Lane CA, Barnes J, Nicholas JM, Sudre CH, Cash DM, Malone IB, Parker TD, Keshavan A, Buchanan SM, Keuss SE, James SN, Lu K, Murray-Smith H, Wong A, Gordon E, Coath W, Modat M, Thomas D, Richards M, Fox NC, Schott JM. Associations Between Vascular Risk Across Adulthood and Brain Pathology in Late Life: Evidence From a British Birth Cohort. JAMA Neurol. 2019 Nov 4;:1-9. PubMed.

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Comments

  1. There are larger and more detailed studies that have previously explored vascular risk with brain volumes and white-matter damage across mid- to later life in greater depth, and the results of this study are in line with the direction previously reported (more vascular risk, less healthy brain). Beyond this, the study offers some valuable and welcome insights.

    Showing links between vascular risk measured at age 36 and some—but not other—aspects of brain health measured decades later is important. It adds further weight to the argument (informed by many studies) that we should not wait until later life to address our cardiovascular health if we want to age healthily. The study also used PET imaging to see if people with greater vascular risk showed greater prevalence of Alzheimer’s related plaques in the brain; they did not.

    The authors themselves caution that their brain measures were not fine-grained: They chose to divide people into approximately high/low plaque groups, which does not allow the possibility to examine the (perhaps more likely) subtler relationship between vascular risk and this brain hallmark of Alzheimer’s disease. In addition, they did not conduct any work to look at whether some risk factors were more important than others, and whether this depended upon the time of life at which they were measured, which could have been highly informative.

    View all comments by Simon R. Cox

  2. This is an interesting article that provides further evidence that vascular risk factors are independently associated with brain volume loss (a likely correlate of neurodegenerative processes). Interesting aspects of this paper include the finding that vascular factors were not associated with plaque accumulation (as assessed by PET scan). This suggests that vascular factors act through a direct pathway rather than by exacerbating AD pathology, as is frequently proposed.

    Other interesting aspects include the finding that the longer people are exposed to vascular risk factors the greater likelihood of brain atrophy and white-matter hyperintensities. It appears that atrophy included both gray- and white-matter areas, showing that all cell types beyond oligodendrocytes are susceptible to chronic hypoperfusion. However, we have recently shown in mice that that myelination of axons is a lifelong process (Hill et al., 2017). Microvascular pathology and brain hypoperfusion could have a detrimental effect on the brain’s capacity to form new myelin internodes even in the absence of ischemia.

    References:

    Hill RA, Li AM, Grutzendler J. Lifelong cortical myelin plasticity and age-related degeneration in the live mammalian brain. Nat Neurosci. 2018 May;21(5):683-695. Epub 2018 Mar 19 PubMed.

    View all comments by Jaime Grutzendler

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