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Brain Fitness for Memory Wellness

Brain Fitness Abstracts

What follows are reviews of recent research articles on factors that may be brain-protective and on intervention programs to maintain or improve cognitive skills. We will update this link with additional summaries as new studies are completed. Click on the links below to jump to the abstract you wish to read.

  1. A Behavioral Rehabilitation Intervention for Amnestic Mild Cognitive Impairment
  2. Evidence for Neurocognitive Plasticity in At-Risk Older Adults: The Experience Corps Program

  3. Effects of Aerobic Exercise on Mild Cognitive Impairment
  4. Older Adults with Mild Memory Impairment Still Benefit from Cognitive Training in Areas Not Reliant on Memorization
  5. The IMPACT Study: A Randomized Controlled Trial of a Brain Plasticity-Based Training Program for Age-Related Cognitive Decline
  6. Relation of Cognitive Activity to Risk of Developing Alzheimer's Disease
  7. Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial

 

 

A Behavioral Rehabilitation Intervention for Amnestic Mild Cognitive Impairment


Theme: Memory rehabilitation techniques may improve cognition and functional ability in people identified with Mild Cognitive Impairment (MCI).


Background:  In the field of Traumatic Brain Injury (TBI), research has shown that memory compensation techniques, such as memory books, prove to be effective in improving function.  Most research in the field of Alzheimer’s Disease has focused on memory building techniques (such as building on existing capabilities with repetitive training, with mixed effectiveness.  Limited or no research has been done on the efficacy of compensatory rehabilitation techniques in persons with MCI.  This study attempts to address this need.


Methods: 24 patients with MCI and their program partners were recruited into this pilot study.  The initial baseline visit included 2 cognitive tests, Dementia Rating Scale-2 and a Caregiver Burden (CB) scale.   These assessments were repeated at 8 weeks post-intervention.
The intervention consisted of orientation, modeling, practice use and homework assignments in using the Memory Support System (MSS).  The MSS is a portable, 2-page per day calendar and note-taking system.  Each dyad received 12 1-hour training sessions over the course of 6 weeks.  In addition to the cognitive assessments, a “compliance assessment” was completed after the initial session and again at the end of 8 weeks to determine how compliant the subject was in using the system outside of the training sessions.


Results:

  1. 20 out of 24 subjects completed the 8-week training program
  2. Participants were significantly more likely to be compliant with the MSS after training.
  3. Dementia Severity rating scores remained stable across the 8 weeks.
  4. Administration of the E-Cog, which is a rating scale completed by caregivers, revealed that there was a medium effect size for improvement in memory-related activities of daily living.

Why this is important: This was one of the first pilot studies to address using a memory notebook system to compensate for memory changes in people with Mild Cognitive Impairment (MCI).  While the improvement in memory related activities of daily living was modest, research subjects described the positive impact on their lives (taking medications, increased confidence, lowered anxiety). The main appeal of this study is that an intervention that is relatively simple and cost-effective may have measurable positive effects on cognition.


Cautions: Since this study was a pilot study, there are several limitations to the conclusions we can draw from it.

  • The MSS will need to be studied with a large sample size and with a randomized control group in order to determine its true effects.
  • This study did not address the question of post-intervention follow-up.  A larger study will need to look at whether or not compliance and compensation benefits are retained over time following the intervention sessions.

Reference: Greenaway, M.C., Hanna, S.M., Lepore, S.W., & Smith, G.E. (2008).  A Behavioral Rehabilitation Intervention for Amnestic Mild Cognitive Impairment.  American Journal of Alzheimer’s Disease & Other Dementias, 23, 5, 451-461.

 

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Evidence for Neurocognitive Plasticity in At-Risk Older Adults: The Experience Corps Program


Theme:  Physical and social activities may enhance cognitive performance in regions of the brain which are highly susceptible to age-related declines or to Alzheimer’s disease.


Background:  Previous research studies have proposed that to help preserve cognitive and functional health, aging individuals need to participate in multifaceted cognitive, physical and social activities. Executive functioning and organizational skills appear to be critical for maintaining one’s independence, while at the same time, being extremely vulnerable to age-related decline. Minimal research has been conducted on the effects of community-based volunteer programs that offer complex cognitive and physical engagement, which has been correlated with improved mentally plasticity in older adults.


