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Alzheimer's Disease Sequencing Project discovery and replication criteria for cases and controls: Data from a community-based prospective cohort study with autopsy follow-up.

TitleAlzheimer's Disease Sequencing Project discovery and replication criteria for cases and controls: Data from a community-based prospective cohort study with autopsy follow-up.
Publication TypeJournal Article
Year of Publication2017
AuthorsCrane, PK, Foroud, T, Montine, TJ, Larson, EB
JournalAlzheimers Dement
Volume13
Issue12
Pagination1410-1413
Date Published2017 Dec
ISSN1552-5279
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Autopsy, Cohort Studies, Female, Humans, Male, Neurofibrillary Tangles, Neuropsychological Tests, Plaque, Amyloid, Psychiatric Status Rating Scales, Residence Characteristics, Thinking
Abstract

INTRODUCTION: The Alzheimer's Disease Sequencing Project (ADSP) used different criteria for assigning case and control status from the discovery and replication phases of the project. We considered data from a community-based prospective cohort study with autopsy follow-up where participants could be categorized as case, control, or neither by both definitions and compared the two sets of criteria.

METHODS: We used data from the Adult Changes in Thought (ACT) study including Diagnostic and Statistical Manual-IV criteria for dementia status, McKhann et al. criteria for clinical Alzheimer's disease, and Braak and Consortium to Establish a Registry for AD findings on neurofibrillary tangles and neuritic plaques to categorize the 621 ACT participants of European ancestry who died and came to autopsy. We applied ADSP discovery and replication definitions to identify controls, cases, and people who were neither controls nor cases.

RESULTS: There was some agreement between the discovery and replication definitions. Major areas of discrepancy included the finding that only 40% of the discovery sample controls had sufficiently low levels of neurofibrillary tangles and neuritic plaques to be considered controls by the replication criteria and the finding that 16% of the replication phase cases were diagnosed with non-AD dementia during life and thus were excluded as cases for the discovery phase.

CONCLUSIONS: These findings should inform interpretation of genetic association findings from the ADSP. Differences in genetic association findings between the two phases of the study may reflect these different phenotype definitions from the discovery and replication phase of the ADSP.

DOI10.1016/j.jalz.2017.09.010
Alternate JournalAlzheimers Dement
PubMed ID29055816
PubMed Central IDPMC5723534
Grant ListU01 AG006781 / AG / NIA NIH HHS / United States