Data from the Framingham Heart Study has found carriers of the ApoE4 gene were much more likely to develop Alzheimer’s if they also had chronic low-grade inflammation. Indeed, the researchers suggest that, in the absence of inflammation, there might be no difference of Alzheimer's risk between ApoE4 and non-ApoE4 carriers.
Data from 1,532 participants in a long-running study, in which participants were tested five times every 3 years (on average), found that those who showed increasing inflammation had greater abnormalities in the brain's white matter structure.
90 people transitioned from low to persistently elevated C-reactive protein during midlife, indicating increasing inflammation. Their brains appear similar to that of a person 16 years older, researchers estimate.
Common causes of chronic inflammation include cardiovascular disease, heart failure, diabetes, high blood pressure and infections such as hepatitis C or HIV.
61% of participants were women, and 28% were African-American. At the final visit, participants were an average age of 76.
 Tao, Q., Ang T. Fang Alvin, DeCarli C., Auerbach S. H., Devine S., Stein T. D., et al.
(2018). Association of Chronic Low-grade Inflammation With Risk of Alzheimer Disease in ApoE4 CarriersChronic Low-grade Inflammation and Risk of Alzheimer Disease in ApoE4 CarriersChronic Low-grade Inflammation and Risk of Alzheimer Disease in ApoE4 Carriers.
JAMA Network Open. 1(6), e183597 - e183597.
 Walker, K. A., B. Windham G., Power M. C., Hoogeveen R. C., Folsom A. R., Ballantyne C. M., et al.
(2018). The association of mid-to late-life systemic inflammation with white matter structure in older adults: The Atherosclerosis Risk in Communities Study.
Neurobiology of Aging. 68, 26 - 33.
A pilot study involving 22 breast cancer patients currently receiving chemotherapy (mean age 54), has found that those with higher levels of inflammatory biomarkers did significantly worse on tests for short-term visual memory. One particular biomarker — tumor necrosis factor-alpha (as reflected through its two soluble receptors, TNFRI and TNFRII) — was the strongest indicator of cognitive problems.
The findings are consistent with an earlier study involving 174 breast cancer patients evaluated before chemotherapy, which found that higher levels of those biomarkers were associated with worse memory, and another study of 49 patients, which found that higher levels of sTNFRII were associated with more memory complaints after chemotherapy.
Cognition was assessed using the Cambridge Neuropsychological Test Automated Battery (CANTAB), looking at those domains previously reported to be affected in cancer survivors: visual memory, executive functioning, attention, verbal memory, and cognitive processing.
Almost all the patients were Caucasian and college-educated.
Williams, AnnaLynn M. et al. 2018. Associations between inflammatory markers and cognitive function in breast cancer patients receiving chemotherapy. Journal of Neuroimmunology, 314, 17-23. Full text available at https://www.jni-journal.com/article/S0165-5728(17)30198-4/fulltext
Patel, S.K., Wong, A.L., Wong, F.L., Breen, E.C., Hurria, A., Smith, M. et al. 2015. Inflammatory biomarkers, comorbidity, and neurocognition in women with newly diagnosed breast cancer. J. Natl. Cancer Inst., 107.
Ganz, P.A., Bower, J.E., Kwan, L., Castellon, S.A., Silverman, D.H., Geist, C. et al. 2013. Does tumor necrosis factor-alpha (TNF-alpha) play a role in post-chemotherapy cerebral dysfunction?. Brain Behav. Immun., 30, S99–108.
Several studies suggest that post-operative cognitive decline in older adults is due to several factors:
It also seems that higher levels of cognitive function, higher levels of engagement in certain cognitive activities, and better cerebrovascular health, all protect against such decline.
Data from the Rush Memory and Aging Project has found that emergency and urgent hospitalizations are associated with an increased rate of cognitive decline in older adults.
Non-elective hospitalizations were associated with an approximately 60% acceleration in the rate of cognitive decline from before hospitalization. Elective hospitalizations, however, were not associated with acceleration in the rate of decline at all.
