Pietro Tiraboschi1, Johannes Attems2, Alan Thomas2, Andrew Brown2, Evelyn Jaros2, Debbie J Lett2, Maria Ossola2, Robert H Perry2, Lynne Ramsay2, Lauren Walker2, Ian G McKeith2. 1. From the Division of Neurology V and Neuropathology (P.T.), IRCCS Foundation, Carlo Besta Neurologic Institute, Milan, Italy; Institute for Aging and Health (J.A., A.T., A.B., E.J., D.J.L., R.H.P., L.R., L.W., I.G.M.), Wolfson Research Center, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne, UK; and Division of Neurology and Neurophysiology (M.O.), Azienda Ospedaliera di Busto Arsizio, Presidio di Tradate, Italy. pietro.tiraboschi@istituto-besta.it. 2. From the Division of Neurology V and Neuropathology (P.T.), IRCCS Foundation, Carlo Besta Neurologic Institute, Milan, Italy; Institute for Aging and Health (J.A., A.T., A.B., E.J., D.J.L., R.H.P., L.R., L.W., I.G.M.), Wolfson Research Center, Campus for Aging and Vitality, Newcastle University, Newcastle upon Tyne, UK; and Division of Neurology and Neurophysiology (M.O.), Azienda Ospedaliera di Busto Arsizio, Presidio di Tradate, Italy.
Abstract
OBJECTIVE: To investigate whether an increasing load of β-amyloid and/or neuritic plaques influences the phenotype, and thus the clinical diagnostic accuracy, of dementia with Lewy bodies (DLB). METHODS: A series of 64 subjects with autopsy-proven DLB was studied. Last diagnosis before death was used to determine the clinical diagnostic accuracy of DLB in relation to Lewy body distribution and extent of Alzheimer β-amyloid and/or neuritic pathology. DLB pathologic diagnosis was made according to consensus criteria, using α-synuclein immunostaining for Lewy body identification. β-Amyloid immunostaining was used for quantifying β-amyloid deposits. The Consortium to Establish a Registry for Alzheimer's Disease criteria and Braak stage were applied for semiquantitative grading of neuritic plaque and neurofibrillary tangle pathology. RESULTS: Overall clinical diagnostic accuracy for the entire DLB cohort was high (80%), reflecting the high prevalence of core clinical features (fluctuations [81%], parkinsonism [77%], visual hallucinations [70%]). Lower frequencies of core clinical features of DLB, resulting in lower accuracy of its clinical diagnosis, were associated with decreasing Lewy body distribution (p < 0.0001) and with increasing neuritic plaque pathology (p = 0.035), but not with the number of β-amyloid plaque deposits. CONCLUSIONS: The likelihood of occurrence of the DLB clinical syndrome is positively related to the extent of Lewy body pathology and negatively related to the severity of Alzheimer neuritic pathology, while β-amyloid load has no effect.
OBJECTIVE: To investigate whether an increasing load of β-amyloid and/or neuritic plaques influences the phenotype, and thus the clinical diagnostic accuracy, of dementia with Lewy bodies (DLB). METHODS: A series of 64 subjects with autopsy-proven DLB was studied. Last diagnosis before death was used to determine the clinical diagnostic accuracy of DLB in relation to Lewy body distribution and extent of Alzheimer β-amyloid and/or neuritic pathology. DLB pathologic diagnosis was made according to consensus criteria, using α-synuclein immunostaining for Lewy body identification. β-Amyloid immunostaining was used for quantifying β-amyloid deposits. The Consortium to Establish a Registry for Alzheimer's Disease criteria and Braak stage were applied for semiquantitative grading of neuritic plaque and neurofibrillary tangle pathology. RESULTS: Overall clinical diagnostic accuracy for the entire DLB cohort was high (80%), reflecting the high prevalence of core clinical features (fluctuations [81%], parkinsonism [77%], visual hallucinations [70%]). Lower frequencies of core clinical features of DLB, resulting in lower accuracy of its clinical diagnosis, were associated with decreasing Lewy body distribution (p < 0.0001) and with increasing neuritic plaque pathology (p = 0.035), but not with the number of β-amyloid plaque deposits. CONCLUSIONS: The likelihood of occurrence of the DLB clinical syndrome is positively related to the extent of Lewy body pathology and negatively related to the severity of Alzheimer neuritic pathology, while β-amyloid load has no effect.
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