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

Abstract

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. 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. 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. The percentage of participants recruited while cognitively normal predicted differences in findings in autopsy research cohorts. Most differences were in non-AD pathologies. 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.