Human Brain Mapping (2024)
DOI: https://doi.org/10.1002/hbm.26798
Summary
In this study we investigated if subtle changes on MRI scans were associated with a risk gene for late-onset Alzheimer’s disease. The Apolipoprotein e4 (APOE4) gene, can be detected by analysing the texture of brain images. One of the most well established changes in people in the early stages of dementia is that they have lower brain volumes in some brain areas such as the hippocampus. This is typically detected using structural MRI scans. However, changes on the MRI scan might be very subtle in early stages of the disease and the analysis of brain volumes might not capture them.
Therefore this study analysed the texture of structural MRI scans in both the PREVENT and the ALFA studies. Data from 1585 participants from these studies was analysed (mean age of 56 years). There were no textural or volumetric differences found in this middle-aged cohort between carriers and non-carriers of the APOE4 gene. These results suggest that structural changes in people at higher risk of dementia based on the APOE4 gene cannot be detected at this stage with simple volume analysis or even with more advanced computational methods.
Brain Communications (2024)
DOI: https://doi.org/10.1093/braincomms/fcae392
Summary
‘This study looked at “Brain Age Gap” (BAG) in middle-aged people. BAG is the difference between a person’s actual age and the age their brain appears to be based on MRI scans. A bigger gap means the brain appears older than it is.
We found that in middle-aged people, a larger BAG was linked to high blood pressure and drinking alcohol, but not to APOE4 genotype, amyloid plaques (a hallmark of Alzheimer’s disease), or how well people did on cognitive tests.
This means that some things that make your brain look older on scans are related to lifestyle factors that we can change. The study is important because it helps us understand how brain aging works in middle age, which could be the best time to start treatments to prevent dementia.
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.
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.
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.
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.
