Summary
Cardiovascular factors have a strong association with Alzheimer’s disease (AD) and brain atrophy. However, until recently, there has been limited longitudinal research in cognitive healthy middle-aged adults investigating these links. A recent PREVENT Dementia study used data from 167 participants in the PREVENT London cohort, to investigate associations between the CAIDE (Cardiovascular Risk Factors, Aging, and Dementia) score and structural MRI scans at both baseline and 2-year follow up. Participants in the high-risk group (i.e., those with a CAIDE score above 6) were on average, found to have a greater rate of brain atrophy. However, to identify the specific regions and structures driving this atrophy pattern, additional analysis was conducted using voxel based morphometry (VBM).
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
Gallery Game: Smartphone-based assessment of long-term memory in adults at risk of Alzheimer’s disease
Claire Lancaster, Ivan Koychev, Jasmine Blane, Amy Chinner, Christopher, Chatham, Kirsten Taylor, Chris Hinds
Journal of Clinical and Experimental Neuropsychology. 2019
This publication lays out plans for the PREVENT Elicitation of Dialogues (PREVENT-ED) substudy. This project aims to analyse specific features of speech during conversation with PREVENT participants. The researchers seek to determine if there are any associations between changes in spoken dialogue and other risk factors for Alzheimer’s disease. Ultimately they want to know whether such dialogue analysis could be useful in screening for early stages of disease.
Allocentric and Egocentric Spatial Processing in Middle-Aged Adults at High Risk of Late-Onset Alzheimer’s Disease: The PREVENT Dementia Study
Karen Ritchie, Isabelle Carriere, David Howett, Li Su, Michael Hornberger, John T. O’Brien, Craig W. Ritchie and Dennis Chan.
Journal of Alzheimer’s Disease 65 (2018)
10.3233/JAD-180432
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.
The midlife cognitive profiles of adults at high risk of late-onset Alzheimer’s disease: The PREVENT study.
Ritchie K, Carrière I, Su L, O’Brien JT, Lovestone S, Wells K, Ritchie CW.
Alzheimer’s & dementia: the journal of the Alzheimer’s Association. 2017
10.1016/j.jalz.2017.02.008
Researchers analysed the results from PREVENT participants on various memory and thinking assessments. They found performance on particular spatial and navigation based tasks may be useful in differentiating between those deemed at high or low risk for later life dementia.
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.