Methods:  The study involved 17 African American women volunteers (age 60 or older), who could participate at least 15 hours each week and who met a minimum level of cognitive functioning based on a set of mental flexibility exams.  The volunteers were divided into two groups, one group of eight test subjects and one group of 9 controls.  The test subject group took part in the Experience Core (EC) program, which is a senior volunteer program that aims to improve memory and executive mental functions by working in various roles to aid children in developing their literacy and problem-solving skills.


The volunteers were trained for two weeks in the following areas of the EC program:

  • General Literacy Support – to aid teachers in the assessment and development of a child’s reading skills.
  • Library Support – to support school library functions and to help children with their library reading needs.
  • Conflict Resolution – to lead recess programs that teach conflict resolution and problem-solving through play.

Volunteers were given two fMRI scans, one before they began their involvement in the EC activity program and one immediately following their completion of 6 months of the program.  While in the fMRI, volunteers completed a selective attention task of identifying the direction of an arrow while mentally inhibiting concurrent distracting information. This task evaluated both the speed and accuracy of the each volunteer’s responses.


Study Findings:

  1. At baseline, prior to involvement in the EC program, there was no difference in either the performance on the fMRI task or on the fMRI scans between the EC participating group and the control group.
  2. When making pre-post comparisons on the fMRI results, the EC participating group demonstrated a greater reduction in distracter interference and, as a result, performed better than the control group.
  3. The pre-post fMRI data displayed significant increases in activity in brain regions associated attention, areas that are particularly susceptible to age-related decline.

Why this is important:  This study demonstrates through the exercising and reactivating of mental skills that were dormant for several years or decades, aging individuals were able to regain and reverse cognitive declines associated with age through environmental enrichment.  A broad range of mental activities in a social setting, such as a community-based volunteer program, may be beneficial for brain functions and may provide protection against age-related decline.


Limitations:  This was a pilot study, so the results were based on a very small sample of participants of African-American females only, making it difficult to project the same results to a larger and more diverse population.  The short study period of only 6 months, leads to the question of whether benefits are only short-term gains in mental improvement or whether the improvements could be sustained.  Before aging adults incorporate this into their lives they need to know who will actually benefit, what types of activities they need to be performing in order to receive these benefits and how much time they need to spend on these activities each week.  This and other studies suggest that continued mental engagement in a social context is beneficial to the human brain, but more research needs to be conducted in order to identify the relative benefits of different activities.


Reference: Carlson MC, Erickson KI, Kramer AF, Voss MW, Bolea N, Mielke M, McGill S, Rebok GW, Seeman T, Fried LP. Evidence for Neurocognitive Plasticity in At-Risk Older Adults: The Experience Corps Program. J Gerontol A Biol Sci Med Sci. 2009;62(12):1275-1282.


Further information about ACTIVE LIFESTYLES AS A PROTECTION AGAINST DEMENTIA:

  • Fratiglioni L, Paillard-Borg S, Winblad B. An active and socially integrated lifestyle in late life might protect against dementia. Lancet Neurol. 2004; 3(6): 343-353.
  • Studenski S, Carlson MC, Fillit H, Greenough WT, Kramer A, Rebok GW. From bedside to bench: does mental and physical activity promote cognitive vitality in late life? Sci Aging Knowledge Environ. 2006;2006(10):pe21.

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Effects of Aerobic Exercise on Mild Cognitive Impairment

 

Theme: Aerobic exercise may have beneficial effects for people with Mild Cognitive Impairment (MCI).

 

Background: Positive effects of exercise on cognitive function have been seen in animal models and a growing number of studies on older adults. Studies done on memory-impaired older adults have focused primarily on measures collected retrospectively (e.g. physical activity and general measures of cognitive function). This study collected current measures from participants with Mild Cognitive Impairment to test the feasibility of an aerobic exercise intervention versus a stretching control group on cognitive benefits.

Methods: 33 sedentary older adults age 55 to 85 years with amnestic Mild Cognitive Impairment were enrolled and randomized into either an aerobic exercise intervention or a stretching control group.

  • The aerobic group (using a treadmill, stationary bicycle or elliptical machine) exercised at 75 to 85% of heart rate reserve for 45-60 minutes per day, 4 days per week for 6 months.
  • The control group performed stretching activities at or below 50% of their heart rate reserve for 45-60 minutes per day, 4 days per week for 6 months.

