In order to translate epidemiologic research into actionable interventions, highly detailed research results are needed. For example, fish intake may associate with reduced risk of Alzheimer's disease but what type of fish and what "dose" or duration of intake? Type 2 diabetes may associate with cognitive decline but which treatments of diabetes can reduce that risk? Does the efficacy of potential prevention treatments or risk factors vary depending on patient characteristics such as age, gender, cognitive status, genotype, or comorbidities?
These questions require extremely large sample sizes that might be best obtained by pooling or meta-analyzing the data from existing cohorts. The Alzheimer's Drug Discovery Foundation is interested in funding cross-cohort pooled analyses of actionable interventions to potentially protect against cognitive aging, Alzheimer's disease, and related dementias.
- Outcomes of interest include cognition (neuropsychologic testing), diagnosis of dementia or mild cognitive impairment, and relevant neurologic biomarkers.
- Exposure/risk factor variables of interest include drugs used to manage other health conditions, natural products, dietary supplements, specific dietary ingredients, and biomarkers that can indicate these choices. Variables related to exercise or public health issues are not a priority.
Successful applications will incorporate data from five or more cohorts that contain quality data relevant to the proposed analysis. Cohorts participating in CAPA are listed below (other cohorts may also be acceptable). Full applications must include a letter of support or proof of access to data for each cohort intended for inclusion. Projects can either pool data harmonized across cohorts in a single analysis, meta-analyze parallel analyses of individual cohorts with the help of a shared analysis script, or both.
Applications should include:
- Pre-specified protocols, hypotheses, and primary and secondary outcomes
- The number of cohorts, total sample size, and sample size calculation to ensure sufficient power for the intended analyses (the inclusion of cohort data that is currently unpublished is strongly encouraged)
- Details of the analytical plan, including careful consideration of the challenges in harmonizing and combining data
- Details of exposure variables and outcomes variables (e.g., cognitive assessment related biomarkers or diagnoses)—although long-term prospective follow-up is preferred, cross-sectional outcomes will be considered if that enables higher quality analyses on exposure variables.
- The risks of confounding and biases such as selection bias, attrition bias, measurement error bias, and (if reviewing clinical care exposure variables) confounding by indication. Applications should discuss how they plan to evaluate and address these issues as well as missing data.
Mechanisms of Support
Up to $100,000 is available in funding for each proposal, provided that it is commensurate with the work plan. Grant funds can be provided fully to the primary investigator, with intent to distribute across participating cohorts as needed. Successful analyses may serve as pilot projects to encourage further funds from the ADDF, other nonprofits, or the NIH.
Review Process
While full applications will require a letter-of-support from every cohort planned to participate in the analysis, the LOI must simply specify which cohorts contain relevant data for the proposed analysis. Full applications will be confidentially reviewed by the ADDF and an external Scientific Review Committee.
Cohorts Participating in the CAPA consortium, as of October 23, 2014
Adult Changes in Thought study (ACT)
Aging Gene-Environment Susceptibility — Reykjavik Study (AGES-Reykjavik)
Australian Longitudinal Study of Aging (ALSA)
Austrian Stroke Prevention Study (ASPS)
Canadian Study of Health and Aging (CSHA)
Erasmus Rucphen Family (ERF) Cohort
Framingham Heart Study (FHS)
Ginkgo biloba for Preventing Cognitive Decline in Older Adults (GEMS)
Gerontological and Geriatric Population Studies in Göteborg, Sweden (H-70)
Health, Aging, and Body Composition Study (Health ABC)
Hertfordshire Cohort Study (HCS)
Irish Longitudinal Study on Ageing (TILDA)
Longitudinal Study of Cognitive Change in Normal, Healthy Old Age (LSCC)
Longitudinal Study of Generations (LSG)
Mayo Clinic Study of Aging (MCSA)
Medical Research Council National Survey of Health and Development (MRC NSHD)
Midlife in the U.S. (MIDUS)
Minority Aging Research Study (MARS)
VA Normative Aging Study (NAS)
The Northern Manhattan Study (NOMAS)
Nurses’ Health Study (NHS)
Osteoporotic Fractures in Men Study (MrOS)
Personality & Total Health (PATH) Through Life
Personnes Agees Quid (PAQUID)
The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER)
Religious Orders Study (ROS)
Rotterdam Study I, II and III
Rush Memory and Aging Project (MAP)
Seattle Longitudinal Study (SLS)
Study of Health in Pomerania (SHIP)
Study of Osteoporotic Fractures (SOF)
University of North Carolina Alumni Heart Study (UNCAHS)
Uppsala Longitudinal Study on Adult Men (ULSAM)
Wisconsin Longitudinal Study (WLS)
Washington Heights/Inwood Columbia Aging Project (WHICAP)
Women's Genome Health Study (WGHS)
Women's Health Initiative Memory Study (WHIMS) — ancillary study to WHI
Women's Health Initiative Study of Cognitive Aging (WHISCA) — ancillary study to WHIMS
WHIMS MRI 1 & 2 — ancillary to WHISCA