EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker.
The 3 matches · 1 of them tie a paragraph to a whole file, not to given lines: a weak match, whose lines are not tinted
- [1] § Methods › Statistical Analysis ↔ GitHub_code/05_calibration_validation.R, lines 101–148 · score 0.77 · Optimism corrected, bootstrap corrected, Internal validation, calibration slope, Harrell, months
- [2] § Results › Neuroanatomical Predictors of Progression to Dementia ↔ GitHub_code/05_calibration_validation.R, lines 101–148 · score 0.74 · optimism corrected calibration, Bootstrap corrected calibration, Internal validation, calibration slope, Harrell, months
- [3] § Methods › Statistical Analysis ↔ GitHub_code/03_cox_models.R, the whole file · a weak match · score 0.54 · Cox proportional hazards, EOAD signature, variables, atrophy, models
Paper
Loaded from Europe PMC by your browser, not stored by OSCR: doi.org · Europe PMC
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The authors' code
R · 148 lines · 5 KB · no license · 2 matches
- # ============================================================
- # Internal validation and calibration of the extended Cox model
- # Paranhos et al. - EOAD Prognostication
- # ============================================================
- library(survival)
- library(rms)
- library(dplyr)
- library(ggplot2)
- # -----------------------------
- # 1) Read data
- # -----------------------------
- # Replace with the path to your dataset
- data <- read.csv("path/to/your/data.csv", check.names = TRUE)
- # Keep model variables and remove missing values
- data2 <- data %>%
- select(Time_to_Event, Progressed_to_Mild,
- age_at_scan, gender, cdrsum, EOADsig_wscore) %>%
- filter(complete.cases(.))
- data2$gender <- as.factor(data2$gender)
- data2$Progressed_to_Mild <- as.integer(data2$Progressed_to_Mild)
- # -----------------------------
- # 2) Prediction horizon
- # -----------------------------
- u <- 24 # months
- # -----------------------------
- # 3) Fit model
- # -----------------------------
- # survival package version (used for Brier score and calibration slope)
- cox_fit <- coxph(
- Surv(Time_to_Event, Progressed_to_Mild) ~ age_at_scan + gender + cdrsum + EOADsig_wscore,
- data = data2, x = TRUE, y = TRUE
- )
- # rms package version (used for bootstrap validation)
- dd <- datadist(data2)
- options(datadist = "dd")
- cph_fit <- cph(
- Surv(Time_to_Event, Progressed_to_Mild) ~ age_at_scan + gender + cdrsum + EOADsig_wscore,
- data = data2, x = TRUE, y = TRUE, surv = TRUE, time.inc = u, units = "Month"
- )
- # -----------------------------
- # 4) Apparent C-index
- # -----------------------------
- conc <- summary(cox_fit)$concordance
- c_index <- unname(conc[1])
- c_se <- unname(conc[2])
- cat("\n--- Apparent C-index ---\n")
- cat("C-index:", round(c_index, 3),
- " (95% CI:", round(c_index - 1.96 * c_se, 3), "to",
- round(c_index + 1.96 * c_se, 3), ")\n")
- # -----------------------------
- # 5) Apparent Brier and scaled Brier
- # -----------------------------
- brier_obj <- brier(cox_fit, times = u)
- cat("\n--- Apparent Brier score ---\n")
- cat("Brier score at", u, "months:", round(brier_obj$brier[1], 3), "\n")
- cat("Scaled Brier score at", u, "months:", round(100 * brier_obj$rsquared[1], 1), "%\n")
- # -----------------------------
- # 6) Apparent calibration slope
- # -----------------------------
- lp <- predict(cox_fit, type = "lp")
- cal_slope_model <- coxph(Surv(Time_to_Event, Progressed_to_Mild) ~ lp, data = data2)
- cal_slope_sum <- summary(cal_slope_model)
- slope <- cal_slope_sum$coef[1, "coef"]
- slope_se <- cal_slope_sum$coef[1, "se(coef)"]
- cat("\n--- Apparent calibration slope ---\n")
- cat("Calibration slope:", round(slope, 3),
- " (95% CI:", round(slope - 1.96 * slope_se, 3), "to",
- round(slope + 1.96 * slope_se, 3), ")\n")
- # -----------------------------
- # 7) Observed-to-expected (O/E) ratio at u months
- # -----------------------------
- surv_func <- Survival(cph_fit)
- pred_risk <- 1 - surv_func(u, lp = lp)
- km_fit <- survfit(Surv(Time_to_Event, Progressed_to_Mild) ~ 1, data = data2)
- obs_risk <- 1 - summary(km_fit, times = u, extend = TRUE)$surv
- exp_risk <- mean(pred_risk)
- cat("\n--- O/E ratio at", u, "months ---\n")
- cat("Observed risk:", round(obs_risk, 3), "\n")
- cat("Mean predicted risk:", round(exp_risk, 3), "\n")
- cat("O/E ratio:", round(obs_risk / exp_risk, 3), "\n")
- # -----------------------------
- # 8) Bootstrap internal validation (1,000 iterations)
- # Harrell FE. Regression Modeling Strategies. 2nd ed. Springer; 2015.
