Novel clinicopathological characteristics differentiate dementia with Lewy bodies from Parkinson’s disease dementia

Hansen, Daniela; Ling, Helen; Lashley, Tammaryn; Foley, Jennifer A.; Strand, Catherine; Eid, Thamir M.; Holton, Janice L.; Warner, Thomas T.

doi:10.1111/nan.12648

Cited by 22 publications

(16 citation statements)

References 77 publications

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“…Here the amount of Aβ deposits in the brain should be much higher than in the PDD. The degree of Alzheimer's pathology, its magnitude within the brain tissue, and the presence of cerebral amyloid angiopathy is probably the most significant pathological difference between these two phenotypes, PDD and DLB 5,10,[39][40][41] . Nevertheless, there is no sharp pathological border between these two pictures, it is a smooth transition from the "pure" PD Lewy pathology to the "mixed" DLB pathology.…”

Section: Blurred Differences Between Pdd and Dlbmentioning

confidence: 99%

Lewy body disease or diseases with Lewy bodies?

Menšíková

Matěj

Colosimo

et al. 2022

npj Parkinsons Dis.

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The current nosological concept of α-synucleinopathies characterized by the presence of Lewy bodies (LBs) includes Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB), for which the term “Lewy body disease” (LBD) has recently been proposed due to their considerable clinical and pathological overlap. However, even this term does not seem to describe the true nature of this group of diseases. The subsequent discoveries of α-synuclein (αSyn), SNCA gene, and the introduction of new immunohistochemical methods have started intensive research into the molecular-biological aspects of these diseases. In light of today’s knowledge, the role of LBs in the pathogenesis and classification of these nosological entities remains somewhat uncertain. An increasingly more important role is attributed to other factors as the presence of various LBs precursors, post-translational αSyn modifications, various αSyn strains, the deposition of other pathological proteins (particularly β-amyloid), and the discovery of selective vulnerability of specific cells due to anatomical configuration or synaptic dysfunction. Resulting genetic inputs can undoubtedly be considered as the main essence of these factors. Molecular–genetic data indicate that not only in PD but also in DLB, a unique genetic architecture can be ascertained, predisposing to the development of specific disease phenotypes. The presence of LBs thus remains only a kind of link between these disorders, and the term “diseases with Lewy bodies” therefore results somewhat more accurate.

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Section: Blurred Differences Between Pdd and Dlbmentioning

confidence: 99%

Lewy body disease or diseases with Lewy bodies?

Menšíková

Matěj

Colosimo

et al. 2022

npj Parkinsons Dis.

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“…Thus, we are still referring to the “one-year rule”, similar to that used to separate DLB and PDD, to distinguish some clinical MCI-LB and PD-MCI cases if the onset and order of parkinsonism and cognitive impairment can be clearly established [ 25 ]. There were significant neuropathological differences between DLB and PDD, as DLB had greater severity of CAA than PDD [ 49 ] and showed higher seeding activity of disease-associated alpha-synuclein than PD [ 50 ]. Nevertheless, the diagnosis was based on clinical findings rather than postmortem finding, which might cause diagnostic bias in this study.…”

Section: Discussionmentioning

confidence: 99%

Sex differences in clinical cognitive impairment with Lewy bodies: a Chinese multicenter study

et al. 2022

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Background Research on sex ratios of Lewy body dementia is controversial, established in small samples, and rarely focused on prodromal stage. The objective is to investigate the clinical sex ratios (men/women) and their associations with clinical features among individuals with mild cognitive impairment with Lewy bodies (MCI-LB), dementia with Lewy bodies (DLB), Parkinson’s disease with mild cognitive impairment (PD-MCI), and Parkinson’s disease with dementia (PDD) in China. Methods We conducted a multicenter cohort study, including 1038 individuals with probable MCI-LB, DLB, PD-MCI, or PDD diagnosis from 22 memory clinics in China from January 2018 to March 2022, and recorded their demographic and clinical data by reviewing medical records. Descriptive and regression analyses were used to calculate the sex ratio (men/women), and its associations with demographic and clinical data. Results In this study, men comprised 35.14% (men/women sex ratio = 0.54) for MCI-LB, 46.72% (men/women sex ratio = 0.88) for DLB, 63.56% (men/women sex ratio = 1.74) for PD-MCI, and 52.40% (men/women sex ratio = 1.10) for PDD. Sex ratios roughly increased with age. Men had more parkinsonism (p = 0.000) and less fluctuating cognition (p = 0.024) in MCI-LB, and those with PD-MCI had more RBD (p = 0.001). Women with PD-MCI had lower MMSE scores (β ± standard error = − 1.24 ± 0.58, p = 0.04), more irritability (0.95 ± 0.46, p = 0.04) and fluctuating cognition (− 3.41 ± 1.31, p = 0.01), and less parkinsonism (− 2.10 ± 0.97, p = 0.03) than men after adjusting for demographic and cardiometabolic conditions. Conclusion There were more women in DLB and MCI-LB, and more men in PD-MCI and PDD. The sex distribution, demographic, and clinical characteristics differed, which strengthened the independence and heterogeneity of the four diseases, and indicated sex-sensitive strategies for management of dementia necessary.

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“…Some studies distinguished between DLB with coexisting AD pathology and DLB without. The prevalence and severity of CAA in LBD appeared to be increased compared to participants with PD without dementia [47,62,[81][82][83][84][85]. The prevalence of CAA ranged from 6% to 100% in LBD, 58%-100% in AD and 0%-50% in controls (Table 4).…”

Section: Cereb R Al Amyloid Ang Iopathy (C a A )mentioning

confidence: 94%

The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson's disease dementia

Hijazi

Yassi

O’Brien

et al. 2022

Euro J of Neurology

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Background and purpose Lewy body dementia (LBD), including dementia with Lewy bodies (DLB) and Parkinson's disease dementia, is a common form of neurodegenerative dementia. The frequency and influence of comorbid cerebrovascular disease is not understood but has potentially important clinical management implications. Methods A systematic literature search was conducted (MEDLINE and Embase) for studies including participants with DLB and/or Parkinson's disease dementia assessing cerebrovascular lesions (imaging and pathological studies). They included white matter changes, cerebral amyloid angiopathy, cerebral microbleeds (CMB), macroscopic infarcts, microinfarcts and intracerebral haemorrhage. Results Of 4411 articles, 63 studies were included. Cerebrovascular lesions commonly studied included white matter changes (41 studies) and CMB (18 studies). There was an increased severity of white matter changes on magnetic resonance imaging (visualized as white matter hyperintensities), but not neuropathology, in LBD compared to Parkinson's disease without dementia and age‐matched controls. CMB prevalence in DLB was highly variable but broadly similar to Alzheimer's disease (0%–48%), with a lobar predominance. No relationship was found between large cortical or small subcortical infarcts or intracerebral haemorrhage and the presence of LBD. Conclusion The underlying mechanisms of white matter hyperintensities in LBD require further exploration, as their increased severity in LBD was not supported by neuropathological examination of white matter. CMB in LBD had a similar prevalence to Alzheimer's disease. There is a need for larger studies assessing the influence of cerebrovascular lesions on clinical symptoms, disease progression and outcomes.

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Novel clinicopathological characteristics differentiate dementia with Lewy bodies from Parkinson’s disease dementia

Cited by 22 publications

References 77 publications

Lewy body disease or diseases with Lewy bodies?

Lewy body disease or diseases with Lewy bodies?

Sex differences in clinical cognitive impairment with Lewy bodies: a Chinese multicenter study

The influence of cerebrovascular disease in dementia with Lewy bodies and Parkinson's disease dementia

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