Lewy bodies (DLB) and Parkinson disease dementia. These progressive, degenerative brain disorders link dementia with psychosis and parkinsonism and are difficult to diagnose. The diagnosis of DLB is challenging, especially in its early phase, because the presentation is variable. Relevant screening tools and a complete physical examination are essential. Making the correct diagnosis lets patients and caregivers make arrangements, have more timely access to services, improve patient quality of life, and lessen the burden on caregivers.

Unraveling the challenges of diagnosing dementia with Lewy bodies in a patient with alcohol and benzodiazepine misuse: A case study-based review

Dementia with Lewy bodies (DLBs) is the second most common cause of neurodegenerative dementia in the United States, after Alzheimer’s disease, and is often misdiagnosed. A history of substance use disorder (SUD) complicates the diagnosis process, and side effects of substance misuse can mirror or mask signs of degenerative dementia. The fluctuating cognition and mobility which would normally point toward DLB are erroneously seen as signs of SUD or polypharmacy. However, a history of SUD should not preclude the diagnosis of DLB or other forms of proteinopathy, as substance misuse can contribute to the development of neurodegenerative dementias. Both alcohol and benzodiazepines have a sedative effect as ligands to gamma-aminobutyric acid (GABA) receptors. Long-term use, misuse, and withdrawals can upset the delicate GABAergic/glutamatergic balance, resulting in adverse neuroimmune and neuroinflammatory responses which contribute to the pathologies seen in degenerative dementias, such as DLB. In this paper, we review the challenges, including limitations of standardized instruments for dementia and the harms of delayed diagnosis, in DLB diagnosis, in combination with our experiences drawn from studying a polypharmacy-practicing 68-year-old man with a 40-year history of benzodiazepine and alcohol use. Understanding the underlying mechanisms of SUD serves to destigmatize the condition to expedite treatment and further our knowledge of the relationship between neuroinflammation and dementia.

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.

Application of Suggestive Biomarkers in Dementia With Lewy Bodies With Masking of Typical Clinical Symptoms by Alzheimer Disease-type Pathology.

Dementia with Lewy bodies (DLB) is strongly associated with Alzheimer disease (AD)-type pathology and tends to mask the core clinical features of DLB. Therefore, there may be cases of undiagnosed DLB without suggestive biomarkers of DLB. We describe the case of a 63-year-old woman who was initially diagnosed as having AD and later diagnosed with DLB based on suggestive biomarkers of DLB. In this case, transient sleep talking with physical movements for several days led to the assessment of suggestive biomarkers for DLB in the absence of the core clinical features of DLB. For clinicians, diagnosing DLB in patients with AD-type pathology is challenging. However, the application of biomarkers suggestive of DLB to all patients with dementia is not realistic. To overcome the difficulties of clinical diagnosis of DLB, further research is needed regarding strategies for the application of suggestive biomarkers for DLB to appropriately diagnose DLB.

Using spatial transcriptomics to investigate region‐specific gene expression in J20 mice

AbstractBackgroundAlzheimer’s disease (AD) and dementia with Lewy bodies (DLB) share various pathological and symptomatic traits. As such, providing an accurate diagnosis of DLB can be difficult, ultimately impacting patient support and care. It is therefore imperative to establish biomarkers which reliably differentiate between disease states. Plasma‐derived exosomes appear to be promising in this regard. Exosomes are extracellular vesicles, containing cargos from the cell from which they originate. Increased concentrations of exosomal disease‐associated proteins, such as p‐T181‐tau and Aβ‐42, have previously been associated with cognitive decline and disease progression among AD patients (Winston et al., 2016; Kapogiannis et al., 2019).MethodWe aim to quantify exosome‐associated proteins from AD patients, DLB patients and healthy controls in order to establish exosomal signatures to differentiate between disease states. Exosomes are being isolated using differential ultracentrifugation. Nanoparticle track analysis (NTA) and western blots are being used to verify isolation, and ELISA assays against p‐T181‐tau, Aβ‐42 and α‐synuclein will be used to quantify proteins of interest. Plasma samples are being collected at baseline and after a 6 month follow‐up period in order to monitor the stability of these potential biomarkers.ResultTo date, full ethics approval has been granted for this study, and the differential ultracentrifugation protocol has been established. Successful isolation of particles in the size range of exosomes (30 – 100nm) has been confirmed using NTA. ELISA assays will be undertaken in the up‐coming months, with the aim of collecting and analysing baseline results by May 2023.ConclusionExosomes already appear to be a reliable, and relatively non‐invasive biomarker for assessing disease state and progression among dementia patients. Our preliminary findings have shown successful isolation, and we believe the findings could be invaluable with regards to improved diagnosis options for DLB.

