Abstract
Brain aging is accompanied by patterns of functional and structural change. Alzheimer’s disease (AD), a representative neurodegenerative disease, has been linked to accelerated brain aging. Here, we developed a deep learning-based brain age prediction model using a large collection of fluorodeoxyglucose positron emission tomography and structural magnetic resonance imaging and tested how the brain age gap relates to degenerative syndromes including mild cognitive impairment, AD, frontotemporal dementia and Lewy body dementia. Occlusion analysis, performed to facilitate the interpretation of the model, revealed that the model learns an age- and modality-specific pattern of brain aging. The elevated brain age gap was highly correlated with cognitive impairment and the AD biomarker. The higher gap also showed a longitudinal predictive nature across clinical categories, including cognitively unimpaired individuals who converted to a clinical stage. However, regions generating brain age gaps were different for each diagnostic group of which the AD continuum showed similar patterns to normal aging.
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Data availability
The Mayo dataset that supports the findings of this study is not publicly available. Anonymized data are available from the corresponding author upon reasonable request. The MRI and PET data from ADNI are available to researchers via the data access procedure described at http://adni.loni.usc.edu/data-samples/access-data/. Source data are provided with this paper.
Code availability
The code developed for this work is available at https://github.com/Neurology-AI-Program/Brain_age_prediction.git.
References
López-Otín, C., Blasco, M. A., Partridge, L., Serrano, M. & Kroemer, G. The hallmarks of aging. Cell 153, 1194–1217 (2013).
Harman, D. Aging: overview. Ann. N. Y. Acad. Sci. 928, 1–21 (2001).
Courchesne, E. et al. Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology 216, 672–682 (2000).
Good, C. D. et al. A voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage 14, 21–36 (2001).
Sowell, E. R. et al. Mapping cortical change across the human life span. Nat. Neurosci. 6, 309–315 (2003).
Lemaitre, H. et al. Normal age-related brain morphometric changes: nonuniformity across cortical thickness, surface area and gray matter volume? Neurobiol. Aging 33, 617.e1–617.e9 (2012).
Raz, N. & Rodrigue, K. M. Differential aging of the brain: patterns, cognitive correlates and modifiers. Neurosci. Biobehav. Rev. 30, 730–748 (2006).
Walhovd, K. B. et al. Effects of age on volumes of cortex, white matter and subcortical structures. Neurobiol. Aging 26, 1261–1270 (2005).
Goyal, M. S. et al. Loss of brain aerobic glycolysis in normal human aging. Cell Metab. 26, 353–360.e3 (2017).
Goyal, M. S., Hawrylycz, M., Miller, J. A., Snyder, A. Z. & Raichle, M. E. Aerobic glycolysis in the human brain is associated with development and neotenous gene expression. Cell Metab. 19, 49–57 (2014).
Zuendorf, G., Kerrouche, N., Herholz, K. & Baron, J.-C. Efficient principal component analysis for multivariate 3D voxel‐based mapping of brain functional imaging data sets as applied to FDG‐PET and normal aging. Hum. Brain Mapp. 18, 13–21 (2003).
Knopman, D. S. et al. 18F-fluorodeoxyglucose positron emission tomography, aging, and apolipoprotein E genotype in cognitively normal persons. Neurobiol. Aging 35, 2096–2106 (2014).
De Leon, M. et al. Prediction of cognitive decline in normal elderly subjects with 2-[18F]fluoro-2-deoxy-D-glucose/positron-emission tomography (FDG/PET). Proc. Natl Acad. Sci. USA 98, 10966–10971 (2001).
De Santi, S. et al. Age-related changes in brain: II. Positron emission tomography of frontal and temporal lobe glucose metabolism in normal subjects. Psychiatr. Q. 66, 357–370 (1995).
Bonte, S. et al. Healthy brain ageing assessed with 18F-FDG PET and age-dependent recovery factors after partial volume effect correction. Eur. J. Nucl. Med. Mol. Imaging 44, 838–849 (2017).
Shen, X., Liu, H., Hu, Z., Hu, H. & Shi, P. The relationship between cerebral glucose metabolism and age: report of a large brain PET data set. PLoS ONE 7, e51517 (2012).
