Long-term brain volume trajectories and lifestyle associations in cognitively normal adults: the BRAIN-STRIDE study.
The 4 matches
- [1] § Materials and methods › Associations with lifestyle and clinical factors ↔ brain_stride_lifestyle_analysis.Rmd, lines 37–47 · score 0.61 · lifestyle variables, lifestyle factors, glucose, HDL, LDL, BMI
- [2] § Materials and methods › Identification of brain atrophy subtypes in cognitively normal adults ↔ brain_stride_apply_lme.Rmd, lines 16–44 · score 0.60 · individual atrophy rates, linear mixed, individual slopes, brain region, predictor, harmonized
- [3] § Results › Atrophy group classification and longitudinal brain volume changes ↔ brain_stride_apply_lme.Rmd, lines 273–325 · score 0.59 · linear fits, volume trajectories, normalized volume, individual baseline, resistant, Age
- [4] § Materials and methods › Brain volume measurement and longitudinal harmonization ↔ brain_stride_apply_longcombat.Rmd, lines 366–429 · score 0.51 · random intercepts, metric, correlation, additive, batch, mixed
Paper
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The authors' code
R Markdown · 325 lines · 10 KB · MIT · 2 matches
- ---
- title: "Individual Brain Atrophy Trajectories: Mixed-Effects Modeling and Bootstrap Grouping"
- output:
- html_document:
- toc: true
- toc_float:
- toc_collapsed: true
- toc_depth: 3
- theme: paper
- ---
- ```{r setup, include=FALSE}
- knitr::opts_chunk$set(echo = TRUE, message = FALSE, warning = FALSE)
- ```
- # Overview
- This script estimates individual atrophy rates for each brain region using
- linear mixed-effects models, then uses a bootstrap procedure to stratify
- subjects into "rapid", "resistant", and "typical" atrophy groups based on the
- distribution of individual slopes within each decade of age. Summary statistics
- and figures are generated for selected regions.
- # Packages and Data
- ```{r load-packages-data}
- ##############################################################################
- ## 0. Packages and data
- ##############################################################################
- library(lme4)
- library(tidyverse)
- library(purrr)
- library(cowplot)
- df_norm <- read.csv("data/df_combat_norm.csv")
- ## Region columns to analyze (harmonized, normalized features)
- regions <- grep("\\.combat\\.norm$", names(df_norm), value = TRUE)
- ## Analysis parameters
- predictors <- c("BMI", "dBP") # Lifestyle factors included as fixed effects
- B <- 2000 # Number of bootstrap iterations
- set.seed(123)
- ```
- # Individual Slope Estimation
- ```{r individual-slopes}
- ##############################################################################
- ## 1. Per-region lmer -> individual slopes -> attach decade -> drop 30s/80s
- ##############################################################################
- get_indiv_coef <- function(region) {
- fml <- as.formula(
- sprintf("`%s` ~ time + %s + (time | subid)",
- region, paste(predictors, collapse = " + "))
- )
- m <- lmer(fml, data = df_norm, REML = FALSE)
- coef(m)$subid %>% # Intercept and time slope
- rownames_to_column("subid") %>%
- select(subid, time) %>% # Keep slope only
- left_join(df_norm %>% select(subid, decade) %>% distinct(),
- by = "subid") %>%
- filter(!decade %in% c("30s", "80s")) %>% # Exclude sparse decades
- mutate(decade = factor(decade, levels = sort(unique(decade))),
- region = region)
- }
- indiv_all <- map_dfr(regions, get_indiv_coef)
- ```
- # Group Assignment
- ```{r group-assignment}
- ##############################################################################
- ## 2. Flag rapid / resistant groups (10% / 90% thresholds)
- ##############################################################################
- flag_groups <- function(df) {
- # Regions where a positive slope reflects atrophy (inverted interpretation)
- invert_regions <- c("Ventricle.combat.norm", "Sulcus.combat.norm")
- df %>%
- group_by(region, decade) %>%
- mutate(
- q10 = quantile(time, 0.10),
- q90 = quantile(time, 0.90),
- grp = case_when(
- time <= q10 ~ if_else(region %in% invert_regions, "resistant", "rapid"),
- time >= q90 ~ if_else(region %in% invert_regions, "rapid", "resistant"),
- TRUE ~ "typical"
- )
- ) %>%
- ungroup()
- }
- ```
- # Bootstrap
- ```{r bootstrap}
- ##############################################################################