Of the 930 participants (average age 81), 613 were hospitalized at least once over an average of almost five years of observation. Of those who were hospitalized, 260 (28%) had at least one elective hospital admission, and 553 (60%) had at least one non-elective hospital admission. These groups included 200 participants (22%) who had both types of hospitalizations.
The data was presented at the Alzheimer's Association International Conference in London on July 17.
There is growing evidence that inflammation might be responsible for the cognitive decline seen in many older adults after surgery. Now a mouse study provides evidence that brain inflammation and cognitive decline following surgery are triggered by the brain's microglia.
When mice had their microglia temporarily depleted before surgery, they didn’t show any cognitive decline several days after surgery. They also had much lower levels of inflammatory molecules in the hippocampus. Controls — those not receiving the experimental drug to deplete microglia to around 5% of normal levels — did typically show a drop in cognitive performance.
Microglia levels returned to normal within two days after the treatment was stopped, and there was no sign of any impairment in surgical wound healing as a result of the intervention.
A 3-year study looking at short-term and long-term cognitive decline in older patients following a surgery found that those who experienced delirium after the surgery showed significantly greater decline than those who didn’t suffer such post-surgical confusion.
The study involved 560 patients (70+), of whom 134 experienced delirium. Both groups showed a significant cognitive decline at one month, followed by a return to their previous level of cognitive function at two months and then a gradual decline for the next 34 months. However, the rate of decline over the three year follow-up was not significant for those who hadn’t experienced delirium.
Those who suffered delirium also had significantly lower cognitive function before surgery.
The odd finding that even the delirium group recovered their cognitive function at two months, before once again declining, suggests that something about the delirium triggers a cascade of events which leads to progressive, long-lasting effects.
Delirium after surgery can lead to long-term cognitive decline in older adults — but not always. So what makes the difference?
A preliminary study involving 126 older adults suggests the answer lies in their cognitive function before surgery. Their global cognition score explained the most variation, with other significant factors including: IQCODE score, cognitive independent activities of daily living impairment, living alone, cerebrovascular disease, Charlson comorbidity index score, and exhaustion level. Taken together, these factors explained 32% of the variation in people’s outcome.
Delirium, an acute state of confusion, is a common condition affecting up to 50% of hospitalized older adults.
A study of 142 older adults who underwent elective surgery found that greater participation in cognitive activities was linked with a lower incidence and lower severity of delirium.
Nearly a third of the patients (average age 71) developed post-operative delirium. Those who did had participated in fewer leisure activities before surgery compared with people who didn't experience delirium.
Out of all the activities, reading books, using email, and playing computer games reduced the risk of delirium. Playing computer games and singing were the only two activities that predicted lower severity of delirium.
The protection afforded was dose-dependent, with each additional leisure activity reducing post-operative delirium by 8%.
 Feng, X., Valdearcos M., Uchida Y., Lutrin D., Maze M., & Koliwad S. K.
(2017). Microglia mediate postoperative hippocampal inflammation and cognitive decline in mice.
JCI Insight. 2(7),
 Inouye, S. K., Marcantonio E. R., Kosar C. M., Tommet D., Schmitt E. M., Travison T. G., et al.
(2016). The short-term and long-term relationship between delirium and cognitive trajectory in older surgical patients.
Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 12(7), 766 - 775.
 Devore, E. E., Fong T. G., Marcantonio E. R., Schmitt E. M., Travison T. G., Jones R. N., et al.
(Submitted). Prediction of Long-term Cognitive Decline Following Postoperative Delirium in Older Adults.
The Journals of Gerontology: Series A.
 Tow, A., Holtzer R., Wang C., Sharan A., Kim S. Jin, Gladstein A., et al.
(2016). Cognitive Reserve and Postoperative Delirium in Older Adults.
Journal of the American Geriatrics Society. 64(6), 1341 - 1346.
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