Brain aging comprises many modes of structural and functional change with distinct genetic and biophysical associations
- University of Oxford, United Kingdom
- Simon Fraser University, Canada
Abstract
Brain imaging can be used to study how individuals’ brains are aging, compared against population norms. This can inform on aspects of brain health; for example, smoking and blood pressure can be seen to accelerate brain aging. Typically, a single 'brain age' is estimated per subject, whereas here we we identified 62 modes of subject variability, from 21,407 subjects' multimodal brain imaging data in UK Biobank. The modes represent different aspects of brain aging, showing distinct patterns of functional and structural brain change, and distinct patterns of association with genetics, lifestyle, cognition, physical measures and disease. While conventional brain-age modelling found no genetic associations, 34 modes had genetic associations. We suggest that it is important not to treat brain aging as a single homogeneous process, and that modelling of distinct patterns of structural and functional change will reveal more biologically meaningful markers of brain aging in health and disease.
Data availability
All source data is available from UK Biobank, as described in Section 5. That section also describes the full availability of all of our code used for this work, and additional supplementary materials. https://www.fmrib.ox.ac.uk/ukbiobank/BrainAgingModes/
Article and author information
Author details
Funding
Wellcome (203139/Z/16/Z)
- Stephen M Smith
- Karla L Miller
Wellcome (098369/Z/12/Z)
- Stephen M Smith
Wellcome (215573/Z/19/Z)
- Stephen M Smith
Wellcome (202788/Z/16/Z)
- Karla L Miller
Medical Research Council (MR/K006673/1)
- Gwenaëlle Douaud
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jonathan Erik Peelle, Washington University in St. Louis, United States
Ethics
Human subjects: The UK Biobank has approval from the North West Multi-centre Research Ethics Committee (MREC) to obtain and disseminate data and samples from the participants (http://www.ukbiobank.ac.uk/ethics/), and these ethical regulations cover the work in this study. Written informed consent was obtained from all participants.
Version history
- Received: October 11, 2019
- Accepted: March 2, 2020
- Accepted Manuscript published: March 5, 2020 (version 1)
- Version of Record published: April 16, 2020 (version 2)
Copyright
© 2020, Smith et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
Metrics
-
- 7,963
- Page views
-
- 1,147
- Downloads
-
- 83
- Citations
Article citation count generated by polling the highest count across the following sources: Crossref, Scopus, PubMed Central.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Brain aging comprises many modes of structural and functional change with distinct genetic and biophysical associations
eLife 9:e52677.
https://doi.org/10.7554/eLife.52677
Further reading
-
- Neuroscience
Storing and accessing memories is required to successfully perform day-to-day tasks, for example for engaging in a meaningful conversation. Previous studies in both rodents and primates have correlated hippocampal cellular activity with behavioral expression of memory. A key role has been attributed to awake hippocampal replay – a sequential reactivation of neurons representing a trajectory through space. However, it is unclear if awake replay impacts immediate future behavior, gradually creates and stabilizes long-term memories over a long period of time (hours and longer), or enables the temporary memorization of relevant events at an intermediate time scale (seconds to minutes). In this study, we aimed to address the uncertainty around the timeframe of impact of awake replay by collecting causal evidence from behaving rats. We detected and disrupted sharp wave ripples (SWRs) - signatures of putative replay events - using electrical stimulation of the ventral hippocampal commissure in rats that were trained on three different spatial memory tasks. In each task, rats were required to memorize a new set of locations in each trial or each daily session. Interestingly, the rats performed equally well with or without SWR disruptions. These data suggest that awake SWRs - and potentially replay - does not affect the immediate behavior nor the temporary memorization of relevant events at a short timescale that are required to successfully perform the spatial tasks. Based on these results, we hypothesize that the impact of awake replay on memory and behavior is long-term and cumulative over time.
-
- Neuroscience
Gradually reducing a source of fear during extinction treatments may weaken negative memories in the long term.
