Cited by 163Dementia and Cognitive Impairment ResearchAlzheimer's disease research and treatmentsCancer-related cognitive impairment studies

Indicators of amyloid burden in a population-based study of cognitively normal elderly

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Mielke, Michelle M., Wiste, Heather J., Weigand, Stephen D., Knopman, David S., Lowe, Val J., Roberts, Rosebud O., Geda, Yonas E., Swenson-Dravis, Dana M. +5 more·2012·Neurology

Abstract

OBJECTIVES: Secondary prevention trials in subjects with preclinical Alzheimer disease may require documentation of brain amyloidosis. The identification of inexpensive and noninvasive screening variables that can identify individuals who have significant amyloid accumulation would reduce screening costs. METHODS: A total of 483 cognitively normal (CN) individuals, aged 70-92 years, from the population-based Mayo Clinic Study of Aging, underwent Pittsburgh compound B (PiB)-PET imaging. Logistic regression determined whether age, sex, APOE genotype, family history, or cognitive performance was associated with odds of a PiB retention ratio >1.4 and >1.5. Area under the receiver operating characteristic curve (AUROC) evaluated the discrimination between PiB-positive and -negative subjects. For each characteristic, we determined the number needed to screen in each age group (70-79 and 80-89) to identify 100 participants with PiB >1.4 or >1.5. RESULTS: A total of 211 (44%) individuals had PiB >1.4 and 151 (31%) >1.5. In univariate and multivariate models, discrimination was modest (AUROC ∼0.6-0.7). Multivariately, age and APOE best predicted odds of PiB >1.4 and >1.5. Subjective memory complaints were similar to cognitive test performance in predicting PiB >1.5. Indicators of PiB positivity varied with age. Screening APOE ε4 carriers alone reduced the number needed to screen to enroll 100 subjects with PIB >1.5 by 48% in persons aged 70-79 and 33% in those aged 80-89. CONCLUSIONS: Age and APOE genotype are useful predictors of the likelihood of significant amyloid accumulation, but discrimination is modest. Nonetheless, these results suggest that inexpensive and noninvasive measures could significantly reduce the number of CN individuals needed to screen to enroll a given number of amyloid-positive subjects.

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Research works printed but not linked: 2

  1. Jack CR Jr, Knopman DS, Weigand SD, et al. An opera- tional approach to NIA-AA criteria for preclinical Alzhei- mer's disease. Ann Neurol 2012;71:765-775.
  2. Fagan AM, Head D, Shah AR, et al. Decreased cerebrospi- nal fluid Abeta(42) correlates with brain atrophy in cogni- tively normal elderly. Ann Neurol 2009;65:176 -183.

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Authors
Mielke, M. M., Wiste, H. J., Weigand, S. D., Knopman, D. S., Lowe, V. J., Roberts, R. O., Geda, Y. E., Swenson-Dravis, D. M., Boeve, B. F., Senjem, M. L., Vemuri, P., Petersen, R. C., & Jack, C. R.
Affiliations
Mayo Clinic (US)
Venue
Neurology
Published
2012-10-09
Volume
79
Issue
15
Pages
1570-1577
ISSN
  • 0028-3878 (ISSN-L)
  • 1526-632X
OpenAlex
W2004344916
Cited by
163
References
34
Citations by year
2026: 1 · 2025: 6 · 2024: 6 · 2023: 12 · 2022: 12 · 2021: 13 · 2020: 12 · 2019: 17 · 2018: 11 · 2017: 15 · 2016: 10 · 2015: 17 · 2014: 14 · 2013: 15 · 2012: 2
FWCI
10.97
Type
journal article
Language
en
Open access
Locations
  • Neurology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Robert Wood Johnson Foundation
  • Alzheimer's Association
  • Eli Lilly and Company
  • Pfizer (R01 AG034676)
  • Baxter International
  • Mayo Foundation for Medical Education and Research (AG034676, AG016574, R01-AG034676)
  • European Commission
  • Eisai
  • National Institutes of Health (AG016574, AG034676, AG006786, AG011378)
  • National Institute on Aging (R01AG034676, AG-034676, U01AG037526, AG016574, AG011378, U01AG006786, AG-006786, R01AG011378, K01AG028573, RO1 AG011378, R01AG041851, R01 AG0113, P50AG016574)
  • National Institute of Mental Health (K01MH068351)
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
cerebral amyloidosis, Pittsburgh compound B PET, preclinical Alzheimer's disease, cognitively normal elderly, APOE ε4, age as predictor, subjective memory complaints, screening biomarkers, number needed to screen, Mayo Clinic Study of Aging
MeSH terms
Aged, Aged, 80 and over, Alzheimer Disease, Amyloid, Apolipoproteins E, Brain, Brain Mapping, Cognition, Female, Genotype, Humans, Male, Neuropsychological Tests, Radionuclide Imaging

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