Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease

Joseph L. Price; Daniel W. McKeel; Virginia D. Buckles; Catherine M. Roe; Chengjie Xiong; Michael Grundman; Lawrence A. Hansen; Ronald C. Petersen; Joseph E. Parisi; Dennis W. Dickson; Charles D. Smith; Daron G. Davis; Frederick A. Schmitt; William R. Markesbery; Jeffrey Kaye; Roger Kurlan; Christine Hulette; Brenda F. Kurland; Roger Higdon; Walter Kukull; John C. Morris

doi:10.1016/j.neurobiolaging.2009.04.002

Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease

Joseph L. Price, Daniel W. McKeel, Virginia D. Buckles, Catherine M. Roe, Chengjie Xiong, Michael Grundman, Lawrence A. Hansen, Ronald C. Petersen, Joseph E. Parisi, Dennis W. Dickson, Charles D. Smith, Daron G. Davis, Frederick A. Schmitt, William R. Markesbery, Jeffrey Kaye, Roger Kurlan, Christine Hulette, Brenda F. Kurland, Roger Higdon, Walter KukullJohn C. Morris

Research output: Contribution to journal › Article › peer-review

441 Scopus citations

Abstract

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.

Original language	English (US)
Pages (from-to)	1026-1036
Number of pages	11
Journal	Neurobiology of aging
Volume	30
Issue number	7
DOIs	https://doi.org/10.1016/j.neurobiolaging.2009.04.002
State	Published - Jul 2009

Keywords

Neuropathological Alzheimer's disease
Nondemented aging
Preclinical Alzheimer's disease

ASJC Scopus subject areas

General Neuroscience
Aging
Clinical Neurology
Developmental Biology
Geriatrics and Gerontology

Access to Document

10.1016/j.neurobiolaging.2009.04.002

Cite this

Price, J. L., McKeel, D. W., Buckles, V. D., Roe, C. M., Xiong, C., Grundman, M., Hansen, L. A., Petersen, R. C., Parisi, J. E., Dickson, D. W., Smith, C. D., Davis, D. G., Schmitt, F. A., Markesbery, W. R., Kaye, J., Kurlan, R., Hulette, C., Kurland, B. F., Higdon, R., ... Morris, J. C. (2009). Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease. Neurobiology of aging, 30(7), 1026-1036. https://doi.org/10.1016/j.neurobiolaging.2009.04.002

Price, JL, McKeel, DW, Buckles, VD, Roe, CM, Xiong, C, Grundman, M, Hansen, LA, Petersen, RC, Parisi, JE, Dickson, DW, Smith, CD, Davis, DG, Schmitt, FA, Markesbery, WR, Kaye, J, Kurlan, R, Hulette, C, Kurland, BF, Higdon, R, Kukull, W & Morris, JC 2009, 'Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease', Neurobiology of aging, vol. 30, no. 7, pp. 1026-1036. https://doi.org/10.1016/j.neurobiolaging.2009.04.002

@article{6ee36c9cd570468db386cf4d4b226bba,

title = "Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease",

abstract = "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.",

keywords = "Neuropathological Alzheimer's disease, Nondemented aging, Preclinical Alzheimer's disease",

author = "Price, {Joseph L.} and McKeel, {Daniel W.} and Buckles, {Virginia D.} and Roe, {Catherine M.} and Chengjie Xiong and Michael Grundman and Hansen, {Lawrence A.} and Petersen, {Ronald C.} and Parisi, {Joseph E.} and Dickson, {Dennis W.} and Smith, {Charles D.} and Davis, {Daron G.} and Schmitt, {Frederick A.} and Markesbery, {William R.} and Jeffrey Kaye and Roger Kurlan and Christine Hulette and Kurland, {Brenda F.} and Roger Higdon and Walter Kukull and Morris, {John C.}",

note = "Funding Information: This study was supported by a National Institute of Aging (NIA) grant to the National Alzheimer Coordinating Center (U01AG16976; P.I., J.C. Morris), by NIA grants to individual Alzheimer Disease Centers (P50AG05681, P01AG03991, P50AG016574, P30AG028383, P30AG028377, P50AG005131, P30AG008017, and P30AG008665), by the Postdoctoral Program of 1UL1RR024992-01 from the National Center for Research Resources, and by the Charles and Joanne Knight Alzheimer Research Initiative of Washington University's Alzheimer's Disease Research Center (ADRC). At Washington University in St Louis, Hieu Van Luu, Javier Agraz, Jessica Church, Debra Carter and Kymberli Sykes provided excellent technical contributions, and Nigel Cairns PhD and James E. Galvin MD provided helpful comments on the manuscript. Geoffrey Murdoch MD, PhD of the University of Pittsburgh School of Medicine provided neuropathological assistance when he was at the Oregon Health Sciences University.",

year = "2009",

month = jul,

doi = "10.1016/j.neurobiolaging.2009.04.002",

language = "English (US)",

volume = "30",

pages = "1026--1036",

journal = "Neurobiology of aging",

issn = "0197-4580",

publisher = "Elsevier Inc.",

number = "7",

}

TY - JOUR

T1 - Neuropathology of nondemented aging

T2 - Presumptive evidence for preclinical Alzheimer disease

AU - Price, Joseph L.

AU - McKeel, Daniel W.

AU - Buckles, Virginia D.

AU - Roe, Catherine M.

AU - Xiong, Chengjie

AU - Grundman, Michael

AU - Hansen, Lawrence A.

AU - Petersen, Ronald C.

AU - Parisi, Joseph E.

AU - Dickson, Dennis W.

AU - Smith, Charles D.

AU - Davis, Daron G.

AU - Schmitt, Frederick A.

AU - Markesbery, William R.

AU - Kaye, Jeffrey

AU - Kurlan, Roger

AU - Hulette, Christine

AU - Kurland, Brenda F.

AU - Higdon, Roger

AU - Kukull, Walter

AU - Morris, John C.

N1 - Funding Information: This study was supported by a National Institute of Aging (NIA) grant to the National Alzheimer Coordinating Center (U01AG16976; P.I., J.C. Morris), by NIA grants to individual Alzheimer Disease Centers (P50AG05681, P01AG03991, P50AG016574, P30AG028383, P30AG028377, P50AG005131, P30AG008017, and P30AG008665), by the Postdoctoral Program of 1UL1RR024992-01 from the National Center for Research Resources, and by the Charles and Joanne Knight Alzheimer Research Initiative of Washington University's Alzheimer's Disease Research Center (ADRC). At Washington University in St Louis, Hieu Van Luu, Javier Agraz, Jessica Church, Debra Carter and Kymberli Sykes provided excellent technical contributions, and Nigel Cairns PhD and James E. Galvin MD provided helpful comments on the manuscript. Geoffrey Murdoch MD, PhD of the University of Pittsburgh School of Medicine provided neuropathological assistance when he was at the Oregon Health Sciences University.

PY - 2009/7

Y1 - 2009/7

N2 - 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.

AB - 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.

KW - Neuropathological Alzheimer's disease

KW - Nondemented aging

KW - Preclinical Alzheimer's disease

UR - http://www.scopus.com/inward/record.url?scp=67349184808&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67349184808&partnerID=8YFLogxK

U2 - 10.1016/j.neurobiolaging.2009.04.002

DO - 10.1016/j.neurobiolaging.2009.04.002

M3 - Article

C2 - 19376612

AN - SCOPUS:67349184808

SN - 0197-4580

VL - 30

SP - 1026

EP - 1036

JO - Neurobiology of aging

JF - Neurobiology of aging

IS - 7

ER -

Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this