Longitudinal assessment of Aβ and cognition in aging and Alzheimer disease
Open accessAbstract
OBJECTIVE: Assess Aβ deposition longitudinally and explore its relationship with cognition and disease progression. METHODS: Clinical follow-up was obtained 20 ± 3 months after [¹¹C]Pittsburgh compound B (PiB)-positron emission tomography in 206 subjects: 35 with dementia of the Alzheimer type (DAT), 65 with mild cognitive impairment (MCI), and 106 age-matched healthy controls (HCs). A second PiB scan was obtained at follow-up in 185 subjects and a third scan after 3 years in 57. RESULTS: At baseline, 97% of DAT, 69% of MCI, and 31% of HC subjects showed high PiB retention. At 20-month follow-up, small but significant increases in PiB standardized uptake value ratios were observed in the DAT and MCI groups, and in HCs with high PiB retention at baseline (5.7%, 2.1%, and 1.5%, respectively). Increases were associated with the number of apolipoprotein E ε4 alleles. There was a weak correlation between PiB increases and decline in cognition when all groups were combined. Progression to DAT occurred in 67% of MCI with high PiB versus 5% of those with low PiB, but 20% of the low PiB MCI subjects progressed to other dementias. Of the high PiB HCs, 16% developed MCI or DAT by 20 months and 25% by 3 years. One low PiB HC developed MCI. INTERPRETATION: Aβ deposition increases slowly from cognitive normality to moderate severity DAT. Extensive Aβ deposition precedes cognitive impairment, and is associated with ApoE genotype and a higher risk of cognitive decline in HCs and progression from MCI to DAT over 1 to 2 years. However, cognitive decline is only weakly related to change in Aβ burden, suggesting that downstream factors have a more direct effect on symptom progression.
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Progression of biomarker measures in Alzheimer's disease is a continuous process that begins before symptoms.
“and that progression of biomarker measures is also a continuous process that begins before symptoms [9–14]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [13]
The Discussion concludes that Aβ deposition increases slowly and continuously from cognitive normality to moderately severe dementia, and that extensive deposition precedes cognitive impairment. This supports the claim for the Aβ biomarker, but the paper does not establish that progression is continuous before symptoms for biomarker measures generally. (LLM, conf=0.82)
Experimental — accuracy not yet measuredCognitively unimpaired individuals with abnormal amyloid biomarkers have more rapid progression of atrophy, hypometabolism, and clinical/cognitive decline than individuals without biomarker evidence of Aβ deposition.
“Numerous studies have shown that CU individuals with abnormal amyloid biomarkers have more rapid progression of atrophy, hypometabolism, and clinical/cognitive decline than individuals without biomarker evidence of Aβ deposition [13,33,80,93–99]”
From NIA‐AA Research Framework: Toward a biological definition of Alzheimer's disease (2018) · cites this paper as [13]
The Results (Follow-up Cognitive Change; page unavailable) show that cognitively healthy participants with high baseline PiB retention were more likely to develop MCI or dementia than those with low retention. The paper does not establish faster progression of atrophy or hypometabolism in that comparison; its longitudinal imaging results concern amyloid deposition. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe ε4 allele increased brain amyloid burden in a dose-dependent manner in normal elderly individuals and in mild cognitive impairment patients.
“The ε4 allele increased brain amyloid burden in a dose-dependent manner in normal elderly individuals and in mild cognitive impairment patients [93,94].”
From Plasma levels of apolipoprotein E, APOE genotype and risk of dementia and ischemic heart disease: A review (2016) · cites this paper as [94]
The PiB Baseline Results report higher amyloid burden in ε4 carriers than noncarriers in both healthy controls and MCI patients. The Follow-up PiB Studies report a dose-dependent relationship only when clinical groups were combined, with no significant differences when each group was examined separately. The copy therefore does not support a dose-dependent finding in each of the two populations named. (LLM, conf=0.90)
Experimental — accuracy not yet measuredPrevious longitudinal studies have either failed to detect an early increase in regional Aβ deposition or identified a rather large early stage Aβ region including the posterior temporal, inferior parietal, posterior cingulate, precuneus, and occipital areas.
“Previous longitudinal studies have either failed to detect an early increase in regional Aβ deposition16 or identified a rather large early stage Aβ region including the posterior temporal, inferior parietal, posterior cingulate, precuneus, and occipital areas4.”
From Earliest accumulation of β-amyloid occurs within the default-mode network and concurrently affects brain connectivity (2017) · cites this paper as [16]
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- Authors
- Villemagne, V. L., Pike, K. E., Chételat, G., Ellis, K. A., Mulligan, R. S., Bourgeat, P., Ackermann, U., Jones, G., Szoeke, C., Salvado, O., Martins, R., O'Keefe, G., Mathis, C. A., Klunk, W. E., Ames, D., Masters, C. L., & Rowe, C. C.
- Affiliations
- Mental Health Research Institute (AU)
- Austin Health (AU)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Australian e-Health Research Centre (AU)
- Edith Cowan University (AU)
- University of Pittsburgh (US)
- National Ageing Research Institute (AU)
- The University of Melbourne (AU)
- Corresponding author
- Villemagne, Victor L.
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2011-01
- Volume
- 69
- Issue
- 1
- Pages
- 181-192
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC3045039
- OpenAlex
- W2051489981
- Cited by
- 833
- References
- 42
- Citations by year
- 2026: 28 · 2025: 32 · 2024: 26 · 2023: 51 · 2022: 42 · 2021: 44 · 2020: 57 · 2019: 60 · 2018: 57 · 2017: 57 · 2016: 60 · 2015: 61 · 2014: 68 · 2013: 86 · 2012: 71
- FWCI
- 57.02
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Edith Cowan University Research Online (Edith Cowan University) (submittedVersion)
- Funders
- National Institute on Aging (P01AG025204, RF1AG025516, P50AG005133, R37AG025516)
- 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-beta deposition, Alzheimer's disease, mild cognitive impairment, Pittsburgh compound B PET, APOE ε4, cognitive decline, disease progression, aging
- MeSH terms
- Aged, Aging, Alzheimer Disease, Aniline Compounds, Brain, Cognition, Cognition Disorders, Female, Follow-Up Studies, Humans, Longitudinal Studies, Magnetic Resonance Imaging, Male, Neuropsychological Tests, Polymorphism, Genetic, Severity of Illness Index, Thiazoles, Amyloid beta-Peptides, Disease Progression, Positron-Emission Tomography, Plaque, Amyloid
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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