Greater Chronic Inflammation Correlates with Greater Cognitive Decline

Along with raised blood pressure, chronic inflammation is one of the most important downstream consequences of (a) the causes of aging, (b) harmful environmental factors such as burden of infectious disease, and (c) poor lifestyle choices, such as becoming overweight. Chronic inflammation in and of itself produces a wide range of harmful consequences, accelerating the development and progression of all of the most common fatal age-related conditions. Inflammation disrupts regeneration, guides normally helpful immune cells into harmful activities, and distorts the operation of cellular metabolism in damaging ways.

In the short term, inflammation is a necessary part of the response to injury or infection. It is when it runs on without cease that the problems start. Cells that are constantly acting as if in response to an emergency perform their usual tasks ever more poorly. Many age-related diseases have a strong inflammatory component, and this is the case for most forms of neurodegenerative condition. The immune cells of the brain are somewhat different from those elsewhere in the body, and are arguably far more essential to correct tissue function. They participate in maintenance of synaptic connections, for example.

The study here finds the expected correlation between degree of chronic inflammation and degree of cognitive decline in aging. The authors conclude that suppression of chronic inflammation should be a priority in the treatment of older individuals. The broad range of evidence regarding inflammation and its role in aging suggests that ways to override the inflammatory response could be beneficial even without addressing the underlying causes of inflammation. This sort of outcome was achieved to some degree in the case of raised blood pressure, via antihypertensive medications that override the responses to molecular damage that lead to hypertension, but dealing with blood pressure is a more straightforward challenge than taming the aged, damaged immune system.

Given the complexity of the immune system, approaches that aim at the much simpler root causes of chronic inflammation are much more likely to (a) succeed at a reasonable cost and (b) produce larger gains. Consider senolytic therapies that selectively destroy senescent cells, for example. These errant cells, that accumulate with age, are a significant source of inflammatory signaling. Remove them, and inflammation is reduced. More prosaically, consider loss of visceral fat tissue through the usual approach of eating fewer calories. Visceral far is metabolically active, producing inflammation throughout the body via a range of mechanisms that can all be dialed down just be reducing the amount of fat tissue present in the body.

Systemic Inflammation Is Associated With Longitudinal Changes in Cognitive Performance Among Urban Adults

Chronic systemic inflammation is a risk for neurodegeneration manifesting as Alzheimer's Disease (AD) and age-related cognitive decline. Markers of inflammation are associated with poorer cross-sectional cognitive performance, faster longitudinal decline in various domains of cognition as well as with structural and functional brain changes representing early markers of AD, including brain region activity, regional cortical thickness and white matter microstructural integrity. However, few studies have examined cross-sectional or longitudinal associations of inflammation with cognitive performance in a bi-racial adult cohort, and none have tested effect modification by race, age, and sex in the relationship between systemic inflammation and rate of change in cognitive performance over time while using a large battery of cognitive tests.

The current study examined associations between systemic inflammation and cognitive performance among African Americans and Whites urban adults participating in the Health Aging in Neighborhoods of Diversity across the Life Span (HANDLS) study. Markers known to either increase or decrease during inflammation were tested against cross-sectional and longitudinal cognitive function, stratifying by key sociodemographic factors, including age, sex, and race.

Among key findings, a composite score combining four markers of systemic inflammation was associated with faster decline on a test of visual memory/visuo-constructive abilities, among older men only (over 50 years of age). Many other associations were detected in the expected direction for all markers except for serum iron, whereby a higher inflammatory status was linked to either worse performance at baseline or faster decline over time for specific age, sex and race groups. Most notably, baseline erythrocyte sedimentation rate (ESR) was associated with a faster decline on verbal memory among older men, whereas serum albumin was linked to slower attention decline among older men and over-time improvement in executive function in the total population. In contrast, high sensitivity C-reactive protein associations with cognition were mostly detected at baseline, for global mental status and the domain of attention.


This article motivates me to do a couple of more days of fasting, which suppresses the inflammation (proven), helps autophagy(kinda proven) and might have senolitic or senoreversing effects (not proven action)

Posted by: Cuberat at October 30th, 2018 9:15 PM

Fasting & exercise should help tamp down chronic inflammation. Bredersen's AD protocol includes a 12- or 13- daily fasting window, IIRC.

One thing that hasn't been researched enough is hyperammonemia and its effect on neuroinflammation.

I've been reading some very interesting things recently about d-mannose improving Treg function.

Of course, therapies designed to rejuvenate the immune system would be most helpful.

Posted by: CD at October 31st, 2018 11:18 AM

12- or 13- daily fasting window = 12 hour nightly fast

Posted by: CD at October 31st, 2018 11:20 AM

Basically it means skipping breakfast ;)

Anything less than 24 is hardly fasting. When we compare mouse results with humans we have to take into account that most mice will die in 2 days without food and it seems 4 days is the limit. Humans at normal BMI can survive a month or even two, if they are overweight. So 1 day fasting for a mouse is at least as stressful as probably a couple of weeks for humans.

Posted by: Cuberat at October 31st, 2018 2:50 PM

For clarity, it probably should be called time restricted feeding/eating, but many cultures around the world refer to such breaks in eating as a 'fast' (that's where the word breakfast comes from, after all). Daily time restricted eating has been shown to produce measurable health benefits in humans and Bredersen's AD protocol has had some impressive results.

Posted by: CD at November 6th, 2018 9:33 AM

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