Elizabeth McKiernan, Elijah Mak, Maria Eleni-Dounavi, Katie Wells, Craig Ritchie, Guy Williams, Li Su, John O’Brien
Journal of Neurology, Neurosurgery and Psychiatry. 2020
This study explored the relationship between dementia and cerebral blood flow (CBF) as cerebral hypoperfusion (reduced blood flow in the brain) is characteristic of cognitive impairment and Alzheimer’s disease.
The current study used data from participants’ ASL MRI scans to investigate whether changes in CBF would be seen in our healthy mid life participants, and whether these would be associated with dementia risk, as defined by ones APOEe4 status, Family history and cognitive performance on the COGNITO assessment.
As expected, perfusion (blood flow) was correlated with the APOEe4 allele and participants family history, however not cognitive performance. Differences in the location of the CBF were found in participants carrying the APOEe4 allele compared to participants with a family history of dementia. However, intriguingly, the direction of change was opposite to what was expected. Rather than finding regional hypoperfusion, our at-risk participants showed regional hyperperfusion (increased blood flow) across these areas.
The impact of these findings is not yet clear, however further examination of longitudinal data, including that of full PREVENT-Dementia cohort will help to determine at what point CBF changes occur and what mechanisms are at play.
Key terms and abbreviations:
- ASL MRI= Arterial spin labelling Magnetic Resonance Imaging: a non-invasive perfusion imaging technique for the measurement of cerebral blood flow
- APOEe4 allele= One of the possible genetic risk factors for dementia
Michael Firbank, John O’Brien, Karen Ritchie, Katie Wells, Guy Williams, Li Su, Craig Ritchie
Journal of Neurology. 2020
Anna McKeever, Alvar Paris, James Cullen, Lawrence Hayes, Craig Ritchie, Karen Ritchie, Adam Waldman, Katie Wells, Albert Busza, Isabelle Carriere, John O’Brien
Journal of Alzheimer’s Disease. 2020
One abnormality commonly found in the brains of those living with Alzheimer’s disease is the reduced volume of a subfield of the hippocampus called the CA1. The current study sought to investigate whether this change is apparent at midlife.
In line with previous research, lower CA1 volume was found to be associated with both a family history of dementia and greater cardiovascular risk factors, and this change was evident at a mean age of 53. This is important, as it demonstrates that the change can be seen in midlife before symptoms of Alzheimer’s disease have begun. This study also revealed a second, unexpected finding: Individuals with a family history of dementia showed an increase in three other hippocampal regions combined (CA3, CA4, DG), perhaps indicating an early inflammatory or neurogenesis response to early Alzheimer’s disease.
Maria-Eleni Dounavi, Elijah Mak, Katie Wells, Karen Ritchie, Craig W. Ritchie, Li Su, John T.O’ Brien
Neurobiology of Ageing. 2020
In this study, we found that participants with an APOEe4 genotype (a known genetic risk factor for dementia) were more likely to have a smaller hippocampal molecular layer, and this change was apparent at both the baseline and 2-year follow up.
Together with previous findings, it appears that the molecular layer may be one of the first areas to show vulnerability to the pathological hallmarks of Alzheimer’s. However, it was noted that differences in the molecular layer were not significantly related to dementia risk defined by family history or cardiovascular factors.
John T O’Brien, Michael J Firbank, Karen Ritchie,, Katie Wells, Guy B Williams, Craig W Ritchie, Li Su
Journal of Neurology, Neurosurgery & Psychiatry. 2019
Individuals with a higher likelihood of developing Alzheimer’s disease dementia in the future, as predicted by their mid-life CAIDE score, show more shrinkage of brain volume, measured over the course of two years.
Known risk factors for heart disease, an individual’s genetic makeup as well as other health factors, are thought to contribute to someone’s risk of developing Alzheimer’s disease (AD). Researchers have put together a scoring system that uses these risk factors in midlife to calculate someone’s risk of developing Alzheimer’s disease dementia in the future. This is known as a CAIDE score.
The authors used data from the first 210 PREVENT participants from the West London group. The participants were split into two groups based on their CAIDE score and each participant had an MRI scan to look at their brain at two time points, their initial visit and then two years later. The researchers found that the group of participants with a CAIDE score of 7 and above showed more overall shrinkage in their brain after two years compared to people with a lower score.
The authors therefore were able to demonstrate that there is an association between CAIDE score and brain volume and that individuals with a higher CAIDE score in midlife are already showing signs of brain changes. It also provides evidence that using an MRI scanner to image individuals thought to be at risk every few years and measuring brain changes, or lack thereof, may be a good way to track disease progression, or how well an intervention is working.
Hinesh Topiwala, Graciela Muniz Terrera, Lucy Stirland, Kathryn Saunderson, Tom C. Russ, Marshall F. Dozier and Craig W. Ritchie
Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 2018