FOA Title: 
Notice to Specify High-Priority Research Topic for PAR-19-070 and PAR-19-071
Grant Type: 
Primary IC: 
Release Date: 
Dec 17 2018
Expiration Date: 
AC Source: 
Notice Specify High-Priority Research Topic PAR-19-070 PAR-19-071 Notice Number: NOT-AG-18-053 Key Dates Release Date: December 17, 2018 Related Announcements PAR-19-070 PAR-19-071 Issued National Institute Aging NIA) Purpose Notice Information specifies high-priority topic interest PAR-19-070 Research Current Topics Alzheimer's Disease Its Related Dementias R01 Clinical Trial Optional)" PAR-19-071 ldquo;Research Current Topics Alzheimer's Disease Its Related Dementias R21 Clinical Trial Allowed)”. Note applications proposing exploratory developmental projects which are insufficient preliminary data well certain focused secondary analysis projects should consider using R21 FOA, whereas projects already sufficient preliminary data a very strong well-developed scientific premise should the R01 FOA. Major Opportunities Research Epidemiology Alzheimer's Disease Related Dementias Cognitive Resilience Background etiology Alzheimer’s disease related dementias AD/ADRD) proven be complex expected. Our existing cohort studies both AD/ADRD cognitive aging include social, behavioral, cognitive, neuroimaging, biomarker, genetic, epigenetic, other measures assessed longitudinally collected initially ever earlier the lifespan. Indeed, is becoming clear both risk protective factors include exposures experiences early mid-life, long before appearance any neuropathology notable cognitive decline. Continued progress the epidemiology both AD/ADRD cognitive resilience therefore likely require cohorts, diverse cohorts, participants, variables, more occasions measurement. Additionally, greater collaboration among diverse scientific disciplines be needed. Research Objectives high-priority topic encourages investigator-initiated research all aspects cognitive epidemiology relevant AD/ADRD cognitive resilience identifies specific areas build current efforts supported NIA new recommendations the 2018 Alzheimer’s Disease Research Summit see: for information). following areas of particular interest the NIA. Augmenting existing longitudinal cohort studies National Institutes Health NIH) supports broad range population studies address questions related the trajectory Alzheimer’s disease other aging phenotypes. collection analysis new phenotypic information, including not limited new biomarkers, neuroimaging, non-traditional data modalities such that wearable sensors, broaden impact existing studies. addition genetic data existing newly collected cohorts the light existing novel phenotypes allow analyses how specific genetic variants polygenic risk scores contribute the risk or protection against AD/ADRD the trajectory cognitive performance. emerging opportunities stem the wider availability electronic health records administrative data e.g., CMS Medicare claims) the ability collect phenotypic data online lower cost. Enabling precision medicine AD/ADRD through deep molecular phenotyping precision-medicine approach see: presents new opportunities understanding molecular determinants AD/ADRD risk cognitive resilience diverse populations at level the individual. Notice invites applications will enhance potential community-based cohort studies enable precision medicine AD/ADRD by, example: expanding types cross-sectional longitudinal ante- post-mortem-biospecimen data-collection needed generate multiple layers ldquo;omics” data; incorporating dense molecular endophenotyping e.g., genomic, epigenomic, proteomic, metabolomic, microbiomic); collecting nontraditional data modalities using wearable sensors mobile-health technologies; embedding biomarkers environmental exposure geocodes. large-scale multidimensional data generated the above approaches serve the basis future systems biology gene-environment studies the development a new taxonomy AD/ADRD prevention. Enhancing power multiethnic cohort studies. multi-factorial etiology heterogeneity AD/ADRD reveal itself racial ethnic differences overall AD/ADRD risk in putative risk protective factors in progression neuropathology. Although multi-ethnic cohorts be very informative, well-powered cohort studies needed identify specific risk protective factors vary between sub)populations. cohorts also benefit the addition measures may better help us identify determinants both disease risk cognitive resilience. 