Eric B. Larson, MD, MPH; Li Wang, MS; James D. Bowen, MD; Wayne C. McCormick, MD, MPH; Linda Teri, PhD; Paul Crane, MD, MPH; Walter Kukull, PhD
Grant Support: By the National Institute of Aging (grant AG06781).
Potential Financial Conflicts of Interest: Grants received: L. Teri (National Institutes of Health).
Requests for Single Reprints: Eric B. Larson, MD, MPH, Center for Health Studies, Group Health Cooperative, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448; e-mail, firstname.lastname@example.org.
Current Author Addresses: Dr. Larson: Center for Health Studies, Group Health Cooperative, 1730 Minor Avenue, Suite 1600, Seattle, WA 98101-1448.
Ms. Wang: VA Puget Sound Health Care System, 1100 Olive Way, Seattle, WA 98101.
Dr. Bowen: Department of Neurology, University of Washington, 1959 NE Pacific, Seattle, WA 98195.
Dr. McCormick: Harborview Medical Center, 325 9th Avenue, Box 359755, Seattle, WA 91895.
Dr. Teri: University of Washington, 9709 3rd Avenue NE, Suite 507, Seattle, WA 91115.
Dr. Crane: University of Washington, 325 9th Avenue, Box 359780, Seattle, WA 91895.
Dr. Kukull: Department of Epidemiology, University of Washington, Box 357236, Seattle, WA 98195.
Author Contributions: Conception and design: E.B. Larson, L. Wang, J.D. Bowen, L. Teri.
Analysis and interpretation of the data: E.B. Larson, L. Wang, J.D. Bowen, W.C. McCormick, L. Teri, P. Crane.
Drafting of the article: E.B. Larson, L. Wang, J.D. Bowen, W.C. McCormick.
Critical revision of the article for important intellectual content: J.D. Bowen, W.C. McCormick, L. Teri, P. Crane, W. Kukull.
Final approval of the article: E.B. Larson, J.D. Bowen, W.C. McCormick, L. Teri, P. Crane.
Provision of study materials or patients: E.B. Larson, J.D. Bowen, W.C. McCormick.
Statistical expertise: L. Wang, W.C. McCormick, P. Crane.
Obtaining of funding: E.B. Larson, L. Teri, W.A. Kukull.
Administrative, technical, or logistic support: E.B. Larson, L. Teri, P. Crane.
Collection and assembly of data: E.B. Larson.
Alzheimer disease and other dementing disorders are major sources of morbidity and mortality in aging societies. Proven strategies to delay onset or reduce risk for dementing disorders would be greatly beneficial.
To determine whether regular exercise is associated with a reduced risk for dementia and Alzheimer disease.
Prospective cohort study.
Group Health Cooperative, Seattle, Washington.
1740 persons older than age 65 years without cognitive impairment who scored above the 25th percentile on the Cognitive Ability Screening Instrument (CASI) in the Adult Changes in Thought study and who were followed biennially to identify incident dementia.
Baseline measurements, including exercise frequency, cognitive function, physical function, depression, health conditions, lifestyle characteristics, and other potential risk factors for dementia (for example, apolipoprotein E ϵ4); biennial assessment for dementia.
During a mean follow-up of 6.2 years (SD, 2.0), 158 participants developed dementia (107 developed Alzheimer disease). The incidence rate of dementia was 13.0 per 1000 person-years for participants who exercised 3 or more times per week compared with 19.7 per 1000 person-years for those who exercised fewer than 3 times per week. The age- and sex-adjusted hazard ratio of dementia was 0.62 (95% CI, 0.44 to 0.86; P = 0.004). The interaction between exercise and performance-based physical function was statistically significant (P = 0.013). The risk reduction associated with exercise was greater in those with lower performance levels. Similar results were observed in analyses restricted to participants with incident Alzheimer disease.
Exercise was measured by self-reported frequency. The study population had a relatively high proportion of regular exercisers at baseline.
These results suggest that regular exercise is associated with a delay in onset of dementia and Alzheimer disease, further supporting its value for elderly persons.
Some studies suggest that people with high levels of physical activity are less likely to develop dementia.
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.
The only measure of exercise intensity was self-reported frequency. The cohort was largely white and well-educated.
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.
Table 1. Baseline Characteristics by Follow-up Status
Table 2. Baseline Characteristics of Study Participants by Exercise Levels
Kaplan–Meier survival estimates for the probabilities of being dementia-free.
Kaplan–Meier survival estimates by exercise and performance-based physical function (PPF) levels.
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People who exercised three or more times a week had a 30 to 40 percent lower risk for developing dementia compared with those who exercised fewer than three times per week.
Hiroshima University Hospital
January 26, 2006
Exercise, dentition status, and risk for incident dementia in the elderly
Larson and colleagues recently reported that the exercise measured by self-reported frequency at baseline was associated with a delay in onset of dementia and Alzheimer disease during follow-up period in 1740 persons older than age 65 years without cognitive impairment1. In their study, several biological benefits such as increased oxygen delivery, improved circulation, induced fibroblast growth in the hippocampus, and reduced cell loss in sensitive area like the hippocampus, were considered to link regular excise at baseline with a delay in subsequent occurrence of dementia and Alzheimer disease.
