BothAlzheimer'sdisease(AD)anddepressionhavebecomeincreasinglymoreprevalentin thehomeboundelderly,leadingtoincreasedratesofmorbidity,nursinghomeplacementand mortality,thanwhatarefoundinthegeneralelderlypopulation.Ourcross!sectionalstudyofan establishedhomeboundpopulationintheBostonareahasfoundthatlowplasmaamyloid!b42 (Ab42)isassociatedwithdepressionindependentlyofcardiovasculardisease.Wefurther foundthatdepressionwithlowAb42combinedwithhighAb40inplasmaisassociatedwith poormemory.SimilarlyotherresearchstudieshaveshownthatahighplasmaA?40/A?42 ratiosignificantlyincreasedtheriskofAD.MultiplestudiesdemonstratethatplasmaA? correlateswithcerebralspinalfluid(CSF)A?whencognitionisnormal,butthisequilibrium disappearsaftertheADcognitivesymptomsoccur.Wehypothesizetheexistenceofa potentialdepressionsubtypeassociatedwithAbpeptidesinplasma,whichwehavetermed "amyloid!associateddepression".ThepurposeofthisR01applicationistovalidatethe existenceofamyloid!associateddepressiondefinedbyahighplasmaA?40/A?42ratio,andto investigatewhetherthisdepressionsubtypeisaprodromaldepressionofAD.Theproposalis basedonourestablishedpopulation,andhastwoaims:
Aim1 istodocumentmemorydecline prospectivelyinthosewithamyloid!associateddepressionvs.thosewithnon!amyloid depressionvs.thecontrols.
Aim2 istoinvestigatetherelationshipbetweenplasmaA?and CSFA?,acentralnervoussystem(CNS)biomarkerofAD,inthedifferentdepression subgroups.Ourlong!termgoalistoidentifyprodromalsignsofADtohelpfacilitateearly treatmentofthediseaseinthehomeboundelderlypopulation.

Public Health Relevance

Theproposedlongitudinalstudyseekstovalidateamyloidassociateddepression byinvestigatingwhetherthecombinationofdepressionandahighplasma A?40/A?42ratiowillleadtogreaterriskofcognitivedeclineandthefindingofthe ADbiomarkersinCSFascomparedtothosewithalowplasmaA?40/A?42ratio orthosewithoutdepression.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG031171-05
Application #
8464619
Study Section
Neural Basis of Psychopathology, Addictions and Sleep Disorders Study Section (NPAS)
Program Officer
Hsiao, John
Project Start
2009-07-15
Project End
2014-06-30
Budget Start
2013-07-01
Budget End
2014-06-30
Support Year
5
Fiscal Year
2013
Total Cost
$328,728
Indirect Cost
$126,434
Name
Boston University
Department
Psychiatry
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02118
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