The rate of cognitive decline with aging is quite variable. 

Identifying important components of this process is needed for developing interventions to reduce the burden of Alzheimer's and other dementias.

Excess inflammation has been linked to obesity as well as aging-related cognitive decline.

Archana Singh-Manoux and colleagues recently published a study of the association between blood markers of inflammation and cognitive decline.

This study used data from the U.K. Whitehall II cohort, a group of men and women between the ages of 35-55 at intake.

This cohort has now been studied over a 20 year follow up with interval assessments about every five years.

Two blood markers of inflammation were studied in this cohort: interleukin-6 (IL-6) and C-reactive protein (CRP).

The study found strong associations between both blood markers of inflammation and rates of obesity (BMI >30) in the chart shown here.

Cognitive decline was measured by decrease scores on the Minimental Status Exam and other neuropsychological tests during the follow up period.

The primary finding from the study was that elevated IL-6 levels but not CRP levels at baseline were associated with accelerated cognitive decline.

Subjects in the highest IL-6 blood level group showed an 85% increased rate in losing 3 or more points on the Minimental Status Exam.

The authors note there study does not prove causality between IL-6 levels and cognitive decline but that:

"Inflammation is likely to play a role because of its impact on cerebral small-vessel disease, which could lead to changes that affect cognitive ageing."

It is also possible, that some of the link between obesity and cognitive decline may be attributable to increased obesity-related inflammation.

The practical clinical potential would be to attempt to identify and reduce inflammation in those most at risk. Anti-inflammatory drugs such as naproxen (Aleve in U.S.) have not been generally effect in trials to reduce rates of Alzheimer's disease.

However, these trials have typically not targeted groups with the highest blood markers of inflammation.

Readers with more interest in this topic can access the free full-text manuscript by clicking on the link in the citation below.

Photo of great blue heron from South Padre Island, TX is from the author's files.

Chart is an original figure from data abstracted from the manuscript.

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Singh-Manoux A, Dugravot A, Brunner E, Kumari M, Shipley M, Elbaz A, & Kivimaki M (2014). Interleukin-6 and C-reactive protein as predictors of cognitive decline in late midlife. Neurology, 83 (6), 486-93 PMID: 24991031

Brain inflammation produces a variety of emotional, behavior and cognitive symptoms.

I remember clearly a patient I cared for with central nervous system lupus erythrematosis (SLE). With SLE flairs she developed flagrant psychotic symptoms including hallucinations requiring inpatient psychiatric care.

Between flares she had no significant psychiatric symptoms.

Nicole Castanon and two colleagues from France have published a review of the role of obesity-associated inflammation and brain dysfunction.

Obesity is linked to a variety of blood markers of inflammation including proinflammatory cytokines, IL-6, interleuking and TNF. These inflammatory markers diminish with weight loss accomplished by either diet restriction or bariatric surgery.

The authors note evidence obesity is associated with the following:

• Depression (not all studies and not confirmed in animal models)
• Anxiety
• Memory and other cognitive impairment
• Increased age-related cognitive decline

So how could primarily a peripheral body condition impact the brain?

Figure from Castonon et al

The authors summarize potential mechanisms in a nice figure that I have reproduced here as it is open-access under the Creative Common Attribution License. See the citation below for the source of this figure.

Increased adipose (fat) tissue is known to promote local inflammation including recruitment of microphages and secretion of inflammatory chemicals. 

This peripheral adipose inflammation can transfer to the brain through the vagus nerve, hormones or other blood inflammtory chemicals and cellular pathways.

Brain evidence for this transfer has been noted via inflammation in the hippocampus, basal ganglia and prefrontal cortex.

Additional obesity-related brain inflammatory effect has been noted through dysruption of the hypothalamic/pituitary/adrenal (HPA) axis and changes in brain serotonin and dopamine metabolism.

A second potential pathway is described as working through changes in the gut in obesity. Obesity is linked to changes in gut bacteria composition, a change that results in increased gut permeability. This permeability change potentially promotes increased gut-blood absorption of endotoxins that can promote a systemic anti-inflammatory response. 

The authors note their review of this topic supports weight management approaches to limit the effect of obesity on the brain. Additionally, there may be some evidence to investigate anti-inflammatory diet and drug interventions for those with combined obesity and brain disorders. 

Readers with more interest in this topic can access the free full-text manuscript by clicking on the link below.

Photo of blue jay in the snow is from the author's files.

Figure of obesity-brain interaction is from Castanon, Lasselin and Capuron, citation below.

