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Cortical Lewy bodies and Aβ burden are associated with prevalence and timing of dementia in Lewy body diseases

Ruffmann, Claudio; Calboli, Federico CF; Bravi, Ilara; Gveric, Djordje; Curry, Lisa K; de Smith, Adam; Pavlou, Stelios; Buxton, Jessica L; Blakemore, Alexandra IF; Takousis, Petros; Molloy, Sophie; Piccini, Paola; Dexter David T; Roncaroli, Federico; Gentleman, Steve M; Middleton, Lefkos T


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    "doi": "10.1111/nan.12294", 
    "description": "<p>Aims: Our main objective was to determine the neuropathological correlates of dementia in patients with Lewy body disease (LBD). Furthermore, we used data derived from clinical, neuropathological and genetic studies to investigate boundary issues between Dementia with Lewy bodies (DLB) and Parkinson&#39;s disease with (PDD) and without (PDND) dementia.</p>\n\n<p>Methods: One hundred and twenty-one cases with a neuropathological diagnosis of LBD and clinical information on dementia status were included in the analysis (55 PDD, 17 DLB and 49 PDND). We carried out topographical and semi-quantitative assessment of Lewy bodies (LB), A&beta; plaques and tau-positive neuropil threads (NT). The APOE genotype and MAPT haplotype status were also determined.</p>\n\n<p>Results: The cortical LB (CLB) burden was the only independent predictor of dementia (OR: 4.12, <em>P</em> &lt; 0.001). The total cortical A&beta; plaque burden was an independent predictor of a shorter latency to dementia from onset of motor signs (<em>P</em> = 0.001). DLB cases had a higher LB burden in the parietal and temporal cortex, compared to PDD. Carrying at least one APOE \u03f54 allele was associated with a higher cortical LB burden (<em>P</em> = 0.02), particularly in the neocortical frontal, parietal and temporal regions.</p>\n\n<p>Conclusions: High CLB burden is a key neuropathological substrate of dementia in LBD. Elevated cortical LB pathology and A&beta; plaque deposition are both correlated with a faster progression to dementia. The higher CLB load in the temporal and parietal regions, which seems to be a distinguishing feature of DLB, may account for the shorter latency to dementia and could be mediated by the APOE \u03f54 allele.</p>", 
    "license": {
      "id": "CC-BY-4.0"
    }, 
    "title": "Cortical Lewy bodies and A\u03b2 burden are associated with prevalence and timing of dementia in Lewy body diseases", 
    "journal": {
      "volume": "42", 
      "issue": "5", 
      "pages": "436-50", 
      "title": "Neuropathology and Applied Neurobiology"
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    "communities": [
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    "grants": [
      {
        "code": "278850", 
        "links": {
          "self": "https://zenodo.org/api/grants/10.13039/501100000780::278850"
        }, 
        "title": "Imaging of Neuroinflammation in Neurodegenerative Diseases", 
        "acronym": "INMIND", 
        "program": "FP7", 
        "funder": {
          "doi": "10.13039/501100000780", 
          "acronyms": [], 
          "name": "European Commission", 
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    "keywords": [
      "alpha-synuclein", 
      "A\u03b2", 
      "dementia", 
      "Lewy bodies", 
      "neuropathology", 
      "Parkinson's disease"
    ], 
    "publication_date": "2015-12-02", 
    "creators": [
      {
        "affiliation": "Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London and Centro Parkinson, Istituti Clinici di Perfezionamento di Milano, Italy", 
        "name": "Ruffmann, Claudio"
      }, 
      {
        "affiliation": "Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London", 
        "name": "Calboli, Federico CF"
      }, 
      {
        "affiliation": "Division of Brain Sciences, Department of Medicine, Imperial College, London", 
        "name": "Bravi, Ilara"
      }, 
      {
        "affiliation": "Division of Brain Sciences, Department of Medicine, Imperial College, London", 
        "name": "Gveric, Djordje"
      }, 
      {
        "affiliation": "Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London", 
        "name": "Curry, Lisa K"
      }, 
      {
        "affiliation": "Genomics of Common Disease, School of Public Health, Imperial College London and Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA", 
        "name": "de Smith, Adam"
      }, 
      {
        "affiliation": "Genomics of Common Disease, School of Public Health, Imperial College London and Department of Molecular Virology, Cyprus Institute of Neurology and Genetics", 
        "name": "Pavlou, Stelios"
      }, 
      {
        "affiliation": "Section of Investigative Medicine, Department of Medicine, Imperial College London", 
        "name": "Buxton, Jessica L"
      }, 
      {
        "affiliation": "Section of Investigative Medicine, Department of Medicine, Imperial College London", 
        "name": "Blakemore, Alexandra IF"
      }, 
      {
        "affiliation": "Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London", 
        "name": "Takousis, Petros"
      }, 
      {
        "affiliation": "Division of Brain Sciences, Department of Medicine, Imperial College, London", 
        "name": "Molloy, Sophie"
      }, 
      {
        "affiliation": "Division of Brain Sciences, Department of Medicine, Imperial College, London", 
        "name": "Piccini, Paola"
      }, 
      {
        "affiliation": "Division of Brain Sciences, Department of Medicine, Imperial College, London", 
        "name": "Dexter David T"
      }, 
      {
        "affiliation": "Institute of Brain Behaviour and Mental Health, University of Manchester", 
        "name": "Roncaroli, Federico"
      }, 
      {
        "affiliation": "Division of Brain Sciences, Department of Medicine, Imperial College, London", 
        "name": "Gentleman, Steve M"
      }, 
      {
        "affiliation": "Neuroepidemiology and Ageing Research Unit, School of Public Health, Imperial College London", 
        "name": "Middleton, Lefkos T"
      }
    ], 
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      "type": "publication", 
      "title": "Journal article"
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