Chronic Inflammation in Midlife May Predispose To Smaller Brain Volumes and Memory Ability In Seniors Interview with:
Keenan A. Walker, PhD
Johns Hopkins University School of Medicine
Baltimore, MD What is the background for this study? What are the main findings?

Response: There is quite a bit of evidence linking immune function with dementia. For example, several of the risk genes for Alzheimer’s disease are known to play a key role in immune functioning and the regulation of inflammation. We conducted the current study to determine whether systemic inflammation earlier in life might be a risk factor for neurodegeneration decades later. This long temporal window allows us to get closer to understanding causality. That is, which comes first – systemic inflammation or brain volume loss.

Using a large community sample, we found that individuals with higher levels of blood inflammatory markers during midlife tended to have smaller brain volumes in select regions and reduced memory ability as older adults. We found the strongest associations between systemic inflammation and brain volume loss in brain regions most vulnerable Alzheimer’s disease. What should clinicians and patients take away from your report?

Response: I think the findings are too preliminary to suggest any drastic changes in medical practice. However, the findings suggest that treatment and prevention of chronic inflammatory diseases is likely important for maintaining brain health into older adulthood. Many disorders, such as diabetes, atherosclerosis, obesity, major psychiatric illness, and major infections are known to promote systemic inflammation. What recommendations do you have for future research as a result of this study?

Response: It is my hope that these findings direct future efforts for dementia prevention and treatment. Our findings support animal research which has implicated systemic inflammation as have a causal, rather than an associative, role  in neurodegenerative disease. I hope these findings encourage future efforts which examine how reducing systemic or brain inflammation might improve neurologic outcomes in older adults. Is there anything else you would like to add?

Response: Yes. This study certainly has several limitations. Although our findings support it, we cannot be sure of causality. We did not have a baseline MRI, so we can’t be sure that the brain volume loss did not occur before the assessment of inflammatory markers. Also, we only had a single timepoint assessment of inflammation. It’s likely that these markers vary across time within an individual, and this may introduce some uncertainty into the inflammation assessment. What we need are studies that assess systemic inflammation across many years to determine how sustained or chronic inflammation relates to late-life neurological outcomes.​ Thank you for your contribution to the community.


Keenan A. Walker, Ron C. Hoogeveen, Aaron R. Folsom, Christie M. Ballantyne, David S. Knopman, B. Gwen Windham, Clifford R. Jack, Rebecca F. Gottesman. Midlife systemic inflammatory markers are associated with late-life brain volume. Neurology, 2017; 10.1212/WNL.0000000000004688 DOI: 10.1212/WNL.0000000000004688

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

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Last Updated on November 4, 2017 by Marie Benz MD FAAD