Both groups were supervised by a trainer for the first 8 sessions. After that, each participant was supervised once per week for the duration of the study. Participants tracked their activities and heart rate in a daily exercise log. Participants had a blood draw and cognitive testing with standardized clinical tests (e.g. Mini Mental Status Examination, Trail Making Test, Stroop Color and Word Test, Story Recall) at baseline, at month 3 and at month 6 of the study.

 

Study Findings:

  1. Aerobic exercise was found to improve executive control processes such as multitasking, efficiency of information-processing, selective attention and cognitive flexibility, especially for women.
    • At baseline, women had higher body fat, higher cholesterol, higher cortisol levels and lower IGF-I levels than men, perhaps giving rationale as to why women were found to improve in executive control processes after an aerobic exercise intervention.
  2. Aerobic exercise reduced the stress hormone, cortisol’s levels for women and increased them for men.
  3. Insulin sensitivity improved for women in the aerobic group and did not change for men. Increased insulin sensitivity means that there is better glucose uptake in the brain, resulting in increased cognitive capacity.

Why This Is Important: Research studying intervention programs for persons with Mild Cognitive Impairment is rare, and few studies are as ambitious in their interventions as the present study. The findings suggest that aerobic exercise can play a protective role by reducing the progression of cognitive symptoms of MCI, especially in sedentary women.

 

Limitations:

  • The small sample size should warrant replication of the study with a larger sample of those with MCI.
  • The selection criteria used (excluding some for medical reasons) may affect the generalizability of the findings to the general population of persons with Mild Cognitive Impairment.
  • Apolipoprotein (APOE) e4 genotype is a well-known link in Alzheimer’s disease research. This study had an unequal representation by APOE e4 – e.g. no women with e4 were enrolled, thereby limiting the analysis of aerobic exercise effects for persons with different genotypes.

Reference: Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Plymate SR, Fishel MA, Watson GS, Cholerton BA, Duncan GE, Mehta PD, Craft S. Effects of Aerobic Exercise on Mild Cognitive Impairment. Arch Neurol, 2010; 67(1): 71-79.

 

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Older Adults with Mild Memory Impairment Still Benefit from Cognitive Training in Areas Not Reliant on Memorization

 

Theme: Cognitive training may be beneficial, even for older adults exhibiting mild cognitive impairment (MCI).

 

Background: Small-scale studies conducted over several decades suggested that cognitively-healthy older adults can improve their memory skills if they enroll in training programs that teach specific memory techniques (e.g., learning how to use mnemonics to remember names). However, this type of non-pharmacologic intervention had never been studied in a large-scale, scientifically rigorous manner, and it was not clear how general, or how long-lasting, the benefits of such training might be. The ACTIVE study (Advanced Cognitive Training for Independent and Vital Elderly) was designed to address these concerns. It is the first large-scale, randomized, controlled trial of cognitive training for healthy older adults.

 

Methods: 2802 healthy elders (age 65 or older) living in the community (of 6 different cities) received cognitive training that focused on specific thinking skills including: reasoning, memory and speed-of-processing. Each of these skills is important for complex everyday activities and living independently.

  • Memory training consisted of learning and remembering a word list and/or short stories.
  • Reasoning training consisted of identifying patterns and utilizing problem-solving skills.
  • Speed-of-processing training consisted of quickness of response to visual stimuli on a computer.

Training was conducted in small groups over a 5-6 week period, with 10 sessions of 60-75 minutes each (essentially, 2 sessions per week). Cognitive skills were evaluated at baseline (before training began), immediately after training ended, and at annual intervals.

 

In addition to the groups who received cognitive training, there was a no-contact control group that had cognitive tests at prescribed intervals, but received no education or training.

 

The results summarized below looked at training benefits for two subgroups of study volunteers: (1) those who had mild performance deficits on a standardized memory test (but no obvious dementia) at the start of the study; and (2) those who performed well on memory tests initially.

 

Study Findings:

  1. Participants who had normal memory ability at the beginning of the study showed improvement in memorization skills upon completion of the memory training. Training benefits diminished over time, but were still detectable after two years.
  2. Participants who had mild deficits in memory function showed NO benefit from the memory training; however, they demonstrated training-related improvement in reasoning and speed-of-processing skills that persisted to some degree for two years.

