Publications

Cardiovascular risk of dementia is associated with brain–behaviour changes in cognitively healthy, middle-aged individuals

Feng Deng, Karen Ritchie, Graciela Muniz-Terrera, Suzanne Hutchinson, Paresh Malhotra, Craig W Ritchie, Brian Lawlor, Lorina Naci.

Neurobiology of Ageing (2024)

DOI: https://doi.org/10.1016/j.neurobiolaging.2024.09.00610.1016/j.neurobiolaging.2024.09.006

Summary

This study examined whether Alzheimer’s Disease (AD) risk factors were associated with cognition and functional connectivity (FC) between two key brain structures involved with the development of AD, the Locus Coeruleus (LC) and the hippocampus.

The study found evidence that in midlife, the role of functional connectivity between the LC and the hippocampus in supporting cognition is disrupted, in individuals with a high dementia risk score. When genetic risk (APOE ε4) or family history were considered on their own, no alterations of brain–behaviour relationships were found. It was only when a risk score (CAIDE) incorporating genetic risk in combination with lifestyle factors, sex and age was considered, that such alterations were unraveled.

These results provide evidence that brain–behaviour changes in individuals with higher dementia risk scores may be driven by lifestyle factors included in the CAIDE score (i.e., blood pressure, cholesterol, physical activity, body mass index, years of education). These findings highlight the importance of modifying cardiovascular factors for the early prevention of dementia.

Neuroimaging and Clinical Findings in Healthy Middle-Aged Adults With Mild Traumatic Brain Injury in the PREVENT Dementia Study

Audrey Low, Elizabeth McKiernan, Maria A. Prats-Sedano, Stephen F. Carter, James D. Stefaniak, Li Su,  Maria-Eleni Dounavi, Graciela Muniz-Terrera, Natalie Jenkins, Katie Bridgeman, Karen Ritchie, Brian Lawlor, Lorina Naci, Paresh Malhotra, Clare Mackay, Ivan Koychev, Tony Thayanandan, Vanessa Raymont, Craig W. Ritchie, William Stewart, John T. O’Brien.

Jama Network Open (2024)

DOI: 10.1001/jamanetworkopen.2024.26774

Summary

Most traumatic brain injury (TBI) research focuses on contact sport athletes and trauma units, which naturally have more severe TBI. Whereas this study explored the impact of mild incidents of TBI in a group of healthy volunteers. Data from over 600 middle-aged adults was analysed, where using a comprehensive screening tool, researchers identified a surprising number of participants with a history of TBI – one in three with a higher rate in men.

The study found that even mild TBIs were linked to signs of brain microbleeds, depression, and poorer sleep in a group of otherwise healthy volunteers as early as midlife. Brain microbleeds are established markers of small vessel disease (SVD), a condition linked to an increased risk of dementia. However, this study found an unexpected disconnect. While other markers of SVD were associated with cardiovascular disease as expected, microbleeds were not. Instead, microbleeds were strongly linked to TBI history.

The data suggest that microbleeds can be a consequence of TBI rather than solely a result of chronic vascular disease. The study underscores the need for a comprehensive approach to TBI prevention, emphasising the role of policymakers, organisations, and the community to mitigate risk through policy changes, public education, and improved safety standards.

Investigating the brain’s neurochemical profile at midlife in relation to dementia risk factors

Maria-Eleni Dounavi, Elizabeth McKiernan, Michael Langsen, Sarah Gregory, Graciela Muniz-Terrera, Maria Angeles Prats-Sedano, Marius Ovidiu Mada, Guy B Williams, Brian Lawlor, Lorina Naci, Clare Mackay, Ivan Koychev, Paresh Malhotra, Karen Ritchie, Craig W Ritchie, Li Su, Adam D Waldman, John T O’ Brien,

Brain Communications (2024)

DOI: https://doi.org/10.1093/braincomms/fcae138

Summary

Changes of functional nature in the brain in people who develop dementia later on, are thought to occur before any anatomical/structural changes and before any cognitive symptoms appear. In this study the concentration of brain metabolites within a region called the ‘posterior cingulate/precuneus’, which is one of the first regions where Alzheimer’s-related changes appear, were investigated. An MRI technique called Magnetic Resonance Spectroscopy was used to do this.

Very subtle differences were found between people with and without dementia family history, people with dementia family history had a lower concentration of a metabolite called N-acetylaspartate. We also found associations between the concentration of several metabolites and cardiovascular risk for dementia. These were mainly driven by older age and a higher body mass index. Presence of a risk gene for future Alzheimer’s disease was not found to have an impact in the concentration of metabolites at this stage.

Dementia risk and thalamic nuclei volumetry in healthy midlife adults: the PREVENT Dementia study

Sita N Shah, Maria-Eleni Dounavi, Paresh A Malhotra, Brian Lawlor, Lorina Naci, Ivan Koychev, Craig W Ritchie, Karen Ritchie, John T O’Brien

Brain Communications (2024)

DOI: https://doi.org/10.1093/braincomms/fcae046

Summary

The Thalamus is an area of the brain involved with several processes, such as cognitive function and sleep, and has been shown to be affected in the dementia disease process. This study sought to investigate volumetric differences in the thalamus and its sub-regions in middle-aged participants in the PREVENT-Dementia study with respect to dementia family history and the apolipoprotein e4 (APOE) allele carriership and its relationship with cognitive function.

No volumetric differences were found in the thalamus and its sub-regions between groups. A larger volume of the medial thalamus was associated with faster processing speeds in individuals without dementia family history. However, larger volumes of the thalamus and posterior thalamus was associated with worse performance on  immediate recall ability in APOE4 allele carriers. The findings could highlight an initial dysregulation in the disease process, but further study is needed to assess for changes in the thalamus over time.

PallorMetrics: Software for Automatically Quantifying Optic Disc Pallor in Fundus Photographs, and Associations With Peripapillary RNFL Thickness

Samuel Gibbon, Graciela Muniz-Terrera, Fabian S. L. Yii, Charlene Hamid, Simon Cox, Ian J. C. Maccormick, Andrew J. Tatham, Craig Ritchie, Emanuele Trucco, Baljean Dhillon, Thomas J. MacGillivray

Neuro-ophthalmology (2024)

DOI: https://doi.org/10.1167/tvst.13.5.20

Summary

In dementia, nerve cells in the brain called neurons stop functioning properly, lose connections with other neurons, and eventually die prematurely. The eye is a window into the human body where we can easily study the nerves of the retina which might reflect the health and condition of similar, but less accessible, tissues in the brain.  In this paper we explain how we have developed software that quantifies the appearance of the optic nerve head in fundus images as a marker of loss of nerve tissue that makes this feature appear lighter and paler. Our technique could potentially become a straightforward test to monitor for change over time and spot people most at risk of developing dementia later in life. In turn, this could help target the recruitment of clinical trials of new treatments at the most suitable individuals.