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Four Clinical Trials Further Clarify the Role of Physical Activity in Cognitive Function and Dementia

Resistance Training Emerging as Particularly Valuable for Older Adults

VANCOUVER, July 15, 2012 –Four studies reported today at the Alzheimer's Association International Conference® 2012 (AAIC® 2012) describe the ability of targeted exercise training to promote improved mental functioning and reduced risk for cognitive impairment and dementia in cognitively healthy older adults and those with mild cognitive impairment (MCI).

The reports, from 6- and 12-month randomized controlled clinical trials, depict the beneficial effects of different types of exercise – resistance training, aerobic training, and balance-stretching training – on a variety of cognitive abilities, brain structure, functional neural plasticity, growth factors, and risk factors for cognitive decline such as depression and sleep quality.

"Currently, the strongest data for lifestyle-based Alzheimer's risk reduction is for physical activity, yet this data is generally observational and considered preliminary, said William Thies, PhD, Alzheimer's Association® Chief Medical and Scientific Officer. "These new intervention studies are taking place over longer periods of time to begin to clarify exactly which types of physical activity are most effective, how much needs to be done, and for how long. In particular, where previously we had seen positive associations between aerobic activity, particularly walking, and cognitive health, these latest studies show that resistance training is emerging as particularly valuable for older adults."

It is generally accepted that regular physical activity is essential to healthy aging; it also may prove to be a strategy to delay or prevent the onset of cognitive impairment and dementia.

"It is very important to learn more about factors that actually raise and lower risk for cognitive decline and Alzheimer's. To do that, we need long-term studies in large, diverse populations, and we need the research funding to conduct those trials. For example, we have learned very practical lifestyle risk factors for heart disease from long-term research like the Framingham Study. Alzheimer's now needs its version of that research," Thies added.

"By midcentury, care for people with Alzheimer's will cost the U.S. over $1 trillion. This will be an enormous and unsustainable strain on the healthcare system, families, and federal and state budgets. The first-ever U.S. National Plan to Address Alzheimer's was unveiled in May, and now this plan must be speedily and effectively implemented. An additional $100 million is needed now for Alzheimer's research, education, outreach and community support," Thies said.

Moderate walking may grow brain region related to memory; increase nerve growth factor

According to Kirk Erickson, PhD, of the University of Pittsburgh, "There is growing interest in lifestyle factors and interventions that enhance the cognitive vitality of older adults and reduce the risk for cognitive impairment. However, very little is understood regarding the molecular processes that contribute to enhanced brain health with exercise, or the impact that greater brain volume has on cognitive function."

Erickson and colleagues randomized 120 older adults without dementia who have been sedentary for the previous six months to a moderate intensity walking group or a stretching-toning group for one year. MRI was used to measure the size of a brain region associated with memory, known as the hippocampus, both before and after the exercise intervention. Blood was drawn to measure concentrations of brain-derived neurotrophic factor (BDNF), and a cognitive testing battery was conducted before and after the intervention.

The researchers found that, in this study group, one year of exercise training increased the size of the hippocampus by two percent (2%) in the walking group compared to the stretching-toning group. (Significant shrinking of the hippocampus is characteristic of Alzheimer's disease.) The increase in hippocampal volume was correlated with similar changes in BDNF.

"Our findings suggest that the aging brain remains modifiable, and that sedentary older adults can benefit from starting a moderate walking regimen," Erickson said.

Resistance training may improve thinking and memory in older adults with MCI

Exercise and regular physical activity may prove to be promising intervention strategies to postpone or prevent Alzheimer's dementia, but perhaps not all types of training are equally effective.

PhD student Lindsay Nagamatsu, of University of British Columbia, Vancouver, Canada, and colleagues with the EXCEL (EXercise for Cognition and Everyday Living) study compared the effects of both twice-weekly resistance training (weight lifting) (n=28) and twice-weekly aerobic training (walking) (n=30) with twice-weekly balance and tone exercises (n=28) on executive cognitive function in women aged 70-80 with probable MCI in a 6-month randomized controlled trial. Teresa Liu-Ambrose, PhD, PT, of the University of British Columbia and Vancouver Coastal Health Research Institute, was the principal investigator of EXCEL and supervises Nagamatsu.

Compared with the balance and tone group, the resistance training group significantly improved performance on the Stroop Test, which measures selective attention and conflict resolution, and a memory task. Resistance training also led to functional changes in three brain regions involved in memory. In contrast, the aerobic training group did not show similar improvements.