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<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<0.001). DLB and AD demonstrated significant increases in NPI‐Q severity during follow up (p < 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.

Decline in cognitive trajectories in the neuropathological spectrum of Lewy Body disease

AbstractBackgroundPathological Lewy body disease (LBD) may commonly present clinically as Parkinson’s disease dementia (PDD), Dementia with Lewy bodies (DLB) or Alzheimer’s disease dementia (ADD). Neuropathological definitions also include a group in which ADD is present, but the postmortem Lewy pathology does not meet threshold density and distribution levels for the neuropathological diagnosis of DLB (ADLB). Little is known about the cognitive profiles of patients with ADLB and despite common underlying pathology, studies delineating neuropsychological profiles in LBD are fraught with inconsistencies. We characterized the longitudinal cognitive trajectories defined by neuropsychological profiles in cases along the pathological spectrum of LBD.MethodCases from the Arizona Study of Aging and Neurodegenerative Disorders (AZSAND) with a cognitive diagnosis of dementia at death and who at minimum, had two neuropsychological evaluations were included. Final neuropathological diagnosis was determined as LBD (neocortical or limbic LB ± AD), ADLB, and AD pathology only. LBD cases were categorized by their cognitive clinical syndromes as PDD and DLB. Global cognition was evaluated using MMSE. Neuropsychological domains of Memory, Executive function, language, attention, and visuospatial were evaluated. Mixed linear methods were used to predict longitudinal change for a given baseline MMSE.Result287 participants and 1874 participant‐years of data were included in this study. LBD (n = 115), and ADLB (52) groups were predominantly male, while AD (n = 114) group was primarily female. Baseline MMSE was similar across all pathologic groups. Linear mixed modelling methods showed faster decrease in memory domain scores (decreasing 0.22 units/year – 0.42 units/year faster, p = 0.01) in ADLB group compared to other groups. Significantly faster decline was noted in LBD and ADLB group in clock drawing (p<0.001), fluency scores (declining 1.02 unit/year faster p<0.001) compared to AD group. There was no difference between PDD and DLB clinical subgroups.ConclusionIn autopsy confirmed cases, ADLB had an accelerated trajectory of decline in memory tasks, while AD, and LBD appeared to have similar trajectories. In contrast, all groups with Lewy bodies progressed faster and showed accelerated decline compared to AD in measures of frontal‐subcortical functions. These results may inform antemortem classification of patients and diagnostic accuracy in these groups.

Clinical Validation and Correlates of the Cingulate Island Sign Visual Rating Scale for the Diagnosis of Dementia with Lewy Bodies

AbstractBackgroundThe cingulate island sign (CIS) is a metabolic pattern on [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) associated with dementia with Lewy bodies (DLB). The aim of this study was to validate the visual CIS rating scale (CISRs) for the diagnosis of DLB and to explore the clinical correlates.MethodThis single‐center, retrospective study included 166 consecutive patients with DLB and 161 patients with Alzheimer’s disease (AD). The CIS on [18F]FDG‐PET scans was rated using the CISRs (0‐4) independently by three readers blinded to other patient data.ResultThe optimal cut‐off to differentiate DLB from AD was a CISRs score ≥ 1 (sensitivity = 66%, specificity = 84%) whereas a CISRs score ≥ 2 (sensitivity = 58%, specificity = 92%) was optimal to differentiate amyloid positive DLB (n = 43 (82.7%)) and AD. To identify DLB with abnormal (n = 53 (72.6%)) versus normal (n = 20 (27.4%)) dopamine transporter imaging (DaT), a CISRs cut‐off of 4 had a specificity of 95% for abnormal DaT. DLB patients with a CISRs score of 4 performed significantly better in tests of free verbal recall and picture based cued recall, but worse in test of processing speed compared with DLB with a CISRs score of 0.ConclusionThis study confirms the CISRs as a valid marker for the diagnosis of DLB with a high specificity and a lower, but acceptable, sensitivity. Concomitant AD pathology does not influence diagnostic accuracy of the CISRs. In DLB patients, presence of CIS is associated with relative preserved memory function and impaired processing speed.

