Procedures-Manual--Control-Series-.ppt

Procedures Manual,Control Series,&Phenotype Committee UpdateStephanie Doan,MPHStephanie Doan,MPHNIA AD Genetics Initiative Co-CoordinatorNIA AD Genetics Initiative Co-CoordinatorColumbia UniversityColumbia UniversityAlzheimers Disease Genetics Initiative Procedures Manualn nwww.NIAgeneticsinitiative.orgn nUsername:LOADUsername:LOADPassword:manual(both case sensitive)Password:manual(both case sensitive)New Additions:New Additions:n nUpdated the Minimum Data Set to include a question Updated the Minimum Data Set to include a question for controls,11 additional autopsy-specific questions,for controls,11 additional autopsy-specific questions,16 new cognitive testing variables,GENRSCH 16 new cognitive testing variables,GENRSCH variable.variable.n nSection 16:Control SeriesSection 16:Control SeriesAlzheimers Disease Genetics Initiative Procedures ManualControl Seriesn nEach center will ascertain 50-60,non-demented Each center will ascertain 50-60,non-demented control subjectscontrol subjectsn nOverall goal of 1,000 controlsOverall goal of 1,000 controlsn nMinimum age of 60Minimum age of 60n nNo subjective complaints of memory loss or No subjective complaints of memory loss or cognitive declinecognitive declinen nNo history of major neurological or psychiatric No history of major neurological or psychiatric disorders and no life-threatening conditionsdisorders and no life-threatening conditionsn nFrequency matching based on demographic profilesFrequency matching based on demographic profiles-will be done at NCRAD-will be done at NCRADControl Series cont.n nExclusion CriteriaExclusion Criteria:-CurrentCurrent diagnosis of schizophrenia,bipolar,diagnosis of schizophrenia,bipolar,disorder,major depression,OCD,anxiety/panicdisorder,major depression,OCD,anxiety/panicDisorder.Disorder.-Current diagnosis-Current diagnosis oror history of PD,AD,MS,brain history of PD,AD,MS,braintumor,and HD.tumor,and HD.n nThere should only be There should only be 1 control per family1 control per family(siblings,(siblings,cousins,etc.should not be enrolled as controls).cousins,etc.should not be enrolled as controls).Family Pedigree 1A Qualifies!Family Pedigree 1B Does not qualify!Does not qualify!Control Series cont.n nAbsence of cognitive impairment must have been Absence of cognitive impairment must have been documented within the last year either by documented within the last year either by neuropsychological testing or by neuropsychological testing or by semiquantitativesemiquantitative neurological or psychiatric examination.neurological or psychiatric examination.n nControl can be a spouse of a Control can be a spouse of a probandproband(up to 50%)(up to 50%)unless his/her offspring has been included in the unless his/her offspring has been included in the family ascertainment and is diagnosed with AD.family ascertainment and is diagnosed with AD.Family Pedigree 2B(LOAD family)(LOAD family)Does not qualify!Does not qualify!Control Series cont.n nThe minimum dataset must be filled out for controls.n nCognitive testing will be administered.n nFollow up a minimum of every 2-3 years.n nID Scheme-Center IDCenter ID-Family ID-Family ID-Individual ID-Individual ID-Mother ID-Mother ID-Father ID-Father IDPhenotype Committeesn nWorking groups appointed to standardize methods for querying n nAge-at-onsetAge-at-onsetn nNeuropathology Neuropathology n nCognitive TestingCognitive Testingn nBiomarkers(collection of biological fluids for Biomarkers(collection of biological fluids for biomarkers)biomarkers)Age at Onset(AAO)Committeen nLOAD minimum data set required variable:LOAD minimum data set required variable:At what age did the subject develop dementiaAt what age did the subject develop dementiasymptoms?symptoms?n nAAO should be identified through a clinical history,AAO should be identified through a clinical history,by a knowledgeable caregiver or family member.by a knowledgeable caregiver or family member.n nMemory decline should be accompanied by Memory decline should be accompanied by symptoms that reflect significant functional change in symptoms that reflect significant functional change in the individuals abilities i.e.in the individuals abilities i.e.in judgementjudgement,home,home activities,and orientation.activities,and orientation.*Probing questions for AAO will be added to Data Element Dictionary of the Procedures Manual.Neuropath/Autopsy Committeen nCentral Question:Central Question:How much How much neuropathicneuropathic information is information is appropriate for the minimum data set?appropriate for the minimum data set?n nThe committee elected to add the following questions to the The committee elected to add the following questions to the database regarding autopsy:database regarding autopsy:12c.Were CERAD criteria used?12c.Were CERAD criteria used?12d.If CERAD were used,what category was assigned?12d.If CERAD were used,what category was assigned?12e.Were NIA-Reagan criteria used?12e.Were NIA-Reagan criteria used?12f.If NIA-Reagan were used,what category was assigned?12f.If NIA-Reagan were used,what category was assigned?12g.Were the 12g.Were the BraakBraak and and BraakBraak criteria used?criteria used?12h.If 12h.If BraakBraak and and BraakBraak were used,what category was assigned?were used,what category was assigned?12i12i.Was another.Was another neuropathologicalneuropathological criteria used?criteria used?12j.Describe the type of 12j.Describe the type of neuropathologicalneuropathological criteria and assigned category.criteria and assigned category.12k.If 12k.If LewyLewy bodies were present,in what part of the brain were they found?bodies were present,in what part of the brain were they found?12l.What stain was used to look for 12l.What stain was used to look for LewyLewy bodies?bodies?12m.Describe the type of stain used to look for 12m.Describe the type of stain used to look for LewyLewy bodies.bodies.Cognitive Testing Committeen nNew battery consists of 7 cognitive tests:New battery consists of 7 cognitive tests:1.1.Logical Memory IALogical Memory IA2.2.Digit Span ForwardDigit Span Forward3.3.Digit Span BackwardDigit Span Backward4.4.Category Fluency:AnimalsCategory Fluency:Animals5.5.Category Fluency:Fruits&VegetablesCategory Fluency:Fruits&Vegetables6.6.Digit OrderingDigit Ordering7.7.Logical Memory IIALogical Memory IIAn nMinimize burden on all programs and sites.Minimize burden on all programs and sites.Biomarkersn nGoal is to collect and store plasma and serum from all participating family members.n nInvestigators will be able to use these samples as quantitative trait biomarkers in families with AD.n nDr.Mayeux has met with Pall Corporation to develop a field method for isolating plasma without centrifugation.n nNot ready to start collecting.