Bonanni, Laura

Abstract BACKGROUND We sought to characterize the cognitive profile among individuals with mild cognitive impairment with Lewy bodies (MCI‐LB) to help guide future clinical criteria. METHODS Systematic review and meta‐analysis included MCI‐LB studies with cognitive data from PubMed, Embase, Web of Science, and PsycINFO (January 1990 to March 2023). MCI‐LB scores were compared to controls, MCI due to Alzheimer's disease (MCI‐AD), and dementia with Lewy bodies (DLB) groups with random‐effects models. RESULTS We included 26 studies and 2823 participants. Across all domains, the MCI‐LB group performed worse than controls and better than DLB. Compared to MCI‐AD, the MCI‐LB group performed worse in attention/processing speed ( g = –0.24, 95% confidence interval [CI]: –0.35, –0.12), attention/executive ( g = –0.42, 95% CI: –0.56, –0.28); better in verbal immediate recall ( g = 0.37; 95% CI: 0.15, 0.59) and delayed memory ( g = 0.40; 95% CI: 0.22, 0.58). DISCUSSION The cognitive profiles in MCI‐LB and MCI‐AD are consistent with established profiles in DLB and AD. Neuropsychological assessment may be helpful in differential diagnosis, even in early disease states. Highlights We performed a systematic review and meta‐analysis for cognition in mild cognitive impairment with Lewy bodies (MCI‐LB). Compared to MCI due to Alzheimer's disease (MCI‐AD), MCI‐LB had worse attention, executive function, and processing speed. Compared to MCI‐AD, MCI‐LB had better verbal immediate and delayed recall. The MCI‐LB group was worse on all cognitive domains than controls, and better than dementia with Lewy bodies. Studies used different tests and there is a need for global efforts for harmonization.

AbstractBackgroundProdromal dementia with Lewy bodies (DLB) research criteria were recently published and further work is needed to characterize the neuropsychological profile and refine clinical criteria. We performed a meta‐analysis to compare the cognitive performance of mild cognitive impairment with Lewy bodies (MCI‐LB) groups to controls, MCI due to Alzheimer’s disease (MCI‐AD), and DLB.MethodFollowing PRISMA guidelines, we searched the literature for 1) English‐language studies on MCI‐LB; 2) published January 1990‐March 2023, 3) with ≥1 standardized cognitive measure; and 4) comparison data from controls, MCI‐AD, and/or DLB. Pooled means with 95% confidence intervals were calculated for demographics. Effect sizes were calculated for group comparisons on cognitive domains. Random effects meta‐analysis models were used for group comparisons.ResultThere were 3440 participants from 27 studies across 10 countries. Mean age did not differ between groups. The percentage of female subjects was lower in the MCI‐LB group than the MCI‐AD group. Mean years of education for the MCI‐LB group was lower than the controls, but similar to MCI‐AD and DLB groups (Table 1). Compared to controls, the MCI‐LB group had lower scores for the global screening, executive function, visuospatial, language, learning, and memory domains. Compared to MCI‐AD, MCI‐LB performed better on learning and delayed recall, but similarly across other domains. Compared to DLB, MCI‐LB had better scores for global screening, executive function, language, and delayed recall (Table 2). Recognition for MCI‐LB vs. MCI‐AD; visuospatial, learning, and recognition for MCI‐LB vs. DLB could not be assessed, as fewer than 3 studies reported this data.ConclusionCognitive measures can help differentiate MCI‐LB from controls and DLB. Neuropsychological measures of learning and memory may be required to discriminate MCI‐LB from MCI‐AD in clinical practice but global screening measure scores appear insufficient in this regard. High heterogeneity across MCI‐LB studies highlights the need for harmonized neuropsychological research protocols.

Abstract INTRODUCTION Sex influences neurodegeneration, but it has been poorly investigated in dementia with Lewy bodies (DLB). We investigated sex differences in brain atrophy in DLB using magnetic resonance imaging (MRI). METHODS We included 436 patients from the European‐DLB consortium and the Mayo Clinic. Sex differences and sex‐by‐age interactions were assessed through visual atrophy rating scales ( n = 327; 73 ± 8 years, 62% males) and automated estimations of regional gray matter volume and cortical thickness ( n = 165; 69 ± 9 years, 72% males). RESULTS We found a higher likelihood of frontal atrophy and smaller volumes in six cortical regions in males and thinner olfactory cortices in females. There were significant sex‐by‐age interactions in volume (six regions) and cortical thickness (seven regions) across the entire cortex. DISCUSSION We demonstrate that males have more widespread cortical atrophy at younger ages, but differences tend to disappear with increasing age, with males and females converging around the age of 75. Highlights Male DLB patients had higher odds for frontal atrophy on radiological visual rating scales. Male DLB patients displayed a widespread pattern of cortical gray matter alterations on automated methods. Sex differences in gray matter measures in DLB tended to disappear with increasing age.