- # -----------------------------
- set.seed(123)
- val_boot <- validate(cph_fit, method = "boot", B = 1000, dxy = TRUE, u = u)
- print(val_boot)
- # Optimism-corrected C-index
- dxy_corr <- val_boot["Dxy", "index.corrected"]
- c_corr <- dxy_corr / 2 + 0.5
- # Optimism-corrected calibration slope
- slope_corr <- val_boot["Slope", "index.corrected"]
- cat("\n--- Bootstrap-corrected estimates ---\n")
- cat("Optimism-corrected C-index :", round(c_corr, 3), "\n")
- cat("Optimism-corrected calibration slope:", round(slope_corr, 3), "\n")
- cat("Shrinkage factor :", round(slope_corr, 3), "\n")
- # -----------------------------
- # 9) Bootstrap-corrected calibration plot
- # -----------------------------
- cal_matrix <- val_boot # calibrate() output if used separately
- # Convert from survival to event probability scale
- cal_risk <- as.data.frame(cal_matrix) %>%
- mutate(
- pred_risk = 1 - pred,
- obs_risk = 1 - calibrated.corrected,
- lower_risk = pmax(1 - (calibrated.corrected + Upper), 0),
- upper_risk = pmin(1 - (calibrated.corrected + Lower), 1)
- )
- ggplot(cal_risk, aes(x = pred_risk, y = obs_risk)) +
- geom_ribbon(aes(ymin = lower_risk, ymax = upper_risk),
- fill = "gray70", alpha = 0.4) +
- geom_line(color = "red", linewidth = 1.4) +
- geom_abline(slope = 1, intercept = 0,
- linetype = "dashed", color = "black", linewidth = 1) +
- labs(
- x = "Predicted 24-month progression probability",
- y = "Observed 24-month progression probability",
- title = "Bootstrap-corrected calibration (t = 2 years)"
- ) +
- coord_cartesian(xlim = c(0, 1), ylim = c(0, 1)) +
- theme_classic(base_size = 16)
05_calibration_validation.R at commit 691a507, no license · at the source
Overview
and 26 other authors
David Glenn Clark5, Gregory S. Day12, Ranjan Duara13, Neill R. Graff-Radford12, Ian M. Grant14, Lawrence S. Honig15, Erik Johnson16, David T. Jones4,12, Joseph C. Masdeu17, Mario F. Mendez18, Erik S. Musiek19, Chiadi U. Onyike20, Meghan Riddle21, Emily Rogalski22, Stephen Salloway21, Sharon J. Sha23, Raymond Scott Turner24, Thomas Wingo25, David A. Wolk26, Kyle B. Womack19, Maria C. Carrillo27, Gil Dan Rabinovici3, Liana G. Apostolova5,28,29, Bradford Clark Dickerson1, Mark C. Eldaief1,30,31, Alexandra Touroutoglou131 affiliations
- Frontotemporal Disorders Unit and Massachusetts Alzheimer's Disease Research Center, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston
- Department of Biostatistics, Center for Biostatistics and Health Data Science, Brown University, Providence, RI
- Department of Neurology, University of California—San Francisco
- Department of Radiology, Mayo Clinic, Rochester, MN
- Department of Neurology, Indiana University School of Medicine, Indianapolis
- Alzheimer's Therapeutic Research Institute, University of Southern California, San Diego
- Department of Public Health Sciences, University of California—Davis
- Department of Radiology, University of Michigan, Ann Arbor
- Department of Neurology, Washington University School of Medicine, Saint Louis, MO
- Laboratory of Neuro Imaging, USC Stevens Neuroimaging and Informatics Institute, Keck School of Medicine of USC, Los Angeles, CA
- Banner Sun Health Research Institute, Sun City, AZ
- Department of Neurology, Mayo Clinic, Jacksonville, FL
- Wien Center for Alzheimer's Disease and Memory Disorders, Mount Sinai Medical Center, Miami, FL
- Department of Psychiatry and Behavioral Sciences, Mesulam Center for Cognitive Neurology and Alzheimer's Disease, Feinberg School of Medicine, Northwestern University, Chicago, IL
