Scientific article

Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum

CollaboratorsFrisoni, Giovanni
Published inJAMA neurology, vol. 79, no. 3, p. 228-243
Publication date2022-03-01
First online date2022-01-31

Importance One characteristic histopathological event in Alzheimer disease (AD) is cerebral amyloid aggregation, which can be detected by biomarkers in cerebrospinal fluid (CSF) and on positron emission tomography (PET) scans. Prevalence estimates of amyloid pathology are important for health care planning and clinical trial design.

Objective To estimate the prevalence of amyloid abnormality in persons with normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia and to examine the potential implications of cutoff methods, biomarker modality (CSF or PET), age, sex, APOE genotype, educational level, geographical region, and dementia severity for these estimates.

Design, Setting, and Participants This cross-sectional, individual-participant pooled study included participants from 85 Amyloid Biomarker Study cohorts. Data collection was performed from January 1, 2013, to December 31, 2020. Participants had normal cognition, subjective cognitive decline, mild cognitive impairment, or clinical AD dementia. Normal cognition and subjective cognitive decline were defined by normal scores on cognitive tests, with the presence of cognitive complaints defining subjective cognitive decline. Mild cognitive impairment and clinical AD dementia were diagnosed according to published criteria.

Exposures Alzheimer disease biomarkers detected on PET or in CSF.

Main Outcomes and Measures Amyloid measurements were dichotomized as normal or abnormal using cohort-provided cutoffs for CSF or PET or by visual reading for PET. Adjusted data-driven cutoffs for abnormal amyloid were calculated using gaussian mixture modeling. Prevalence of amyloid abnormality was estimated according to age, sex, cognitive status, biomarker modality, APOE carrier status, educational level, geographical location, and dementia severity using generalized estimating equations.

Results Among the 19 097 participants (mean [SD] age, 69.1 [9.8] years; 10 148 women [53.1%]) included, 10 139 (53.1%) underwent an amyloid PET scan and 8958 (46.9%) had an amyloid CSF measurement. Using cohort-provided cutoffs, amyloid abnormality prevalences were similar to 2015 estimates for individuals without dementia and were similar across PET- and CSF-based estimates (24%; 95% CI, 21%-28%) in participants with normal cognition, 27% (95% CI, 21%-33%) in participants with subjective cognitive decline, and 51% (95% CI, 46%-56%) in participants with mild cognitive impairment, whereas for clinical AD dementia the estimates were higher for PET than CSF (87% vs 79%; mean difference, 8%; 95% CI, 0%-16%; P = .04). Gaussian mixture modeling–based cutoffs for amyloid measures on PET scans were similar to cohort-provided cutoffs and were not adjusted. Adjusted CSF cutoffs resulted in a 10% higher amyloid abnormality prevalence than PET-based estimates in persons with normal cognition (mean difference, 9%; 95% CI, 3%-15%; P = .004), subjective cognitive decline (9%; 95% CI, 3%-15%; P = .005), and mild cognitive impairment (10%; 95% CI, 3%-17%; P = .004), whereas the estimates were comparable in persons with clinical AD dementia (mean difference, 4%; 95% CI, −2% to 9%; P = .18).

Conclusions and Relevance This study found that CSF-based estimates using adjusted data-driven cutoffs were up to 10% higher than

  • Aged
  • Alzheimer Disease / cerebrospinal fluid
  • Alzheimer Disease / diagnostic imaging
  • Alzheimer Disease / epidemiology
  • Amyloid beta-Peptides / cerebrospinal fluid
  • Amyloidogenic Proteins
  • Amyloidosis
  • Apolipoproteins E / genetics
  • Biomarkers / cerebrospinal fluid
  • Cognitive Dysfunction / diagnostic imaging
  • Cognitive Dysfunction / epidemiology
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptide Fragments / cerebrospinal fluid
  • Positron-Emission Tomography
  • Prevalence
  • Tau Proteins / cerebrospinal fluid
Citation (ISO format)
JANSEN, Willemijn J. et al. Prevalence Estimates of Amyloid Abnormality Across the Alzheimer Disease Clinical Spectrum. In: JAMA neurology, 2022, vol. 79, n° 3, p. 228–243. doi: 10.1001/jamaneurol.2021.5216
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Article (Published version)
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ISSN of the journal2168-6149

Technical informations

Creation11/16/2022 1:10:53 PM
First validation09/25/2023 10:57:41 AM
Update time09/25/2023 10:57:41 AM
Status update09/25/2023 10:57:41 AM
Last indexation02/01/2024 10:42:23 AM
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