Why this is important: This study demonstrates that older adults can benefit from an organized program of training in specific cognitive skills, even if they have some mild memory problems. Although memory training per se was not helpful to the memory-impaired volunteers, other types of cognitive skills did improve with training for these participants. That may be because some brain regions remain healthy and fully functional for older adults who are undergoing mild memory changes. Another important finding is that benefits persisted to some degree for at least two years. We do not know if the persisting benefits were a direct result of training or a "placebo" effect (e.g., due to improved confidence among participants that might have come about with any intervention).

 

Cautions: This study did not tackle the question of whether training benefited everyday life skills. An earlier analysis from the ACTIVE study (Willis and colleagues, JAMA, 2006) found that volunteers who received training did report slightly better maintenance of everyday skills for up to five years after training. But, there was little benefit of training on simulated everyday tasks. The question of strength of benefits (what researchers call "effect size") is an important question to ask about all types of treatments or interventions.

 

Reference:
Unverzagt FW, Kasten L, Johnson KE, Rebok GW, Marsiske M, Mann Koepke K, Elias JW, Morris KN, Willis SL, Ball K, Rexroth DF, Smith DM, Wolinsky FD, Tennstedt SL. Effect of memory impairment on training outcomes in ACTIVE. Journal of the International Neuropsychological Society 2007;13:953-960.

 

Further information about the ACTIVE STUDY:

  • Willis SL, Tennstedt SL, Marsiske M, Ball K, Elias J, Koepke KM, Morris JN, Rebok GW, Unverzagt FW, Stoddard AM, Wright E, and ACTIVE Study Group. Long-term effects of cognitive training on everyday functional outcomes in older adults. JAMA, 2006;296(23):2852-2854.
  • Ball K, Berch DB, Helmers KF, Jobe JB, Leveck MD, Marsiske M, Morris JN, Rebok GW, Smith DM, Tennstedt SL, Unverzagt FW, Willis SL and Advanced Cognitive Training for Independent and Vital Elderly Study Group. Effects of cognitive training interventions with older adults: A randomized controlled trial. JAMA, 2002;288(18):2271-2281.

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The IMPACT Study: A Randomized Controlled Trial of a Brain Plasticity-Based Training Program for Age-Related Cognitive Decline

 

Poster by Zelinsky EM, Yaffe K, Ruff RM, Kennison RK, and Smith GE, Presented at the Gerontological Society of America Meeting, November 16-20, 2007, San Francisco, CA

 

Theme: Computer-based cognitive training may be beneficial for healthy older adults.

 

Methods: Over 400 healthy, well-educated (>15 years education) older adults over the age of 65, with normal cognition (MMSE >26) were split into an experimental and control group in order to test the effectiveness of a computerized training program. The purpose of the program was to determine whether participants who complete a cognitive training program, designed to increase brain processing speed and "plasticity", improve on measures of attention and memory compared to participants who complete a control training program using a more traditional, education-based approach.

 

Experimental group: received the Posit Science Brain Fitness Program, a computerized training program with 6 comprehensive listening exercises focused on memory, speed of processing and brain plasticity (changes in information processing efficiency and flexibility).

 

Active Control group: received a program simulating physician recommendations for memory complaints via DVD-based education training on a computer as well as paper and pencil quizzes on memory and comprehension. This program was reported to be comparable in intensity, complexity and time, to the Brain Fitness Program regimen.

 

Training was conducted over a 10-week period, with sessions of at least 60 minutes per day, 5 days per week. Before and after training, participants were given neuropsychological tests of processing speed, attention, and memory which were different from the tasks directly involved in the Brain Fitness training program. They also completed a self-report questionnaire about their everyday cognitive abilities.

 

Conclusions: Compared to the active control group, participants in the experimental Brain Fitness group:

  1. had strong increases in speed-of-processing skills;
  2. had moderate improvement in memory performance;
  3. reported mild improvements in everyday cognitive skills.

Why this is important: This is the first large, randomized controlled trial to show improvement in untrained measures of mental speed and memory as a result of computer-based cognitive training. Results also suggest that memory and attention can be improved by a specific, focused cognitive training program beyond what may be gained by general cognitive stimulation.