B - 43 Case Study: Native Hawaiian/Pacific Islander Female Veteran with Dementia with Lewy Bodies.

Recent research suggests there is a lack of consensus regarding current data on the racial/ethnic profiles of cognitively impaired persons with dementia with Lewy bodies (DLB) despite DLB being among the most common neurodegenerative dementias. This case study reviews a Native Hawaiian/Pacific Islander (NHPI) with probable DLB and discusses challenges encountered to emphasize the importance of appropriate normative data to help detect DLB in diverse populations. A 78-year-old NHPI female veteran presented for repeat neuropsychological evaluation to track her cognitive symptoms. Chief complaints included concurrent cognitive and motor difficulties, fully formed visual hallucinations, nighttime confusion, and reduplicative paramnesias which have significantly impacted her instrumental activities of daily living. Neuropsychological testing is suggestive of progressive decline in several cognitive domains, including visuospatial ability, executive functioning, semantic fluency, and verbal and visual learning and memory. Consistent with a DLB diagnosis, her cognitive symptoms emerged concurrently with motor symptom onset. There is also evidence of significant visuospatial and executive difficulties, as well as previously reported reduplicative paramnesia, confusion, and weekly fully-formed hallucinations. Additionally, there is evidence of concurrent parkinsonism's such as bradykinesia, rigidity, hypophonia, and tremor. The constellation of symptoms reported by the patient, combined with the results of neuropsychological assessment, was highly congruent with prototypical DLB; however, lack of proper normative data to accurately assess for decline in her scores led to significant caution in interpretation of her neuropsychological performance. This case demonstrates the importance of proper normative data in diverse populations and the role of neuropsychological evaluations in specific cultural contexts.

The clinical phenotype of psychiatric-onset prodromal dementia with Lewy bodies: a scoping review

BackgroundRecent consensus research criteria have identified a ‘psychiatric onset’ form of prodromal dementia with Lewy bodies (DLB) characterised by prominent late-onset psychiatric symptoms. Although recognised as important to raise the index of diagnostic suspicion, evidence regarding this cohort was deemed too limited to impose formal criteria. We reviewed the published literature on psychiatric-onset DLB to identify key clinical characteristics and evidence gaps to progress our understanding of this entity.MethodsMedline, PubMed and Embase were searched for relevant articles containing longitudinal follow-up of patients initially presenting with a psychiatric illness who subsequently developed DLB according to the diagnostic criteria available at the time.ResultsTwo cohort studies (18 and 21 patients) along with 12 case series (13 cases) were identified totalling 52 patients (63% female). Initial psychiatric presentation occurred at a mean of 63 years (range 53–88), with depression being the most frequently reported psychiatric presentation (88%). Psychotic presentations were less common on presentation (11%) but became more prevalent throughout the prodromal period before the diagnosis of DLB (83%). Relapses of the psychiatric disease were common occurring in 94% (32/34) of patients. Parkinsonism, cognitive fluctuations, visual hallucinations, and REM sleep behaviour disorder were uncommonly reported at initial presentation (3.8%).ConclusionsPsychiatric-onset DLB is characterized by a female predominant relapsing–remitting psychiatric illness presenting with affective symptoms but later developing psychotic features prior to the onset of DLB. Additional prospective studies including other neurodegenerative cohorts with harmonised assessments are required to inform definitive diagnostic criteria for this condition.

Combined 18F-FDG PET-CT markers in dementia with Lewy bodies.

18F-Fluoro-deoxyglucose-positron emission tomography (FDG-PET) is a supportive biomarker in dementia with Lewy bodies (DLB) diagnosis and its advanced analysis methods, including radiomics and machine learning (ML), were developed recently. The aim of this study was to evaluate the FDG-PET diagnostic performance in predicting a DLB versus Alzheimer's disease (AD) diagnosis. FDG-PET scans were visually and semi-quantitatively analyzed in 61 patients. Radiomics and ML analyses were performed, building five ML models: (1) clinical features; (2) visual and semi-quantitative PET features; (3) radiomic features; (4) all PET features; and (5) overall features. At follow-up, 34 patients had DLB and 27 had AD. At visual analysis, DLB PET signs were significantly more frequent in DLB, having the highest diagnostic accuracy (86.9%). At semi-quantitative analysis, the right precuneus, superior parietal, lateral occipital, and primary visual cortices showed significantly reduced uptake in DLB. The ML model 2 had the highest diagnostic accuracy (84.3%). FDG-PET is a valuable tool in DLB diagnosis, having visual and semi-quantitative analyses with the highest diagnostic accuracy at ML analyses.

