Neuropathology of nondemented aging: Presumptive evidence for preclinical Alzheimer disease

Department of Anatomy and Neurobiology, Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO, USA.
Neurobiology of aging (Impact Factor: 5.01). 05/2009; 30(7):1026-36. DOI: 10.1016/j.neurobiolaging.2009.04.002
Source: PubMed


To determine the frequency and possible cognitive effect of histological Alzheimer's disease (AD) in autopsied older nondemented individuals.
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.
Washington University Alzheimer's Disease Research Center.
Ninety-seven nondemented participants who were age 60 years or older at death (mean=84 years).
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.
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.

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    • "This study builds on the results from these previous patient studies and critically the focus shifts from differential diagnosis of established dementia to that of MCI. In view of the substantial neuropathological evidence of hippocampal damage in AD occurring prior to the onset of dementia (Braak and Braak, 1991;Arriagada et al., 1992;Price et al., 2009) the central study hypothesis was that spatial memory performance (as tested using the 4MT) is impaired in prodromal AD, manifest as MCI. As proof of hypothesis would have significant implications for the use of this test in clinical diagnostic practice, and in view of the importance attached worldwide to the detection of AD prior to the onset of dementia, several study objectives were defined. "
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    • "One the other hand, critics have found to focus on limitations in the methodology of clinical trials and on bias in the way the data are introduced, especially in trials sponsored by drug companies, and have concluded that efficay of drugs are inflated (Casey et al., 2010). One of the most important problems leading to difficulty in disease management is AD pathology existed in brain cells many years before the appearance of clinical symptoms (Price et al., 2009). AD is distinguished mainly by neuronal loss. "

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