Neuropathology of nondemented aging: presumptive evidence for preclinical Alzheimer disease.
OBJECTIVE
To determine the frequency and possible cognitive effect of histological Alzheimer's disease (AD) in autopsied older nondemented individuals.


METHODS
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.


METHODS
Washington University Alzheimer's Disease Research Center.


METHODS
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.
Department of Anatomy and Neurobiology, Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Joseph L
JL
Price
Daniel W
DW
McKeel
Virginia D
VD
Buckles
Catherine M
CM
Roe
Chengjie
C
Xiong
Michael
M
Grundman
Lawrence A
LA
Hansen
Ronald C
RC
Petersen
Joseph E
JE
Parisi
Dennis W
DW
Dickson
Charles D
CD
Smith
Daron G
DG
Davis
Frederick A
FA
Schmitt
William R
WR
Markesbery
Jeffrey
J
Kaye
Roger
R
Kurlan
Christine
C
Hulette
Brenda F
BF
Kurland
Roger
R
Higdon
Walter
W
Kukull
John C
JC
Morris
D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D042241:Early Diagnosis; D005260:Female; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D016874:Neurofibrillary Tangles / Q000473:pathology; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology; D011594:Psychometrics; D012720:Severity of Illness Index; D013223:Statistics as Topic