Design Considerations for Characterizing Psychiatric Trajectories Across the Lifespan: Application to Effects of APOE-ε4 on Cerebral Cortical Thickness in Alzheimer's Disease
Open accessAbstract
Characterization of developmental trajectories across the lifespan is integral to understanding the prodromal course of many neuropsychiatric illnesses and the significant risk factors for disease onset or unfavorable outcomes. However, the standard experimental designs used in psychiatric research are not ideal for this purpose. The authors review the limitations of the most commonly employed designs in studies that make developmental or lifespan inferences in psychiatry: cross-sectional, single-cohort longitudinal, and unstructured multicohort longitudinal designs. Cross-sectional studies completely confound within- and between-subject sources of variation and hence rely on the presence of parallel trajectories and negligible sampling and age cohort differences for making valid developmental inferences. Delineating trajectories of within-individual change over substantial periods of time requires data covering long age spans that often cannot be covered using single-cohort longitudinal designs. Unstructured multicohort longitudinal designs are a commonly used alternative that can cover a longer age span in a shorter interval than necessary for a single-cohort design. However, the impact of cohort and sampling effects is often minimized or ignored in unstructured multicohort longitudinal designs. The authors propose that structured multicohort longitudinal designs are a particularly viable and underutilized class of designs in psychiatry that represents a significant improvement over cross-sectional designs and unstructured multicohort longitudinal designs for making developmental inferences while being more practical to implement than single-cohort longitudinal designs. As an example of this approach, the authors analyze changes in entorhinal cortex thickness in Alzheimer's disease in relation to APOE-ε4 genotype.
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Longitudinal analyses can provide a better estimate of the true pathological trajectories.
“Longitudinal analyses can provide a better estimate of the true pathological trajectories.17,18”
From Spatial patterns of neuroimaging biomarker change in individuals from families with autosomal dominant Alzheimer's disease: a longitudinal study (2018) · cites this paper as [17]
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- Authors
- Thompson, W. K., Hallmayer, J., O'Hara, R., & Initiative, T. A. D. N.
- Affiliations
- United States Department of Veterans Affairs (US)
- Venue
- American Journal of Psychiatry
- Published
- 2011-09
- Volume
- 168
- Issue
- 9
- Pages
- 894-903
- ISSN
- 0002-953X (ISSN-L)
- 1535-7228
- PMC
- PMC5493321
- OpenAlex
- W1970086933
- Cited by
- 79
- References
- 30
- Citations by year
- 2025: 5 · 2024: 2 · 2023: 5 · 2022: 2 · 2021: 8 · 2020: 7 · 2019: 5 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 6 · 2014: 10 · 2013: 5 · 2012: 6
- FWCI
- 4.76
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (5u01ag024904-10)
- National Institute on Aging (U01-AG-024904, AG-17824, AG18784, P30AG010129, P30AG017824, K01AG030514, P01AG018784)
- National Institute of Mental Health (R01MH070886, MH070886, R01MH067005, K25MH076981)
- National Institute of General Medical Sciences (R01GM104400)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods and Bayesian Inference
- Keywords
- lifespan development, research design, cross-section design, cohort effects, sampling effects, APOE ε4, Alzheimer's disease, entorhinal cortex thickness, prodromal neurodegeneration
- MeSH terms
- Age Factors, Aged, Aged, 80 and over, Alzheimer Disease, Cerebral Cortex, Female, Genotype, Humans, Individuality, Longitudinal Studies, Magnetic Resonance Imaging, Male, Middle Aged, Organ Size, Research Design, Cohort Studies, Age of Onset, Disease Progression, Entorhinal Cortex, Apolipoprotein E4
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