Petit-Taboué, M., Landeau, B., Desson, J. F., Desgranges, B. & Baron, J. C. Effects of healthy aging on the regional cerebral metabolic rate of glucose assessed with statistical parametric mapping. Neuroimage 7, 176–184 (1998).
Goyal, M. S. et al. Persistent metabolic youth in the aging female brain. Proc. Natl Acad. Sci. USA 116, 3251–3255 (2019).
Cole, J. H. & Franke, K. Predicting age using neuroimaging: innovative brain ageing biomarkers. Trends Neurosci. 40, 681–690 (2017).
Cole, J. H. Multimodality neuroimaging brain-age in UK biobank: relationship to biomedical, lifestyle, and cognitive factors. Neurobiol. Aging 92, 34–42 (2020).
Bashyam, V. M. et al. MRI signatures of brain age and disease over the lifespan based on a deep brain network and 14 468 individuals worldwide. Brain 143, 2312–2324 (2020).
Abrol, A. et al. Deep learning encodes robust discriminative neuroimaging representations to outperform standard machine learning. Nat. Commun. 12, 353 (2021).
Cole, J. H. et al. Predicting brain age with deep learning from raw imaging data results in a reliable and heritable biomarker. Neuroimage 163, 115–124 (2017).
Levakov, G., Rosenthal, G., Shelef, I., Raviv, T. R. & Avidan, G. From a deep learning model back to the brain—identifying regional predictors and their relation to aging. Hum. Brain Mapp. 41, 3235–3252 (2020).
Jonsson, B. A. et al. Brain age prediction using deep learning uncovers associated sequence variants. Nat. Commun. 10, 5409 (2019).
Cole, J. H. et al. Brain age predicts mortality. Mol. Psychiatry 23, 1385–1392 (2018).
Gaser, C. et al. BrainAGE in mild cognitive impaired patients: predicting the conversion to Alzheimer’s disease. PLoS ONE 8, e67346 (2013).
Huang, G., Liu, Z., Van Der Maaten, L. & Weinberger, K. Q. Densely Connected Convolutional Networks. In Proc. IEEE Conference on Computer Vision and Pattern Recognition (eds Rehg, J. et al.) 4700–4708. (Institute of Electrical and Electronics Engineers, 2017).
MacMahon, S. et al. Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias. Lancet 335, 765–774 (1990).
Smith, S. M., Vidaurre, D., Alfaro-Almagro, F., Nichols, T. E. & Miller, K. L. Estimation of brain age delta from brain imaging. Neuroimage 200, 528–539 (2019).
Peng, H., Gong, W., Beckmann, C. F., Vedaldi, A. & Smith, S. M. Accurate brain age prediction with lightweight deep neural networks. Med. Image Anal. 68, 101871 (2021).
Morris, J. C. Clinical dementia rating: a reliable and valid diagnostic and staging measure for dementia of the Alzheimer type. Int. Psychogeriatr. 9, 173–176 (1997).
Kokmen, E., Smith, G. E., Petersen, R. C., Tangalos, E. & Ivnik, R. C. The short test of mental status: correlations with standardized psychometric testing. Arch. Neurol. 48, 725–728 (1991).
Folstein, M. F., Folstein, S. E. & McHugh, P. R. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J. Psychiatr. Res. 12, 189–198 (1975).
Chételat, G. et al. Direct voxel-based comparison between grey matter hypometabolism and atrophy in Alzheimer’s disease. Brain 131, 60–71 (2008).
Salat, D. H. et al. Thinning of the cerebral cortex in aging. Cereb. Cortex 14, 721–730 (2004).
Buckner, R. L. et al. Molecular, structural, and functional characterization of Alzheimer’s disease: evidence for a relationship between default activity, amyloid, and memory. J. Neurosci. 25, 7709–7717 (2005).
Curiati, P. K. et al. Age-related metabolic profiles in cognitively healthy elders: results from a voxel-based [18F]fluorodeoxyglucose–positron-emission tomography study with partial volume effects correction. AJNR Am. J. Neuroradiol. 32, 560–565 (2011).
