Different cohort, disparate results: Selection bias is a key factor in autopsy cohorts

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26 Scopus citations

Abstract

INTRODUCTION: Research-oriented autopsy cohorts provide critical insights into dementia pathobiology. However, different studies sometimes report disparate findings, partially because each study has its own recruitment biases. We hypothesized that a straightforward metric, related to the percentage of research volunteers cognitively normal at recruitment, would predict other inter-cohort differences. METHODS: The National Alzheimer's Coordinating Center (NACC) provided data on N = 7178 autopsied participants from 28 individual research centers. Research cohorts were grouped based on the proportion of participants with normal cognition at initial clinical visit. RESULTS: Cohorts with more participants who were cognitively normal at recruitment contained more individuals who were older, female, had lower frequencies of apolipoprotein E ε4, Lewy body disease, and frontotemporal dementia, but higher rates of cerebrovascular disease. Alzheimer's disease (AD) pathology was little different between groups. DISCUSSION: The percentage of participants recruited while cognitively normal predicted differences in findings in autopsy research cohorts. Most differences were in non-AD pathologies. Highlights: Systematic differences exist between autopsy cohorts that serve dementia research. We propose a metric to use for gauging a research-oriented autopsy cohort. It is essential to consider the characteristics of autopsy cohorts.

Original languageEnglish
Pages (from-to)266-277
Number of pages12
JournalAlzheimer's and Dementia
Volume20
Issue number1
DOIs
StatePublished - Jan 2024

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.

Funding

The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA-funded ADCs: P50 AG005131 (PI James Brewer, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG005138 (PI Mary Sano, PhD), P50 AG005142 (PI Helena Chui, MD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005681 (PI John Morris, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG008051 (PI Thomas Wisniewski, MD), P50 AG008702 (PI Scott Small, MD), P30 AG010124 (PI John Trojanowski, MD, PhD), P30 AG010129 (PI Charles DeCarli, MD), P30 AG010133 (PI Andrew Saykin, PsyD), P30 AG010161 (PI David Bennett, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG013854 (PI Robert Vassar, PhD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P30 AG019610 (PI Eric Reiman, MD), P50 AG023501 (PI Bruce Miller, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG028383 (PI Linda Van Eldik, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P30 AG035982 (PI Russell Swerdlow, MD), P50 AG047266 (PI Todd Golde, MD, PhD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG049638 (PI Suzanne Craft, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Marwan Sabbagh, MD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD). Dr. Nelson is supported by NIA/NIH grants R01 AG061111, RF1 NS118584. Dr. Katsumata is supported by NIA/NIH grants R56AG057191, R01AG057187, R21AG061551, R01AG054060, and the UK-ADC P30AG028383 from the National Institute on Aging. No direct funding for this study to report. The NACC database is funded by NIA/NIH Grant U24 AG072122. NACC data are contributed by the NIA‐funded ADCs: P50 AG005131 (PI James Brewer, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG005138 (PI Mary Sano, PhD), P50 AG005142 (PI Helena Chui, MD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005681 (PI John Morris, MD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG008051 (PI Thomas Wisniewski, MD), P50 AG008702 (PI Scott Small, MD), P30 AG010124 (PI John Trojanowski, MD, PhD), P30 AG010129 (PI Charles DeCarli, MD), P30 AG010133 (PI Andrew Saykin, PsyD), P30 AG010161 (PI David Bennett, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG013846 (PI Neil Kowall, MD), P30 AG013854 (PI Robert Vassar, PhD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P30 AG019610 (PI Eric Reiman, MD), P50 AG023501 (PI Bruce Miller, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P30 AG028383 (PI Linda Van Eldik, PhD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P30 AG035982 (PI Russell Swerdlow, MD), P50 AG047266 (PI Todd Golde, MD, PhD), P50 AG047270 (PI Stephen Strittmatter, MD, PhD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG049638 (PI Suzanne Craft, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG066546 (PI Sudha Seshadri, MD), P20 AG068024 (PI Erik Roberson, MD, PhD), P20 AG068053 (PI Marwan Sabbagh, MD), P20 AG068077 (PI Gary Rosenberg, MD), P20 AG068082 (PI Angela Jefferson, PhD), P30 AG072958 (PI Heather Whitson, MD), P30 AG072959 (PI James Leverenz, MD). Dr. Nelson is supported by NIA/NIH grants R01 AG061111, RF1 NS118584. Dr. Katsumata is supported by NIA/NIH grants R56AG057191, R01AG057187, R21AG061551, R01AG054060, and the UK‐ADC P30AG028383 from the National Institute on Aging. No direct funding for this study to report.

FundersFunder number
UK-ADC
UK-ADCP30AG028383
National Institutes of Health (NIH)P30 AG013846, P30 AG028383, P30 AG008017, P30 AG053760, R01AG057187, P30 AG010133, P50 AG005146, P50 AG033514, P50 AG005142, P50 AG005681, R56AG057191, P50 AG047366, P50 AG047266, R21AG061551, P20 AG068053, P20 AG068077, P30 AG019610, RF1 NS118584, P50 AG023501, P30 AG008051, P30 AG010129, P30 AG013854, P30 AG072958, P30 AG072959, P50 AG005138, P50 AG008702, P30 AG010124, P30 AG012300, P50 AG005134, P50 AG005136, P50 AG025688, P50 AG047270, R01AG054060, P30 AG035982, P30 AG010161, P30 AG066546, P50 AG005131, P50 AG005133, P30 AG049638, P50 AG016574, P20 AG068082, U24 AG072122, P20 AG068024, P50 AG016573, R01 AG061111
National Institutes of Health (NIH)
National Institute on Aging

    UN SDGs

    This output contributes to the following UN Sustainable Development Goals (SDGs)

    1. SDG 3 - Good Health and Well-being
      SDG 3 Good Health and Well-being

    Keywords

    • Alzheimer's disease neuropathologic change
    • TAR DNA-binding protein 43
    • cerebrovascular
    • dementia with Lewy bodies
    • epidemiology
    • frontotemporal dementia
    • frontotemporal lobar degeneration with TDP-43
    • infarction
    • limbic-predominant age-related TDP-43 encephalopathy neuropathologic change
    • neuropathology
    • plaques
    • prevalence
    • stroke
    • synuclein
    • tangles

    ASJC Scopus subject areas

    • Epidemiology
    • Health Policy
    • Developmental Neuroscience
    • Clinical Neurology
    • Geriatrics and Gerontology
    • Cellular and Molecular Neuroscience
    • Psychiatry and Mental health

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