brain degeneration in 676 subjects with impairment, and healthy controls

Transcription

1 Neroimaging i biomarkers track brain degeneration in 676 sbjects with Alheimer s disease, mild cognitive impairment, and health controls Laborator of Nero Imaging Xe Ha, Sh Lee, Ale Leow, Igor Yanovsk, Arthr W. Toga, Michael W. Wi Weiner, Pal lm. Thompson, et. al. and the Alheimer's Disease Neroimaging Initiative

2 Alheimer's Disease Neroimaging Initiative (ADNI) ADNI is a large five ear research project 200 AD, 400 MCI and 200 elderl controls info.org/

3 Tensor Based Morphometr (TBM) l Cross sectional Design,, MDT I di id ls Jacobian Map MDT Individal Scan ( ) ( ) ( ) ( ) ( ) ( ) J ( ) ( ) ( ) ( ) ( ) ( ) = J ( ) Epansion Volme r J 1 det > ( ) Loss Volme r J 1 det <

4 Tracking brain degeneration in 676 sbjects with AD (N=165), MCI (N=330), and health controls (N=181) AD vs. CTL MCI vs. CTL AD vs. MCI Ha X, Toga AW, Thompson PM, et al. (2008) Neroimage 43(3):

5 Baseline TBM correlate with Sm of Boes CDR Baseline TBM correlate with FUTURE CHANGES in Sm of Boes CDR Ha X, Toga AW, Thompson PM, et al. (2008) Neroimage 43(3):

6 Baseline TBM correlate with MMSE Baseline TBM correlate with FUTURE CHANGES in MMSE Ha X, Toga AW, Thompson PM, et al. (2008) Neroimage 43(3):

7 Association between Jacobian vales and conversion to AD in a ear 40 MCI sbjects became AD after a ear, corresponding to a conversion rate of 21.5% Ha X, Toga AW, Thompson PM, et al. (2008) Neroimage 43(3):

8 ApoE and brain strctre Ha X, Toga AW, Thompson PM, et al. (2008) Neroimage 43(3):

9 Tensor Based Morphometr (TBM) Longitdinal Design MDT,, Baseline 12 mo Jacobian Map ( ) ( ) ( ) J = ( ) ( ) ( ) ( ) ( ) ( ) ( r ) Volme Epansion det J > 1 ( r) Volme Loss det J < 1

10 AD (N=104) verss Normal (N=157) Mean Atroph Rates Ha X, Toga AW, Thompson PM, et al. (2009) Neroimage 48(4):

11 MCI (N=254) verss Normal (N=157) Mean Atroph Rates Ha X, Toga AW, Thompson PM, et al. (2009) Neroimage 48(4):

12 Region of interest of interest (ROI) Temporal lobes Statistical ROI derived from an independent training sample of 22 AD patients Ha X, Toga AW, Thompson PM, et al. (2009) Neroimage 48(4):

13 Estimated sample sies (n80) needed to detect a 25% redction in the mean annal change with a two sided test and α=0.05 at 80% power, for a two arm std n = ˆ ( + ) 2 2 2σ D 1 α / 2 power ( 0.25 ˆ β ) 2 Sm of boesclinical Dementia Rating (CDR) gives best power among the clinical scores, bt the TBM method is 9 times better AD MCI TBM CDR-SB ADAS-Cog MMSE Ha X, Toga AW, Thompson PM, et al. (2009) Neroimage 48(4):

14 The rates of temporal lobe atroph correlate with the levelsof CSF biomarkers A longitdinal std of 100 sbjects (20 AD, 40 MCI and 20 controls) Leow AD, Ha X, Toga AW, Thompson PM, et al. (2009) Neroimage 45(3):

15 Smmar TBM as a neroimaging marker Correlate with clinical decline, CSF biomarkers, and predict ftre conversion to AD Ui Using TBM as a potential ti srrogate marker, onl 48 AD and 88 MCI sbjects are needed to detect t 25% slowing of disease in clinical i l trials (9 better than best clinical score)

16 Acknowledgements UCLA ADNI Team Pal Thompson PhD (PI) Arthr Toga PhD (PI) ShLee Igor Yanovsk PhD Ale D. Leow MD PhD Ming Chang Chiang Yi Y Cho MS April J. Ho Boris Gtman Non UCLA Collaborators Clifford R. Jack Jr MD Matt A. Bernstein PhD Eric M. Reiman MD Danielle Harve PhD John Kornak PhD Norbert Schff PhD Gene E. Aleander PhD Michael W. Weiner MD ADNI (PI: Michael Weiner; NIH grant nmber U01 AG024904) National Institte of Aging National Institte of Biomedical Imaging and Bioengineering (NIBIB) Fondation for the National Instittes of Health, Pfier Inc. Weth Research Bristol Mers Sqibb Eli Lill and Compan GlaoSmithKline Merck & Co. Inc. AstraZeneca AB Novartis Pharmaceticals Corporation Alheimer s Association Eisai Global Clinical Development Elan Corporation plc, Forest Laboratories Institte for the Std of Aging (ISOA), U.S. Food and Drg Administration Algorithm development was also fnded b the NIA, NIBIB, the National Librar of Medicine, and the National Center for Research Resorces (AG016570, EB01651, LM05639, RR to PT).