Long, X. et al. Healthy aging: an automatic analysis of global and regional morphological alterations of human brain. Acad. Radiol. 19, 785–793 (2012).
Jack, C. R. Jr. et al. Rate of medial temporal lobe atrophy in typical aging and Alzheimer’s disease. Neurology 51, 993–999 (1998).
Davis, P. C., Mirra, S. S. & Alazraki, N. The brain in older persons with and without dementia: findings on MR, PET, and SPECT images. AJR Am. J. Roentgenol. 162, 1267–1278 (1994).
Habes, M. et al. White matter hyperintensities and imaging patterns of brain ageing in the general population. Brain 139, 1164–1179 (2016).
Ossenkoppele, R. et al. Associations between tau, Aβ, and cortical thickness with cognition in Alzheimer disease. Neurology 92, e601–e612 (2019).
Franke, K. & Gaser, C. Longitudinal changes in individual BrainAGE in healthy aging, mild cognitive impairment, and Alzheimer’s disease. GeroPsych (Bern) 25, 235–245 (2012).
Shivamurthy, V. K., Tahari, A. K., Marcus, C. & Subramaniam, R. M. Brain FDG PET and the diagnosis of dementia. AJR Am. J. Roentgenol. 204, W76–W85 (2015).
Brown, R. K., Bohnen, N. I., Wong, K. K., Minoshima, S. & Frey, K. A. Brain PET in suspected dementia: patterns of altered FDG metabolism. Radiographics 34, 684–701 (2014).
Kanda, T. et al. Comparison of grey matter and metabolic reductions in frontotemporal dementia using FDG-PET and voxel-based morphometric MR studies. Eur. J. Nucl. Med. Mol. Imaging 35, 2227–2234 (2008).
Castelnovo, V. et al. Heterogeneous brain FDG-PET metabolic patterns in patients with C9orf72 mutation. Neurol. Sci. 40, 515–521 (2019).
McKeith, I. G. et al. Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB Consortium. Neurology 89, 88–100 (2017).
Graff-Radford, J. et al. 18F-fluorodeoxyglucose positron emission tomography in dementia with Lewy bodies. Brain Commun. 2, fcaa040 (2020).
Hayflick, L. Biological aging is no longer an unsolved problem. Ann. N. Y. Acad. Sci. 1100, 1–13 (2007).
Berg, L. Does Alzheimer’s disease represent an exaggeration of normal aging? Arch. Neurol. 42, 737–739 (1985).
Toepper, M. Dissociating normal aging from Alzheimer’s disease: a view from cognitive neuroscience. J. Alzheimers Dis. 57, 331–352 (2017).
Rieke, J., Eitel, F., Weygandt, M., Haynes, J.-D. & Ritter, K. Visualizing convolutional networks for MRI-based diagnosis of Alzheimer’s disease. In Proc. Understanding and Interpreting Machine Learning in Medical Image Computing Applications (eds Stoyanov, D. et al.) 24–31 (Springer, 2018).
Jones, D. T. et al. Tau, amyloid, and cascading network failure across the Alzheimer’s disease spectrum. Cortex 97, 143–159 (2017).
Roberts, R. O. et al. The Mayo Clinic Study of Aging: design and sampling, participation, baseline measures and sample characteristics. Neuroepidemiology 30, 58–69 (2008).
Albert, M. S. et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 270–279 (2011).
McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269 (2011).
Petersen, R. C. Mild cognitive impairment as a diagnostic entity. J. Intern. Med. 256, 183–194 (2004).
Neary, D. et al. Frontotemporal lobar degeneration: a consensus on clinical diagnostic criteria. Neurology 51, 1546–1554 (1998).
Klunk, W. E. et al. Imaging brain amyloid in Alzheimer’s disease with Pittsburgh Compound‐B. Ann. Neurol. 55, 306–319 (2004).
Xia, C.-F. et al. [18F]T807, a novel tau positron emission tomography imaging agent for Alzheimer’s disease. Alzheimers Dement. 9, 666–676 (2013).
Schwarz, C. G. et al. A comparison of partial volume correction techniques for measuring change in serial amyloid PET SUVR. J. Alzheimers Dis. 67, 181–195 (2019).