Clinical characteristics of pathological confirmed prodromal dementia with Lewy bodies

IntroductionMisdiagnosis rate of Dementia with Lewy Bodies (DLB) remains high despite being second most common cause of neurodegenerative dementia. To date, understanding of clinical profile of pathologically confirmed prodromal DLB remains limited. The main objective of this study was to describe and compare it with pathologically confirmed Alzheimer's disease (AD). MethodsWe accessed the National Alzheimer's Coordinating Center database from 2005 to December 2022 data freeze and included 111 and 501 prodromal DLB and AD patients respectively. First visit data was analyzed. ResultsClinician-determined memory impairment is common in prodromal DLB (>70%) but associated with higher risk for AD diagnosis (OR 0.355, p = 0.0003). DLB had a higher proportion of non-amnestic mild cognitive impairment (MCI) diagnoses but statistically insignificance in differentiating the two. Inattention (OR 2.273, p = 0.0015), and neuropsychiatric features, such as visual hallucinations (OR 11.98, p < 0.0001), depressed mood (OR1.709, p = 0.0292), apathy (1.824, p = 0.0345), and night/REM sleep behaviors, are associated with DLB diagnosis. Hallucinations are infrequent (7–11%). Motor symptoms, particularly gait disorders (OR 4.570, p < 0.001), falls (OR3.939, p = 0.0003), tremors (OR2.237, p = 0.0154), slowness (OR3.573, p < 0.0001), and parkinsonism signs (OR2.443, p < 0.0001), are common. 32% showed no parkinsonism during initial presentation. Neuropsychological examination revealed less impaired memory and language but impaired executive function in DLB. ConclusionIn clinical practice, it is important to note that memory symptoms although being higher risk associated with AD diagnosis, are prominent in prodromal DLB. Psychosis is infrequent, and non-amnestic MCI is not necessarily associated with higher risk of DLB diagnosis. A careful clinical approach is key to improve the diagnosis of prodromal DLB.

Plasma Phosphorylated Tau181 and Amyloid-β42 in Dementia with Lewy Bodies Compared with Alzheimer's Disease and Cognitively Healthy People.

Increasing evidence illustrates the value of plasma biomarkers of Alzheimer's disease (AD) to screen for and identify dementia with Lewy bodies (DLB). However, confirmatory studies are needed to demonstrate the feasibility of these markers. To determine the feasibility of plasma tau phosphorylated at threonine 181 (p-tau181) and amyloid-β42 (Aβ42) as potential biomarkers to differentiate AD and DLB. We evaluated plasma samples from patients with DLB (n = 47) and AD (n = 55) and healthy controls (HCs, n = 30), using ELISAs to measure p-tau181 and Aβ42. Additionally, we examined neuropsychological assessment scores for participants. The plasma biomarkers were investigated for correlation with neuropsychological assessments and discriminant ability to identify DLB. Plasma p-tau181 was significantly lower in DLB than in AD and HCs. Plasma Aβ42 was significantly higher in DLB than in AD but lower in DLB than in HCs. We found good correlations between plasma Aβ42 and neuropsychological scores in the whole cohort, while p-tau181 was associated with cognitive status in DLB. In the distinction between DLB and HCs, plasma p-tau181 and Aβ42 showed similar accuracy, while Aβ42 showed better accuracy than p-tau181 in discriminating DLB and AD. In a single-center clinical cohort, we confirmed the high diagnostic value of plasma p-tau181 and Aβ42 for distinguishing patients with DLB from HCs. Plasma Aβ42 improved the differential diagnosis of DLB from AD.

Late Presentation of Chronic Traumatic Encephalopathy in a Former Association Football Player.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease characterized by widespread accumulation of hyperphosphorylated tau that typically occurs in people who have suffered repetitive head impacts. To date, very few cases have been reported in association football players. To describe the clinicopathological features of a case of CTE in an 84-year-old former football player who was clinically diagnosed as having dementia with Lewy bodies (DLB). A retrospective review of the patient's primary care and hospital medical records was performed along with a comprehensive neuropathological examination. This patient presented at age 84 with symmetrical parkinsonism and cognitive impairment that was exacerbated by prochlorperazine. His condition was rapidly progressive with recurrent falls within 1 year. Other features included headaches, depression, anxiety, suicidal ideation, disturbed sleep and aggression. He received a clinical diagnosis of DLB and died approximately 2 years after the onset of symptoms. A post-mortem examination revealed stage 4 CTE. While the contemporaneous onset of parkinsonism and cognitive symptoms in the context of possible neuroleptic sensitivity is suggestive of DLB, the additional symptoms of aggressive behavior, depression and suicidality in a former football player are consistent with the neuropathological diagnosis of CTE. This case, which is notable for the late presentation, demonstrates that CTE may masquerade as other dementias and highlights the importance of seeking a history of repetitive head impacts.

