Brain Bank of the Brazilian Aging Brain Study Group a Collection Focused in Human Control Cases
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1 Brain Bank of the Brazilian Aging Brain Study Group a Collection Focused in Human Control Cases Lea Tenenholz Grinberg, M.D, Ph.D Associate Professor of Pathology University of the City of São Paulo Medical School Director of the Dept. of Pathology University of São Paulo Medical School Research Associate Albert Einstein Research And Education Institute, Sao Paulo Georg Foster Fellow Alexander von Humboldt Foundation
2 Summary Why to create a brain bank in Brazil? Objectives Procedures Results
3 Why to create a Why to create a brain bank in Brazil?
4 Demographics of Aging in Brazil Life expectancy in Brazil (in years) MALE FEMALE
5 393% From: Ferri CP, Prince M, Brayne C et al. (2003) Global prevalence of dementia: a Delphi consensus study. The Lancet 366:
6 Objectives
7 Started in October 2003 multidisciplinary and multi institutional group based on the University of Sao Paulo Medical School for studies focused on brain aging
8 To perform a large number of autopsies of elderly individuals; the donors come to autopsy through a general autopsy service specific dissection protocols The collected cases should comprise a large number of non demented subjects a vast spectrum of pathologies related to aging brain To provide high quality material to a multidisciplinary research network unraveling multiple aspects of aging brain processes and related neurodegenerative diseases.
9 Complementation to the other collections Neuropathological changes symptoms 50 y 60y 70y 80y 90y
10 University of Sao Paulo Medical School
11 University of Sao Paulo Medical School Third Medical School in Brazil, since st on the publication ranking in Brazil (ISI 2008) Linked to Hospital of Clinics a large volume facility high complexity procedures covers all main medical and surgical specialties, including transplantation
12 AUTOPSY SERVICE (SPAS) UNIVERSITY OF SAO PAULO Sao Paulo city ~ 11 million inhabitants Autopsies are compulsory for those with no established cause of death SPAS is the site of autopsies of all natural deaths ~ 13,000 autopsies per year All autopsies complete and documented, are performed by a certified pathologist 24/7 Number of employees Pathologists 12 Technicians 48 Administrative staff 30 Total 90
13 AUTOPSY SERVICE (SPAS) UNIVERSITY OF SAO PAULO Number of autopsies/ number of natural deaths of people over 50 years old in Sao Paulo Male Female Total Autopsies/Natural Deaths 8,071/46,194-5,967/44,467 14,038/ 90,661-
14 Procedures
15
16
17
18 Ethical Issues BBBABSG s procedures are approved by the Ethical Board of USPMS the Brazilian Federal Health Department. A voluntary Informed Consent Form (ICF) is obtained by the interviewer and must signed by each next of kin before any procedure. The ICF can be withdrawn at any time from the study. If any procedure is refused by the NOK, the case is not banked. All the material is anonymous and coded Specimen identification can be retrieved in case of legal or public health requirements, according to Brazilian regulations.
19 Types of Tissue Collected BRAIN CIRCLE OF WILLIS CERVICAL CAROTIDS HEART KIDNEY SAMPLE POST MORTEM CSF ARTERIAL BLOOD
20 Carotids Circle of Willis Heart Kidney Blood
21 Clinicofunctional assessment Through an informant DOMAIN Cognitive Behavioral changes Affective disorders Functional Assessment Parkinson s Disease Social information SCALES Clinical Dementia Rating Scale - CDR (Morris, 1993) Informant quest. cognitive decline in the elderly IQCODE (Jorm, 1994) Neuropsychiatric Inventory - NPI (Cummings et al., 1994) DSM IV Structured Clinical Interview (SCID) for depression and manic disorders (Del-Ben et al., 1996; Spitzer et al., 1992) The Katz Index (Katz S et al., 1963) Instrumental Activities of Daily Living (Lawton and Brody, 1969) The Brief Screening Questionnaire for Parkinsonism (Tanner et al., 1990) ABIPEME a Brazilian scale used to determine social-economic condition (Almeida and Wickerhauser, 1991)
22 Nosologic Diagnosis As recommended by the Brazilian Academy of Neurology (Nitrini et al., 2005) Alzheimer s Disease NINCDS ADRDA Work Group (McKhann et al., 1984), Vascular dementia The NINDS AIREN Criteria (Roman et al., 1993) Frontotemporal lobar degeneration Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria (Neary et al., 1998) Dementia with Lewy Body Diagnosis and management of dementia with Lewy bodies Third report of the DLB consortium (McKeith et al.,2005)
23 Neuropathological assessment Disease Alzheimer s disease Parkinson s disease Lewy body dementia Frontotemporal lobar degeneration Vascular changes Criteria CERAD (Mirra, 1991) Braak and Braak scale system (Braak et al., 2006) Ronald Reagan- NIA pathological criteria for AD (1997) Stages in the development of Parkinson's disease-related pathology (Braak et al., 2006) Consensus guidelines for the clinical and pathologic diagnosis of dementia with Lewy bodies (DLB) (McKeith et al., 1996) Neuropathologic diagnostic and nosologic criteria for frontotemporal lobar degeneration: consensus of the Consortium for FTLD (Cairns et al., 2007) By change, size and location
24 Double staining PHF1 against phospho tau (Peter Davies, NY) and 4G8 against B amyloid (Signet) EQV 1 against α synuclein (Kenji Ueda, Tokio) 4G8 against B amyloid (Signet) RD3 and RD4 against tau (Rohan de Silva, UK)
25 Pre selection Flow Chart Thread 1 Thread 2 Informed Consent Pathological Assessment Step 1 Skull and body measurements Clinical and Functional Assessment Final evaluation of criteria requirements CSF and blood sampling Brain removal Heart and cervical carotids removal Kidney sampling Step 2 Brain and heart measurements Circle of Willis dissection Digital Pictures Sampling of frozen tissue Fixation Final Report Step 3 Part A Carotids macroscopic assessment Kidney processing staining and analyses Step 3 Part B1 Brain processing and staining Step 3 Part B2 Histological analyses, grating and diagnosis
26 SQL based database HTML interface Electronic Database
27 Results
28 Time line of BBBABSG s series from April 2004 to December 2007 (in absolute numbers) jul/04 ago/04 set/04 out/04 nov/04 dez/04 jan/05 fev/05 mar/05 abr/05 mai/05 jun/05 jul/05 ago/05 set/05 out/05 nov/05 dez/05 jan/06 total included exclusion criteria CS unsuitable refusal
29 Demographics Age at death Gender 78.7± 10.1y 56% M Ethnicity Afr. 11% Mixed 11% Cauc. 78% AGE (y)
30 RESULTS POST MORTEM DELAY 4 20h (mean 10.4h)
31 Subject distribution according to the CDR ( )
32 Neuropathological distribution CDR 1
33 Collaborations Colaboracoes roberto raphe
34 J Neurol Sci. in press
35
36 J Comp Neurol. In press
37 Brazilian Aging Brain Study Group Dr. J. M. Farfel R. E. L. Ferretti Dr. Lea T. Grinberg Prof. W. Jacob Filho R. E. P. Leite Prof. R. Nitrini Prof. C. Pasqualucci Prof. P. Saldiva Prof. S. Rosemberg Special thanks for Dr. Peter Davies,Dr. Kenji Ueda and Dr. Rohan de Silva for providing the antibodies Website Sao Paulo Financial Support FAPESP Brazil Albert Einstein Res. and Educ. Inst., Sao Paulo CNPq Brazil CAPES Brazil Humboldt Foundation Germany
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