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

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

Happy New Year to All! Hoping everyone has a healthy, happy and productive year in 2015.

I have been working on a topic list for 2015. I will be following my pattern of focusing on a specific brain research topic each month.

During the month I will post primarily on that topic after reviewing relevant research abstracts and manuscripts.

The topic list is taken from areas showing the most reader interest as well as covering area not recently reviewed.

I occasionally post off topic when a specific issue of importance arises.

The topic outline for 2015 will be:
January: Diet, Weight Loss and the Brain
February: Exercise
March: Parenting
April: Attention deficit disorder
May: Conduct disorder
June: Alzheimer's disease
July: Bipolar disorder
August: Social anxiety disorder
September: Migraine headaches
October: Neuropsychology
November: Brain imaging
December: Genetics

Brain Posts aims to select brain research relevant to translation to better clinical care for brain disorders.

Additionally, the blog provides an incentive for me to continue reading, learning and trying to keep up with key brain research advances.

Today's photo is from my files of an edited photo from the Rhema church Christmas lights.

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