In the viewpoint of oral health, Shimazaki and colleagues demonstrated in a six-year prospective cohort study that worse dentition status at baseline led to significantly worse physical and mental impairment, and higher mortality2. Onozuka and colleagues found a possible link between reduced mastication (worse dentition) and hippocampal neuron loss that may be one risk factor for senile impairment of spatial memory in aged SAMP8 mice3. Maintenance of normal chewing might prevent the brain from degenerating4. Since increased physical activity may reduce prevalence of periodontal disease that is a major risk factor for worse dentition5, it is likely that regular exercise at baseline may contribute to the maintenance of better dentition at baseline and during follow-up period in the study of Larson and colleagues, resulting in a delay in onset of dementia and Alzheimer disease. If dentition status is one of potential pathways linked regular exercise with a delay in onset of dementia and Alzheimer disease in their study, the improvement of dentition status might be a new strategy to prevent dementia and Alzheimer disease in the elderly. It would be beneficial for the dentists as well as the elderly if Larson and colleagues can clarify this hypothesis in the database of their cohort study.
1. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, et al. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81.
2. Shimazaki Y, Soh I, Saito T, Yamashita Y, Koga T, Miyazaki H, et al. Influence of dentition status on physical disability, mental impairment, and mortality in institutionalized elderly people. J Dent Res. 2001;80:340- 5.
3. Onozuka M, Watanabe K, Mirbod SM, Ozono S, Nishiyama K, Karasawa N, et al. Reduced mastication stimulates impairment of spatial memory and degeneration of hippocampal neurons in aged SAMP8 mice. Brain Res. 1999;826:148-53.
4. Miyamoto I, Yoshida K, Tsuboi Y, Iizuka T. Rehabilitation with dental prosthesis can increase cerebral regional blood volume. Clin Oral Implants Res. 2005;16:723- 7.
5. Al-Zahrani MS, Borawski EA, Bissada NF. Increased physical activity reduces prevalence of periodontitis. J Dent. 2005;33:703-10.
University of Michigan at Ann Arbor
March 6, 2006
The Use of Measures of Impact in Clinical Trials
TO THE EDITOR:
While many studies examine causality through measures of association such as relative risks or hazard ratios, measures of impact are often ignored. The recent article by Dr. Larson and colleagues(1) is used as a case in point. Although physicians tout the benefits of exercise in preventing or delaying the onset of several chronic illnesses(2), prospective trials examining this relationship are rare. In this regard, Dr. Larson has made a significant contribution with his article. However, he failed to report his important findings in terms of the excess risk due to infrequent exercise. This measure of impact is a more relevant epidemiologic measure to relay to our patient population than incidence or hazard rates alone.
For purposes of simplifying his study terminology in the following calculations, we shall classify those patients aged 65 years and older who exercise less than 3 times per week as non-excercisers, and those who exercise three or more times per week as exercisers. Using this terminology, the incidence rate of dementia in the exercisers is 13 per 1000 person-years, and in the non-exercisers is 19.7 per 1000 person- years. The excess risk is therefore 6.7, i.e., around 7 new cases of dementia per 1000 person-years among non-exercisers are directly attributable to lack of exercise. Using the above, we can calculate that 34% of new dementia cases per 1000 person-years among non-exercisers are due to lack of exercise.
Although Dr. Larson did not mention the overall incidence of dementia in his population, we have calculated it from the data provided: given 158 new cases of dementia, 1740 patients at risk originally, and 397 censored observations (121 withdrew, 276 died), the population incidence rate over 6.2 years is 16.5 per 1000 person-years. The population excess risk is therefore 4, i.e., if we assume that 1000 new cases of dementia will be diagnosed in the population this year, 4 cases will be directly due to lack of exercise. This means that 21% of new cases of dementia in this population are due to lack of exercise (population attributable risk percent).
Studies like these are pivotal in identifying modifiable risk factors towards the development of chronic illnesses. The measures of impact shown above may help in explaining the findings to our patient population; such calculations should be included in all published clinical trials.
1. Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, Kukull W. Exercise is associated with reduced risk for incident dementia among persons 65 years of age and older. Ann Intern Med. 2006;144:73-81
2. Institute of Medicine. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids (Macronutrients). Washington, DC: National Academy Pr, 2002: 880- 932. Accessed at http://www.nap.edu/openbook/0309085373/html/
Larson EB, Wang L, Bowen JD, McCormick WC, Teri L, Crane P, et al. Exercise Is Associated with Reduced Risk for Incident Dementia among Persons 65 Years of Age and Older. Ann Intern Med. ;144:73–81. doi: 10.7326/0003-4819-144-2-200601170-00004
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Published: Ann Intern Med. 2006;144(2):73-81.
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