Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older

Context Some studies suggest that people with high levels of physical activity are less likely to develop dementia. Content All 1740 participants in this cohort study were 65 years of age or older and were cognitively intact at baseline. Over 6.2 years, the rate of dementia was 13.0 per 1000 person-years in those who exercised 3 or more times per week and 19.7 per 1000 person-years in those who exercised less than 3 times per week. Limitations The only measure of exercise intensity was self-reported frequency. The cohort was largely white and well-educated. Implications This study adds to the evidence that regular exercise is associated with a lower risk for dementia. However, the existing evidence does not prove that regular exercise is associated with a lower dementia risk. The Editors Alzheimer disease and other dementing illnesses are major sources of morbidity and mortality (1-3) that affect millions of persons in the increasingly aging society of the United States. Research designed to discover strategies to delay onset and progression of these potentially devastating illnesses is ongoing worldwide. Effective prevention strategies would result in substantial benefits through improved quality of life, prolonged independent life expectancy, and reduced economic cost and social burdens. Regular physical exercise is an important element in overall health promotion (4) and might also be an effective strategy to delay onset of dementia (5). A biological basis for how physical exercise might preserve brain function includes improved cerebral blood flow and oxygen delivery (6) and inducing fibroblast growth factor in the hippocampus (7). More recent evidence suggests that reduced loss of hippocampal brain tissue in the aging brain is related to level of physical fitness (8). Evidence from some longitudinal studies and randomized trials suggests that physical exercise enhances cognitive function in older adults (9-15), whereas other studies have failed to observe the benefits of physical exercise in preserving cognitive function (16-19). Many people regard Alzheimer disease as one of the most dreaded consequences of aging. If regular physical exercise were shown to be effective in reducing the risk or delaying the onset of dementing illnesses, it would be another compelling reason to promote physical exercise. Few population-based longitudinal studies have examined the role of physical exercise on the risk for dementia in elderly persons. One recent longitudinal study showed that physical exercise was associated with decreased risk for decline in cognitive function (odds ratio [OR], 0.58), Alzheimer disease (OR, 0.50), and any dementia (OR, 0.63) (11), whereas another longitudinal study showed no association between physical exercise and dementia (16). More recent studies showed that walking was associated with a reduced risk for dementia and Alzheimer disease in a cohort of Japanese-American men (20) and that engaging in more diverse physical activities was associated with a reduced risk for dementia in the Cardiovascular Health Study (21). The purpose of this study was 2-fold: 1) to determine whether regular exercise is associated with a reduced risk for incidence of dementia (in particular, Alzheimer disease) in a cohort followed biennially over 6 years and 2) to examine whether the association of physical exercise with incident dementia is modulated by other potential risk factors, such as depression, cardiovascular and cerebrovascular disease, diabetes, apolipoprotein E 4 allele, cognitive function, physical function, self-rated health, and lifestyle characteristics. Methods Study Sample The Adult Changes in Thought (ACT) study is a population-based, longitudinal study of aging and dementia. The ACT study was designed to determine the incidence of Alzheimer disease, other types of dementia, and cognitive impairment as well as to determine risk factors for these conditions. The details of the ACT study have been described elsewhere (22, 23). Briefly, a random sample of 6782 individuals was drawn from Seattle-area members of Group Health Cooperative (GHC), a consumer-governed health maintenance organization. The participants were 65 years of age and older when the study began in 1994 to 1996. Those who had an existing diagnosis of dementia, were current residents of a nursing home, or were participating in other studies were ineligible (n= 1360). Of 5422 eligible persons, 2581 participated and 2841 declined participation. Age, sex, and ethnicity of the remaining 2581 participants did not differ significantly from those who were excluded. Nonresponse has been described elsewhere (22). Declining to participate was more common among the oldest age group (>85 years), women, and African-American and minority groups (22). Additional details regarding the incident rates of dementia and Alzheimer disease from the ACT study have been published