Clinical validation of the cingulate island sign visual rating scale in dementia with Lewy bodies

IntroductionThe cingulate island sign (CIS) is a metabolic pattern on [18F]fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) associated with dementia with Lewy bodies (DLB). The aim of this study was to validate the visual CIS rating scale (CISRs) for the diagnosis of DLB and to explore the clinical correlates. MethodsThis single-center study included 166 DLB patients and 161 patients with Alzheimer's disease (AD). The CIS on [18F]FDG-PET scans was rated using the CISRs independently by three blinded raters. ResultsThe optimal cut-off to differentiate DLB from AD was a CISRs score ≥ 1 (sensitivity = 66%, specificity = 84%) whereas a CISRs score ≥ 2 (sensitivity = 58%, specificity = 92%) was optimal to differentiate amyloid positive DLB (n = 43 (82.7%)) and AD. To identify DLB with abnormal (n = 53 (72.6%)) versus normal (n = 20 (27.4%)) dopamine transporter imaging, a CISRs cut-off of 4 had a specificity of 95%. DLB with a CISRs score of 4 performed significantly better in tests on free verbal recall and picture based cued recall, but worse on processing speed compared to DLB with a CISRs score of 0. ConclusionThis study confirms the CISRs as a valid marker for the diagnosis of DLB with a high specificity and a lower, but acceptable, sensitivity. Concomitant AD pathology does not influence diagnostic accuracy of the CISRs. In DLB patients, presence of CIS is associated with relative preserved memory function and impaired processing speed.

Pacemaker Implants and Their Influence on the Daily Life of Patients with Dementia with Lewy Bodies: A Qualitative Case Study.

Dementia with Lewy bodies (DLB) is an incurable form of dementia associated with detriments to the daily life of patients and carers from their family. Symptoms of orthostatic hypotension, syncope, and falls are supportive of DLB diagnosis. These symptoms may also be present among people with sick sinus syndrome (SSS), and subsequent pacemaker treatment to manage bradyarrhythmia is associated with improved cognitive function. The prevalence of SSS seems to be higher among people with underlying Lewy body pathology compared to the general age-matched population (5.2% vs. 0.17%). To our knowledge, how people with DLB and their family carers may experience pacemaker treatment to manage bradyarrhythmia has not been previously reported. Therefore, the aim of this study was to explore how people with DLB experience daily life following a pacemaker implant to manage associated symptoms of bradyarrhythmia. A qualitative case study design was used. Two men with DLB and their spouse carers were repeatedly interviewed as a dyad within 1year following implant of a dual-chamber rate-adaptive (DDD-CLS) pacemaker to manage SSS in the men. Content analysis was used to assess the qualitative interview data collected. Three categories emerged: (1) gaining control, (2) maintaining a social life, and (3) being influenced by concurrent diseases. Less syncope/falls and remote pacemaker monitoring increased a sense of control in everyday life, while perceived physical and/or cognitive improvements influenced social participation. The men were still affected by concurrent diseases, which continuously influenced each couple's daily life. Identifying and managing concurrent bradyarrhythmia through a pacemaker implant could improve well-being for people with DLB.

Clinical trials in dementia with Lewy bodies: the evolving concept of co-pathologies, patient selection and biomarkers.

Currently, no disease modifying therapies (DMTs) have been approved for use in dementia with Lewy bodies (DLB). Clinical trials face difficulties due to the clinical and neuropathological heterogeneity of the condition with a diverse array of neuropathogenic mechanisms contributing to the clinical phenotype. The purpose of this review is to describe how recent advances in the development of biofluid biomarkers may be used in clinical trials to tackle some of these challenges. Biomarkers are essential both to support the accurate diagnosis of DLB and to delineate the influence of coexisting pathologies. Recent advances in the development of α-synuclein seeding amplification assays (SAA) allow accurate identification of α-synuclein from the prodromal stages in DLB. Additionally, validation of plasma phosphorylated tau assays in DLB is ongoing and offers an accessible biomarker to indicate the existence of AD co-pathology. Use of biomarkers for diagnosis and group stratification in clinical trials of DLB is growing and likely to be of increasing importance in the future. In vivo biomarkers can enhance patient selection in clinical trials allowing greater diagnostic accuracy, a more homogeneous trial population, and stratification by co-pathology to create subgroups most likely to derive therapeutic benefit from DMTs.

