Procedures Manual, Control Series, & Phenotype Committee Update Stephanie Doan, MPH NIA AD Genetics Initiative Co-Coordinator Columbia University

Alzheimer’s Disease Genetics Initiative Procedures Manual Username: LOAD Username: LOAD Password: manual (both case sensitive) New Additions: Updated the Minimum Data Set to include a question for controls, 11 additional autopsy-specific questions, 16 new cognitive testing variables, GENRSCH variable. Updated the Minimum Data Set to include a question for controls, 11 additional autopsy-specific questions, 16 new cognitive testing variables, GENRSCH variable. Section 16: Control Series Section 16: Control Series

Alzheimer’s Disease Genetics Initiative Procedures Manual

Control Series Each center will ascertain 50-60, non-demented control subjects Each center will ascertain 50-60, non-demented control subjects Overall goal of 1,000 controls Overall goal of 1,000 controls Minimum age of 60 Minimum age of 60 No subjective complaints of memory loss or cognitive decline No subjective complaints of memory loss or cognitive decline No history of major neurological or psychiatric disorders and no life-threatening conditions No history of major neurological or psychiatric disorders and no life-threatening conditions Frequency matching based on demographic profiles Frequency matching based on demographic profiles -will be done at NCRAD

Control Series cont. Exclusion Criteria: Exclusion Criteria: -Current diagnosis of schizophrenia, bipolar, disorder, major depression, OCD, anxiety/panic Disorder. -Current diagnosis or history of PD, AD, MS, brain tumor, and HD. There should only be 1 control per family (siblings, cousins, etc. should not be enrolled as controls). There should only be 1 control per family (siblings, cousins, etc. should not be enrolled as controls).

Family Pedigree 1A Qualifies! Qualifies!

Family Pedigree 1B Does not qualify! Does not qualify!

Control Series cont. Absence of cognitive impairment must have been documented within the last year either by neuropsychological testing or by semiquantitative neurological or psychiatric examination. Absence of cognitive impairment must have been documented within the last year either by neuropsychological testing or by semiquantitative neurological or psychiatric examination. Control can be a spouse of a proband (up to 50%) unless his/her offspring has been included in the family ascertainment and is diagnosed with AD. Control can be a spouse of a proband (up to 50%) unless his/her offspring has been included in the family ascertainment and is diagnosed with AD.

Family Pedigree 2B (LOAD family) Does not qualify! Does not qualify!

Control Series cont. The minimum dataset must be filled out for controls. The minimum dataset must be filled out for controls. Cognitive testing will be administered. Cognitive testing will be administered. Follow up a minimum of every 2-3 years. Follow up a minimum of every 2-3 years. ID Scheme ID Scheme - Center ID -Family ID -Individual ID -Mother ID -Father ID

Phenotype Committees Working groups appointed to standardize methods for querying Working groups appointed to standardize methods for querying Age-at-onset Age-at-onset Neuropathology Neuropathology Cognitive Testing Cognitive Testing Biomarkers (collection of biological fluids for biomarkers) Biomarkers (collection of biological fluids for biomarkers)

Age at Onset (AAO) Committee LOAD minimum data set required variable: LOAD minimum data set required variable: At what age did the subject develop dementia symptoms? AAO should be identified through a clinical history, by a knowledgeable caregiver or family member. AAO should be identified through a clinical history, by a knowledgeable caregiver or family member. Memory decline should be accompanied by symptoms that reflect significant functional change in the individual’s abilities i.e. in judgement, home activities, and orientation. Memory decline should be accompanied by symptoms that reflect significant functional change in the individual’s abilities i.e. in judgement, home activities, and orientation. *Probing questions for AAO will be added to Data Element Dictionary of the Procedures Manual.

Neuropath/Autopsy Committee Central Question: How much neuropathic information is appropriate for the minimum data set? Central Question: How much neuropathic information is appropriate for the minimum data set? The committee elected to add the following questions to the database regarding autopsy: The committee elected to add the following questions to the database regarding autopsy: 12c. Were CERAD criteria used? 12d. If CERAD were used, what category was assigned? 12e. Were NIA-Reagan criteria used? 12f. If NIA-Reagan were used, what category was assigned? 12g. Were the Braak and Braak criteria used? 12h. If Braak and Braak were used, what category was assigned? 12i. Was another neuropathological criteria used? 12j. Describe the type of neuropathological criteria and assigned category. 12k. If Lewy bodies were present, in what part of the brain were they found? 12l. What stain was used to look for Lewy bodies? 12m. Describe the type of stain used to look for Lewy bodies.

Cognitive Testing Committee New battery consists of 7 cognitive tests : New battery consists of 7 cognitive tests : 1. Logical Memory IA 2. Digit Span Forward 3. Digit Span Backward 4. Category Fluency: Animals 5. Category Fluency: Fruits & Vegetables 6. Digit Ordering 7. Logical Memory IIA Minimize burden on all programs and sites. Minimize burden on all programs and sites.

Biomarkers Goal is to collect and store plasma and serum from all participating family members. Goal is to collect and store plasma and serum from all participating family members. Investigators will be able to use these samples as quantitative trait biomarkers in families with AD. Investigators will be able to use these samples as quantitative trait biomarkers in families with AD. Dr. Mayeux has met with Pall Corporation to develop a field method for isolating plasma without centrifugation. Dr. Mayeux has met with Pall Corporation to develop a field method for isolating plasma without centrifugation. Not ready to start collecting. Not ready to start collecting.