MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies

Inguanzo, Anna; Poulakis, Konstantinos; Mohanty, Rosaleena; Schwarz, Christopher G.; Przybelski, Scott A.; Diaz-Galvan, Patricia; Lowe, Val J.; Boeve, Bradley F.; Lemstra, Afina W.; Beek, Marleen van de; Flier, Wiesje Van der; Barkhof, Frederik; Blanc‬, ‪Frederic; Sousa, Paulo Loureiro de; Philippi, Nathalie; Crétin, Benjamin; Demuynck, Catherine; Nedelská, Zuzana; Hort, Jakub; Segura, Bàrbara; Junqué, Carme; Oppedal, Ketil; Aarsland, Dag; Westman, Eric; Kantarci, Kejal; Ferreira, Daniel

doi:10.1038/s41531-023-00448-6

Cited by 11 publications

(16 citation statements)

References 46 publications

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“…Longitudinal patterns of atrophy could improve our understanding of the role of sex along the disease course. In this context, the role of sex in DLB heterogeneity should be elucidated, for example aligning with recent studies on disease subtypes based on MRI measures (40).…”

Section: Discussionmentioning

confidence: 87%

“…This avenue is of further interest to advance our current knowledge about the less investigated 'olfactory bulb only' pathological subtype of DLB (39). We recently showed that atrophy in olfactory cortex is one of the brain regions that best discriminates between a DLB subtype with widespread predominant cortical atrophy and a DLB subtype with predominant fronto-occipital atrophy (40). Hence, the interplay between sex, age, and heterogeneity in regional atrophy and clinical phenotype in DLB deserves future investigation.…”

Section: Discussionmentioning

confidence: 98%

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Sex differences in brain atrophy in dementia with Lewy bodies

Oltra

Habich

Schwarz

et al. 2023

Preprint

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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.

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Section: Discussionmentioning

confidence: 87%

Section: Discussionmentioning

confidence: 98%

Sex differences in brain atrophy in dementia with Lewy bodies

Oltra

Habich

Schwarz

et al. 2023

Preprint

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“…13 Findings thus support the claim that occipital damage may be an early signature of the whole DLB spectrum. 14 We acknowledge that this study has some limitations, mainly related to its cross-sectional single-center design and limited sample size. One limitation of the study relies on the age difference between patients and controls; all the analyses were conducted adjusting for age effect, but the sample was limited in size for a proper matching without constraining the statistical model.…”

Section: Discussionmentioning

confidence: 94%

Occipital atrophy signature in prodromal Lewy bodies disease

Galli,

Pilotto,

Chiarini

et al. 2023

Alz & Dem Diag Ass & Dis Mo

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INTRODUCTIONDementia 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.

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“…A number of recent studies have searched for endophenotypes within DLB to delineate the influence of the various neuropathologies [39,40]. Disentangling the influence of respective neuropathies to allow a precision medicine approach is of increasing importance with the advent of DMTs aiming to target specific neuropathological changes.…”

Section: Challenges In Clinical Trialsmentioning

confidence: 99%

Section: Neuropathological Heterogeneitymentioning

confidence: 99%

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

Gibson

Abdelnour

Chong

et al. 2023

Current Opinion in Neurology

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Purpose of review 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. Recent findings 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. Summary 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.

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MRI data-driven clustering reveals different subtypes of Dementia with Lewy bodies

Cited by 11 publications

References 46 publications

Sex differences in brain atrophy in dementia with Lewy bodies

Sex differences in brain atrophy in dementia with Lewy bodies

Occipital atrophy signature in prodromal Lewy bodies disease

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

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