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Cited by 11Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsMedical Imaging Techniques and Applications

Evaluation of in vivo staging of amyloid deposition in cognitively unimpaired elderly aged 78–94

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Michalowska, Malgorzata M., Herholz, Karl, Hinz, Rainer, Amadi, Chinenye, McInnes, Lynn, Anton-Rodriguez, Jose M., Karikari, Thomas K., Blennow, Kaj +4 more·2022·Molecular Psychiatry
DOI 10.1038/s41380-022-01685-6PMC PMC9718666
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Abstract

Amyloid-beta (Aβ) deposition is common in cognitively unimpaired (CU) elderly >85 years. This study investigated amyloid distribution and evaluated three published in vivo amyloid-PET staging schemes from a cognitively unimpaired (CU) cohort aged 84.9 ± 4.3 years (n = 75). SUV-based principal component analysis (PCA) was applied to 18 F-flutemetamol PET data to determine an unbiased regional covariance pattern of tracer uptake across grey matter regions. PET staging schemes were applied to the data and compared to the PCA output. Concentration of p-tau181 was measured in blood plasma. The PCA revealed three distinct components accounting for 91.2% of total SUV variance. PC1 driven by the large common variance of uptake in neocortical and striatal regions was significantly positively correlated with global SUVRs, APOE4 status and p-tau181 concentration. PC2 represented mainly non-specific uptake in typical amyloid-PET reference regions, and PC3 the occipital lobe. Application of the staging schemes demonstrated that the majority of the CU cohort (up to 93%) were classified as having pathological amount and distribution of Aβ. Good correspondence existed between binary (+/−) classification and later amyloid stages, however, substantial differences existed between schemes for low stages with 8–17% of individuals being unstageable, i.e., not following the sequential progression of Aβ deposition. In spite of the difference in staging outcomes there was broad spatial overlap between earlier stages and PC1, most prominently in default mode network regions. This study critically evaluated the utility of in vivo amyloid staging from a single PET scan in CU elderly and found that early amyloid stages could not be consistently classified. The majority of the cohort had pathological Aβ, thus, it remains an open topic what constitutes abnormal brain Aβ in the oldest-old and what is the best method to determine that.

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  • Amyloid PET does not correlate with symptom onset and disease severity.

    “The use of amyloid PET imaging has several limitations as it does not correlate with symptom onset and disease severity, cannot predict time of onset of dementia syndrome while its use in older populations seem to require more research as amyloid pathology is prevalent in a large proportion of elderly cognitively unimpaired individuals [177].”

    From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [177]

    The Introduction reports little relation between amyloid staging and cognitive function or prior decline in cognitively unimpaired people over 80, which supports a narrower limitation. It does not establish that amyloid PET fails to correlate with symptom onset or disease severity generally. The Discussion also reports a weak but significant correlation between an amyloid-related PET measure and memory-test performance. (LLM, conf=0.85)

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  • Amyloid PET cannot predict time of onset of dementia syndrome.

    “The use of amyloid PET imaging has several limitations as it does not correlate with symptom onset and disease severity, cannot predict time of onset of dementia syndrome while its use in older populations seem to require more research as amyloid pathology is prevalent in a large proportion of elderly cognitively unimpaired individuals [177].”

    From The use of neuroimaging techniques in the early and differential diagnosis of dementia (2023) · cites this paper as [177]

    The Discussion (page not provided) says the study was cross-sectional and that longitudinal research is needed to assess cognitive decline alongside amyloid deposition. The Abstract reports difficulty classifying early amyloid stages from a single PET scan, but neither passage addresses whether PET can predict the time of dementia onset. Searches for dementia-onset prediction and longitudinal cognitive decline found no decisive passage. (LLM, conf=0.76)

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Authors
Michalowska, M. M., Herholz, K., Hinz, R., Amadi, C., McInnes, L., Anton-Rodriguez, J. M., Karikari, T. K., Blennow, K., Zetterberg, H., Ashton, N. J., Pendleton, N., & Carter, S. F.
Affiliations
  • Karolinska Institutet (SE)
  • University of Manchester (GB)
  • Northumbria University (GB)
  • University of Pittsburgh (US)
  • Sahlgrenska University Hospital (SE)
  • King's College London (GB)
  • University of Cambridge (GB)
Corresponding author
Carter, Stephen F.
ORCID
Venue
Molecular Psychiatry
Publisher
Springer Science and Business Media LLC
Published
2022-07-20
Volume
27
Issue
10
Pages
4335-4342
ISSN
  • 1359-4184 (ISSN-L)
  • 1476-5578
DOI
10.1038/s41380-022-01685-6
PMC
PMC9718666
OpenAlex
W4285900099
Cited by
11
References
9
Citations by year
2026: 1 · 2025: 3 · 2024: 3 · 2023: 4
FWCI
1.63
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Psychiatry (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Research Explorer (The University of Manchester) (publishedVersion, cc-by)
  • White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (acceptedVersion)
  • Northumbria Research Link (Northumbria University) (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
  • Apollo (University of Cambridge) (submittedVersion, cc-by)
  • Apollo
Funders
  • European Federation of Pharmaceutical Industries and Associations (BRC-1215-20014, 115372)
  • National Institute for Health and Care Research ([IS-BRC-1215-20014, BRC1215-20014)
  • Department of Health and Social Care
  • European Commission (115372)
  • Erasmus+
  • NIHR Cambridge Biomedical Research Centre ((BRC-1215-20014), 1215-20014, BRC-1215)
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 › Radiology, Nuclear Medicine and Imaging › Medical Imaging Techniques and Applications
Keywords
amyloid-beta deposition, 18F-flutemetamol, oldest old, p-tau181, APOE ε4, default mode network, striatal uptake
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Amyloidosis, Brain, Humans, Amyloid beta-Peptides, Positron-Emission Tomography

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