Schwarz, C. et al. The mayo clinic adult lifespan template (MCALT): better quantification across the lifespan. In Proc. Alzheimer’s Association International Conference 13: P792. (The Alzheimer's Association, 2017).
Ashburner, J. & Friston, K. J. Unified segmentation. Neuroimage 26, 839–851 (2005).
Jack, C. R. Jr. et al. Defining imaging biomarker cut points for brain aging and Alzheimer’s disease. Alzheimers Dement. 13, 205–216 (2017).
Shinohara, R. T. et al. Statistical normalization techniques for magnetic resonance imaging. Neuroimage Clin. 6, 9–19 (2014).
Abadi, M. et al. Tensorflow: A system for large-scale machine learning. In Proc. 12th (USENIX) Symposium on Operating Systems Design and Implementation (eds Keeton, K. & Roscoe, T.) 265–283. (USENIX Association, 2016).
Kingma, D. P. & Ba, J. Adam: a method for stochastic optimization. Preprint at arXiv https://doi.org/10.48550/arXiv.1412.6980 (2014).
He, K., Zhang, X., Ren, S. & Sun, J. Delving deep into rectifiers: Surpassing human-level performance on imagenet classification In Proc. IEEE International Conference on Computer Vision (eds Ikeuchi, K. et al.) 1026–1034. (Institute of Electrical and Electronics Engineers, 2015).
He, K., Zhang, X., Ren, S. & Sun, J. Deep residual learning for image recognition. In Proc. IEEE Conference on Computer Vision and Pattern Recognition (eds Agapito, L. et al.) 770–778. (Institute of Electrical and Electronics Engineers, 2016).
Zeiler, M. D. & Fergus, R. Visualizing and understanding convolutional networks. In Proc. European Conference on Computer Vision (eds Fleet, D. et al.) 818–833 (Springer, 2014).
Genovese, C. R., Lazar, N. A. & Nichols, T. Thresholding of statistical maps in functional neuroimaging using the false discovery rate. Neuroimage 15, 870–878 (2002).
Dale, A. M., Fischl, B. & Sereno, M. I. Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9, 179–194 (1999).
Acknowledgements
We acknowledge the support of the NVIDIA Corporation with the donation of the Tesla P100 GPU used for this research. This work was funded in part by National Institutes of Health grant nos. P30 AG62677 (D.J.), R01 AG011378 (C.J.), R01 AG041851 (C.J.), P50 AG016574 (R.P.), U01 AG06786 (R.P.) and RO1 AG073282 (V.L.), and by the Elsie and Marvin Dekelboum Family Foundation, Edson Family Foundation, Liston Family Foundation, GHR Foundation, Foundation Dr. Corinne Schuler (Geneva, Switzerland), Race Against Dementia and the Mayo Foundation.
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J.L., H.K.M. and D.T.J. conceptualized the study. J.L. and L.R.B. were responsible for the software. M.L.S. was responsible for preprocessing the data. J.L., H.K.M., M.L.S., E.S.L., H.B., J.G., J.L.G. and C.G.S. were responsible for the study methodology. J.L., B.J.B., H.K.M., V.J.L. and D.T.J. wrote the original manuscript. All authors revised the draft. K.K., D.S.K., B.F.B., V.J.L., R.C.P., C.R.J. and D.T.J. supervised the study. All authors gave final approval for this version of the article.
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Extended data
Extended Data Fig. 1 Brain age predictions on the ADNI dataset.
(a-f) 3D Densenet model trained on the Mayo dataset was applied to the ADNI data. (a-c) FDG based brain age prediction. (d-f) MRI based brain age prediction. (g-l) Prediction performance of 3D Densenet model trained on the Mayo and ADNI dataset together. (g-i) FDG based brain age prediction. (j-l) MRI based brain age prediction. The black solid line and dotted lines in each figure represent a regression line and its 95% confidence bands, respectively. m, The corrected MAE evaluated on the test data (n = 5) was compared between the datasets using a two−sided two-sample Student's t-test. The data is shown as mean ± SD. * p < 0.05, ** p < 0.005.
Extended Data Fig. 2 Regional mean saliency.