- Taub Institute and Department of Neurology, Columbia University Irving Medical Center, New York
- Department of Neurology, Emory University School of Medicine, Atlanta, GA
- Nantz National Alzheimer Center, Houston Methodist and Weill Cornell Medicine, Houston, TX
- Department of Neurology, David Geffen School of Medicine at UCLA, Los Angeles, CA
- Department of Neurology, Washington University in St. Louis, MO
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD
- Department of Neurology, Alpert Medical School, Brown University, Providence, RI
- Department of Neurology, University of Chicago, IL
- Department of Neurology and Neurological Sciences, Stanford University, Palo Alto, CA
- Department of Neurology, Georgetown University, Washington, DC
- Department of Neurology, UC Davis Alzheimer's Disease Research Center, University of California—Davis
- Department of Neurology, Perelman School of Medicine, University of Pennsylvania, Philadelphia
- Medical & Scientific Relations Division, Alzheimer's Association, Chicago, IL
- Department of Radiology and Imaging Sciences, Center for Neuroimaging, Indiana University School of Medicine Indianapolis, Indianapolis
- Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis
- Department of Psychiatry, Massachusetts General Hospital and Harvard Medical School, Boston; and
- Center for Brain Sciences, Harvard University, Cambridge, MA
Abstract
The abstract is not reproduced here: the paper's license (CC BY-NC-ND) does not allow it. Read it in the paper, at the publisher or on Europe PMC.
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thiagoparanhos/EOAD-prognostication
691a507440da83c70221e5de5d7f67932ad806bc, 14 May 2026Availability: 1 check, the latest on 27 September 2026: the link answers
- 27 September 2026: the link answers
6 files
- GitHub_code/
01_sample_size_estimatio , R, 24 linesn.R - GitHub_code/
02_survival_analysis.R , R, 36 lines - GitHub_code/
03_cox_models.R , R, 59 lines, 1 match - GitHub_code/
04_model_comparison.R , R, 73 lines - GitHub_code/
05_calibration_validatio , R, 148 lines, 2 matchesn.R - README.md, Text, 54 lines
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Version 2, 28 September 2026
- Publisher: n/a → Lippincott Williams & Wilkins
- Funding: added Alzheimer's Association: GENETICS-19-639372, LEADS GENETICS-19, 19‐639372, U01AG6057195, LEADS GENETICS-19-639372, LDRFP-21-824473, 21-824473, P30 AG062421, U24AG021886, LDRFP-21-818464, P30 AG062422, P30 AG010133, LDRFP-21-828356, R56 AG057195; Massachusetts General Hospital: P50 AG005134, P41EB015896; Centre d'Imagerie BioMédicale; National Institutes of Health: U01AG6057195; Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital: S10RR021110, P41-EB015896, S10 RR023401, S10 RR023043; National Institute on Aging: P30 AG066506, AG010133, P30AG062677, P30-AG066507, AG066507, U24‐AG021886, AG062421, R21 AG080588, AG072979, P41EB015896, R56AG057195, P30AG072977, AG005134, AG057195, P30-AG062421, P30 AG072980, U24AG072122, P30 AG010133, AG066511, P30AG066444, AG072977, R01 AG085377, P30AG066462, AG066444, R01DC014296, AG072122, P30-AG066511, U01‐AG6057195, P30-AG-072979, AG066462, AG072980, P30 AG066515, P50 AG 005134, AG066515, K23 DC016912, AG062422, P30 AG062422, AG062677, R21 AG073744; National Institute of Biomedical Imaging and Bioengineering: P30 AG062421, P41EB-015896, S10-RR023043, U24AG021886, S10RR023401, S10RR021110, R01 DC014296
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 46 authors, 14 MeSH terms, 45 references.