"MCI is a critical window to intervene against dementia," Liu-Ambrose said. "We found that twice-weekly resistance training is a promising strategy to alter the trajectory of cognitive decline in seniors with MCI."

"Furthermore, we found that the aerobic training group had improved performance on a different memory task called the Rey Auditory Visual Learning Test. So both exercise groups improved their memory scores, but on different types of memory. More research is needed to determine the differential effects of these two types of exercise training," Nagamatsu added.

Higher functioning older adults may be more likely to show cognitive benefits from resistance training

Nader Fallah, PhD, and colleagues at the University of British Columbia, Vancouver used multi-state modeling* to investigate: 1) the simultaneous effect of exercise training and baseline factors on changes in executive cognitive function, and 2) the effect of exercise training on an individual's probability for cognitive improvement, maintenance, or decline.

* Multi-state models are models for processes that at any time occupy one of a few possible conditions or situations. For example, this model can be used to estimate the impact of physical activity on the individual probabilities of cognitive improvement, stability or decline. It allows analysis of changes in all directions, especially improvement – which has had relatively little attention but appears to be essential to understanding how neurodegenerative disease occurs.

Specifically, they performed a secondary analysis of a 12-month randomized, controlled clinical trial conducted in Vancouver of 155 community-dwelling women aged 65 to 75 years old who were randomly assigned to either resistance training or balance and tone training. The primary outcome measure was performance on the Stroop Test, an executive cognitive test of selective attention and conflict resolution. Teresa Liu-Ambrose, PhD, PT, of the University of British Columbia and Vancouver Coastal Health Research Institute, was the principal investigator of this study and supervises Fallah.

The scientists found that:

"To our knowledge, this is the first study to demonstrate that an individual's baseline self-regulatory capacity impacts the amount of cognitive benefit the person will reap from targeted exercise training," Fallah said.

"Before our study, we had no appreciation of the simultaneous impact of targeted exercise training and other factors, such as baseline cognitive status, on cognitive change in older adults. By using a multi-state transition model, we demonstrated that the probability of improving selective attention and conflict resolution in older adults is most evident among those with higher baseline cognitive status – which is different from the current general opinion," Liu-Ambrose said.

Combination training (aerobic + strength + balance) may improve memory in people with MCI

Hiroyuki Shimada, PhD, and colleagues at the National Center for Geriatrics and Gerontology, Obu, Aichi, Japan, conducted a randomized trial to test the impact of a 12-month, supervised, multicomponent exercise on cognitive function among older adults with amnestic (memory-related) MCI. The exercise program included aerobic exercise, muscle strength training, and postural balance retraining.

"Previous reviews suggested that combined aerobic exercise and strength training improved cognitive and physical functions more than aerobic exercise alone," Shimada said.

The final study population consisted of 47 older adults with amnestic MCI, 65 to 93 years old. Participants were randomized either to multicomponent exercise (n = 25) or an education control group (n = 25). People in the multicomponent exercise group exercised under the supervision of physiotherapists for 90 minutes/day, 2 days/week, 80 times for 12 months. People in the control group attended three education classes about health during the 12-month period. Measurements of cognitive function (Logical Memory II subtest of the Wechsler memory scale-revised, letter and category fluency, digit symbol coding, and Stroop color word test) were administered after 6 and 12 months.

The scientists found that the multicomponent exercise and educational program improved performance on Logical Memory II subtest of the Wechsler memory scale-revised. Additionally, there was a significant interaction effect for letter fluency test between groups.

"In other words, the ability to use language of the multicomponent exercise group improved significantly compared with the educational program group," Shimada said. "Our findings suggest that an exercise intervention can, at least partly, improve or maintain cognitive performance in older adults with amnestic MCI."

About AAIC®
The Alzheimer's Association International Conference® (AAIC) is the world's largest conference of its kind, bringing together researchers from around the world to report and discuss groundbreaking research and information on the cause, diagnosis, treatment and prevention of Alzheimer's disease and related disorders. As a part of the Alzheimer's Association's research program, AAIC serves as a catalyst for generating new knowledge about dementia and fostering a vital, collegial research community.

About the Alzheimer's Association®
The Alzheimer's Association is the world's leading voluntary health organization in Alzheimer's care, support and research. Our mission is to eliminate Alzheimer's through the advancement of research, to provide and enhance care and support for all affected, and to reduce the risk of dementia through the promotion of brain health. Our vision is a world without Alzheimer's. Visit www.alz.org or call 800-272-3900.

