ORIGINAL CONTRIBUTION

Physical Exercise, Aging, and Mild

Cognitive Impairment
A Population-Based Study
Yonas E. Geda, MD, MSc; Rosebud O. Roberts, MBChB, MS; David S. Knopman, MD;
Teresa J. H. Christianson, BSc; V. Shane Pankratz, PhD; Robert J. Ivnik, PhD; Bradley F. Boeve, MD;
Eric G. Tangalos, MD; Ronald C. Petersen, MD, PhD; Walter A. Rocca, MD, MPH

Background: Physical exercise is associated with de-
creased risk of dementia and Alzheimer disease.
Objective: To investigate whether physical exercise is
associated with decreased risk of mild cognitive impair-
ment (MCI).
Design: Population-based case-control study.
Setting: The Mayo Clinic Study of Aging, an ongoing
population-based cohort study in Olmsted County, Min-
nesota.
Participants: A total of 1324 subjects without demen-
tia who completed a Physical Exercise Questionnaire.
Main Outcome Measures: An expert consensus panel
classified each subject as having normal cognition or MCI
based on published criteria.
Results: We compared the frequency of physical exer-
cise among 198 subjects with MCI with that among 1126
subjects with normal cognition and adjusted the analy-
ses for age, sex, years of education, medical comorbid-
ity, and depression. The odds ratios for any frequency
of moderate exercise were 0.61 (95% confidence inter-
val, 0.43-0.88; P=.008) for midlife (age range, 50-65 years)
and 0.68 (95% confidence interval, 0.49-0.93; P=.02) for
late life. The findings were consistent among men and
women. Light exercise and vigorous exercise were not
significantly associated with decreased risk of MCI.
Conclusion: In this population-based case-control study,
any frequency of moderate exercise performed in midlife
or late life was associated with a reduced odds of having
MCI.
Arch Neurol. 2010;67(1):80-86

Author Affiliations:
Departments of Psychiatry and
Psychology (Drs Geda and
Ivnik), Neurology
(Drs Knopman, Boeve,
Petersen, and Rocca), and
Primary Care Internal Medicine
(Dr Tangalos) and Divisions of
Epidemiology (Drs Geda,
Roberts, Petersen, and Rocca)
and Biomedical Statistics and
Informatics (Ms Christianson
and Dr Pankratz), Department
of Health Sciences Research,
College of Medicine, Mayo
Clinic, Rochester, Minnesota.
M
ILD COGNITIVE IMPAIR-
ment (MCI) is an in-
termediate state be-
tween the cognitive
changes of normal
cognitive aging and dementia.1-6 Subjects
with MCI constitute a high-risk group be-
cause they develop dementia at a rate of
10% to 15% per year compared with 1%
to 2% per year among the general popu-
lation.7 Therefore, it is critical to identify
potential protective factors against MCI.
Physical exercise is associated with re-
duced risk of heart disease, coronary ar-
tery disease, type 2 diabetes mellitus, some
types of cancers, and overall mortality.8,9
Several observational studies10-17 showed
that physical exercise may also be protec-
tive against dementia and Alzheimer dis-
ease, with few discrepant findings.18 Re-
sults of 2 studies19,20 suggested a similar
protective effect for MCI. We investi-
gated whether physical exercise in midlife
or proximate to the age at onset of MCI is
associated with a reduced odds ratio (OR)
for MCI in a case-control study derived
from the Mayo Clinic Study of Aging.21
METHODS
SETTING AND STUDY DESIGN
We conducted a population-based case-
control study comparing subjects having MCI
with subjects having normal cognition. This
study was derived from the Mayo Clinic Study
of Aging, which is described in detail else-
where.21 Briefly, it is a population-based study
designed to estimate the prevalence and inci-
dence of MCI in Olmsted County, Minnesota.
Subjects were recruited using stratified ran-
dom sampling from the target population of al-
most 10 000 older individuals living in Olm-
sted County on October 1, 2004. The sampling
involved equal allocation of men and women

