Growing evidence links physical activity to improved cognitive outcome in elderly individuals.

Few studies have examined effects of exercise on those at highest risk for Alzheimer's disease.

J Carson Smith and colleagues recently published a prospective study of a cohort of older adults using structural magnetic resonance imaging.

The key elements of the design of their study included the following elements:
Participants: 97 adults between the ages of 65 and 89
Physical activity level: Frequency and intensity of leisure activity was assessed using the Stanford Brief Activity Survey
Alzheimer's risk status: Assessed using APOE genotype
Brain scanning protocol: Magnetic resonance imaging of brain using a 3T scanner at baseline and 18 months later. The brain hippocampal volume was identified as a key structure involved in APOE-related atrophy and memory decline
Statistical analysis: Participants were grouped in low and high physical activity groups and those with and without high-risk APOE Alzheimer's risk

The research team identified a statistically significant interaction between high-risk Alzheimer's participant and physical activity:

"Hippocampal volume decreased 3% in the High Risk/Low PA (physical activity) group whereas the volumetric changes in the remaining three groups were negligible."

The high-risk Alzheimer's group that participated in higher levels of physical activity appeared to have significant protection against hippocampal atrophy. To reach the higher levels of physical activity in the study they had to endorse one of the following levels:

• Brisk walking 15 minutes daily three or more days per week
• Jogging 15 minutes daily three or more days per week
• Swimming 15 minutes daily three or more days per week
• Moderately difficult chores 45 minutes daily three or more days per week
• Regular jogging, running, bicycling or swimming 30 minutes or more
• Playing sports such as handball or tennis an hour or more 

The authors examine the potential mechanisms for physical activity to reduce hippocampal atrophy in those with the high risk APOE genotype.

They note the beneficial effect of exercise may be through effects on cholinergic function, brain lipid metabolism or reduced neuroinflammation.

If this study is replicated it is an important finding with several implications.

One implication is that it may be one of the first research findings to support routine genetic testing for APOE and Alzheimer's risk. Those identified as high risk by APOE status could be targeted for aggressive behavioral interventions to increase physical activity along with increased surveillance of cognitive function.

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

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Photo of roseate spoonbill at sunset is from the author's files.

Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Hazlett KE, Figueroa CM, Kandah CC, Kay CD, Matthews MA, & Rao SM (2014). Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer's disease. Frontiers in aging neuroscience, 6 PMID: 24795624

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