OBJECTIVES: To examine the extent to which persons with mild cognitive impairment have intermediate levels of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body disease. METHODS: A total of 180 Catholic clergy participating in the Religious Orders Study underwent annual detailed evaluation and brain autopsy. Blocks of midfrontal, superior temporal, medial temporal lobe, inferior parietal, entorhinal cortex, hippocampus, and substantia nigra were paraffin embedded, and sectioned at 6 mum. Cortical neuritic plaques, diffuse plaques, and neurofibrillary tangles were visualized with Bielschowsky silver stain, and counted and summarized to yield a Braak stage, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) diagnosis, National Institute on Aging (NIA)-Reagan diagnosis, and composite measure of AD pathology. The authors recorded the number and location of all gross chronic cerebral infarctions. Lewy bodies were identified with antibodies to alpha-synuclein. Multiple regression analyses were used to examine the relation of AD pathology and cerebral infarctions to clinical diagnosis proximate to death, controlling for age, sex, and education. RESULTS: A total of 37 had mild cognitive impairment, 60 did not have cognitive impairment, and 83 had dementia proximate to death. Nearly all persons had at least some AD pathology. Cerebral infarctions were present in 35.2%, and 15.6% had Lewy body disease. Persons with mild cognitive impairment were intermediate in terms of Braak stage and CERAD and NIA-Reagan neuropathologic criteria for AD compared to the other two groups. In multiple regression analyses, persons with mild cognitive impairment had intermediate levels of AD pathology from those without cognitive impairment and those with dementia (test for trend, F = 45.2, p < 0.001). Further, the relation between cognition and AD pathology in persons with mild cognitive impairment did not differ significantly from the relation between cognition and AD pathology in persons with dementia or those without cognitive impairment. Persons with mild cognitive impairment also had intermediate levels of cerebral infarctions (test for trend, p = 0.04). Only 3 (8.1%) persons with mild cognitive impairment had Lewy body disease. CONCLUSION: These data suggest that mild cognitive impairment may be the earliest clinical manifestation of common age-related neurologic diseases.
OBJECTIVES: To examine the extent to which persons with mild cognitive impairment have intermediate levels of Alzheimer disease (AD) pathology, cerebral infarcts, and Lewy body disease. METHODS: A total of 180 Catholic clergy participating in the Religious Orders Study underwent annual detailed evaluation and brain autopsy. Blocks of midfrontal, superior temporal, medial temporal lobe, inferior parietal, entorhinal cortex, hippocampus, and substantia nigra were paraffin embedded, and sectioned at 6 mum. Cortical neuritic plaques, diffuse plaques, and neurofibrillary tangles were visualized with Bielschowsky silver stain, and counted and summarized to yield a Braak stage, Consortium to Establish a Registry for Alzheimer's Disease (CERAD) diagnosis, National Institute on Aging (NIA)-Reagan diagnosis, and composite measure of AD pathology. The authors recorded the number and location of all gross chronic cerebral infarctions. Lewy bodies were identified with antibodies to alpha-synuclein. Multiple regression analyses were used to examine the relation of ADpathology and cerebral infarctions to clinical diagnosis proximate to death, controlling for age, sex, and education. RESULTS: A total of 37 had mild cognitive impairment, 60 did not have cognitive impairment, and 83 had dementia proximate to death. Nearly all persons had at least some AD pathology. Cerebral infarctions were present in 35.2%, and 15.6% had Lewy body disease. Persons with mild cognitive impairment were intermediate in terms of Braak stage and CERAD and NIA-Reagan neuropathologic criteria for AD compared to the other two groups. In multiple regression analyses, persons with mild cognitive impairment had intermediate levels of AD pathology from those without cognitive impairment and those with dementia (test for trend, F = 45.2, p < 0.001). Further, the relation between cognition and AD pathology in persons with mild cognitive impairment did not differ significantly from the relation between cognition and AD pathology in persons with dementia or those without cognitive impairment. Persons with mild cognitive impairment also had intermediate levels of cerebral infarctions (test for trend, p = 0.04). Only 3 (8.1%) persons with mild cognitive impairment had Lewy body disease. CONCLUSION: These data suggest that mild cognitive impairment may be the earliest clinical manifestation of common age-related neurologic diseases.
Authors: Patricia L Kramer; Haiyan Xu; Randall L Woltjer; Shawn K Westaway; David Clark; Deniz Erten-Lyons; Jeffrey A Kaye; Kathleen A Welsh-Bohmer; Juan C Troncoso; William R Markesbery; Ronald C Petersen; R Scott Turner; Walter A Kukull; David A Bennett; Douglas Galasko; John C Morris; Jurg Ott Journal: Neurobiol Aging Date: 2010-05-07 Impact factor: 4.673
Authors: Jean C Augustinack; Kristen E Huber; Gheorghe M Postelnicu; Sita Kakunoori; Ruopeng Wang; André J W van der Kouwe; Lawrence L Wald; Thor D Stein; Matthew P Frosch; Bruce Fischl Journal: Acta Neuropathol Date: 2011-12-13 Impact factor: 17.088
Authors: Clifford R Jack; Marilyn S Albert; David S Knopman; Guy M McKhann; Reisa A Sperling; Maria C Carrillo; Bill Thies; Creighton H Phelps Journal: Alzheimers Dement Date: 2011-04-21 Impact factor: 21.566
Authors: Michelle M Mielke; Ozioma C Okonkwo; Kenichi Oishi; Susumu Mori; Sarah Tighe; Michael I Miller; Can Ceritoglu; Timothy Brown; Marilyn Albert; Constantine G Lyketsos Journal: Alzheimers Dement Date: 2012 Impact factor: 21.566
Authors: Marilyn S Albert; Steven T DeKosky; Dennis Dickson; Bruno Dubois; Howard H Feldman; Nick C Fox; Anthony Gamst; David M Holtzman; William J Jagust; Ronald C Petersen; Peter J Snyder; Maria C Carrillo; Bill Thies; Creighton H Phelps Journal: Alzheimers Dement Date: 2011-04-21 Impact factor: 21.566
Authors: Lei Yu; Joshua M Shulman; Lori Chibnik; Sue Leurgans; Julie A Schneider; Philip L De Jager; David A Bennett Journal: Aging Cell Date: 2011-12-29 Impact factor: 9.304
Authors: Robert S Wilson; Patricia A Boyle; Aron S Buchman; Lei Yu; Steven E Arnold; David A Bennett Journal: Psychosom Med Date: 2011-09-23 Impact factor: 4.312
Authors: Sylvia E Perez; Bin He; Muhammad Nadeem; Joanne Wuu; Stephen W Scheff; Eric E Abrahamson; Milos D Ikonomovic; Elliott J Mufson Journal: Biol Psychiatry Date: 2014-01-11 Impact factor: 13.382
Authors: Elliott J Mufson; Bin He; Muhammad Nadeem; Sylvia E Perez; Scott E Counts; Sue Leurgans; Jason Fritz; James Lah; Stephen D Ginsberg; Joanne Wuu; Stephen W Scheff Journal: J Neuropathol Exp Neurol Date: 2012-11 Impact factor: 3.685