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 in 2 age strata (70-79 and 80-89 years). During the first fol-
low-up period from April 2006 through July 2008, subjects were
asked to complete a self-reported Physical Exercise Question-
naire; therefore, the sample of this study was restricted to 1324
subjects without dementia who completed the questionnaire.
DEFINITION OF CASES AND CONTROLS
Each subject in the Mayo Clinic Study of Aging underwent a
baseline face-to-face evaluation that included the following 3
components: (1) a neurologic evaluation by a physician (Y.E.G.,
D.S.K., B.F.B., E.G.T., or R.C.P.), (2) a risk factor assessment
by a nurse or study coordinator, and (3) neuropsychologic test-
ing, which was interpreted by a neuropsychologist (R.J.I.). The
interview by the nurse or study coordinator included admin-
istration of the Clinical Dementia Rating Scale (CDR)22 to the
subject and to an informant. The neurologic evaluation was per-
formed by a physician and included administration of the Short
Test of Mental Status,23 a medical history review, and a com-
plete neurologic examination.
Neuropsychologic testing was performed using 9 cognitive
tests to assess the following 4 cognitive domains: (1) memory
(logical memory II and visual reproduction II [both delayed
recall] from the Wechsler Memory Scale–Revised and delayed
recall from the Auditory Verbal Learning Test),24-27 (2) execu-
tive function (Trail Making Test B28 and digit symbol substi-
tution from the Wechsler Adult Intelligence Scale–Revised),
(3) language (Boston Naming Test29 and category fluency),30
and (4) visuospatial skills (picture completion and block de-
sign from the Wechsler Adult Intelligence Scale–Revised). We
transformed the raw scores on each test into age-adjusted
scores using Mayo’s Older American Normative Studies27
data. These adjusted scores were also scaled to have a mean
(SD) of 10 (3).24-27
Cognitive domain scores were obtained for every subject
by summing the age-adjusted scores within each domain.
Because different numbers of tests were used to compute
cognitive domain scores (ie, 2 tests for the executive func-
tion, language, and visuospatial skills domains vs 3 tests for
memory), the domain scores were also scaled to allow com-
parisons across domains. In summary, the performance of a
subject in a particular cognitive domain was measured by
comparing his or her domain score with the score among
persons with normal cognition, available from previous
normative work among this same population.24-27,31,32 How-
ever, the final decision about impairment in any cognitive
domain was made by consensus agreement among the exam-
ining physician, nurse, and neuropsychologist, taking into
account years of education, prior occupation, and other
information.21
We considered as cases all subjects who met the following
revised Mayo Clinic criteria for MCI4,5: (1) cognitive concern
expressed by a physician, informant, subject, or nurse; (2) cog-
nitive impairment in 1 or more domains (memory, executive
function, language, or visuospatial skills); (3) normal func-
tional activities; and (4) without dementia. Subjects with MCI
could have a CDR score of 0 or 0.5; however, the final diagno-
sis of MCI was not based exclusively on the CDR score but rather
on all available data. We considered as controls all subjects who
had normal cognition according to published normative data
developed among this population.24-27
MEASUREMENT OF PHYSICAL EXERCISE
We studied the frequency and intensity of exercise using a self-
reported questionnaire with ordinal responses. We used ques-
tions from 2 previously validated instruments (the 1985 Na-
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tional Health Interview Survey33 and the Minnesota Heart Survey
intensity codes34). Subjects were asked to provide information
about physical exercise performed within 1 year of the date of
cognitive assessment (late-life physical exercise) and performed
at age 50 to 65 years (midlife physical exercise). The question-
naire inquired about light, moderate, and vigorous exercise.
Light exercise was defined as bowling, leisurely walking,
stretching, slow dancing, and golfing using a golf cart. Mod-
