Frequent amyloid deposition without significant cognitive impairment among the elderly
Open accessAbstract
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.
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Cognitive decline itself is poorly correlated with changes in amyloid burden.
“Furthermore, cognitive decline itself is poorly correlated with changes in amyloid burden”
From Alzheimer's Protection by <scp>PLCγ2</scp> Compacts Plaques, Redistributes Microglia, and Protects Synapses in <scp> <i>App</i> <sup> <i>NL</i> </sup> </scp> <sup> <i>‐G‐F</i> </sup> Mice (2026) · cites this paper as Aizenstein et al. 2008
The Results and COMMENT report that amyloid-positive, clinically unimpaired elderly participants did not perform significantly worse than amyloid-negative participants. But the claim concerns cognitive decline correlated with changes in amyloid burden over time; the Conclusions say longitudinal follow-up is still required, so this study does not establish that relationship. (LLM, conf=0.86)
Experimental — accuracy not yet measuredA similar proportion of cognitively unimpaired elderly persons has abnormal amyloid biomarkers.
“and a similar proportion has abnormal amyloid biomarkers [33,53–55,60,70–73].”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [71]
Significant numbers of aged cognitively normal individuals exhibit some level of amyloid deposition.
“and significant numbers of aged cognitively normal individuals exhibit some level of amyloid deposition”
From Alzheimer's Protection by <scp>PLCγ2</scp> Compacts Plaques, Redistributes Microglia, and Protects Synapses in <scp> <i>App</i> <sup> <i>NL</i> </sup> </scp> <sup> <i>‐G‐F</i> </sup> Mice (2026) · cites this paper as Aizenstein et al. 2008
The proportion of cognitively normal older adults with moderate or frequent CERAD NP score matches well with reports using fibrillar Aβ PET imaging in cognitively normal individuals.
“The proportion of CN older adults with moderate or frequent CERAD NP score, a metric significantly correlated with Aβ peptide-immunoreactive plaque area and detergent-insoluble Aβ42 accumulation, matches well with reports using fibrillar Aβ PET imaging in cognitively normal individuals.”
From Ecology of the Aging Human Brain (2011) · cites this paper as [34]
Studies of non-demented elderly cohorts overall report approximately 20-40% are PIB-positive.
“Studies of non-demented elderly cohorts overall report approximately 20–40% are PIB-positive [67, 68, 71–78].”
From Brain aging, Alzheimer's disease, and mitochondria (2011) · cites this paper as [71]
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- Authors
- Aizenstein, H. J., Nebes, R. D., Saxton, J. A., Price, J. C., Mathis, C. A., Tsopelas, N. D., Ziolko, S. K., James, J. A., Snitz, B. E., Houck, P. R., Bi, W., Cohen, A. D., Lopresti, B. J., DeKosky, S. T., Halligan, E. M., & Klunk, W. E.
- Affiliations
- University of Pittsburgh (US)
- ORCID
- Venue
- Archives of Neurology
- Publisher
- American Medical Association (AMA)
- Published
- 2008-11-10
- Volume
- 65
- Issue
- 11
- Pages
- 1509
- ISSN
- 0003-9942 (ISSN-L)
- PMC
- PMC2636844
- OpenAlex
- W2075348467
- Cited by
- 1,059
- References
- 52
- Citations by year
- 2026: 30 · 2025: 43 · 2024: 41 · 2023: 47 · 2022: 36 · 2021: 55 · 2020: 66 · 2019: 54 · 2018: 67 · 2017: 52 · 2016: 49 · 2015: 74 · 2014: 74 · 2013: 75 · 2012: 88
- FWCI
- 48.00
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Archives of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Energy (DE-FD02-03 ER63590, ER63590, DE-FD02-03)
- Alzheimer's Association
- National Institute on Aging (R01AG018402, P01AG025204, RF1AG025516, P50AG005133, R01AG020226, K02AG001039, R37AG025516)
- National Institute of Mental Health (R01MH070729, K01MH001976)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- amyloid deposition, Pittsburgh compound B, amyloid PET, cognitively normal elderly, preclinical Alzheimer's disease, cognitive function, Alzheimer disease pathogenesis
- MeSH terms
- Aged, Aged, 80 and over, Alleles, Amyloid, Aniline Compounds, Brain, Cognition, Female, Heterozygote, Humans, Male, Neuropsychological Tests, Reference Values, Thiazoles, Positron-Emission Tomography, Apolipoprotein E4
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