elsewhere and are consistent with rates reported in U.S. and European cohort studies (22). The institutional review boards of the University of Washington and Group Health Cooperative approved the ACT study. Participants received the Cognitive Ability Screening Instrument (CASI) (24) as initial screening for cognitive function and were interviewed with structured questionnaires to obtain data, including demographic characteristics, medical history, memory and general functioning, and potential epidemiologic risk factors. Persons scoring 86 or higher on the CASI were entered directly into the ACT cohort as being cognitively intact. (The CASI scores range from 0 to 100; a score of 86 corresponds to a Mini-Mental State Examination score of 25 to 26.) Persons with a score lower than 86 had additional medical record review and standardized clinical and neuropsychological evaluation for dementia. Persons who did not meet established criteria for dementia (25) were included in the ACT cohort. The current study sample was selected from the 2581 ACT participants to examine the temporal relationship of physical exercise preceding development of dementia. By design, we selected the 1895 persons whose CASI scores were above the 25th percentileCASI scores 91 to 100. We excluded 686 persons whose CASI scores were in the lowest quartileCASI scores 62 to 90because the lowest quartile group might include persons who had mild cognitive impairment or impending dementia (26). We did not collect information about the history of exercise before the participants entered the study. Therefore, in the group with low CASI scores, we could not be certain whether a reported low level of physical exercise preceded the development of dementia or was a consequence of the development of cognitive impairment or dementia. Of 1895 participants selected, 155 withdrew after the baseline visit and did not have a follow-up examination and were thus excluded from the analyses, leaving the analytic sample of 1740 persons. Incident Dementia We conducted biennial examinations to identify cases of incident dementia, when participants were rescreened with the CASI. Those who scored 86 or higher on the CASI remained in the ACT cohort. Scores on the CASI that were less than 86 at follow-up prompted a full standardized clinical examination. The results of rescreening by the CASI and by the clinical and neuropsychological examinations were reviewed at a consensus diagnosis conference that included at least the examining physician, a neuropsychologist, another study physician, and the study nurse. Persons who did not meet the criteria for dementia were considered as not having dementia and were followed in the ACT cohort (22, 23). Persons who met the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), criteria (25) for dementia were considered to have incident dementia. Dementia type was determined by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association (NINCDS-ADRDA) criteria (27) for Alzheimer disease and by the DSM-IV criteria (25) for other types of dementia. Level of physical activity was not considered at the consensus conference. Physical Exercise Physical exercise was assessed at baseline by asking participants the number of days per week they did each of the following activities for at least 15 minutes at a time during the past year: walking, hiking, bicycling, aerobics or calisthenics, swimming, water aerobics, weight training or stretching, or other exercise. The frequency of exercise was calculated by the times per week that participants engaged in any of these forms of exercise. In this study, persons who exercised at least 3 times a week, above the lowest quartile, were classified as exercising regularly. Baseline Variables as Potential Confounders Numerous factors may influence the relationship between exercise and risk for dementia, including physical functioning, cognitive function, depression, health conditions, and lifestyle characteristics. Physical function was assessed by a performance-based physical function (PPF) test (23), which consisted of 4 performance tests: 10-foot timed walk, time to stand from a seated position in a chair to a standing position 5 times, balance test, and grip strength in the dominant hand. Each test was scored from 0 to 4 points. The final PPF score was the sum of the scores for the 4 performance tests and ranged from 0 to 16; higher scores indicated better physical function. Details of the PPF test have been reported elsewhere (23). Cognitive function was assessed by using the CASI, which provides quantitative assessment of attention, concentration, orientation, short-term memory, long-term memory, language ability, visual construction, list-generating fluency, abstraction, and judgment (24). At baseline, depression was measured by using the 11-item Center for Epidemiologic Studies Depression (CES-D) scale (28). The CES-D scores ranged from 0 to 33, with higher scores represe