 

F1-03 Physical Activity to Promote Cognitive Function
F1-03-01 Sunday, July 16 / AAIC 2012 Featured Research Session, 8:30-10 am

The Influence of an Aerobic Exercise Intervention on Brain Volume in Late Adulthood

Kirk Erickson1, Andrea M. Weinstein1, Timothy D. Verstynen1, Michelle W. Voss2, Ruchika Shaurya Prakash3, Jeffrey Woods2, Edward McAuley2, Arthur F. Kramer2
1University of Pittsburgh, Pittsburgh, Pennsylvania, United States; 2University of Illinois, Champaign, Illinois, United States; 3Ohio State University, Columbus, Ohio, United States
Presenting author e-mail: kiericks@pitt.edu

Background: There is growing interest in lifestyle factors and interventions that enhance the cognitive vitality of older adults and reduce the risk for cognitive impairment. Aerobic exercise is a promising method for enhancing cognitive and brain health throughout the lifespan. However, very little is understood regarding the molecular processes in humans that contribute to enhanced brain health with exercise or the impact that greater brain volume has on cognitive function.

Methods: One-hundred twenty older adults without dementia were randomized to a moderate intensity walking group or to a stretching-toning control group for one-year. Magnetic resonance imaging (MRI) was used to assess cortical and hippocampal volume both before and after the intervention. Serum was obtained to assess concentrations of brain-derived neurotrophic factor (BDNF) and a cognitive battery was conducted before and after the intervention.

Results: One year of aerobic exercise training increased the size of the anterior hippocampus by 2% in the exercise group as compared to the stretching-toning control group. These changes in hippocampal volume were positively correlated with changes in serum levels of BDNF. In addition, higher cardiorespiratory fitness was associated with greater volume of the prefrontal cortex, which mediated the link between fitness and cognitive performance.

Conclusions: Overall, these findings suggest that the aging brain remains modifiable and that older adults who have been sedentary for at least 6-months can still benefit from starting a moderate walking regimen. Increases in hippocampal and prefrontal cortex volume are linked to improved cognitive function and increased levels of serum BDNF.

 

F1-03-02 Sunday, July 16 / AAIC 2012 Featured Research Session, 8:30-10 am

Resistance training promotes cognitive functions and functional plasticity in senior women with probable mild cognitive impairment: A 6-month randomized controlled trial

Lindsay Nagamatsu1, Todd Handy1, C. Liang Hsu1, Michelle Voss2, Alison Chan1, Jennifer C. Davis1, B. Lynn Beattie1, Peter Graf1, Teresa Liu-Ambrose1
1University of British Columbia, Vancouver, British Columbia, Canada; 2University of Illinois, Urbana-Champaign, Champaign, Illinois, United States
Presenting author e-mail: lindsay@psych.ubc.ca

Background: Mild cognitive impairment (MCI) represents a critical window to intervene against dementia. Exercise training is a promising intervention strategy, but not all types of training are equally effective. Thus, we compared the effects of both twice-weekly resistance and twice-weekly aerobic training with twice-weekly balance and tone exercises on executive cognitive functions in senior women with probable MCI.

Methods: The EXCEL (EXercise for Cognition and Everyday Living) study was a 6-month randomized controlled trial. Eighty-six community-dwelling women aged 70-80 years old living in Vancouver, Canada were randomly allocated to twice-weekly resistance training (n=28), twice-weekly aerobic training (n=30), or twice-weekly balance and tone training (i.e., control group) (n=28). The primary outcome measure was performance on the Stroop Test, an executive cognitive test of selective attention and conflict resolution. Secondary measures of executive cognitive functions included set shifting and working memory. Associative memory, regional patterns of functional brain plasticity, everyday problem solving ability, general balance and mobility, and general cardiovascular capacity were also secondary outcome measures.

Results: Compared with the balance and tone group, the resistance training group significantly improved performance on the Stroop Test (p=0.04) and the associative memory task (p<0.03). Resistance training also led to functional changes in three regions of cortex involved in the encoding and memorization of non-verbal associations -- the right lingual gyrus, the occipital fusiform gyrus, and the right frontal pole. The aerobic training group significantly improved general balance and mobility (p=0.03) and cardiovascular capacity (p=0.04).

Conclusions: Twice-weekly resistance training is a promising strategy to alter the trajectory of cognitive decline in seniors with MCI.

