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.