Neuropathology of Nondemented Aging: Presumptive Evidence for Preclinical Alzheimer Disease

By Joseph L. Price, D. McKeel, V. Buckles, C. Roe, C. Xiong, M. Grundman, L. Hansen, Ronald C. Petersen, Joseph E. Parisi, Dennis W. Dickson and 11 more. Neurobiology of Aging, 2009

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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.

Subfields: Physiology, Psychiatry and Mental health, Radiology, Nuclear Medicine and Imaging

View Paper: https://www.semanticscholar.org/paper/56b77cd6ec3334e93ca55ab8412c4c9a608abbd6

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Citations in the corpus

An epigenetic blockade of cognitive functions in the neurodegenerating brain (2012, background): “, with control cases being brains completely devoid of tau pathologies (Braak and Braak stage 0”
Neuropathological alterations in Alzheimer disease. (2011, background): “Longitudinal prospective clinicopathological studies in nondemented elderly people have revealed that up to 45% of nondemented elderly would meet the NIA-RI criteria for AD had they been demented, usually the intermediate likelihood category of these criteria, and rarely the high likelihood category”
White matter changes in Alzheimer’s disease: a focus on myelin and oligodendrocytes (2018, neutral): “Further, senile plaques can be found in about 20–40% of older adults without symptoms of dementia and cognitive impairment [14, 62].”
Biomarkers for Alzheimer's disease: current status and prospects for the future (2018, background): “with that found in cognitively unimpaired elderly (14-18).”
Oxidative Stress and Mitochondrial Dysfunction in Alzheimer’s Disease (2013, positive): “Recent studies demonstrated that the onset of AD is commonly preceded by an interim phase known as mild cognitive impairment (MCI), when there is no signi ﬁ cant increase of senile plaques and NFTs [51 – 53].”
Alzheimer Disease: An Update on Pathobiology and Treatment Strategies (2019, positive): “Neuropathological studies in humanshave demonstrated that tau pathology generally does not progress from the entorhinal cortex into the neocortex in the absence of co-occurring amyloid pathology (Pontecorvo et al., 2019; Price and Morris, 1999; Price et al., 2009; Wang et al., 2016).”
Reconsideration of Amyloid Hypothesis and Tau Hypothesis in Alzheimer's Disease (2018, background): “Further, in the brain of elderly non-demented patients, the distribution of senile plaques is sometimes as extensive as that of dementia patients (Davis et al., 1999; Fagan et al., 2009; Price et al., 2009; Chetelat et al., 2013).”
Pathogenic Protein Seeding in Alzheimer’s Disease and Other Neurodegenerative Disorders (2011, background): “Advancing age is the most prevalent risk factor for the accumulation of A β in the brain 10, 11 , possibly because of the decline of cellular protein quality control processes 12 .”
Multi-modal techniques for diagnosis and prognosis of Alzheimer’s disease (2009, result): “Consistent with this, neuropathological studies involving large numbers of non-demented subjects have identified significant Alzheimer's disease pathology in the brains of older individual”
National Institute on Aging–Alzheimer’s Association guidelines for the neuropathologic assessment of Alzheimer’s disease (2012, neutral): “Moreover, data have accumulated demonstrating that some older individuals who were cognitively intact proximate to death had significant AD neuropathologic change [4–17].”