Cite
This paper
Paranhos, T., Katsumi, Y., Brickhouse, M. J., Eloyan, A., Eckbo, R., Zaitsev, A., Du, A., La Joie, R., Thangarajah, M., Taurone, A., Vemuri, P., Jack, C. R., as the LEADS Consortium, Hammers, D. B., Aisen, P. S., Beckett, L. A., Koeppe, R., Kukull, W. A., Toga, A. W., . . . Touroutoglou, A. (2026). EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker. Neurology, 107(7), e218519. https://
BibTeX
@article{paranhos2026eoa
author = {Paranhos, Thiago and Katsumi, Yuta and Brickhouse, Michael Joseph and Eloyan, Ani and Eckbo, Ryan and Zaitsev, Alexander and Du, Anna and La Joie, Renaud and Thangarajah, Maryanne and Taurone, Alexander and Vemuri, Prashanthi and Jack, Clifford R. and {as the LEADS Consortium} and Hammers, Dustin B. and Aisen, Paul S. and Beckett, Laurel A. and Koeppe, Robert and Kukull, Walter A. and Toga, Arthur W. and Atri, Alireza and Clark, David Glenn and Day, Gregory S. and Duara, Ranjan and Graff-Radford, Neill R. and Grant, Ian M. and Honig, Lawrence S. and Johnson, Erik and Jones, David T. and Masdeu, Joseph C. and Mendez, Mario F. and Musiek, Erik S. and Onyike, Chiadi U. and Riddle, Meghan and Rogalski, Emily and Salloway, Stephen and Sha, Sharon J. and Turner, Raymond Scott and Wingo, Thomas and Wolk, David A. and Womack, Kyle B. and Carrillo, Maria C. and Rabinovici, Gil Dan and Apostolova, Liana G. and Dickerson, Bradford Clark and Eldaief, Mark C. and Touroutoglou, Alexandra},
title = {{EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker}},
journal = {Neurology},
year = {2026},
month = aug,
volume = {107},
number = {7},
pages = {e218519},
publisher = {Lippincott Williams \& Wilkins},
issn = {0028-3878},
doi = {10.1212/
url = {https://
pmid = {42647766},
pmcid = {PMC13528895}
}
RIS
TY - JOUR
AU - Paranhos, Thiago
AU - Katsumi, Yuta
AU - Brickhouse, Michael Joseph
AU - Eloyan, Ani
AU - Eckbo, Ryan
AU - Zaitsev, Alexander
AU - Du, Anna
AU - La Joie, Renaud
AU - Thangarajah, Maryanne
AU - Taurone, Alexander
AU - Vemuri, Prashanthi
AU - Jack, Clifford R.
AU - as the LEADS Consortium
AU - Hammers, Dustin B.
AU - Aisen, Paul S.
AU - Beckett, Laurel A.
AU - Koeppe, Robert
AU - Kukull, Walter A.
AU - Toga, Arthur W.
AU - Atri, Alireza
AU - Clark, David Glenn
AU - Day, Gregory S.
AU - Duara, Ranjan
AU - Graff-Radford, Neill R.
AU - Grant, Ian M.
AU - Honig, Lawrence S.
AU - Johnson, Erik
AU - Jones, David T.
AU - Masdeu, Joseph C.
AU - Mendez, Mario F.
AU - Musiek, Erik S.
AU - Onyike, Chiadi U.
AU - Riddle, Meghan
AU - Rogalski, Emily
AU - Salloway, Stephen
AU - Sha, Sharon J.
AU - Turner, Raymond Scott
AU - Wingo, Thomas
AU - Wolk, David A.
AU - Womack, Kyle B.
AU - Carrillo, Maria C.
AU - Rabinovici, Gil Dan
AU - Apostolova, Liana G.
AU - Dickerson, Bradford Clark
AU - Eldaief, Mark C.
AU - Touroutoglou, Alexandra
TI - EOAD-Signature Atrophy Predicts Dementia in Early-Onset MCI due to Alzheimer Disease: An MRI-Based Prognostic Biomarker
T2 - Neurology
J2 - Neurology
PY - 2026
DA - 2026/
VL - 107
IS - 7
SP - e218519
SN - 0028-3878
PB - Lippincott Williams & Wilkins
DO - 10.1212/
UR - https://
LA - en
ER -
CSL-JSON
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