Mapping out specific cognitive abilities in midlife might predict future dementia risk

Prof Karen Ritchie

We are thrilled that the PREVENT Dementia study has reached a point where the study follow-up visits are on-going and preliminary results from the baseline assessments have just been published in Alzheimer’s & Dementia. The PREVENT Dementia study is looking to identify early indicators of dementia in middle aged people that may appear decades before any dementia symptoms occur. The authors analysed the cross-sectional data to begin mapping out cognitive profiles of adults who are at high risk of late-onset Alzheimer’s disease. We are delighted to explain these preliminary findings in more detail.

A recent review of innovation in the field of dementia identified prevention and risk reduction as one of the key themes in finding a solution to a growing global dementia problem. We know from existing research that the underlying pathology to Alzheimer’s dementia might start developing decades earlier when a person is outwardly healthy. Risk factors for the development of Alzheimer’s disease include diseases affecting heart and blood vessels and problems involving the breakdown and build-up of substances in the body. As people get exposed to these – cardiovascular and metabolic – risk factors particularly in midlife then this period is a critical window to prevent the disease progression.

Traditional memory tests not sensitive to very early cognitive changes

Alzheimer’s disease studies with people who are in the stage just before they develop dementia commonly use similar tests to assess memory performance. The lead author of the paper and the co-lead of the PREVENT Dementia study, Prof Karen Ritchie (pictured) from the Centre for Dementia Prevention, explained that looking at their study group, people in their midlife, then overall these traditional tests did not show an association between cognitive performance and later-life dementia risk. However, there was some evidence that the people at higher risk performed worse on tasks that measured specifically spatial awareness. These results from the first wave of the PREVENT data highlight the need to include tests that focus more on spatial and navigational tasks in future dementia prevention studies in order to accurately identify people at higher risk.

There is emerging evidence that the accumulation of certain proteins such as amyloid-beta precedes cognitive decline by decades. Prof Ritchie and colleagues argue that cognitive changes may not only appear at the same time but also interact with these biological changes. This is vital as cognitive functioning is a central clinical concern and something that is monitored closely in dementia studies. The nuance in detecting cognitive decline at such an early time point, decades before a person would be showing signs of dementia, comes from looking at an appropriate much more specific part of the brain. Many of the current studies, therefore, use brain scanning methods that are not sensitive enough to the truly subtle brain changes that occur so long before dementia onset.

Focusing on spatial awareness

In the current paper, the authors aimed to examine associations between cognitive performance at mid-life and various indicators of dementia risk. While these early findings cannot be used to explain the underlying causes between the associations, then the authors found that a higher dementia risk score was associated with a small number of specific tests which have a strong spatial component – such as linking a person’s photo with their name. It is also noteworthy that dementia risk factors change over time. Looking at genetics, while APOE ε4 allele is generally considered a higher risk factor for developing dementia then in the PREVENT study, participants with an APOE ε4 allele performed better on a specific visuospatial task matching geometric figures. The authors conclude that while APOE ε4 allele is associated with a number of poorer health outcomes in old age, it may have a positive effect earlier in life as it is associated with higher intelligence.

For the PREVENT study sample, a high cardiovascular risk score was found to be associated with poorer visual association learning as well as a decrease in both brain volume and smaller size of specific regions in the brain such as hippocampus which is associated with spatial navigation, spatial memory and the combining of spatial location with personal memories. It is an important finding that a high cardiovascular risk score impacts on a person’s dementia risk already in midlife – emphasising the critical role of cardiovascular health in longer-term outcomes.

First results in the context of longitudinal follow-up data still to come

The authors emphasise that the spatial and navigational tests that are highlighted in the paper as potential avenues for cognitive testing should, at this early stage, be used in dementia research and not to inform individual risk statuses. The current findings from the PREVENT Dementia study are preliminary as they are based on 210 people enrolled in the study so far – half of whom have a family history of dementia and half of whom do not. The study is on going and will aim to recruit 700 participants in order to follow an even larger number of people over time and get a more in depth understanding of dementia risk factors. Nevertheless, the findings of this paper serve as a vital contribution to the prevention and risk reduction work that is globally recognised as a key part of tackling dementia.

Ritchie K, Carrière I, Su L, O’Brien JT, Lovestone S, Wells K, Ritchie CW. (2017). The mid-life cognitive profiles of adults at high risk of late-onset Alzheimer’s disease: the PREVENT Study. Alzheimer’s and Dementia