Episodic memory loss is related to hippocampal-mediated -amyloid deposition in elderly subjects
Open accessAbstract
Although beta-amyloid (Abeta) plaques are a primary diagnostic criterion for Alzheimer's disease, this pathology is commonly observed in the brains of non-demented older individuals. To explore the importance of this pathology in the absence of dementia, we compared levels of amyloid deposition (via 'Pittsburgh Compound-B' (PIB) positron emission tomography (PET) imaging) to hippocampus volume (HV) and episodic memory (EM) in three groups: (i) normal controls (NC) from the Berkeley Aging Cohort (BAC NC, n = 20); (ii) normal controls (NC) from the Alzheimer's disease neuroimaging initiative (ADNI NC, n = 17); and (iii) PIB+ mild cognitive impairment subjects from the ADNI (ADNI PIB+ MCI, n = 39). Age, gender and education were controlled for in each statistical model, and HV was adjusted for intracranial volume (aHV). In BAC NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.0016) and worse EM (P = 0.0086). Within ADNI NC, elevated PIB uptake was significantly associated with smaller aHV (P = 0.047) but not EM (P = 0.60); within ADNI PIB+ MCI, elevated PIB uptake was significantly associated with both smaller aHV (P = 0.00070) and worse EM (P = 0.046). To further understand these relationships, a recursive regression procedure was conducted within all ADNI NC and PIB+ MCI subjects (n = 56) to test the hypothesis that HV mediates the relationship between Abeta and EM. Significant correlations were found between PIB index and EM (P = 0.0044), PIB index and aHV (P < 0.0001), as well as between aHV and EM (P < 0.0001). When both aHV and PIB were included in the same model to predict EM, aHV remained significant (P = 0.0015) whereas PIB index was no longer significantly associated with EM (P = 0.50). These results are consistent with a model in which Abeta deposition, hippocampal atrophy, and EM occur sequentially in elderly subjects, with Abeta deposition as the primary event in this cascade. This pattern suggests that declining EM in older individuals may be caused by Abeta-induced hippocampus atrophy.
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Amyloid positron emission tomography shows that amyloid-beta deposition reaches a plateau before brain atrophy can be identified from structural magnetic resonance imaging and cognitive symptoms.
“Molecular imaging studies such as those using amyloid positron emission tomography (PET) have shown that Aβ deposition reaches a plateau before brain atrophy can be identified from structural magnetic resonance imaging (MRI) and cognitive symptoms [15, 19].”
From Clinical trials of new drugs for Alzheimer disease (2020) · cites this paper as [19]
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Understanding the cause of sporadic Alzheimer’s disease
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Preclinical AD Workgroup staging: Pathological correlates and potential challenges
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- Authors
- Mormino, E. C., Kluth, J. T., Madison, C. M., Rabinovici, G. D., Baker, S. L., Miller, B. L., Koeppe, R. A., Mathis, C. A., Weiner, M. W., Jagust, W. J., & Initiative, T. A. D. N.
- Affiliations
- University of California, Berkeley (US)
- Lawrence Berkeley National Laboratory (US)
- University of California, San Francisco (US)
- University of Michigan (US)
- University of Pittsburgh (US)
- San Francisco VA Medical Center (US)
- ORCID
- Venue
- Brain
- Publisher
- Oxford University Press (OUP)
- Published
- 2008-11-28
- Volume
- 132
- Issue
- 5
- Pages
- 1310-1323
- ISSN
- 0006-8950 (ISSN-L)
- 1460-2156
- PMC
- PMC2677792
- OpenAlex
- W2003428745
- Cited by
- 684
- References
- 17
- Citations by year
- 2026: 16 · 2025: 25 · 2024: 26 · 2023: 16 · 2022: 31 · 2021: 28 · 2020: 34 · 2019: 28 · 2018: 38 · 2017: 29 · 2016: 44 · 2015: 43 · 2014: 60 · 2013: 63 · 2012: 67
- FWCI
- 31.39
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Brain (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Alzheimer's Disease Neuroimaging Initiative (AG024904)
- National Institute for Health and Care Research (NF-SI-0508-10123)
- National Institutes of Health (5u01ag024904-10, AG024904)
- National Institute on Aging (U01-AG-024904, P01AG010491, AG 024904, R01AG027342, R01AG027859, AG027859, P30AG019610, K23AG031861, U19AG010483, R01AG034570, P50AG023501)
- 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
- episodic memory, amyloid-beta deposition, hippocampal volume, hippocampal atrophy, Pittsburgh compound B PET, mild cognitive impairment, Alzheimer's disease, non-demented elderly, aging, amyloid plaques, cognitive aging, brain atrophy
- MeSH terms
- Age Factors, Aged, Aging, Alzheimer Disease, Aniline Compounds, Atrophy, Carbon Radioisotopes, Educational Status, Female, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Memory Disorders, Middle Aged, Organ Size, Psychiatric Status Rating Scales, Sex Factors, Thiazoles, Multivariate Analysis, Linear Models, Case-Control Studies, Amyloid beta-Peptides, Radiopharmaceuticals, Positron-Emission Tomography
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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