Alzheimer’s & Dementia (2025)

DOI: 10.1002/alz.70244

Summary

Sleep problems are common in people with dementia and often start years before the diagnosis. However, it is not known to what extent these sleep problems are caused by early changes in the brain areas involved in controlling sleep. In this study we used data from sleep questionnaires and MRI brain scans in the PREVENT and ALFA cohorts, which are both large studies of middle-aged participants without dementia. We found that participants with an increased genetic risk of Alzheimer’s disease (APOE4 gene carriers) had early changes in the hypothalamus, a brain region which is essential for sleeping well. These participants also had more sleep problems. Finally, we found that sleep problems increased with older age, but only in participants with a smaller hypothalamus. These results suggest that early changes in the hypothalamus may partially explain the relationship between sleep problems and the increased risk of dementia.

Alzheimer’s & dementia (2025)

DOI: https://doi.org/10.1002/dad2.70075

Summary

The study explores whether there is a connection between the tiny blood vessels in the eye’s choroid (a layer behind the retina) and the risk of developing Alzheimer’s disease in middle-aged adults who are cognitively healthy. It included 69 middle-aged adults from the PREVENT Dementia programme who had undergone optical coherence tomography (OCT) scanning. We used OCT to measure the choroidal blood vessels. Participants were divided into low, medium, and high-risk groups based on genetic factors, family history of dementia, and the CAIDE score. We found that individuals with a higher genetic risk for Alzheimer’s had thicker choroidal blood vessels and more vascular tissue compared to those with lower risk. Specifically, a small increase in choroidal vascular area was linked to a higher likelihood of having Alzheimer’s risk markers. The results suggest a potential link between the choroidal microvasculature and Alzheimer’s disease risk, but the findings are preliminary and need to be confirmed in larger, more diverse studies. This research highlights the potential of using eye exams to identify early signs of Alzheimer’s disease, which could lead to earlier interventions and better outcomes for those at risk.

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.