- ## 3. Bootstrap (stratified by region x decade)
- ##############################################################################
- boot_once <- function(data) {
- sampled <- data %>%
- group_by(region, decade) %>%
- sample_frac(replace = TRUE) %>%
- ungroup()
- grp_tbl <- flag_groups(sampled)
- diff_tbl <- grp_tbl %>%
- filter(grp != "typical") %>%
- group_by(region, decade, grp) %>%
- summarise(med = median(time), .groups = "drop") %>%
- pivot_wider(names_from = grp, values_from = med) %>%
- mutate(med_diff = resistant - rapid)
- list(diff = diff_tbl,
- subj = grp_tbl %>% select(subid, region, decade, grp))
- }
- boot_out <- map(1:B, ~ boot_once(indiv_all))
- ```
- # Final Labels and Per-Region Plots
- ```{r final-labels}
- ##############################################################################
- ## 4. Stable labels (probability >= 0.8) and per-region boxplots
- ##############################################################################
- subj_stab <- map_dfr(boot_out, "subj") %>%
- count(subid, region, grp) %>%
- pivot_wider(names_from = grp, values_from = n, values_fill = 0) %>%
- mutate(across(rapid:resistant, ~ .x / B)) # Convert counts to probabilities
- final_lab <- subj_stab %>%
- mutate(final_grp = case_when(
- rapid >= 0.8 ~ "rapid",
- resistant >= 0.8 ~ "resistant",
- TRUE ~ "typical"
- )) %>%
- select(subid, region, final_grp)
- plot_df <- indiv_all %>%
- left_join(final_lab, by = c("subid", "region")) %>%
- mutate(final_grp = factor(final_grp,
- levels = c("rapid", "typical", "resistant")))
- ## Color palette
- fill_pal <- c(rapid = "#E15759", typical = "grey60", resistant = "#4E79A7")
- point_pal <- fill_pal
- ## Save a jitter plot per region
- walk(unique(plot_df$region), function(reg) {
- p <- ggplot(filter(plot_df, region == reg),
- aes(x = decade, y = time * 100, fill = final_grp)) +
- geom_jitter(aes(colour = final_grp),
- width = 0.15, size = 1.5, alpha = 0.55) +
- geom_hline(yintercept = 0, linetype = "dashed") +
- scale_fill_manual(values = fill_pal, drop = FALSE) +
- scale_colour_manual(values = point_pal, drop = FALSE) +
- labs(title = paste(reg, ": Atrophy rate by decade/group"),
- x = "", y = "Annual slope (%)",
- fill = "Group", colour = "Group") +
- theme_cowplot(12) +
- theme(legend.position = "right")
- ggsave(sprintf("%s_boxplot.png", reg), p,
- width = 5, height = 4.5, dpi = 300)
- })
- cat("Analysis complete: PNG figures written to the working directory.\n")
- ```
- # Combined Faceted Plot
- ```{r faceted-plot, fig.width=14, fig.height=3}
- ## Display labels and ordering for selected regions
- region_labels <- c(
- "WholeBrain.combat.norm" = "Whole brain",
- "CerebralCortex.combat.norm" = "Cortical",
- "WhiteMatter.combat.norm" = "WM",
- "Ventricle.combat.norm" = "Ventricle",
- "Sulcus.combat.norm" = "Sulcus"
- )
- region_order <- names(region_labels)
- ## Fix region order and keep only selected regions
- plot_df_subset <- plot_df %>%
- filter(region %in% region_order) %>%
- mutate(region = factor(region, levels = region_order))
- p_all <- ggplot(
- plot_df_subset,
- aes(x = decade, y = time * 100,
- fill = final_grp, colour = final_grp)
- ) +
- geom_jitter(width = 0.15, size = 0.5, alpha = 0.55) +
- geom_hline(yintercept = 0, linetype = "dashed") +
- scale_fill_manual(values = fill_pal, drop = FALSE) +
- scale_colour_manual(values = point_pal, drop = FALSE) +
- facet_wrap(
- ~ region,
- scales = "free_y",
- nrow = 1,
- labeller = as_labeller(region_labels)
- ) +
- labs(
- title = "Atrophy rate by decade / region / group",
- x = "",
- y = "Annual slope (%)",
- fill = "Group",
- colour = "Group"
- ) +
- theme_cowplot(12) +
- theme(legend.position = "right")
- print(p_all)
- ```
- # Summary Table
- ```{r summary-table}
- ##############################################################################
- ## 6. Summary statistics by region x decade x group (median [IQR])
- ##############################################################################
- region_labels <- c(
- "WholeBrain.combat.norm" = "Whole brain",
- "CerebralCortex.combat.norm" = "Cortical",
- "WhiteMatter.combat.norm" = "WM",
- "Ventricle.combat.norm" = "Ventricle",
- "Sulcus.combat.norm" = "Sulcus"
- )
- summary_tbl <- indiv_all %>% # subid, region, time, decade
- left_join(final_lab, by = c("subid", "region")) %>% # Add final_grp
- mutate(rate_pct = time * 100) %>% # Annual rate (%)