 

P1-121 Sunday, July 16 / Poster session

Refining Exercise Prescription to Promote Executive Functions in Older Adults using Multi-State Transition Modeling

Nader Fallah, Chun Liang Hsu, Niousha Bolandzadeh, B. Lynn Beattie, Peter Graf, Teresa Liu-Ambrose
University of British Columbia, Vancouver, British Columbia, Canada
Presenting author e-mail: nader.fallah@ubc.ca

Background:  Current evidence strongly suggests that physical activity is a promising approach to reduce the risk of cognitive impairment and dementia. Despite this accumulating evidence, we still do not have a comprehensive understanding of the impact of physical activity on cognitive health. For example, we currently do not know the simultaneous impact of different types of targeted exercise training and relevant person factors on changes, or transitions, in cognitive function. Also, we do not know the effect of different types of targeted exercise training the probability for cognitive improvement, maintenance, or decline. Thus, we used multi-state modeling to investigate: 1) the simultaneous effect of targeted exercise training and baseline factors on changes in executive cognitive functions; and 2) the effect of targeted exercise training on an individual's probability for cognitive improvement, maintenance, or decline.

Methods: A secondary analysis of a 12-month randomized, controlled trial in Vancouver. Of 155 community-dwelling women aged 65 to 75 years old who were randomly allocated to resistance training (RTE), or to balance and tone training (BAT). Primary outcome measure was performance on the Stroop Test, an executive cognitive test of selective attention and conflict resolution. Secondary outcomes of executive cognitive functions included set shifting and working memory.

Results: RTE has state-specific effects on transitions in selective attention and conflict resolution. Among those who with higher function at baseline, the probability of improving or maintaining selective attention and conflict resolution were higher with RTE compared with BAT. Both RTE and BAT had similar effect among those with lower function at baseline. Overall, those in the BAT group demonstrated a significantly lower probability for improved performance on the Stroop Test (32.6%; 95% CI 25.2% to 40%) compare with those in the RTE group (49.1%; 95% CI 41.2% to 57%). Conversely, the probability of decline was significantly higher for BAT (36.8%, 95% CI 29.2% to 44.4%) compared with RTE (21.7%, 95% CI 15.2% to 28.2%).

Conclusions: RTE is more efficacious than BAT in improving or maintaining selective attention and conflict resolution - but only among older women with higher baseline function. Among those with low baseline function, both types of training demonstrated similar efficacy.

 

P1-109 Sunday, July 16 / Poster session

Effects of Multicomponent Exercise on Cognitive Function in the Older Adults with Amnestic Mild Cognitive Impairment: A Randomized Control Trial

Hiroyuki Shimada, Takao Suzuki, Hyuma Makizako, Takehiko Doi, Daisuke Yoshida, Kota Tsutsumimoto, Yuya Anan, Kazuki Uemura, Hyuntae Park
National Center for Geriatrics and Gerontology, Obu, Aichi, Japan
Presenting author e-mail: shimada@ncgg.go.jp

Background: Current results of RCT were conducted to determine the effect of exercise or physical activity on cognitive functions in the mild cognitive impairment (MCI) older adults. These studies identified the effect of exercise or physical activity on cognitive function including general cognitive function and executive function in the older adults with MCI.We designed the present randomized trial to test whether 12 months supervised multicomponent exercise to improve cognitive function among older adults with amnestic MCI (aMCI). The multicomponent exercise included aerobic exercise, muscle strength training, and postural balance retraining because previous reviews suggested that combined aerobic exercise and strength training interventions improved cognitive and physical functions to a greater extent than aerobic exercise alone. 

Methods: Fifty older adults (27 men) with aMCI ranging in age from 65 to 93 years (mean age, 75 years) participated in the study. Subjects were randomized either to a multicomponent exercise (n = 25) or education control group (n = 25). Subjects in the multicomponent exercise group exercised under the supervision of physiotherapists for 90 minutes/day, 2 days/week, 80 times for 12 months. The exercise was included aerobic exercise, muscle strength training, and postural balance retraining which was conducted under multitask conditions to stimulate cognitive functions. Subjects in the control group attended three times education class about health during 12-month period. Before and after 6 months and 12 months of the intervention, measurements were administered. Measurements of cognitive function were the Logical Memory II subtest of the Wechsler memory scale-revised, letter and category fluency, digit symbol coding, and stroop color word test.

Results: There were no significant differences in baseline characteristics between the exercise and education control groups. Forty-seven subjects (exercise group, n = 24) completed the 12-month follow-up. The multicomponent exercise and educational program improved performance on Logical Memory II subtest of the Wechsler memory scale-revised. There was a significant interaction effect for letter fluency test between groups.

Conclusions: This study provides support for an exercise intervention that improves or maintains cognitive performances, at least partly, in the older adults with aMCI.


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Alzheimer's Association
Media line: 312.335.4078
E-mail: media@alz.org

 

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