Thursday, November 16, 2017

Chronic Inflammation as a Risk Factor for Alzheimer’s Disease

Acute or short-term inflammation is a protective response that occurs in injury or infection to help the body defend itself and begin repair.  It is one of the tools the immune system uses to attack whatever is injuring us.  It is, however, a nonselective response taking a toll on us as well. While this is OK when fighting a virus for a week, it causes important damage to the body if continued over very long periods of time.

Chronic inflammation is involved in virtually all chronic degenerative disease.  It has long been established as an important mechanism of degenerative brain disease, especially Alzheimer’s disease.  Over 5400 studies discussing both “Alzheimer’s” and “Inflammation” appear in a search of PubMed, the search engine of the National Library of Medicine.

While the data linking chronic inflammation to Alzheimer’s disease has been growing, one of the strongest links has recently been found.  The study examined the presence of midlife inflammatory markers and the presence of one of the important diagnostic indicators of Alzheimer’s disease, loss of volume or physical size in key brain areas involved in memory processing and storage.

The study population involved 1633 subjects with a mean age of 53 years. Two- thirds were women reflecting the female predominance seen in the disease. Five inflammatory markers were used to create an "inflammatory composite score". Volumetric MRI scans which accurately digitize the volume of each brain area were used to compare brain volume losses.

The images show the loss of volume in the key memory areas typical of Alzheimer’s disease.  The gray areas are areas of brain cells, while the black is cerebrospinal fluid that fills empty areas. The image on the left shows the loss of volume in the hippocampus (pink area in green circle) and temporal lobe (red circle), key areas in memory function.  It also shows increased volume of CSF fluid in the ventricles (black area in the white circle) which results from gray matter/brain cell loss.

Follow-up testing was done 24 years later. The results of the study were striking.  For every 1 standard deviation higher inflammatory composite score at midlife, there was a 110 mm3 loss in hippocampal volume, and 532 mm3 loss in the total region where Alzheimer’s affects the brain. There was also a 1788 mm3 increase in the ventricle volume representing cell loss at the center of the brain.

In addition to the brain volume changes correlating to level of midlife inflammation the researchers also correlated changes in episodic memory which is the memory of events including when, where, what and other details.  Episodic memory decline paralleled with brain volume loss connecting loss of memory function with brain volume loss driven by chronic inflammation.
There were also trends for the correlations being stronger in whites and in those of younger age at the beginning of the study.  The latter suggests that the longer inflammation has to work on the brain, the more damage it will do by the typical age of onset of Alzheimer’s disease.

A major emphasis of the Bredesen or ReCode Protocol for the treatment of Alzheimer’s is measuring inflammatory markers and using intense treatment efforts to reduce them.  Of course, the best time to address inflammation would be in prevention but as Dr. Bredesen has shown, it is an important piece of reversing early stages of the disease itself if coordinated with all other contributing disease mechanisms.

Walker et al.  Midlife systemic inflammatory markers are associated with late-life brain volume: The ARIC study.   Neurology, 2017 ePub

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