 

Limitations/Cautions:

  • Study participants were primarily Caucasian older adults who were well-educated and motivated. The Posit Science program has not been used with people of low education or minority status.
  • The only measure of impact on everyday skills was a self-report questionnaire. There were no direct functional measures of everyday cognition.
  • There is no long-term follow-up on participants of the study, aside from a short-term 3-month assessment visit.
  • Although statistically significant improvements were observed in memory, the size of the benefit (effect size) was fairly small. For example, on a test involving memory for a list of 15 words, the Brain Fitness group exceeded the Control group by only 6/10ths of one word at the end of the study.
  • This study was funded by the same people who developed the Brain Fitness Program. The Brain Fitness Program is a commercial product and is fairly expensive (about $400 for individuals for the initial 10-week program).

Further Information: Posit Science's website (www.positscience.com) contains more information about the Brain Fitness program.

 

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Relation of Cognitive Activity to Risk of Developing Alzheimer's Disease

 

Theme: Older adults who have cognitively active lifestyles appear to have a reduced risk of developing Alzheimer's disease.

 

Methods: 700 older adults were recruited from continuing care retirement communities and subsidized housing facilities in the city of Chicago to participate in a research study (Rush Memory and Aging Project) examining risk factors for common health conditions in old age, including Alzheimer's disease. Three-fourths of the older adults were female, and 91% of the participants were white and non-Hispanic.

At the beginning of the study, participants rated their current and past frequency of cognitive activity, and then throughout the study, their current activity was measured at yearly clinical evaluations for up to 5 years. The study also gathered information on a variety of other factors, including: participants' physical activity, early life household socioeconomic status, mother's education, father's education and father's occupation; current income and income at age 40; vascular risk factors (i.e. diabetes, hypertension, smoking), and vascular conditions (i.e. heart attack, stroke, congestive heart failure).

During the study, assessment of cognitive function was measured by a battery of 20 cognitive tests that focused on cognitive measures such as episodic memory, semantic memory, working memory, perceptual speed and visuospatial ability.

 

Results:

  1. Cognitively inactive participants were 2.6 times more likely to develop Alzheimer's disease than a cognitively active person;
  2. Past cognitive activity was also associated with the risk of Alzheimer's disease;
  3. Participants with lower socioeconomic status were less likely to be cognitively active than those with higher income or education.

Why this is important: This large prospective study shows a fairly strong correlation between cognitive activity and risk of developing dementia. It is one of several recent studies that provide support for the hypothesis that keeping the mind active is beneficial for maintaining a healthy brain.

 

Limitations: This is an observational study. It measured relationships between predictors (cognitive activity) and outcomes as they occur in natural settings. It does not establish a cause-and-effect relationship between mental activity and risk of Alzheimer's disease. For example, reduced cognitive activity may simply be an early (preclinical) sign that a person is already developing Alzheimer's disease.

 

Controlled clinical trials, where participants might be assigned to different cognitive activity regimens and then followed long-term, would be the best way to understand cause-and-effect relationships between mental activity and Alzheimer's disease, but there are many practical obstacles to doing such studies. One approach to learning more quickly about the potential benefits of treatments or preventive approaches is to study the effects of the intervention on biomarkers for Alzheimer's disease pathology (e.g., functional neuroimaging profiles) that may be precursors of the clinical Alzheimer's disease syndrome.

 

Reference: Wilson RS, Scherr PA, Schneider JA, Tang Y, and Bennett DA. Relation of cognitive activity to risk of developing Alzheimer's disease. Neurology 2007:69;1911-1920.

 

Other epidemiologic studies on cognitive activity and Alzheimer's disease risk:

  • Crowe M, Andel R, Pedersen NL, Johansson B, Gatz M. Does participation in leisure activities lead to reduced risk of Alzheimer's disease? A prospective study of Swedish twins. J Gerontol: Psychol Sci 2003;58B:P249-P255.
  • Scarmeas N, Levy G, Tang M-X, Manly J, Stern Y. Influence of leisure activity on the incidence of Alzheimer's disease. Neurology 2001;57:2236-2242.
  • Verghese J, Lipton RB, Katz MJ, et al. Leisure activities and the risk of dementia in the elderly. N Engl J Med 2003;348:2508-2516.
  • Wang H-X, Karp A, Winbald B, Fratiglioni L. Late-life engagement in social and leisure activities is associated with a decreased risk of dementia: a longitudinal study from the Kungsholmnen Project. Am J Epidemiol 2002;155:1081-1087.
  • Wilson RS, Mendes de Leon CF, Barnes LL, et al. Participation in cognitively stimulating activities and risk of incident Alzheimer's disease. JAMA 2002;287:742-748.