After calculating the saliency map from occlusion analysis, mean saliency value was calculated for each ROI. Box plots represent the minimum and maximum values (whiskers), the first and third quartile (box boundaries), and the median (internal line) for the 5-fold cross-validations (n = 5). Yellow-colored boxes indicate the left hemisphere and blue-colored boxes indicate the right hemisphere.
Extended Data Fig. 3 Comparison of correlation between FDG- and MRI-based brain age gap.
Error bars indicate 95% confidence intervals of Pearson’s correlation coefficient. A statistical comparison was performed with the CU group. Pearson’s r (95% confidence interval) = 0.5873 (0.5628 to 0.6108), 0.6396 (0.5945 to 0.6847), 0.6735 (0.6138 to 0.7255), 0.7824 (0.6697 to 0.8598), and 0.6548 (0.5489 to 0.7400), for CU, MCI, AD, FTD, and DLB, respectively. Exact p values: CU versus MCI, p = 1.5 × 10−9; CU versus AD, p < 1 × 10−15; CU versus FTD, p < 1 × 10−15; CU versus DLB, p < 1 × 10−15, *** p < 0.001. *** p < 0.001, two-sided z test after Fisher’s r to z transformation.
Extended Data Fig. 4 Regression plots of a corrected brain age gap as a function of chronological age for clinical diagnostic groups in ADNI cohort.
a, Violin plots of corrected brain age gap for each diagnostic group. The corrected brain age gap of disease groups was compared with CU using one-way ANOVA with Holm-Sidak’s multiple comparisons test. *** p < 0.001. b, FDG-based brain age gap estimation for MCI and AD, respectively. c, Violin plots of corrected brain age gap for each clinical diagnosis group. The corrected brain age gap of disease groups was compared with CU using one-way ANOVA with Holm-Sidak’s multiple comparisons test. *** p < 0.001. d, MRI-based brain age gap estimation for MCI and AD, respectively. e, Relationship between FDG- and MRI-based brain age gap. The black solid line and dotted lines in each figure represent a regression line and its 95% confidence bands, respectively. r indicates Pearson’s correlation coefficient.
Extended Data Fig. 5 Association of a brain age gap with cognitive scores.
(a-c) Scatter plots of FDG model-based brain age gap with Mini-Mental State Examinations (MMSE), Short Test of Mental Status (STMS) and Clinical Dementia Rating Sum of boxes (CDR-SB), respectively. (d-f) Scatter plots of MRI model-based brain age gap with MMSE, STMS and CDR-SB, respectively. r, Pearson correlation coefficient; p, correlation test p value.
Extended Data Fig. 6 Association of brain age gap with meta-ROI Amyloid- and Tau PET SUVr in ADNI cohort.
a, Scatter plots between FDG-based brain age gap with meta-ROI amyloid PET SUVr for MCI and AD, respectively. b, Scatter plots between FDG-based brain age gap with meta-ROI tau PET SUVr. c, Scatter plots between MRI-based brain age gap with meta-ROI PiB PET SUVr. d, Scatter plots between MRI-based brain age gap with meta-ROI Tau PET SUVr. The black solid line and dotted lines in each figure represent a regression line and its 95% confidence bands, respectively. r, Pearson correlation coefficient; p, correlation test p value.
Extended Data Fig. 7 Association of sex to the age gap estimation.
The blue-colored dot indicates female and red indicates male individuals. Comparisons were calculated by two-sided Student's t-test. Exact p values: for FDG, CU, t(2877) = 4.088, p = 4.5 × 10−5; MCI, t(664) = 0.3193, p = 0.7496; AD, t(370) = 2.625, p = 0.009; FTD, t(67) = 0.3496, p = 0.7277; DLB, t(139) = 0.7241, p = 0.4702; for MRI, CU, t(2877) = 3.290, p = 0.001; MCI, t(664) = 0.6509, p = 0.5154; AD, t(370) = 2.809, p = 0.0052; FTD, t(67) = 0.3811, p = 0.7043; DLB, t(139) = 2.886, p = 0.0045; * p < 0.05, **p < 0.005, *** p < 0.001.
