Jonathan Graff-Radford1, Jeremiah Aakre2, Rodolfo Savica1, Bradley Boeve1, Walter K Kremers2, Tanis J Ferman3, David T Jones4, Kejal Kantarci5, David S Knopman1, Dennis W Dickson6, Walter A Kukull7, Ronald C Petersen1. 1. Department of Neurology, Mayo Clinic, Rochester, Minnesota. 2. Department of Health Sciences Research, Mayo Clinic and Foundation, Rochester, Minnesota. 3. Department of Psychiatry and Psychology, Mayo Clinic, Jacksonville, Florida. 4. Department of Neurology, Mayo Clinic, Rochester, Minnesota4Department of Radiology, Mayo Clinic, Jacksonville, Florida. 5. Department of Radiology, Mayo Clinic, Jacksonville, Florida. 6. Department of Pathology and Laboratory Medicine, Mayo Clinic, Jacksonville, Florida. 7. National Alzheimer's Coordinating Center, Department of Epidemiology, University of Washington, Seattle.
Abstract
IMPORTANCE: Although patients with dementia with Lewy bodies (DLB) have shorter disease duration than patients with Alzheimer disease dementia, little is known about which factors influence disease duration among patients with DLB. OBJECTIVE: To identify pathologic correlates of disease duration in participants with Lewy body disease (LBD). DESIGN, SETTING, AND PARTICIPANTS: This observational study, performed from September 1, 2005, to June 1, 2015, using the National Alzheimer's Coordinating Center database included 807 participants with transitional or diffuse LBD. MAIN OUTCOMES AND MEASURES: The study used Braak neurofibrillary tangle (NFT) stage, frequency of neuritic plaques, and LBD stage to determine whether pathologic variables are associated with disease duration. RESULTS: This study included 807 participants with transitional or diffuse LBD (mean [SD] age, 70.0 [9.9] at the onset of cognitive decline and 79.2 [9.8] years at death; 509 male [63.1%]). Shorter disease duration from cognitive symptom onset to death was observed in men (β, -0.73; 95% CI, -1.33 to -0.14; P = .02) and in those with a later age at onset (β, -0.11; 95% CI, -0.14 to -0.08; P < .001). Diffuse (neocortical) LBD was associated with shorter disease duration compared with transitional LBD (β, -1.52; 95% CI, -2.11 to -0.93; P < .001). Braak NFT stage and the presence of neuritic plaques were not significantly associated with differences in disease duration. CONCLUSIONS AND RELEVANCE: Diffuse LBD was associated with shorter disease duration compared with transitional LBD, and this effect is independent of Braak NFT stage or extent of neuritic plaque disease. Identifying antemortem biomarkers of LBD stage may provide important prognostic information to patients with DLB.
IMPORTANCE: Although patients with dementia with Lewy bodies (DLB) have shorter disease duration than patients with Alzheimer disease dementia, little is known about which factors influence disease duration among patients with DLB. OBJECTIVE: To identify pathologic correlates of disease duration in participants with Lewy body disease (LBD). DESIGN, SETTING, AND PARTICIPANTS: This observational study, performed from September 1, 2005, to June 1, 2015, using the National Alzheimer's Coordinating Center database included 807 participants with transitional or diffuse LBD. MAIN OUTCOMES AND MEASURES: The study used Braak neurofibrillary tangle (NFT) stage, frequency of neuritic plaques, and LBD stage to determine whether pathologic variables are associated with disease duration. RESULTS: This study included 807 participants with transitional or diffuse LBD (mean [SD] age, 70.0 [9.9] at the onset of cognitive decline and 79.2 [9.8] years at death; 509 male [63.1%]). Shorter disease duration from cognitive symptom onset to death was observed in men (β, -0.73; 95% CI, -1.33 to -0.14; P = .02) and in those with a later age at onset (β, -0.11; 95% CI, -0.14 to -0.08; P < .001). Diffuse (neocortical) LBD was associated with shorter disease duration compared with transitional LBD (β, -1.52; 95% CI, -2.11 to -0.93; P < .001). Braak NFT stage and the presence of neuritic plaques were not significantly associated with differences in disease duration. CONCLUSIONS AND RELEVANCE: Diffuse LBD was associated with shorter disease duration compared with transitional LBD, and this effect is independent of Braak NFT stage or extent of neuritic plaque disease. Identifying antemortem biomarkers of LBD stage may provide important prognostic information to patients with DLB.
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