erate exercise was defined as brisk walking, hiking, aerobics,
strength training, swimming, tennis doubles, yoga, martial arts,
weight lifting, golfing without using a golf cart, and moderate
use of exercise machines (eg, an exercise bike). Vigorous ex-
ercise was defined as jogging, backpacking, bicycling uphill,
tennis singles, racquetball, skiing, and intense or extended use
of exercise machines. For each category of intensity, further
inquiry was made as to the frequency of exercise (times per
month or per week).
MEASUREMENT OF COVARIATES
We considered age, sex, years of education, medical comor-
bidity, and depression as covariates. We measured medical co-
morbidity using the weighted index by Charlson et al,35 which
considers the number and severity of diseases (range, 0-33).
We measured depression using the Beck Depression Inven-
tory.36
STATISTICAL ANALYSIS
We conducted a set of primary analyses considering only in-
tensity of exercise to test whether any frequency of exercise was
associated with decreased risk of MCI. The “once a month or
less” category served as the reference. Prompted by the results
of the primary analyses, we also conducted a set of secondary
analyses considering the frequency and intensity of exercise.
The strength of the association between physical exercise and
MCI was measured using ORs and corresponding 95% confi-
dence intervals (CIs) after adjusting for age (continuous vari-
able), sex, years of education (continuous variable), medical
comorbidity (weighted Charlson Comorbidity Index as a con-
tinuous variable), and depression (Beck Depression Inventory
score of ⬍13 vs ⱖ13).
Analyses were conducted separately for physical exercise per-
formed at age 50 to 65 years and for physical exercise per-
formed within 1 year of the date of cognitive assessment. We
considered 3 levels of intensity of exercise (light, moderate, and
vigorous) and 6 levels of frequency of exercise (ⱕ1 time per
month , 2-3 times per month, 1-2 times per week, 3-4 times
per week, 5-6 times per week, and daily). Because the 3 cat-
egories of intensity of exercise were not mutually exclusive, it
was impossible to collapse these categories.
We also conducted a set of sensitivity analyses using a com-
posite score obtained by assigning a numeric score to the fre-
quency of physical exercise and by adding the scores across the
light, moderate, and vigorous strata (equal weighting was given
to all strata). The scores were 0 for 1 time per month or less,
0.5 for 2 to 3 times per month, 1.5 for 1 to 2 times per week,
3.5 for 3 to 4 times per week, 5.5 for 5 to 6 times per week,
and 7 for daily. The total composite score ranged from 0 to 21.
We consider these as secondary (sensitivity) analyses because
the results varied noticeably depending on the assumptions made
in computing the scores (weights were assigned to different re-
sponses).
Statistical testing was performed at the conventional 2-tailed
␣=.05. All analyses were performed using commercially avail-
able statistical software (SAS, version 8; SAS Institute, Cary,
North Carolina).
WWW.ARCHNEUROL.COM
 consistent among men and women (Table 2 [footnotes
Table 1. Demographic Characteristics of Cases and Controls b and c]). Vigorous exercise had ORs of 0.82 (95% CI,
0.59-1.15; P =.25) for midlife and 1.14 (95% CI, 0.72-
Cases With Cases With 1.81; P=.58) for late life. As expected, fewer subjects re-
Mild Cognitive Normal
Impairment Cognition P
ported vigorous exercise in late life; therefore, the non-
Variable (n=198) (n=1126) Value significant associations for this analysis may be due in
Male sex, No. (%) 117 (59.1) 564 (50.1) .02
part to the lack of statistical power. Results using a com-
Age, y posite score of physical exercise were comparable (Table 2
Median (interquartile range) 83 (78-86) 80 (76-84) ⬍.001 [footnote a]).
70-79, No. (%) 61 (30.8) 532 (47.2)
80-93, No. (%) 137 (69.2) 594 (52.8) SECONDARY ANALYSES CONSIDERING
Education, y
FREQUENCY AND INTENSITY OF EXERCISE
Median (interquartile range) 12 (12-16) 13 (12-16) .001
⬎12, No. (%) 92 (46.5) 652 (57.9)
Beck Depression Inventory, 30 (15.2) b 62 (5.5) ⬍.001 Table 3 summarizes the results of our case-control analy-