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Castanon N, Lasselin J, & Capuron L (2014). Neuropsychiatric comorbidity in obesity: role of inflammatory processes. Frontiers in endocrinology, 5 PMID: 24860551

Here are links to a series of abstracts that I am reviewing for this month.

I will do a full post on some of the most interesting and important research on this topic over the next month. 

Clicking on the title will link you to the PubMed abstract. Most articles highlighted in this post have free full-text access.

Mediterranean Diet and Chromosome Telomere Length

This recent study from the Harvard Nurse cohort examined telomere length in reference to a score of adherence to a Mediterranean type diet. Nurses with higher Mediterranean type diets had longer telomere lengths suggesting better chromosome aging.

Genotype, Cognition and the Mediterranean Diet

This prospective study of diet intervention examined the role of genes on response to diet for changes in cognition measured by the Mini-mental Status Examination and the Clock Drawing Test. The study found positive effects of a Mediterranean diet intervention on cognition although effects were not as robust in those with the Alzheimer's linked APOE gent.

Obesity, Inflammation and Brain Disorders

This review article summarizes some of the current knowledge on the link between obesity, inflammation and potential brain effects. The authors note these effects may be due to changes in neurocircuitry, brain hormones, neurotransmitters or neurogenesis.

Brain Inflammatory Markers and Cognitive Decline

This prospective study examine levels of two blood markers of inflammation, IL-6 and CRP from the Whitehall prospective cohort. Elevated IL-6 but CRP predicted greater cognitive decline over a 6 year period. 

Water for Soda Switch Lowers Metabolic Syndrome Risk

In a prospective study of switching water for soda, the research team found reduced rates of metabolic syndrome in obese subjects but not overweight subjects. 

Effects of CPAP With or Without Weight Loss in Sleep Apnea

The authors in this New England Journal of Medicine study found superiority of adding weight loss to CPAP in the outcome of a series of subjects with sleep apnea.

Low Carb versus Low Fat Diets in Type 2 Diabetes

This study compared outcome in Type 2 diabetes between those following a low carbohydrate versus a low fat diet. The team found both groups lost similar amounts of weight but the low carbohydrate groups had superior improvement in levels of markers for inflammation.

Bariatric versus Medical Treatment of Type 2 Diabetes

This study compared two types of bariatic surgery to medical weight loss intervention in one year outcome for type 2 diabetics. Surgical interventions showed superiority in weight loss and diabetes control.

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The recent revision of the American Psychiatric Associations Diagnostic and Statistical Manual for Mental Disorders, Fifth Edition (DSM-5) altered several eating disorder diagnostic criteria.

Some have expressed concern that these revisions are overly broad and may result in over diagnosis in some clinical populations. One clinical population where this is a concern is obesity.

A research study has been recently published addressing this issue.

Jennifer Thomas and colleagues at Harvard University and Massachusetts General Hospital recruited a series of subjects from an obesity program for eating disorder diagnostic assessment.

All subjects completed an assessment for presence of an eating disorder 
diagnosis using both DSM-IV and DSM-5 criteria.

For DSM-IV eating disorder diagnoses, the research team used a validated module from a validated measure known as SCID-IV. For DSM-5 eating disorder diagnosis an early structured interview developed by the DSM-5 Eating Disorders Task Group was used.

The key findings from the study included:

• Prevalence rates for eating disorders using DSM-5 criteria did not increase compared to DSM-IV criteria
• Bulimia nervosa prevalence rates were 2% in both interviews
• Binge eating disorder prevalence rates were 9% in both interviews
• An additional 20% of the obese sample met residual eating disorder criteria in both interviews

Obese individuals with a formal eating disorder diagnosis endorsed higher rates of psychological impairment, depression and anxiety validating the impact of eating disorder comorbidity.

Assessment for the presence of eating disorders is an important part of treatment planning. Eating disorders are more prevalent in obese populations are relatively easy to diagnose.

Some studies have found poor outcomes in obese populations with severe binge eating behaviors.

Treatment of a comorbid eating disorder in obese populations may improve weight and psychological outcomes.

Readers with more interest in this research can access the free full-text manuscript by clicking on the PMID link below.

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Thomas JJ, Koh KA, Eddy KT, Hartmann AS, Murray HB, Gorman MJ, Sogg S, & Becker AE (2014). Do DSM-5 eating disorder criteria overpathologize normative eating patterns among individuals with obesity? Journal of obesity, 2014 PMID: 25057413