Exercise May Have Neuroprotective Effect - Medscape Article

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August 11, 2006 - Exercise helps maintain brain structure and function with

aging and may delay onset of Alzheimer's disease and other dementias,

according to a review presented at the 114th annual convention of the

American Psychological Association (APA).

" There is a diverse body of evidence from retrospective and prospective

clinical studies, as well as from animal research, all of which suggests

that exercise has beneficial effects from middle age to old age, " presenter

Arthur F. Kramer, PhD, a faculty member in neuroscience and psychology at

the University of Illinois at Urbana in Champaign, told Medscape.

" Exercise has neuroprotective effects enabling higher levels of cognition

and delaying the onset of various forms of dementia such as Alzheimer's

disease in prospective epidemiological studies, " Dr. Kramer continued. " It

also has positive effects on brain structure and function, both from human

research with magnetic resonance imaging (MRI), functional MRI, and

event-related potentials, and especially from the animal literature showing

proliferation of active capillary beds, new dendritic connections, and even

new neurons in selective areas such as the hippocampus. "

Data Review

Along with coauthors Kirk I. kson, PhD, and Stanley J. Colcombe, Dr.

Kramer reviewed research evidence accumulated during the past 4 decades,

including epidemiologic studies of the relationship between exercise and

physical activity at various ages with cognitive ability and subsequent

probability of developing Alzheimer's disease or other age-related

neurologic diseases. They also reviewed longitudinal randomized trials

studying the effect of specific fitness training on cognition and brain

function in older adults, as well as animal studies of the molecular and

cellular basis of exercise effects on brain structure and function.

" Clinical data [show that] people who exercise several times per week show a

reduced rate of cognitive decline with age [compared with] those who have

low levels of activity, " Carl Cotman, PhD, director of the Institute for

Brain Aging at the University of California, Irvine, told Medscape. Dr.

Cotman was not involved with Dr. Kramer's presentation but reviewed it for

Medscape as an independent expert. " The best evidence, though, comes from

animal studies, where it has been established that voluntary running

increases neuroprotective molecules in the brain, such as brain-derived

neurotrophic factor (BDNF), and also reduces the accumulation of molecules

associated with Alzheimer's disease, such as beta-amyloid. "

In the review by Dr. Kramer and colleagues, the epidemiologic literature

showed a significant protective effect of physical activity on cognitive

function and on decreased incidence of dementia, with the benefits lasting

up to several decades. A few studies of human subjects older than 65 years

showed that exercise lasting at least 15 to 30 minutes, 3 times weekly,

reduced the probability of developing Alzheimer's disease, even in subjects

who were genetically predisposed.

Clinical trials also suggest a relationship between fitness training and

improved cognition, more efficient brain function, and prevention of brain

atrophy in the elderly. A 4-year study of the relationship between physical

activity and cognition and brain function in subjects aged 62 to 70 years

showed that those who were still employed and retirees who exercised

regularly had sustained levels of cerebral blood flow and superior

performance on general measures of cognition compared with inactive

retirees. In a 6-month study, elderly subjects who participated in aerobic

exercise had a significant increase in gray matter volume in regions of the

frontal and superior temporal lobe compared with controls.

No Downside to Recommending Exercise

" With the human data, there have been enough meta-analyses over the last 10

years suggesting that exercise does have neuroprotective effects and also

does tend to decrease depression ratings, " Dr. Kramer said. " I don't see any

downside to recommending exercise, even if the effects aren't as large or as

robust as we think they are, because we already know that exercise tends to

reduce mortality and decrease the incidence of cardiovascular disease, type

2 diabetes, and osteoporosis. I think there is no reason not to come up with

a set of recommendations based upon both the disease literature and the

animal literature. "

Aerobic exercise appears to confer more positive effects on brain function

with aging than do other forms of exercise. In a study of older adults,

those who were randomized to a walking group for 6 months performed better

on a distractibility task than did those randomized to a stretching and

toning control group. Furthermore, the aerobically trained group had

increased neural activities in frontal and parietal brain regions mediating

attention, and reduced activity in the dorsal region of the anterior

cingulate cortex, which is thought to be sensitive to behavioral conflict,

or the need for increased cognitive control. Aerobic exercise also appears

to help the brain maintain its plasticity.

" Physical activities that have a fairly strong aerobic component appear to

be associated with spared cognition and delayed onset of dementia, " Dr.

Kramer said. " Other forms of exercise that have to do with toning and

stretching, that lead to increased flexibility and decreased falls in older

adults, are also beneficial, but they don't seem to be implicated in the

cognitive-sparing effects. The animal literature suggests that learning new

psychomotor skills can be beneficial in increasing new dendritic

connections. "

Animal studies offer additional insight into the neuroprotective effects of

physical activity because they allow direct observation of morphologic,

neurochemical, and neurophysiologic changes associated with exercise. In

studies using voluntary wheel running as a measure of aerobic activity,

animals with increased wheel running performed better on spatial learning

tasks mediated by the hippocampus. In other studies, aged rodents that

exercised in a water maze learned and retained information about a hidden

platform better than did age-matched controls. Both young and aged animals

benefited from exercise, as reflected in increases in nerve growth factor

levels that can offset or prevent certain age-related diseases.

Questions Remain

In terms of clinical implications of these findings, certain questions

remain unanswered.

" There are certainly unknowns, such as dose-response relationship in humans:

how much exercise leads to how much cognitive benefit or decrease in odds

ratios for Alzheimer's disease or vascular dementias, " Dr. Kramer pointed

out. " We also need studies that combine various lifestyle choices or

interventions that research suggests are neuroprotective for humans, such as

intellectual engagement, nutritional choices, use of antioxidants and other

supplements, to determine the way these various interventions are additive

or multiplicative. "

Dr. Cotman agreed that clinical trials are needed to answer these questions.

He recommended that exercise should have some type of aerobic component, but

that the exact type is probably not as critical.

" The current data support that levels of activity will help but they do not

provide an exact prescription, " he concluded. " Based on epidemiological data

and animal data, however, it is likely that exercise for 3 or more times per

week is beneficial.... Walking 3 or more times per week for 30 to 45 minutes

also is beneficial. "

Dr. Kramer is funded by the National Institutes of Health. Dr. Cotman

reports no relevant financial relationships. Preparation of Dr. Kramer's

manuscript was supported by the National Institute on Aging, the Institute

for the Study of Aging, and the Riken Brain Science Institute.

APA 2006 Annual Convention: Session 2028 - Invited Symposium: Optimal Aging

and Cognition - Moderators of Cognitive Change and Decline. Presented August

11, 2006.