No. (%) a ses considering the frequency and intensity of exercise
Weighted Charlson Comorbidity 3 (2-6) 2 (1-5) ⬍.001 performed in midlife (age range, 50-65 years). The point
Index, median (interquartile
range)
estimates for almost all frequencies of light and vigor-
ous exercise were between 0 and 1, suggesting a poten-
a Score of at least 13. tial “protective” effect. However, none of these associa-
b n=197. tions were statistically significant. In contrast, several
frequencies of moderate exercise were significantly as-
sociated with decreased risk of MCI. Table 4 summa-
RESULTS
rizes the results of our case-control analyses consider-
ing the frequency and intensity of exercise performed in
CHARACTERISTICS OF STUDY SUBJECTS late life (within 1 year of the date of cognitive assess-
ment). Except for 1 variable, no significant association
Table 1 summarizes the demographic characteristics of was noted between physical exercise and decreased risk
198 subjects with MCI and 1126 subjects with normal of MCI in any of the analyses.
cognition. Among subjects with normal cognition, there
were equal numbers of men and women, whereas there
were more men than women among subjects with MCI. COMMENT
The median ages were 83 years (interquartile range, 78-86
years) among subjects with MCI and 80 years (inter- In this population-based case-control study, midlife mod-
quartile range, 76-84 years) among subjects with nor- erate exercise was associated with a 39% reduced OR for
mal cognition. MCI. Similarly, late-life moderate exercise was associ-
ated with a 32% reduced OR for MCI. The ORs for light
RELIABILITY OF THE PHYSICAL EXERCISE and vigorous exercise were also consistently less than 1.00
QUESTIONNAIRE in most primary analyses; however, most of these asso-
ciations were not statistically significant. This may be due
We assessed the reliability of the Physical Exercise Ques- in part to the limited statistical power.
tionnaire in 2 ways. First, we studied its internal consis- Observational studies10-14,16,17,37-42 have reported pos-
tency using Cronbach ␣ and observed a value of 0.71 (in sible beneficial effects of physical exercise among older
the moderate to good range). Second, among a sub- subjects with normal cognition and among subjects with
sample of 87 subjects who completed the questionnaire dementia and Alzheimer disease. In contrast, investiga-
at 2 successive visits, we computed a test-retest Spear- tors from the Chicago Health and Aging Project re-
man rank correlation coefficient. The correlations in the ported that physical activity conducted within 2 weeks
overall group were 0.47 for light exercise, 0.50 for mod- of the date of cognitive assessment was associated with
erate exercise, and 0.33 for vigorous exercise. The test- no decreased risk of cognitive decline among an older
retest correlations were similar among 73 subjects with population.18 That negative finding may have been due
normal cognition and among 14 subjects with MCI (of in part to the timing of physical exercise proximate to
87 subjects with 2 interviews [data not shown]). the assessment of cognition.
One study19 reported a suggestive but nonsignificant
PRIMARY ANALYSES STRATIFIED association between physical activity and reduced risk
BY INTENSITY OF EXERCISE of amnestic MCI. Several observational studies also have
reported an association of physical exercise with de-
Table 2 summarizes the results of the primary analy- creased risk of cognitive decline. Although cognitive de-
ses dichotomizing physical exercise into any frequency cline does not coincide with our definition of MCI, these
of exercise vs none. Light exercise had ORs of 0.90 (95% studies are relevant to the interpretation of our find-
CI, 0.55-1.47; P=.68) for midlife and 0.69 (95% CI, 0.47- ings. The Nurses’ Health Study, involving 18 766 women
1.00; P=.048) for late life. Moderate exercise had ORs aged 70 to 81 years, reported that long-term physical ac-
of 0.61 (95% CI, 0.43-0.88; P=.008) for midlife and 0.68 tivity was associated with reduced risk of cognitive de-
(95% CI, 0.49-0.93; P=.02) for late life. The findings were cline.43 Similarly, the Monongahela Valley Independent

