OBJECTIVE: To determine the frequency and possible cognitive effect of histological Alzheimer's disease (AD) in autopsied older nondemented individuals. DESIGN: Senile plaques (SPs) and neurofibrillary tangles (NFTs) were assessed quantitatively in 97 cases from 7 Alzheimer's Disease Centers (ADCs). Neuropathological diagnoses of AD (npAD) were also made with four sets of criteria. Adjusted linear mixed models tested differences between participants with and without npAD on the quantitative neuropathology measures and psychometric test scores prior to death. Spearman rank-order correlations between AD lesions and psychometric scores at last assessment were calculated for cases with pathology in particular regions. SETTING: Washington University Alzheimer's Disease Research Center. PARTICIPANTS: Ninety-seven nondemented participants who were age 60 years or older at death (mean=84 years). RESULTS: About 40% of nondemented individuals met at least some level of criteria for npAD; when strict criteria were used, about 20% of cases had npAD. Substantial overlap of Braak neurofibrillary stages occurred between npAD and no-npAD cases. Although there was no measurable cognitive impairment prior to death for either the no-npAD or npAD groups, cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs. CONCLUSIONS: Neuropathological processes related to AD in persons without dementia appear to be associated with subtle cognitive dysfunction and may represent a preclinical stage of the illness. By age 80-85 years, many nondemented older adults have substantial AD pathology.
OBJECTIVE: To determine the frequency and possible cognitive effect of histological Alzheimer's disease (AD) in autopsied older nondemented individuals. DESIGN: Senile plaques (SPs) and neurofibrillary tangles (NFTs) were assessed quantitatively in 97 cases from 7 Alzheimer's Disease Centers (ADCs). Neuropathological diagnoses of AD (npAD) were also made with four sets of criteria. Adjusted linear mixed models tested differences between participants with and without npAD on the quantitative neuropathology measures and psychometric test scores prior to death. Spearman rank-order correlations between AD lesions and psychometric scores at last assessment were calculated for cases with pathology in particular regions. SETTING: Washington University Alzheimer's Disease Research Center. PARTICIPANTS: Ninety-seven nondemented participants who were age 60 years or older at death (mean=84 years). RESULTS: About 40% of nondemented individuals met at least some level of criteria for npAD; when strict criteria were used, about 20% of cases had npAD. Substantial overlap of Braak neurofibrillary stages occurred between npAD and no-npAD cases. Although there was no measurable cognitive impairment prior to death for either the no-npAD or npAD groups, cognitive function in nondemented aging appears to be degraded by the presence of NFTs and SPs. CONCLUSIONS: Neuropathological processes related to AD in persons without dementia appear to be associated with subtle cognitive dysfunction and may represent a preclinical stage of the illness. By age 80-85 years, many nondemented older adults have substantial AD pathology.
Authors: C H Kawas; M M Corrada; R Brookmeyer; A Morrison; S M Resnick; A B Zonderman; D Arenberg Journal: Neurology Date: 2003-04-08 Impact factor: 9.910
Authors: D S Knopman; J E Parisi; A Salviati; M Floriach-Robert; B F Boeve; R J Ivnik; G E Smith; D W Dickson; K A Johnson; L E Petersen; W C McDonald; H Braak; R C Petersen Journal: J Neuropathol Exp Neurol Date: 2003-11 Impact factor: 3.685
Authors: William E Klunk; Henry Engler; Agneta Nordberg; Yanming Wang; Gunnar Blomqvist; Daniel P Holt; Mats Bergström; Irina Savitcheva; Guo-feng Huang; Sergio Estrada; Birgitta Ausén; Manik L Debnath; Julien Barletta; Julie C Price; Johan Sandell; Brian J Lopresti; Anders Wall; Pernilla Koivisto; Gunnar Antoni; Chester A Mathis; Bengt Långström Journal: Ann Neurol Date: 2004-03 Impact factor: 10.422
Authors: Lin Wai Hung; Giuseppe D Ciccotosto; Eleni Giannakis; Deborah J Tew; Keyla Perez; Colin L Masters; Roberto Cappai; John D Wade; Kevin J Barnham Journal: J Neurosci Date: 2008-11-12 Impact factor: 6.167
Authors: Karen S SantaCruz; Joshua A Sonnen; Maryam Kherad Pezhouh; Mark F Desrosiers; Peter T Nelson; Suzanne L Tyas Journal: J Neuropathol Exp Neurol Date: 2011-10 Impact factor: 3.685
Authors: Christopher J Holler; Robin L Webb; Ashley L Laux; Tina L Beckett; Dana M Niedowicz; Rachel R Ahmed; Yinxing Liu; Christopher R Simmons; Amy L S Dowling; Angela Spinelli; Moshe Khurgel; Steven Estus; Elizabeth Head; Louis B Hersh; M Paul Murphy Journal: Am J Pathol Date: 2011-11-07 Impact factor: 4.307
Authors: Elliott J Mufson; Lester Binder; Scott E Counts; Steven T DeKosky; Leyla de Toledo-Morrell; Stephen D Ginsberg; Milos D Ikonomovic; Sylvia E Perez; Stephen W Scheff Journal: Acta Neuropathol Date: 2011-11-19 Impact factor: 17.088
Authors: Bradley T Hyman; Creighton H Phelps; Thomas G Beach; Eileen H Bigio; Nigel J Cairns; Maria C Carrillo; Dennis W Dickson; Charles Duyckaerts; Matthew P Frosch; Eliezer Masliah; Suzanne S Mirra; Peter T Nelson; Julie A Schneider; Dietmar Rudolf Thal; Bill Thies; John Q Trojanowski; Harry V Vinters; Thomas J Montine Journal: Alzheimers Dement Date: 2012-01 Impact factor: 21.566
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
Authors: Matthew R Brier; Jewell B Thomas; Anne M Fagan; Jason Hassenstab; David M Holtzman; Tammie L Benzinger; John C Morris; Beau M Ances Journal: Neurobiol Aging Date: 2013-10-18 Impact factor: 4.673