Frequent Amyloid Deposition Without Significant Cognitive Impairment Among the Elderly

By H. Aizenstein, R. Nebes, J. Saxton, J. Price, Chester A. Mathis, N. Tsopelas, S. Ziolko, J. James, B. Snitz, P. Houck and 6 more. Archives of Neurology, 2008

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Objective To characterize the prevalence of amyloid deposition in a clinically unimpaired elderly population, as assessed by Pittsburgh Compound B (PiB) positron emission tomography (PET) imaging, and its relationship to cognitive function, measured with a battery of neuropsychological tests. Design Subjects underwent cognitive testing and PiB PET imaging (15 mCi for 90 minutes with an ECAT HR + scanner). Logan graphical analysis was applied to estimate regional PiB retention distribution volume, normalized to a cerebellar reference region volume, to yield distribution volume ratios (DVRs). Setting University medical center. Participants From a community-based sample of volunteers, 43 participants aged 65 to 88 years who did not meet diagnostic criteria for Alzheimer disease or mild cognitive impairment were included. Main Outcome Measures Regional PiB retention and cognitive test performance. Results Of 43 clinically unimpaired elderly persons imaged, 9 (21%) showed evidence of early amyloid deposition in at least 1 brain area using an objectively determined DVR cutoff. Demographic characteristics did not differ significantly between amyloid-positive and amyloid-negative participants, and neurocognitive performance was not significantly worse among amyloid-positive compared with amyloid-negative participants. Conclusions Amyloid deposition can be identified among cognitively normal elderly persons during life, and the prevalence of asymptomatic amyloid deposition may be similar to that of symptomatic amyloid deposition. In this group of participants without clinically significant impairment, amyloid deposition was not associated with worse cognitive function, suggesting that an elderly person with a significant amyloid burden can remain cognitively normal. However, this finding is based on relatively small numbers and needs to be replicated in larger cohorts. Longitudinal follow-up of these subjects will be required to support the potential of PiB imaging to identify preclinical Alzheimer disease, or, alternatively, to show that amyloid deposition is not sufficient to cause Alzheimer disease within some specified period.

Subfields: Neurology, Physiology, Psychiatry and Mental health

View Paper: https://www.semanticscholar.org/paper/272cf10989142a2f1e439dd15cc481a6a13524a4

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Citations in the corpus

Amyloid deposition is associated with impaired default network function in older persons without dementia (2009, neutral): “, 1996), recent PiB-PET studies have reported amyloid deposition in significant percentages of nondemented older subjects (Aizenstein et al., 2008; Buckner et al., 2005; Gomperts et al., 2008; Johnson et al., 2007; Mintun et al., 2006; Pike et al., 2007).”
The Role of the Anaphylatoxins in Health and Disease (2009, neutral): “Veerhuis R, Van Breemen MJ, Hoozemans JM, Morbin M, Ouladhadj J, Tagliavini F, Eikelenboom P. Amyloid beta plaque-associated proteins C1q and SAP enhance the Abeta(1-42)peptide-induced cytokine secretion by adult human microglia in vitro.”
Brain imaging in Alzheimer disease. (2012, background): “Reviewing recent publications from 15 research groups who have performed amyloid PET on clinically diagnosed AD patients, 96% of AD patients were amyloid positive (Fig. 4; Kemppainen et al. 2006; Aizenstein et al. 2008; Edison et al. 2008; Shin et al. 2008; Drzezga et al. 2009; Hedden et al. 2009; L”
Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease (2009, methodology): “This predefined threshold was based on a reanalysis of the previous older control data (11) with no correction for the combined effects of brain atrophy and partial-volume averaging, elimination of the occipital ROI to minimize the contribution of vascular A to this assessment (31), and application ”
An Operational Approach to NIA-AA Criteria for Preclinical Alzheimer’s Disease (2012, neutral): “e4 noncarrier 12 [32] 1618 [76] 287 [74] MMSE, median (IQR) 20 (14, 23) 28 (27, 29) 28 (27, 29) Cognitive domain z scores, median (IQR)”
Episodic memory loss is related to hippocampal-mediated beta-amyloid deposition in elderly subjects. (2009, background): “…high tracer uptake in Alzheimer’s disease (Klunk et al., 2004; Kemppainen et al., 2006; Rowe et al., 2007) and elevated tracer uptake in a subset of normal individuals (Mintun et al., 2006; Pike et al., 2007; Rowe et al., 2007; Aizenstein et al., 2008; Fotenos et al., 2008; Jack et al., 2008b).”
The Centiloid Project: Standardizing Quantitative Amyloid Plaque Estimation by PET (2014, neutral): “Both of the AD-CTX and OC-CTX groups were evaluated and scanned at the University of Pittsburgh using the same methods described previously [13,19].”
Toward defining the preclinical stages of Alzheimer's disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease (2011, result): “There have been variable reports in the previously published data thus far, regarding whether Aβpositive individuals demonstrate lower neuropsychological test scores at the time of biomarker study [50–54], which may represent heterogeneity in where these individuals fall on the preclinical continuum”