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 Table 2. Primary Analyses for Any Frequency of Exercise vs None (ⱕ1 Time per Month)

No. (%)

Frequency of Mild Cognitive Impairment Normal Cognition

Exercise Intensity (n=198) (n = 1126) OR (95% CI) a P Value
Physical Exercise in Midlife
Light
None 25 (12.6) 104 (9.2) 1.00 [Reference]
Any 173 (87.4) 1022 (90.8) 0.90 (0.55-1.47) .68
Moderate
None 58 (29.3) 193 (17.1) 1.00 [Reference]
Any 140 (70.7) 933 (82.9) 0.61 (0.43-0.88) .008 b
Vigorous
None 127 (64.1) 670 (59.5) 1.00 [Reference]
Any 71 (35.9) 456 (40.5) 0.82 (0.59-1.15) .25
Physical Exercise in Late Life
Light
None 52 (26.3) 184 (16.3) 1.00 [Reference]
Any 146 (73.7) 942 (83.7) 0.69 (0.47-1.00) .048
Moderate
None 103 (52.0) 426 (37.8) 1.00 [Reference]
Any 95 (48.0) 700 (62.2) 0.68 (0.49-0.93) .02 c
Vigorous
None 171 (86.4) 969 (86.1) 1.00 [Reference]
Any 27 (13.6) 157 (13.9) 1.14 (0.72-1.81) .58

Abbreviations: CI, confidence interval; OR, odds ratio.

a Adjusted for age (continuous variable), sex, years of education (continuous variable), medical comorbidity (weighted Charlson Comorbidity Index as a
continuous variable), and depression (Beck Depression Inventory score of ⬍13 vs ⱖ13). In a set of sensitivity analyses using a composite score to combine the
frequency and intensity of physical exercise, the OR for quartile 4 vs quartile 1 of the composite score distribution was 0.83 (95% CI, 0.54-1.28; P = .40) for midlife
and 0.74 (95% CI, 0.45-1.21; P =.23) for late life.
b The findings were consistent for men (OR, 0.56; 95% CI, 0.34-0.91; P= .02) and for women (OR, 0.68; 95% CI, 0.39-1.17; P= .16). A test for interaction
between moderate exercise and age at the time of cognitive assessment (continuous variable) was not significant (P = .33).
c The findings were consistent for men (OR, 0.69; 95% CI, 0.45-1.06; P = .09) and for women (OR, 0.65; 95% CI, 0.39-1.08; P= .10).

Table 3. Secondary Analyses for Physical Exercise in Midlife (Age 50-65 Years)

No. (%)

Mild Cognitive Impairment Normal Cognition

Frequency of Exercise (n=198) (n = 1126) OR (95% CI) a P Value
Light
None 25 (12.6) 104 (9.2) 1.00 [Reference]
2-3/mo 18 (9.1) 103 (9.1) 0.83 (0.42-1.67) .61
1-2/wk 34 (17.2) 211 (18.7) 0.83 (0.46-1.50) .53
3-4/wk 31 (15.7) 206 (18.3) 0.76 (0.42-1.38) .36
5-6/wk 26 (13.1) 163 (14.5) 0.94 (0.50-1.76) .84
Daily 64 (32.3) 339 (30.1) 1.07 (0.62-1.83) .82
Moderate
None 58 (29.3) 193 (17.1) 1.00 [Reference]
2-3/mo 19 (9.6) 140 (12.4) 0.56 (0.32-1.01) .05
1-2/wk 31 (15.7) 216 (19.2) 0.55 (0.34-0.91) .02
3-4/wk 41 (20.7) 244 (21.7) 0.71 (0.45-1.12) .14
5-6/wk 16 (8.1) 162 (14.4) 0.42 (0.23-0.77) .005
Daily 33 (16.7) 171 (15.2) 0.76 (0.47-1.24) .28
Vigorous
None 127 (64.1) 670 (59.5) 1.00 [Reference]
2-3/mo 17 (8.6) 142 (12.6) 0.62 (0.35-1.09) .10
1-2/wk 15 (7.6) 119 (10.6) 0.69 (0.38-1.24) .21
3-4/wk 14 (7.1) 100 (8.9) 0.84 (0.46-1.55) .59
5-6/wk 10 (5.1) 44 (3.9) 1.07 (0.51-2.24) .86
Daily 15 (7.6) 51 (4.5) 1.31 (0.70-2.47) .40

Abbreviations: CI, confidence interval; OR, odds ratio.

a Adjusted for age (continuous variable), sex, years of education (continuous variable), medical comorbidity (weighted Charlson Comorbidity Index as a
continuous variable), and depression (Beck Depression Inventory score of ⬍13 vs ⱖ13).

