Cognition

By using VBM to build on existing findings, the current study found significant associations between risk status determined based on the CAIDE score and grey matter atrophy in several regions, including the temporal, occipital, and fusiform cortex and lingual gyrus at baseline. Longitudinally, the supramarginal gyrus, angular gyrus, precuneus, lateral occipital cortex, superior parietal lobule and cingulate gyrus demonstrated accelerated atrophy over time. Many of these regions belong to the “AD signature cortical region” and are involved in processes such as consciousness and memory. This study highlights the potential for early interventions that focus on modifiable midlife vascular risk factors.

Key terms and abbreviations:

• Atrophy= the progressive reduction in tissue
• CAIDE score =Cardiovascular Risk Factors, Aging, and Incidence of Dementia score; A validated midlife dementia risk score, based on several factors, including age, gender, education, blood pressure, cholesterol, body mass index, physical activity and APOEe4 allele carriership.
• VBM= Voxel based morphometry: An MRI technique that enables investigation of focal differences in anatomy throughout the brain
• APOEe4 allele= One of the strongest genetic risk factors for Alzheimer’s disease​

Some of the earliest brain regions to be affected by Alzheimer’s disease are thought to be those involved in memory and spatial orientation. Researchers led by PREVENT Co-Chief Investigator Prof Karen Ritchie were interested in how the PREVENT cohort performed on  tasks involving particular orientation skills. The ‘4 Mountains Task’ is used to measure navigation through allocentric space (person-independent, relating to the location of particular objects in relation to other objects in space). The ‘Virtual Supermarket Task’ involves orientation of egocentric space (person-dependent, relating to the location of objects in space relative to one’s own body position).   

 

They found that participants with a higher ‘Dementia Risk Score’ (calculated from a combination of known risk factors such as genetics and cardiovascular health) scored significantly lower overall on the ‘4 Mountains’ allocentric orientation task. There was no significant association between Dementia Risk Score and performance on the ‘Virtual Supermarket’ test of egocentric space.

 

These findings would support the idea that the earliest brain changes associated with Alzheimer’s disease may be able to be detected through specific tests of spatial orientation. Developing behavioural tests that are sensitive to these very earliest changes could be vital in supporting earlier identification of disease burden, long before symptoms become apparent. They could also prove important in offering a way of measuring the effectiveness of future early interventions, including drug trials. 

 

This investigation included only a small initial population of what will form the eventual 700-strong PREVENT cohort. The researchers are keen to repeat this analysis once more participants have completed the spatial processing tasks.

In this analysis, researchers were interested in the performance of PREVENT participants on a range of memory and thinking tasks in their mid-life to determine if there were any associations with increased risk of dementia in later life.

It is likely that traditional memory tests such as those used in memory clinic or in drug trials involving participants with established dementia may not be sensitive enough to identify the very earliest subtle changes in brain health. In this report the authors suggest that volunteers deemed at greater risk for dementia based on factors such as genetics and cardiovascular health, seemed to perform slightly worse on certain tasks, principally those which involved detailed spatial and navigation skills.

This initial data came from a relatively small number of the very first volunteers to enter the study. The results also come from only the first study visit and so capture only one snapshot in time. Whilst these findings alone are not enough to inform any one individual’s risk profile they do generate interesting areas to focus on when following participants throughout the duration of the study.