- group_by(region, decade, final_grp) %>%
- summarise(
- n = n(),
- median = median(rate_pct),
- p25 = quantile(rate_pct, 0.25),
- p75 = quantile(rate_pct, 0.75),
- .groups = "drop"
- ) %>%
- mutate(
- stat = sprintf("%.2f (%.2f to %.2f)", median, p25, p75)
- ) %>%
- select(region, decade, final_grp, stat) %>%
- pivot_wider(
- names_from = final_grp,
- values_from = stat
- ) %>%
- rename(
- `Typical volume change rate (annual %)` = typical,
- `Rapid-atrophy group` = rapid,
- `Atrophy-resistant group` = resistant
- ) %>%
- mutate(
- Structure = recode(region, !!!region_labels),
- Structure = factor(Structure, levels = region_labels)
- ) %>%
- arrange(Structure, decade) %>%
- select(Structure, decade,
- `Typical volume change rate (annual %)`,
- `Rapid-atrophy group`,
- `Atrophy-resistant group`)
- print(summary_tbl, n = Inf)
- ```
- # Age vs. Volume Trajectories
- ```{r age-volume-smooth, fig.width=14, fig.height=3}
- plot_lab <- final_lab
- regions_selected <- c("WholeBrain.combat.norm",
- "CerebralCortex.combat.norm",
- "WhiteMatter.combat.norm",
- "Sulcus.combat.norm",
- "Ventricle.combat.norm")
- plot_agevol <- df_norm %>%
- pivot_longer(cols = all_of(regions_selected),
- names_to = "region",
- values_to = "volume") %>%
- left_join(plot_lab, by = c("subid", "region")) %>%
- mutate(region = factor(region, levels = regions_selected))
- ## Version 1: per-subject linear fits for rapid / resistant groups
- ggplot(plot_agevol,
- aes(x = age, y = volume * 100, colour = final_grp)) +
- geom_jitter(alpha = 0.6, size = 0.3, width = 0.3) +
- geom_smooth(
- data = plot_agevol %>% filter(final_grp %in% c("rapid", "resistant")),
- aes(group = subid, colour = final_grp),
- method = "lm", se = FALSE,
- linewidth = 0.4, alpha = 0.7
- ) +
- facet_wrap(~ region, scales = "free_y", nrow = 1) +
- scale_colour_manual(values = point_pal) +
- labs(x = "Age (years)",
- y = "Normalized volume \n (% of individual baseline)",
- colour = "Group") +
- theme_cowplot(12)
- ## Version 2: connected observed points for rapid / resistant groups
- ggplot(plot_agevol,
- aes(x = age, y = volume * 100, colour = final_grp)) +
- geom_jitter(alpha = 0.6, size = 0.3, width = 0.3) +
- geom_line(
- data = plot_agevol %>%
- filter(final_grp %in% c("rapid", "resistant")) %>%
- arrange(subid, age),
- aes(group = subid),
- linewidth = 0.4, alpha = 0.7
- ) +
- facet_wrap(~ region, scales = "free_y", nrow = 1) +
- scale_colour_manual(values = point_pal) +
- labs(x = "Age (years)",
- y = "Normalized volume \n (% of individual baseline)",
- colour = "Group") +
- theme_cowplot(12)
- ```
brain_stride_apply_lme.Rmd, under MIT · at the source
Overview
- Department of Radiology, The University of Tokyo, Tokyo, 113-8655, Japan
- Department of Radiology, Juntendo University, Tokyo, 113-8421, Japan
- Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Boston, MA 02129, USA
- Department of Radiology, Harvard Medical School, Boston, MA 02115, USA
- Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA
- F.M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, Baltimore, MD 21205, USA
- Department of Computational Diagnostic Radiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, 113-8655, Japan
- Center for Frontier Medical Engineering, Chiba University, Chiba, 263-8522, Japan
- Department of Biostatistics, School of Public Health, The University of Tokyo, Tokyo, 113-0033, Japan
Abstract
Brain ageing is a major determinant of cognitive health, yet the extent of inter-individual variability in structural trajectories and its links to lifestyle factors remain incompletely understood. We conducted a single-centre, prospective longitudinal cohort study within an urban academic health screening programme in Japan (November 2006 to April 2021), with up to 15 years of follow-up. Among 10 209 individuals who underwent screening, those with more than 10 years of serial visits were eligible; 186 participants were excluded for major intracranial findings, 3 for cognitive decline during follow-up and 3 for contraindications or ineligibility, yielding 653 cognitively normal adults [207 women (31.6%); mean (SD) age at baseline, 55.1 (9.3) years]. Participants underwent serial magnetic resonance imaging and Mini-Mental State Examination, along with baseline assessments of lifestyle and vascular risk factors including body mass index, blood