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 Table 4. Secondary Analyses for Physical Exercise in Late Life (ⱕ1 Year From the Date of Cognitive Assessment)

No. (%)

Mild Cognitive Impairment Normal Cognition

Frequency of Exercise (n=198) (n = 1126) OR (95% CI) a P Value
Light
None 52 (26.3) 184 (16.3) 1.00 [Reference]
2-3/mo 17 (8.6) 87 (7.7) 0.73 (0.39-1.37) .33
1-2/wk 28 (14.1) 172 (15.3) 0.74 (0.44-1.25) .26
3-4/wk 25 (12.6) 229 (20.3) 0.48 (0.28-0.82) .007
5-6/wk 18 (9.1) 143 (12.7) 0.62 (0.34-1.14) .12
Daily 58 (29.3) 311 (27.6) 0.81 (0.53-1.25) .35
Moderate
None 103 (52.0) 426 (37.8) 1.00 [Reference]
2-3/mo 16 (8.1) 106 (9.4) 0.72 (0.40-1.29) .27
1-2/wk 21 (10.6) 154 (13.7) 0.65 (0.38-1.09) .10
3-4/wk 23 (11.6) 198 (17.6) 0.63 (0.38-1.04) .07
5-6/wk 15 (7.6) 115 (10.2) 0.69 (0.37-1.25) .22
Daily 20 (10.1) 127 (11.3) 0.73 (0.43-1.24) .24
Vigorous
None 171 (86.4) 969 (86.1) 1.00 [Reference]
2-3/mo 9 (4.5) 52 (4.6) 1.24 (0.59-2.64) .57
1-2/wk 5 (2.5) 34 (3.0) 0.89 (0.33-2.40) .81
3-4/wk 9 (4.5) 42 (3.7) 1.52 (0.71-3.26) .28
5-6/wk 2 (1.0) 11 (1.0) 1.06 (0.23-4.95) .94
Daily 2 (1.0) 18 (1.6) 0.64 (0.15-2.85) .56

Abbreviations: CI, confidence interval; OR, odds ratio.

a Adjusted for age (continuous variable), sex, years of education (continuous variable), medical comorbidity (weighted Charlson Comorbidity Index as a
continuous variable), and depression (Beck Depression Inventory score of ⬍13 vs ⱖ13).

Elders Survey project13 reported that higher exercise level
(defined as aerobic exercise for ⱖ30 minutes performed
ⱖ3 times per week) was associated with reduced risk of
cognitive decline. The Monongahela Valley Indepen-
dent Elders Survey project included a complete assess-
ment of physical exercise (including the frequency, in-
tensity, and duration); however, its outcome measure was
limited to a Mini-Mental State Examination score.44 The
Canadian Health and Aging Study10 examined the asso-
ciation of physical exercise with cognitive impair-
ment–no dementia (CIND) and dementia in a nested case-
control study. Although CIND and MCI differ, they both
describe the gray zone between normal cognitive aging
and dementia. The Canadian Health and Aging Study in-
vestigators reported that physical activity was associ-
ated with a 42% reduced risk of CIND.
Recently, a team of Australian investigators con-
ducted a clinical trial of 170 volunteers 50 years and older
who reported memory problems but who did not meet
the criteria for dementia.20 Subjects were randomized to
a program of education and usual care or to a 24-week
home-based program of physical activity. Physical exer-
cise improved cognitive function among older adults at
risk for Alzheimer disease, including an unspecified num-
ber of subjects with MCI. These benefits were observed
6 months after initiation of the physical activity and were
sustained 12 months after the intervention had been dis-
continued.
All of these observational studies used retrospective
questionnaires and interviews to measure physical ex-
ercise; hence, some degree of recall bias is inherent.
However, a University of California, San Francisco,
study11,40 that objectively measured physical fitness re-
ported similar findings. The investigators prospectively
followed up 349 community-dwelling older women for
6 to 8 years. At baseline, they objectively measured
physical fitness using a treadmill duration test and a
peak oxygen consumption test. They also used the oxy-
gen uptake efficiency slope, which is a measure of car-
diorespiratory fitness independent of motivation and
effort. The investigators observed that subjects who
were in the highest tertile of cardiorespiratory fitness
experienced less cognitive decline over a 6-year fol-
low-up period.
The findings of our study should be interpreted within
the context of the following limitations. The first limi-
tation pertains to study design. The exposure (physical
exercise) and the outcome (MCI) were measured at a
cross-sectional point in time. Therefore, it is difficult to
study the direction of causality. The second limitation
relates to the measurement of physical exercise. As in
many other observational studies, we used a self-
reported questionnaire to collect physical exercise data.
Such measurement is prone to recall bias.13,45 The third
limitation is that few subjects engaged in vigorous exer-
cise in late life; therefore, statistical power was limited
for that analysis.
Our study did not address mechanisms of action. Based
on the literature, we can speculate that physical exer-
cise may be directly protective against MCI via in-
creased production of neurotrophic factors,46 greater ce-
rebral blood flow, improved neurogenesis, enhanced
neuronal survival, mobilization of gene expression af-
fecting neuronal plasticity,47,48 and decreased risk of car-

