Publications

Brain age gap, dementia risk factors and cognition in middle age

James D. Stefaniak, Elijah Mak, Li Su, Stephen F Carter, Maria-Eleni Dounavi, Graciela Muniz Terrera, Katie Bridgeman, Karen Ritchie, Brian Lawlor, Lorina Naci, Ivan Koychev, Paresh Malhotra, Craig W. Ritchie, John T. O’Brien

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.

Associations between sex and lifestyle activities with cognitive reserve in mid-life adults with genetic risk for Alzheimer’s disease

Qi Q, Deng F, Sammon R, Ritchie K, Muniz-Terrera G, Koychev I, Hutchinson S, Robinson D, Malhotra P. O’Brien J, Ritchie CW, Lawlor B, Naci, L.

Alzheimer’s Research & Therapy (2024)

DOI: https://doi.org/10.1186/s13195-024-01610-9

Summary

Building cognitive reserve through stimulating activities and occupational attainment represents a crucial yet under-explored approach to dementia prevention in mid-life. However, it remains unclear whether modifiable lifestyle factors can protect against Alzheimer’s disease (AD) processes from mid-life, differentially for females and males who carry inherited risk for late-life dementia.

This study found that engagement in stimulating activities was positively associated with episodic and relational memory, regardless of sex and APOE4 genetic status. Notably, among APOE4 carriers, this study found significant sex differences in the association between occupational attainment and episodic and relational memory: APOE4 carrier females with higher occupational attainment showed better cognition, whereas APOE4 carrier males showed the opposite effect.

These findings indicate that occupational attainment in mid-life may enhance cognitive reserve against inherited dementia risk in females but not in males. They underscore the necessity for high-precision approaches that account for biological sex and APOE4 carrier status to better inform AD prevention strategies and clinical trials.

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.