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Effect of Physical Activity on Cognitive Function in Older Adults at Risk for Alzheimer Disease: A Randomized Trial

 

Theme: Physical activity may benefit cognitive function among older adults at risk for Alzheimer's disease.

 

Background: Observational studies have shown that people who are physically active appear less likely to develop cognitive decline and dementia later in life. This finding has been confirmed by prospective studies which reveal an association between physical activity and reduced incidence of dementia. Interestingly, this association has been evident even if exercise is only implemented later in life. The problem, however, was that randomized, controlled trials had not yet tested this observation. The following study aimed to address this problem.

 

Methods: 170 adults aged 50 or older (average=69 years) who reported memory problems- but did not meet criteria for dementia- were randomly assigned to a usual care group or to a physical activity group. 100 of the 170 participants had objective evidence of mild cognitive impairment (MCI) on a cognitive screening battery. Persons with significant physical or mental health problems were not included.

  • The usual care group received educational information about memory loss, stress management, healthy eating, alcohol consumption, and smoking, but received NO information about physical activity.
  • The physical activity group received the same educational information described above PLUS a 24-week physical activity intervention. This group was encouraged to get at least 150 minutes of moderate-intensity physical exercise (like walking) per week in three 50-minute sessions. Persons who already engaged in 150 minutes of physical activity weekly were encouraged to add one 50-minute session per week. Participants recorded physical activity in diaries.
  • The physical activity group also received a modified behavioral program intended to increase adherence to the physical activity regimen. This behavioral program disseminated information related to exercise, goal setting, time management, and potential barriers; it was delivered through a workshop, a manual, newsletters, and phone calls.
  • phone interviews were conducted by study staff in order to monitor progress and encourage ongoing compliance among physical activity group members.
  • Assessment of physical activity, cognitive function, mood, and quality of life was done at 6, 12, and 18-month intervals after baseline.

Results:

  1. Participants in the physical activity group had better scores in the areas of memory, language, and visual-perceptual skills as compared to the usual care group. The physical activity group also had better delayed recall.
  2. These benefits persisted at least 12 months after the intervention was discontinued.
  3. Participants with MCI were as likely to benefit from the physical activity intervention as those who had only subjective memory concerns.

Why this is important: This was the first randomized trial to demonstrate that a program of physical activity can improve cognitive function in older adults with mild cognitive impairment. The degree of improvement on cognitive testing among the physical activity group members was modest, but it was greater than the cognitive benefits reported in a comparable study of treatment with cholinesterase inhibitor over an 18-month period. The main appeal of this study is that an intervention as simple and widely available as walking has measurable positive effects on cognition. Moreover, the measurable benefits of exercise may extend beyond improved cognitive function, to areas of more general health.

 

Cautions: Although this study demonstrates the potential benefit of exercise in maintaining brain health, there are some limitations to the conclusions we can draw from it.

  • Study participants were relatively young and free of other serious medical conditions. This may not reflect the population of persons age 70 or older who are most at risk for cognitive decline or who have medical conditions that may affect exercise benefits.
  • The mechanisms by which the positive effect of exercise works are unclear. This study did not determine how brain function is improved by regular physical activity. Is it the reduction of vascular risk? Improvement of cerebrovascular function and brain perfusion? Increased brain plasticity? These questions may be examined in future studies.
  • Although the effect of physical activity on cognition was statistically significant, the degree of benefit was modest and the clinical significance of these findings is still unknown. We do not know whether these results are applicable to the general population. Larger, multi-site studies involving older participants may help determine this.

Reference: Lautenschlager, Nicola T, MD, Cox, Kay L, PhD, Flicker, Leon, MBBS,PhD, Foster, Jonathan K, DPhil, Bockxmeer, Frank M, PhD, Xiao, Jianguo, MD, PhD, Greenop, Kathryn R, PhD, Almeida, Osvaldo P, MD, PhD. Effect of physical activity on cognitive function in older adults at risk for Alzheimer disease. JAMA, 2008; 300(9):1027-1037.

 

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