Published: Apr 8, 2014
By Salynn Boyles, Contributing Writer, MedPage Today

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Regular aerobic exercise appeared to enlarge a key area of the brain associated with memory in older women with mild cognitive impairment (MCI), according to an imaging study.

Older women with probable MCI who engaged in a 6-month, twice weekly aerobic exercise program showed significant improvements in left, right, and total hippocampal volumes (P≤0.03), compared with women who engaged in stretching and balance exercises only, reported Teresa Liu-Ambrose, PHD, PT, of the University of British Columbia in Vancouver, and colleagues.

Based on MRI studies, “we observed a 5.6% increase in the left hippocampus, a 2.5% increase in the right hippocampus, and a 4% increase in the total hippocampus,” the researchers wrote in the April 8 British Journal of Sports Medicine.

This was twice the hippocampal volume increase seen in cognitively healthy older adults who engaged in a 12-month, thrice weekly aerobic exercise program in a study from 2011.

“If anything, our research seems to suggest that the degree of benefit, in terms of brain structure, might be greater in people with early functional complaints than in healthy older people,” Liu-Ambrose told MedPage Today. “The relationship between physical activity and brain health is pretty robust and has been demonstrated in healthy older adults, but we haven’t known much about its impact in people with MCI who have the greatest risk for dementia.”

Currently, 35.6 million people worldwide have dementia and this number is expected to increase to 115.4 million by the year 205o, the researchers wrote.

MCI is well recognized as a risk factor for dementia and Alzheimer’s disease and older adults with MCI develop Alzheimer’s at a rate of 10% to 30% annually, while those without MCI develop dementia at a rate of 1% to 2% annually.

The authors conducted the EXCEL trial (EXercise for Cognition and Everyday Living) in 2009 and primary analysis of those results indicated that resistance training appeared to promote cognitive and functional brain plasticity in older females, and that exercise improves verbal and spatial memory. It also found that resistance training positively impacted the regional patterns of functional brain plasticity during associative memory task performance.

But the researchers noted that no intervention study, prior to their latest analysis, has examined the impact of exercise on brain structure in older adults with MCI.

“With respect to dementia risk, the hippocampus is a brain structure of intense interest,” they wrote. “The hippocampus is sensitive to aging effects and significant hippocampal atrophy is a hallmark of [Alzheimer’s disease]. Thus, understanding the effect of exercise on the hippocampus will increase our appreciation of the role exercise may play in dementia prevention.”

Study Details

The secondary analysis of EXCEL included neuroimaging data from 86 women, ages 70 to 80, with probable MCI at enrollment. They were randomly assigned to a 6-month, twice weekly program of aerobic exercise, resistance training, or balance and tone training (BAT). The BAT group served as the control.

The aerobic training consisted of a walking program and the intensity of the training was approximately 40% of the individual participant’s age-specific target heart rate (heart rate reserve or HRR), which progressed over the first 12 weeks to the range of 70% to 80% of HRR. Exercise intensity was monitored using heart rate monitors.

Resistance training included free weights and Keiser-based exercises, which consisted of biceps curls, triceps extensions, seated row, latissimus dorsi pull downs, leg presses, hamstring curls, and calf raises. The intensity of the training stimulus was at a work range of six to eight repetitions (two sets). The training stimulus was increased when two sets of six to eight repetitions were completed with proper form and without discomfort.

The BAT program consisted of stretching exercises, range of motion exercises, balance exercises, and functional and relaxation techniques.

Other strength exercises included mini-squats, mini-lunges, and lunge walks. The participants subjectively monitored the intensity of their workouts by Borg’s Rating of Perceived Exertion(RPE).

Thirty-nine of the 86 participants in the original study underwent MRI scanning at baseline. At the completion of the trial, 10 of 39 dropped out and 29 completed a second MRI. Exercise compliance was not significantly different between the groups.

The aerobic training group had significantly increased total hippocampal volume compared with the BAT group (P=0.01) after the 6-month trial completion. Hippocampal volume change (mm³) was 260.90 (standard deviation 607.96) for the aerobic training group and -105.91 (SD 220.56) for the BAT group.

The change in left hippocampus was 178.30 (SD 297.56) in the aerobic training group and 24.10 (SD 209.70) in the BAT group.

However, the resistance training group did not demonstrate a significant increase in total hippocampal volume at trial completion (P=0.76) versus the BAT group.

In addition, neither left nor right hippocampal volumes improved significantly in the resistance training group compared with the BAT group (P=0.83 and 0.70, respectively).

What the Results May Mean

Increased left hippocampal volume has been shown in other research to be associated with better performance on verbal memory testing, but this was not the case in the current study.

Increased left hippocampal volume was associated with greater loss in the number of words recalled post-interference (poorer performance) on the verbal memory learning Rey Auditory Visual Learning Test (RAVLT).

Liu-Ambrose said the findings indicate that the association between hippocampal volume and memory may be more complicated than has been previously recognized.

“We might have assumed a 1% gain in hippocampal volume should improve verbal learning memory by 1%, but our results suggest that it may not be that simple,” she said. “There may be other factors we are not considering.”

She said if people with the most deficits in verbal learning memory actually do derive the greatest improvements in hippocampal volume by exercising, they still may not perform as well as those with fewer deficits on memory tests.

“They would have more catching up to do,” she said, adding that more research is needed to examine this hypothesis.

Although resistance training did not show significant effects on hippocampal volume in the study, it was the “first to explore the effect of resistance training on hippocampal volume and hippocampal-dependent memory in older adults with MCI, future studies are needed to further elucidate these relationships,” the researchers wrote.

The exclusion of men from the present analysis was a study limitation along with the exclusion of participants older and younger than ages 70 to 80.

The group also cautioned that other factors, such as white matter degeneration, may impact the association between brain volume and cognitive performance. White matter abnormalities in people with MCI or Alzheimer’s disease can disrupt the connectivity between the hippocampus and other brain areas.

“Thus, increasing hippocampus volume alone in these populations may not result in improved memory performance,” they explained.

The authors called for future studies with larger sample sizes and greater characterization of MCI subtypes, such as single-domain versus multidomain MCI, to corroborate the current findings, “and to extend our understanding of the role of exercise training in promoting cognitive and neural brain plasticity in older adults with MCI.”

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