Aerobic Training Boosts Hippocampal Volume in MCI

Pauline Anderson

April 11, 2014

Elderly women with probable mild cognitive impairment (MCI) undergoing a 6-month aerobic training program had increased hippocampal volume compared with women doing balance and toning exercises during that period, new research shows.

However, in this analysis, the change in left hippocampal volume was not associated with improved performance on a verbal memory test; on the contrary, increased volume was associated with poorer performance.

MCI represents a window of "opportunity" for altering the trajectory of cognitive decline, said study author Teresa Liu-Ambrose, PhD, associate professor, Department of Physical Therapy University of British Columbia, Vancouver, and Canada Research Chair in Physical Activity, Mobility, and Cognitive Neuroscience.

"People with MCI have a greater risk of developing dementia than older adults without MCI. At the same time, although they probably have some complaints about their cognitive ability, overall, they are still very functional; they still have the capacity both physically and cognitively to uptake interventions that you prescribe."

Still, their findings illustrate that the relationship between volume and cognition is complex. "This is simply not a one-to-one ratio whereby if you increase the hippocampal volume by 1% you get a 1% increase in performance," commented Dr. Liu-Ambrose.

There could be a lag between a change in brain structure and a change in cognitive performance, she said. "Those people who may gain the most in terms of hippocampal volume from aerobic training may be those with greater deficits at the start of the study. Then, with time, you would observe a sort of catch-up phase in the verbal memory performance."

The authors also noted that in patients with MCI or AD, white matter abnormalities greatly disrupt the connectivity between the hippocampus and other brain areas. In that case, increasing hippocampal volume alone in these patients may not improve memory performance.

The study was published online April 7 in the British Journal of Sports Medicine.

Proof of Concept

The proof-of-concept, single-blinded study included 86 women aged 70 to 80 years who were living independently, scored 24 or more on the Mini-Mental State Examination and less than 26 on the Montreal Cognitive Assessment, and reported some memory problems. Women with a psychiatric condition were excluded, as were those taking estrogen replacement therapy (possibly beneficial to the brain, this therapy might represent a confounder).

Researchers randomly assigned patients to 1 of 3 sixty-minute twice-weekly exercise groups:

  • Resistance training (RT): Patients in this group used free weights to do such exercises as biceps curls, triceps extensions, leg presses, hamstring curls, and calf raises.

  • Aerobic training (AT): Participants wore a heart rate monitor while completing a moderately paced outdoor walking program, initially at about 40% of their age-specific target rate, and increasing to 70% to 80%.

  • Balance and tone (BAT): This group of controls carried out stretching, range-of-motion, and balance exercises and practiced relaxation techniques.

Adherence did not significantly differ between the groups (60% for the AT group, 54% for the RT group, and 59% for the BAT group).

From MRI measurements, researchers calculated left, right, and total hippocampal volume. The hippocampus is sensitive to the effects of aging, and significant hippocampal atrophy is a hallmark of Alzheimer's disease.

Memory Evaluation

Researchers evaluated verbal memory and learning using the Rey Auditory Verbal Learning Test. Participants were asked to recall as many words as possible from a list of 15 words that were read to them 5 times. Then, after a distracting "interference" test, they were asked to recall the original words again.

The subanalysis included 29 of the 86 patients (10 in the AT group, 8 in the RT group, and 11 in the BAT group).

The study found that the AT group had significantly increased total hippocampal volume compared with the BAT group (P = 0.01). The authors noted a 5.4% volume increase in the left hippocampus, a 2.5% increase in the right hippocampus, and a 4% increase in the total hippocampus in this AT group.

As the authors explained, aerobic training may increase hippocampal volume by increasing levels of brain-derived neurotrophic factor, which stimulates neurogenesis and increases the complexity of the dendritic network.

The RT and the BAT groups both had nonsignificant decreases in right and total hippocampal volume.

In a prior analysis of all 86 participants in 2013, performance on the verbal learning test significantly improved in the AT group. However, among the 29 patients who underwent MRI, the degree of this improvement didn't match the increase in hippocampal volume.

"If people improve in hippocampal volume, we would expect they would also demonstrate a similar magnitude improvement in performance" on verbal memory, said Dr. Liu-Ambrose.

In fact, patients who gained more hippocampal volume actually showed less improvement on verbal performance.

Changes in hippocampal volume observed in this study were greater than in past studies, possibly because it included only women. The cognitive benefit of exercise is more pronounced in women than in men, said Dr. Liu-Ambrose, and it's possible that this sex difference extends to exercise-induced changes in brain structure.

Dr. Liu-Ambrose surmises that aerobic activity may have a greater effect in those already facing some cognitive issues. She noted that previous research over a longer period (12 months) showed cognitive benefits of exercise training in healthy adults without MCI, but the gains weren't as great as in the current study.

"This potentially suggests that those at greater deficit at baseline could get greater gains in a shorter period of time."

Within 5 years, 50% of patients diagnosed with MCI will convert to dementia, said Dr. Liu-Ambrose.

"Interesting Mystery"

For comment on this study, Medscape Medical News approached Atsumu Yuki, PhD, Center for Development of Advanced Medicine for Dementia, National Center for Geriatrics and Gerontology, Obu City, Japan, who has done research on the relationship between physical activity and brain atrophy progression.

The finding that an increase in hippocampal volume didn't necessarily induce improved memory function is an "interesting mystery," and unlocking such a mystery could contribute to dementia prevention, said Dr. Yuki.

Relevant factors could include involvement of white matter degeneration, as was suggested by the authors, or the effects of other brain regions, such as the frontal lobe and temporal lobe, added Dr. Yuki.

He noted that this research divides the population into essentially 4 groups: those with a larger hippocampus and poor memory function, a larger hippocampus and good memory function, a smaller hippocampus and good memory, and a smaller hippocampus and poor memory function. Of interest would be to see who among these has the best quality of life, who develops dementia in the future, and who has the highest survival, he suggested.

Kirk Erikson, MD, PhD, assistant professor, Department of Psychology, University of Pittsburgh, Pennsylvania, also remarked on the disconnect between improved hippocampal size and cognitive improvement.

"Overall I think this paper has made an important first step in understanding the potential for physical activity to increase the size of brain areas implicated in dementia and mild cognitive impairment," he told Medscape Medical News. "It nicely extends prior observations made in healthy older adults and suggests that even in a state of mild cognitive impairment the brain retains some plasticity."  

"Although this result is promising there is a need for much more research to identify the pathways of improvements from physical activity," Dr. Erikson added. "Furthermore, the results from this study do not make a strong case for the brain volume outcomes to be associated with better memory function, so more research is needed to identify the behavioral consequences of these changes."   

Funding for this study was provided to Dr. Liu-Ambrose by the Pacific Alzheimer's Research Foundation and the Jack Brown and Family Alzheimer Research Foundation Society. The authors have disclosed no relevant financial relationships.

Br J Sports Med. Published online April 7, 2014. Abstract

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