Physical activity reduced hippocampal atrophy in elders at genetic risk for Alzheimer’s disease.  Published in 2014.  University of Maryland, United States.

Simple Summary

Individuals at higher risk for Alzheimer’s who engaged in little to no physical activity lost 3% of their hippocampal volume after only 18 months.  Those who did moderate physical activity showed no change in the volume of the hippocampus.

More Detail

Subjects were divided into four groups.  The first division was between low physical activity (Low PA) and high physical activity (High PA).  Activity levels were measured using the Stanford Brief Activity Survey (SBAS).  Those in the Low PA group indicated two or fewer days per week of activity such as slow walking, light chores or no physical activity.  The High PA group indicated engaging in 3 or more days per week of moderate to vigorous intensity PA such as brisk walking, jogging, swimming, etc.

The second division was between low risk and high risk for Alzheimer’s.  Risk was determined by the presence or absence of the ApoE 4 allele.

Both high risk groups scored slightly lower on the Mini-Mental State Exam (MMSE), but all four groups were within the range of normal cognitive function.

All subjects had MRI scans performed to measure the 7 different brain regions the researchers wanted to track.

The four groups were comparable for age, sex, and education at baseline.

After 18 months MRI measurements were taken again.  Six of the seven brain regions showed no change in any group.  However, the hippocampus of the high risk/low PA group showed a 3% reduction in size (the kind of hippocampal atrophy that is a hallmark of Alzheimer’s progression).  Reductions in the hippocampus of the other three groups were deemed negligible.

The results after 18 months show no difference between the two low-risk groups and the high risk/high PA group, indicating that higher levels of physical activity greatly reduce the risk of Alzheimer’s.

This adds to a growing body of evidence that moderate to vigorous physical activity benefits high risk individuals (those with the ApoE 4 allele) in the following ways:

Into The Weeds

The ApoE gene has three major alleles: ApoE-ε2, ApoE-ε3, and ApoE-ε4.  The ApoE 4 allele is the most significant genetic risk factor for Alzheimer’s.  The risk increases even more if the second allele is also e4.  The ApoE gene provides instructions for making a protein called apolipoprotein E.

Apolipoprotein E combines with fats (lipids) in the body to form molecules called lipoproteins.  Lipoproteins with the ApoE component (there are other Apo’s) are able to cross the blood brain barrier.  Apolipoprotein E is thus important to lipid transport and lipoprotein metabolism and regulates several important neuronal actions including neuronal repair, synaptogenesis, nerve growth, and development (R).

In addition to serving as a predictor of the probability (not the certainty) of developing Alzheimer’s, ApoE genotype also predicts the severity of Alzheimer’s pathology in that the presence of ApoE 4 alleles increases both the rate and amount of Aβ deposition (R).

In other words:

  • ApoE transports phospholipids and cholesterol to damaged neurons to assist with repair
  • Carriers of the e4 allele produce a lipoprotein that is more easily removed, therefore they have less available ApoE available in the brain
  • When lipoprotein lipase activity is decreased there are fewer free fatty acids available for neuron repair and feeding
  • This, in turn, alters APP metabolism and increases the production and accumulation of Aß in the brain.
  • a lipid imbalance also negatively effects neurotransmitter function

Here’s what other studies (Erickson, et al. 2001 and Trejo and Torres-Aleman 2001) have shown are some of the brain benefits of physical activity:

  • promotes the release of neurotrophins that increase neurogenesis:
    • BDNF (brain derived neurotrophic factor)
    • insulin-like growth factor-1 (IGF1)
  • increases cerebral blood flow
  • enhances neural activation
  • possibly relieves amyloid burden
  • produces neurogenesis in the young and old
  • increases the size of the anterior hippocampus, leading to improvements in spatial memory
  • increases hippocampal volume by 2%, effectively reversing age-related loss in volume
  • improves neurotransmitter function in the hippocampus and cerebral cortex
  • increase production of anti-inflammatory cytokines
  • Just added February 7, 2018 – increases the effectiveness of waste removal from the brain

Physical activity appears to offset the imbalances caused by the ApoE 4 allele, at least enough to protect ApoE 4 carriers for an 18 month period.

Limitations of the study include self reporting of physical activity, which is prone to bias.  The authors also point out that they “did not manipulate levels of PA nor randomly assign participants to groups in a controlled trial.”  They also “did not control for other health -related behaviors (e.g. diet) or measure BDNF genotype.”  Finally, the sample was mostly Caucasian.

Controlled studies have shown an increase in hippocampal volume with moderate exercise.  This study does not, which may owe to its use of self reporting of physical activity by participants.  In other words, the effects of exercise may be even greater than those shown here.

Update September 7, 2018   Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer’s mouse model