2015 Alzheimer’s Disease Research Summit includes recommendation establish new cohorts intense endophenotyping are sufficiently powered analyze effects gender diverse populations. Exploring trends the risk AD/ADRD their explanation via putative risk protective factors. Recent research well-characterized cohorts suggests age-specific risk AD/ADRD be declining some populations increasing others. answer the trend question clear implications public health policy. Trend data also provide potentially powerful to test whether putative risk protective factors truly causal. example, educational attainment appears be protective against AD/ADRD whereas both cardiovascular disease CVD) female sex confer additional risk. the reasons these observed patterns not yet clear. risk posed female sex status, example, reflect sex differences affecting disease process, may include differences the trajectory hormonal changes age in sex chromosome, gender differences educational attainment all these. Comparisons between cohorts differing these factors over time be informative may require sophisticated analyses meta-analyses replication plans. Collecting sequencing DNA samples well-characterized cases controls. Research conducted investigators the Alzheimer’s Disease Sequencing Project ADSP; see: others demonstrated value whole-genome whole-exome sequencing the detection genetic variants may modify AD risk protection. sequencing more genomes well-characterized cases controls family based cohorts large multiply-affected families accelerate gene discovery target identification efforts to accelerate progress the drug development pipeline. Well-characterized subjects diversity sample sets especially needed augment statistical power. Applicants interested this line research should aware current emerging NIH guidance respect sharing genomic data see: are expected facilitate rapid data-sharing according existing ADSP NIA policies, include providing types data the ADSP NIAGADS/dbGaP database Electronic archiving cohort studies Although NIH encourages broad inclusive data-sharing large studies, electronic archiving data many longitudinal cohorts either incomplete relies data infrastructure is vulnerable research-funding lapses. current NIH Strategic Plan Data Science see: for additional information) focuses enhancing discoverability usability data sets developing appropriate analysis tools, providing special opportunities collaboration between epidemiologists survey scientists the hand computer data scientists the other. addition a wealth information relevant cognitive epidemiology is trapped non-digitized obsolete formats, are highly relevant data sets biospecimen collections have never publicly shared well surveys where greater availability paradata metadata benefit researchers. welcome applications will more data available use the research community expeditiously possible, likewise encourage dissemination efforts enhance discoverability these data. Harmonizing complex data sets relevant AD/ADRD Although have substantial efforts NIH develop brief, reliable measures e.g., PROMIS® the NIH Toolbox®; see: for information) well recommendations the of off-the-shelf phenotypic measures e.g., PhenX) large epidemiological studies, has less work creating crosswalks between measures those have historically used cohort studies. need harmonization across platforms particularly acute studies include longitudinal clinical, neuroimaging, genetic genomic, biomarker data are costly obtain. Coordination harmonization data existing cohort studies the Alzheimer’s Disease Neuroimaging Initiative ADNI; see: more), Accelerating Medicines Partnership AMP) effort AD/ADRD see:, the ADSP see: also welcome. Harmonizing dementia assessment enhance cross-national comparisons. important harmonization to study dementia trends the risk protective factors against dementia) differ between cohorts, work needed the harmonization dementia-assessment methods could inform cross-national comparisons. requires than simple translation instruments, since even best ones not operate equivalently developing countries where literacy rates levels educational attainment much lower. recent examples where work being done the 10/66 Dementia Research Group see: lower income countries more recent work done within US-based Health Retirement Study HRS; see: Both examples a harmonized cognitive assessment protocol HCAP) can used compare dementia prevalence higher- lower-income countries. Applications use extend approaches develop new approaches harmonize dementia assessment suitable cross-national comparisons feasible both clinical field settings encouraged. Inquiries Please direct inquiries to: Dallas W. Anderson, Ph.D. Division Neuroscience  National Institute Aging NIA) Telephone: 301-496-1494  Email: Jonathan W. King, Ph.D. Division Behavioral Social Research  National Institute Aging NIA)  Telephone: 301-402-4156  Email:
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