Extended Data Fig. 8 Interscan interval bias test.
a, Interscan interval for total subjects. A statistical test was performed within the same baseline groups (one-way ANOVA with Holm-Sidak post hoc test). Exact p values: CU to CU versus CU to MCI/AD, p = 0.004; MCI to MCI versus MCI to AD, p = 0.79; MCI to MCI versus MCI to FTD, p = 0.95; MCI to MCI versus MCI to DLB, p = 0.95. n = 1054, 104, 169, 49, 6, and 11 for CU to CU, CU to MCI/AD, MCI to MCI, MCI to AD, MCI to FTD, and MCI to DLB group, respectively. b, Interscan interval after excluding participants with interscan interval of >2 years (one-way ANOVA with Holm-Sidak post hoc test). Exact p values: CU to CU versus CU to MCI/AD, p = 0.77; MCI to MCI versus MCI to AD, p = 0.29; MCI to MCI versus MCI to FTD, p = 0.77; MCI to MCI versus MCI to DLB, p = 0.77. n = 258, 52, 127, 41, 4, and 8 for CU to CU, CU to MCI/AD, MCI to MCI, MCI to AD, MCI to FTD, and MCI to DLB group, respectively. (c,d) Baseline brain age gap comparison between groups after excluding participants with interscan interval of >2 years for FDG and MRI, respectively. The comparison was performed within the same baseline groups (one-way ANOVA with Holm-Sidak post hoc test). For c panel, Exact p values: CU to CU versus CU to MCI/AD, p = 0.001; MCI to MCI versus MCI to AD, p = 0.07; MCI to MCI versus MCI to FTD, p = 3.2 × 10−5; MCI to MCI versus MCI to DLB, p = 0.38. For d panel, Exact p values: CU to CU versus CU to MCI/AD, p = 9.1 × 10−4; MCI to MCI versus MCI to AD, p = 0.02; MCI to MCI versus MCI to FTD, p = 0.12; MCI to MCI versus MCI to DLB, p = 0.94. * p < 0.05, **p < 0.005, *** p < 0.001. n = 258, 52, 127, 41, 4, and 8 for CU to CU, CU to MCI/AD, MCI to MCI, MCI to AD, MCI to FTD, and MCI to DLB group, respectively. Box plots represent the minimum and maximum values (whiskers), the first and third quartile (box boundaries), and the median (internal line).
Extended Data Fig. 9 Longitudinal nature of the brain age gap in ADNI cohort.
a, Baseline brain age gap comparison between groups for FDG model. A statistical test was performed within the same baseline groups using a two-sided two-sample Student's t-test. b, For FDG model, the annual Δ brain age gap of each group was compared with the CU to CU group using one-way ANOVA with Holm-Sidak post hoc. c, Baseline brain age gap comparison between groups for MRI model. A statistical test was performed within the same baseline groups using a two-sided two-sample Student's t-test. d, For MRI model, the annual Δ brain age gap of each group was compared with the CU to CU group using one-way ANOVA with Holm-Sidak post hoc test). * p < 0.05, **p < 0.005, *** p < 0.001. n = 124, 20, 237, 46, and 28 for CU to CU, CU to MCI/AD, MCI to MCI, MCI to AD, and AD to AD group, respectively. Box plots represent the minimum and maximum values (whiskers), the first and third quartile (box boundaries), and the median (internal line).
Extended Data Fig. 10 Voxel-wise linear regression analysis of brain age gap shown on coronal slices.
Clinical diagnosis group (MCI, AD, FTD and DLB)-specific results from voxel-wise whole-brain linear regression examining the brain age gap-related change (FDR corrected, q < 0.01). The chronological age was specified as nuisance covariance. For CU (bottom row), voxel-wise linear regression analysis was performed using the chronological age as a regressor to show the age-related change. A left panel shows the results for the FDG-based model and a right panel shows the results for the MRI-based model.
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Lee, J., Burkett, B.J., Min, HK. et al. Deep learning-based brain age prediction in normal aging and dementia. Nat Aging 2, 412–424 (2022). https://doi.org/10.1038/s43587-022-00219-7
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DOI: https://doi.org/10.1038/s43587-022-00219-7
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