AbstractINTRODUCTIONDementia with Lewy bodies (DLB) is typically characterized by parietal, temporal, and occipital atrophy, but less is known about the newly defined prodromal phases. The objective of this study was to evaluate structural brain alterations in prodromal DLB (p‐DLB) as compared to healthy controls (HC) and full‐blown dementia (DLB‐DEM).METHODSThe study included 42 DLB patients (n = 20 p‐DLB; n = 22 DLB‐DEM) and 27 HC with a standardized neurological assessment and 3‐tesla magnetic resonance imaging. Voxel‐wise analyses on gray‐matter and cortical thickness were implemented to evaluate differences between p‐DLB, DLB‐DEM, and HC.RESULTSp‐DLB and DLB‐DEM exhibited reduced occipital and posterior parieto‐temporal volume and thickness, extending from prodromal to dementia stages. Occipital atrophy was more sensitive than insular atrophy in differentiating p‐DLB and HC. Occipital atrophy correlated to frontotemporal structural damage increasing from p‐DLB to DLB‐DEM.DISCUSSIONOccipital and posterior‐temporal structural alterations are an early signature of the DLB continuum and correlate with a long‐distance pattern of atrophy.

AbstractIntroductionOperationalized research criteria for mild cognitive impairment with Lewy bodies (MCI‐LB) were published in 2020. The aim of this systematic review and meta‐analysis was to review the evidence for the diagnostic clinical features and biomarkers in MCI‐LB set out in the criteria.MethodsMEDLINE, PubMed, and Embase were searched on 9/28/22 for relevant articles. Articles were included if they presented original data reporting the rates of diagnostic features in MCI‐LB.ResultsFifty‐seven articles were included. The meta‐analysis supported the inclusion of the current clinical features in the diagnostic criteria. Evidence for striatal dopaminergic imaging and meta‐iodobenzylguanidine cardiac scintigraphy, though limited, supports their inclusion. Quantitative electroencephalogram (EEG) and fluorodeoxyglucose positron emission tomography (PET) show promise as diagnostic biomarkers.DiscussionThe available evidence largely supports the current diagnostic criteria for MCI‐LB. Further evidence will help refine the diagnostic criteria and understand how best to apply them in clinical practice and research.Highlights A meta‐analysis of the diagnostic features of MCI‐LB was carried out. The four core clinical features were more common in MCI‐LB than MCI‐AD/stable MCI. Neuropsychiatric and autonomic features were also more common in MCI‐LB. More evidence is needed for the proposed biomarkers. FDG‐PET and quantitative EEG show promise as diagnostic biomarkers in MCI‐LB.

Abstract Background and objectives. Sex is an important contributing factor to neuroimaging phenotypes in brain disorders. However, little is known about the contribution of sex differences to the neurodegeneration in dementia with Lewy bodies (DLB). We investigated sex differences in probable DLB patients by using both visual rating scales of lobar atrophy and automated estimations of regional atrophy. Methods. We included 442 probable DLB patients from the European-DLB consortium and the Mayo Clinic who have magnetic resonance imaging (MRI) data available. We assessed sex differences and the sex-by-age interaction in two largely independent samples through visual rating scales of lobar atrophy (n = 333; mean age 73 ± 8 years, 62% males) and automated regional estimations of gray matter (GM) volume and mean cortical thickness (CTh) (n = 165; mean age 69 ± 9 years, 72% males). We used binary logistic regression and ANOVA for statistical analysis. Results. We found a statistically significantly higher likelihood of frontal atrophy measured by the global cortical atrophy-frontal subscale (GCA-F) in males (40% of males had an abnormal GCA-F score versus 29% of females, P-value = 0.006). Using automated estimations, we found smaller GM volumes in 6 cortical regions in males compared with females, as well as smaller GM volume in the entorhinal cortex and thinner olfactory cortices in females, compared with males. The sex-by-age interaction showed statistically significant results in 6 cortical volumes and 7 mean CTh estimations (P-value ≤ 0.05), accentuated in the right middle frontal gyrus (FDR-adjusted P-value = 0.047). These cross-sectional interactions indicated that while females have statistically significantly less atrophy than males at younger ages, differences become non-significant at older ages, with females showing the same level of atrophy than males around the age of 75. Conclusions. This study demonstrates sex differences on brain atrophy in probable DLB. While male DLB patients have a more widespread pattern of cortical atrophy at younger ages, these sex differences tend to disappear with increasing age. Longitudinal studies will help establish these cross-sectional findings and inform on sex and age considerations to the use of MRI in clinical routine, as the field moves towards precision medicine.

Abstract Dementia with Lewy bodies (DLB) research has seen a significant growth in international collaboration over the last three decades. However, researchers face a challenge in identifying large and diverse samples capable of powering longitudinal studies and clinical trials. The DLB research community has begun to focus efforts on supporting the development and harmonization of consortia, while also continuing to forge networks within which data and findings can be shared. This article describes the current state of DLB research collaborations on each continent. We discuss several established DLB cohorts, many of whom have adopted a common framework, and identify emerging collaborative initiatives that hold the potential to expand DLB networks and diversify research cohorts. Our findings identify geographical areas into which the global DLB networks should seek to expand, and we propose strategies, such as the creation of data‐sharing platforms and the harmonization of protocols, which may further potentiate international collaboration.