β-Amyloid Load on PET Along the Continuum of Dementia With Lewy Bodies.

β-Amyloid (Aβ) plaques can co-occur with Lewy-related pathology in patients with dementia with Lewy bodies (DLB), but Aβ load at prodromal stages of DLB still needs to be elucidated. We investigated Aβ load on PET throughout the DLB continuum, from an early prodromal stage of isolated REM sleep behavior disorder (iRBD) to a stage of mild cognitive impairment with Lewy bodies (MCI-LB), and finally DLB. We performed a cross-sectional study in patients with a diagnosis of iRBD, MCI-LB, or DLB from the Mayo Clinic Alzheimer Disease Research Center. Aβ levels were measured by Pittsburgh compound B (PiB) PET, and global cortical standardized uptake value ratio (SUVR) was calculated. Global cortical PiB SUVR values from each clinical group were compared with each other and with those of cognitively unimpaired (CU) individuals (n = 100) balanced on age and sex using analysis of covariance. We used multiple linear regression testing for interaction to study the influences of sex and APOE ε4 status on PiB SUVR along the DLB continuum. Of the 162 patients, 16 had iRBD, 64 had MCI-LB, and 82 had DLB. Compared with CU individuals, global cortical PiB SUVR was higher in those with DLB (p < 0.001) and MCI-LB (p = 0.012). The DLB group included the highest proportion of Aβ-positive patients (60%), followed by MCI-LB (41%), iRBD (25%), and finally CU (19%). Global cortical PiB SUVR was higher in APOE ε4 carriers compared with that in APOE ε4 noncarriers in MCI-LB (p < 0.001) and DLB groups (p = 0.049). Women had higher PiB SUVR with older age compared with men across the DLB continuum (β estimate = 0.014, p = 0.02). In this cross-sectional study, levels of Aβ load was higher further along the DLB continuum. Whereas Aβ levels were comparable with those in CU individuals in iRBD, a significant elevation in Aβ levels was observed in the predementia stage of MCI-LB and in DLB. Specifically, APOE ε4 carriers had higher Aβ levels than APOE ε4 noncarriers, and women tended to have higher Aβ levels than men as they got older. These findings have important implications in targeting patients within the DLB continuum for clinical trials of disease-modifying therapies.

Validation of the Turkish version of the Lewy body composite risk score

The Lewy Body Composite Risk Score (LBCRS) has been developed to increase the sensitivity and specificity of the diagnosis attributable to Lewy body pathology outside of specialty centers. We aimed to assess the validity and reliability of the Turkish version of the LBCRS in patients with dementia with Lewy Bodies (DLB) and investigate the discriminative power of the test in Turkish patients with Alzheimer’s disease (AD) and DLB, and control group. The sample population (n = 512) comprised DLB (n = 113), DLB-Mild Cognitive Impairment (MCI)(n = 12), AD (n = 42), AD-MCI (n = 21), and control group (n = 324). A significant group difference was observed in the Turkish version of the LBCRS scores of the five groups (p < .001). The Cronbach’s α value was 0.82 (95% CI: 0.799–0.868). The test–retest reliability score of the scale was r = 0.94 and p < .001. The subscales of the LBCRS (motor and nonmotor subdomains of the disease) were determined to explain 65.961% of the total variance with an eigenvalue >1. In patients with DLB, the cutoff score of ≥3 showed sensitivity (92%) and specificity (81%) (area under the curve [AUC] = 0.883, 95% CI: 0.815–0.951), p < .001) compared with the AD. Compared to the control group, the cutoff score of ≥3 showed a sensitivity of 98% and specificity of 97% (AUC = 0.994, 95% CI: 0.989–0.999, p < .001). The Turkish version of LBCRS permits accurate diagnosis of DLB with high sensitivity and specificity. Also, it can be useful to inform the caregivers regarding the course of the disease during the follow-up.

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)