pressure, smoking exposure and lipid profile. Annual percentage change in whole-brain and regional volumes was estimated using linear mixed-effects models after harmonization for scanner effects, and participants were categorized as rapid atrophy, typical, or atrophy-resistant based on percentile thresholds. Across 7915 MRI scans, whole-brain volume decline accelerated from 0.24% per year in the 40s to 0.44% per year in the 70s. Individuals classified as having rapid atrophy in their 40s exhibited rates of decline of 0.46% per year, comparable to population averages in the 70s, whereas atrophy-resistant individuals in their 70s demonstrated rates as low as 0.27% per year. Faster whole-brain atrophy was associated with higher body mass index [β = 0.027; 95% confidence interval (CI), 0.0058–0.049], greater smoking exposure (β = 0.032; 95% CI, 0.012–0.053), elevated diastolic blood pressure (β = 0.044; 95% CI, 0.021–0.067) and higher low-density lipoprotein cholesterol (β = 0.043; 95% CI, 0.021–0.065) (all P < 0.01). Utilizing an uncommonly long and densely sampled longitudinal design, this study demonstrates that structural brain ageing among cognitively normal adults follows highly heterogeneous trajectories, spanning from marked decline to near-complete resistance. Modifiable lifestyle and vascular risk factors were associated with faster atrophy, supporting opportunities for risk stratification and targeted prevention strategies.
Reproduced under the paper's license (CC BY), from the paper cited above.
Repository
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Zenodo 20819668
Availability: 1 check, the latest on 26 September 2026: the link answers (HTTP 200)
- 26 September 2026: the link answers (HTTP 200)
4 files
- brain_stride_apply_lme.R
md — R, 325 lines, 2 matches - brain_stride_apply_longc
ombat.Rmd — R, 429 lines, 1 match - brain_stride_lifestyle_a
nalysis.Rmd — R, 202 lines, 1 match - README.md — Text, 140 lines
The paper's code and data availability statement is in the Data section.
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Data
No dataset and no data link were found in the paper.
Data availability
MRI data and individual measurements are currently unavailable because the hospital has withheld them to protect participant privacy. The scripts used for analyses are available via code repository link: https://
Reproduced under the paper's license (CC BY), from the paper cited above.
Versions
The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.
Version 3, 28 September 2026
- Funding: added University of Tokyo
Version 1, 27 September 2026: the first record
Recorded: type, language, journal, volume, issue, pages, dates, 11 authors, 5 keywords, 33 references.
Cite
This paper
Fujita, S., Mori, S., Onda, K., Hanaoka, S., Nomura, Y., Nakao, T., Hagiwara, A., Hagiwara, Y., Takao, H., Yoshikawa, T., & Abe, O. (2026). Long-term brain volume trajectories and lifestyle associations in cognitively normal adults: the BRAIN-STRIDE study. Brain communications, 8(5), fcag343. https://
BibTeX
@article{fujita2026long,
author = {Fujita, Shohei and Mori, Susumu and Onda, Kengo and Hanaoka, Shouhei and Nomura, Yukihiro and Nakao, Takahiro and Hagiwara, Akifumi and Hagiwara, Yasuhiro and Takao, Hidemasa and Yoshikawa, Takeharu and Abe, Osamu},
title = {{Long-term brain volume trajectories and lifestyle associations in cognitively normal adults: the BRAIN-STRIDE study}},
journal = {Brain communications},
year = {2026},
month = sep,
volume = {8},
number = {5},
pages = {fcag343},
publisher = {Oxford University Press},
issn = {2632-1297},
doi = {10.1093/
url = {https://
pmid = {42765092},
pmcid = {PMC13590224}
}
RIS
TY - JOUR
AU - Fujita, Shohei
AU - Mori, Susumu
AU - Onda, Kengo
AU - Hanaoka, Shouhei
AU - Nomura, Yukihiro
AU - Nakao, Takahiro
AU - Hagiwara, Akifumi
AU - Hagiwara, Yasuhiro
AU - Takao, Hidemasa
AU - Yoshikawa, Takeharu
AU - Abe, Osamu
TI - Long-term brain volume trajectories and lifestyle associations in cognitively normal adults: the BRAIN-STRIDE study
T2 - Brain communications
J2 - Brain Commun
PY - 2026
DA - 2026/
VL - 8
IS - 5
SP - fcag343
SN - 2632-1297
PB - Oxford University Press
DO - 10.1093/
UR - https://
LA - en
ER -
CSL-JSON
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"issued": {
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