Pattern of thinning may predict dementia risk a decade before symptoms

Work on blood tests that might identify people at high risk of developing Alzheimer's disease a decade or more before symptoms appear is well under way. Recent work from a US-based team, however, reports finding another signature of high Alzheimer's risk. In their study of 1,500 older Americans from diverse racial and demographic backgrounds, the team found that a pattern of grey matter thinning was linked to a significantly increased risk of developing Alzheimer's and related dementias five to ten years later. 

Claudia L. Satizabal at the University of Texas and colleagues looked at data on 1,000 mostly White participants in the long-running Framingham Heart Study, as well as a separate study group of 500 older adults, just under half of whom were Black or Hispanic. 

The team first used comparisons of brain scans of a subset of participants with and without a diagnosis of Alzheimer's disease or a related dementia (ADRD) to identify an ADRD 'signature' pattern of cortical thinning in sections of the frontal, parietal, and temporal lobes. Then they went back to look at MRI brain scans of other participants taken a decade earlier, and found that people whose brains showed this pattern of cortical thinning ten years ago were more likely to have been diagnosed with Alzheimer's disease or a similar dementia since. 

The link with dementia risk was striking. Among the (mostly White) Framingham group, those whose cortical thickness measures fell into the bottom 25% of results had a three times higher risk of later being diagnosed with dementia. For similar participants in the other, more racially diverse group, the risk was five times greater. Even slight differences in this cortical thickness signature had an incremental effect on dementia risk. 

More work is now needed to validate the use of this measure for assessing future dementia risk. But the work does suggest that the relationship between thinning and dementia risk behaves in the same way in different races and ethnic groups, comments Satizabal. If these findings prove to be replicable and accurate, in future it may be possible to compare the thickness of a person's grey matter to expected values for those of similar ages in order to determine dementia risk. 

The team also explored whether there was any link between cortical thinning and the APOE4 gene, the main genetic risk factor for Alzheimer's. They didn't find any. The team hopes that this may mean that modifying lifestyle factors, such as diet and exercise levels, might restrict or even prevent this thinning, and reduce dementia risk. 

Other work has found links between high blood pressure, diabetes, and unhealthy blood fat profiles and thinning of certain regions of the cortex, especially in the presence of amyloid beta. Though more work is clearly needed to explore the potential causes of cortical thinning, and how it factors into Alzheimer's disease, this new study is another step towards a better understanding of the disease, and potentially how to tackle it.  

Read the paper in full: https://doi.org/10.1002/alz.13600