The Alzheimer's Disease Prediction Of Longitudinal Evolution (TADPOLE) Challenge: Results after 1 Year Follow-up
Authors: Marinescu Razvan V. , Oxtoby Neil P. , Young Alexandra L. , Bron Esther E. , Toga Arthur W. , Weiner Michael W. , Barkhof Frederik , Fox Nick C. , Eshaghi Arman , Toni Tina , Salaterski Marcin , Lunina Veronika , Ansart Manon , Durrleman Stanley , Lu Pascal , Iddi Samuel , Li Dan , Thompson Wesley K. , Donohue Michael C. , Nahon Aviv , Levy Yarden , Halbersberg Dan , Cohen Mariya , Liao Huiling , Li Tengfei , Yu Kaixian , Zhu Hongtu , Tamez-Peña José G. , Ismail Aya , Wood Timothy , Bravo Hector Corrada , Nguyen Minh , Sun Nanbo , Feng Jiashi , Yeo B.T. Thomas , Chen Gang , Qi Ke , Chen Shiyang , Qiu Deqiang , Buciuman Ionut , Kelner Alex , Pop Raluca , Rimocea Denisa , Ghazi Mostafa M. , Nielsen Mads , Ourselin Sebastien , Sørensen Lauge , Venkatraghavan Vikram , Liu Keli , Rabe Christina , Manser Paul , Hill Steven M. , Howlett James , Huang Zhiyue , Kiddle Steven , Mukherjee Sach , Rouanet Anaïs , Taschler Bernd , Tom Brian D. M. , White Simon R. , Faux Noel , Sedai Suman , de Velasco Oriol Javier , Clemente Edgar E. V. , Estrada Karol , Aksman Leon , Altmann Andre , Stonnington Cynthia M. , Wang Yalin , Wu Jianfeng , Devadas Vivek , Fourrier Clementine , Raket Lars Lau , Sotiras Aristeidis , Erus Guray , Doshi Jimit , Davatzikos Christos , Vogel Jacob , Doyle Andrew , Tam Angela , Diaz-Papkovich Alex , Jammeh Emmanuel , Koval Igor , Moore Paul , Lyons Terry J. , Gallacher John , Tohka Jussi , Ciszek Robert , Jedynak Bruno , Pandya Kruti , Bilgel Murat , Engels William , Cole Joseph , Golland Polina , Klein Stefan , Alexander Daniel C. ,   The EuroPOND Consortium,   The Alzheimer's Disease Neuroimaging Initiative
Published: May 2023

Accurate prediction of progression in subjects at risk of Alzheimer's disease is crucial for enrolling the right subjects in clinical trials. However, a prospective comparison of state-of-the-art algorithms for predicting disease onset and progression is currently lacking. We present the findings of "The Alzheimer's Disease Prediction Of Longitudinal Evolution" (TADPOLE) Challenge, which compared the performance of 92 algorithms from 33 international teams at predicting the future trajectory of 219 individuals at risk of Alzheimer's disease. Challenge participants were required to make a prediction, for each month of a 5-year future time period, of three key outcomes: clinical diagnosis, Alzheimer's Disease Assessment Scale Cognitive Subdomain (ADAS-Cog13), and total volume of the ventricles. The methods used by challenge participants included multivariate linear regression, machine learning methods such as support vector machines and deep neural networks, as well as disease progression models. No single submission was best at predicting all three outcomes. For clinical diagnosis and ventricle volume prediction, the best algorithms strongly outperform simple baselines in predictive ability. However, for ADAS-Cog13 no single submitted prediction method was significantly better than random guesswork. Two ensemble methods based on taking the mean and median over all predictions, obtained top scores on almost all tasks. Better than average performance at diagnosis prediction was generally associated with the additional inclusion of features from cerebrospinal fluid (CSF) samples and diffusion tensor imaging (DTI). On the other hand, better performance at ventricle volume prediction was associated with inclusion of summary statistics, such as the slope or maxima/minima of patient-specific biomarkers. On a limited, cross-sectional subset of the data emulating clinical trials, performance of the best algorithms at predicting clinical diagnosis decreased only slightly (2 percentage points) compared to the full longitudinal dataset. The submission system remains open via the website https://tadpole.grand-challenge.org, while TADPOLE SHARE (https://tadpole-share.github.io/) collates code for submissions. TADPOLE's unique results suggest that current prediction algorithms provide sufficient accuracy to exploit biomarkers related to clinical diagnosis and ventricle volume, for cohort refinement in clinical trials for Alzheimer's disease. However, results call into question the usage of cognitive test scores for patient selection and as a primary endpoint in clinical trials.