In this population-based case-control study, midlife moderate physical exercise was associated with a 39% reduced OR for MCI. Similarly, late life moderate physical exercise was associated with a 32% reduced OR for MCI. The ORs for light and vigorous exercise were also consistently smaller than 1.0 in most primary analyses; however, most of these associations were not statistically significant. This may be due in part to the limited statistical power.
Several observational studies have reported possible beneficial effects of physical exercise in cognitively normal elderly as well as in subjects with dementia and Alzheimer disease.10–14,16,17,37–42
By contrast, investigators from the Chicago Health and Aging Project reported that physical activity conducted within 2 weeks of the date of cognitive assessment was not associated with a decreased risk of cognitive decline in elderly population.18
That negative finding may have been caused in part by the timing of exercise proximate to the assessment of cognition.
One study reported a suggestive but not significant association between physical activity and reduced risk of amnestic MCI.19
A number of observational studies also reported an association of physical exercise with decreased risk of cognitive decline. Although cognitive decline does not coincide with our definition of MCI, these studies are relevant to the interpretation of our findings. The Nurses’ Health Study involving 18 766 women participants aged 70 to 81 years reported that long term physical activity was associated with a reduced risk of cognitive decline.43
Similarly, the Monongahela Valley Independent Elders Survey (MoVIES) reported that higher exercise level (defined as aerobic exercise for 30 or more minutes carried out 3 or more times per week) was associated with a reduced risk of cognitive decline.13
The MoVIES study had a complete survey of exercise including duration, intensity and frequency of exercise; however, its outcome measure was limited to a Mini-Mental State Examination score.44
The Canadian Health and Aging Study examined the association of physical exercise with Cognitive Impairment No Dementia (CIND) and dementia in a nested case-control study. Even though CIND is not identical with MCI, CIND and MCI are similar constructs describing the gray zone between normal cognitive aging and dementia. The Canadian investigators reported that physical activity was associated with a 42% reduced risk of CIND.10
Recently, a team of Australian investigators conducted a clinical trial of 170 volunteers aged 50 years and older who reported memory problems but did not meet the criteria for dementia. The participants were randomized to either a program of education and usual care or to a 24-week home-based program of physical activity. Exercise improved cognitive function in older adults at risk for Alzheimer disease including an unspecified number of subjects with MCI. These benefits were observed 6 months after initiation of the physical activity, and were sustained at 12 months after the intervention was discontinued.20
All the above observational studies used retrospective questionnaires and interviews to measure physical exercise; hence, some degree of recall bias is inherent in all of them. However, it is reassuring that a University of San Francisco study that objectively measured physical fitness, reported similar findings. The investigators prospectively followed 349 community dwelling elderly women for a duration of 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 oxygen uptake efficiency slope which is a measure of cardiorespiratory 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 years follow-up period.11,40
The findings of our study should be interpreted within the context of the following limitations. The first limitation pertains to study design. Both 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 pertains to the measurement of exercise. As in many other observational studies, we used a self-reported questionnaire to collect exercise data. Such a measurement is prone to recall bias.13,45
Third, few people engaged in vigorous exercise in late life; thus, the statistical power was limited for that analysis.
Our study did not address mechanisms of action. Based on the literature, we can speculate that physical exercise may be directly protective against MCI via increased production of neurotrophic factors,46
increased cerebral blood flow, increased neurogenesis, enhanced neuronal survival, mobilization of gene expression impacting neuronal plasticity,47,48
and decreased risk of cardiovascular and cerebrovascular diseases.49
A second possibility is that physical exercise may be a marker for a healthy life style. A person who engages in regular physical exercise may also show the same type of discipline in dietary habits, accident prevention, compliance with preventive 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 beneficial relationship between physical exercise and cognition. A future population-based cohort study is needed to confirm whether physical exercise is associated with a decreased risk of incident MCI. The population-based setting will improve generalizability, and the prospective cohort design will strengthen etiologic inferences.