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 diovascular and cerebrovascular diseases.49 A second pos-
sibility is that physical exercise may be a marker for a
healthy lifestyle. A subject who engages in regular physi-
cal exercise may also show the same type of discipline
in dietary habits, accident prevention, adherence to pre-
ventive intervention, compliance with medical care, and
similar health-promoting behaviors.
In summary, our findings contribute to the growing
body of literature that indicates the potentially benefi-
cial relationship between physical exercise and cogni-
tion. A future population-based cohort study is needed
to confirm whether physical exercise is associated with
decreased risk of incident MCI. The population-based set-
ting will improve generalizability, and the prospective co-
hort design will strengthen causal inferences.
Accepted for Publication: August 20, 2009.
Correspondence: Yonas E. Geda, MD, MSc, Mayo Clinic,
200 First Street SW, Rochester, MN 55905 (geda.yonas
@mayo.edu).
Author Contributions: Dr Geda had full access to all the
data in the study and takes responsibility for the integ-
rity of the data and the accuracy of the data analysis. Study
concept and design: Geda, Roberts, Knopman, Petersen,
and Rocca. Acquisition of data: Geda, Knopman, Ivnik,
Boeve, Tangalos, and Petersen. Analysis and interpreta-
tion of data: Geda, Christianson, Pankratz, and Rocca.
Drafting of the manuscript: Geda. Critical revision of the
manuscript for important intellectual content: Geda, Rob-
erts, Knopman, Christianson, Pankratz, Ivnik, Boeve, Tan-
galos, Petersen, and Rocca. Statistical analysis: Christian-
son and Pankratz. Obtained funding: Geda and Petersen.
Administrative, technical, and material support: Geda and
Petersen. Study supervision: Roberts and Petersen.
Financial Disclosure: Dr Knopman serves on a data safety
monitoring board for Eli Lilly and is an investigator for
clinical trials sponsored by Baxter Pharmaceuticals, Elan
Pharmaceuticals, and Forest Pharmaceuticals. He is an
associate editor of Neurology, for which he receives com-
pensation from the American Academy of Neurology. He
served as a one-time consultant to GlaxoSmithKline in
the past year.
Funding/Support: This study was supported by grant K01
MH068351, career transition award U01 AG006786 (Dr
Geda), K01 AG028573, P50 AG016574, R01 AR030582,
and R01 NS033978 from the National Institutes of Health;
by the Robert H. and Clarice Smith and Abigail Van Buren
Alzheimer’s Disease Research Program; and by the Har-
old Amos (Robert Wood Johnson) Medical Faculty De-
velopment Program.
Additional Contributions: David A. Mrazek, MD,
FRCPsych, provided administrative support in the de-
sign and conduct of grant K01 MH068351.
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