Journal of Gerontological Nursing

Feature Article 

The Relationship Between Physical Activity and Dementia: A Systematic Review and Meta-Analysis of Prospective Cohort Studies

Junga Lee, PhD

Abstract

Physical activity may decrease the risk of dementia; however, conflicting findings exist. The purpose of the current meta-analysis was to investigate the relationship between physical activity and dementia risk based on physical activity type, amount, and intensity, and to propose an effective minimal physical activity amount for older adults. Forty-four studies were selected for the meta-analysis. Participation in high (a total of >2 hours of activity over the course of three sessions per week) and moderate (a total of >1 hour of activity over the course of two sessions per week) amounts of physical activity showed decreased dementia risks compared to physical inactivity. Vigorous exercise, regular exercise, leisure time physical activities, and gardening showed a positive effect toward lowering dementia risk, but walking was not associated with dementia risk. Physically inactive individuals had a higher dementia risk than those who participated in physical activity. Participation in physical activities produces a favorable effect toward lowering dementia risk. Participating in regular physical activity of >1 hour over the course of two sessions per week and avoiding physical inactivity are recommended for lowering dementia risk. [Journal of Gerontological Nursing, 44(10), 22–29.]

Abstract

Physical activity may decrease the risk of dementia; however, conflicting findings exist. The purpose of the current meta-analysis was to investigate the relationship between physical activity and dementia risk based on physical activity type, amount, and intensity, and to propose an effective minimal physical activity amount for older adults. Forty-four studies were selected for the meta-analysis. Participation in high (a total of >2 hours of activity over the course of three sessions per week) and moderate (a total of >1 hour of activity over the course of two sessions per week) amounts of physical activity showed decreased dementia risks compared to physical inactivity. Vigorous exercise, regular exercise, leisure time physical activities, and gardening showed a positive effect toward lowering dementia risk, but walking was not associated with dementia risk. Physically inactive individuals had a higher dementia risk than those who participated in physical activity. Participation in physical activities produces a favorable effect toward lowering dementia risk. Participating in regular physical activity of >1 hour over the course of two sessions per week and avoiding physical inactivity are recommended for lowering dementia risk. [Journal of Gerontological Nursing, 44(10), 22–29.]

Dementia is a brain illness that influences memory, thinking, behavior, and daily tasks (Christensen et al., 2013). Patients with dementia are mostly older adults, and dementia is an abnormal process of aging (Viswanathan, Rocca, & Tzourio, 2009). Forty-seven million older adults experienced dementia in 2017, and the estimated number of patients with dementia will approximately triple to 141 million by 2050 (Hebert, Weuve, Scherr, & Evans, 2013). The estimated worldwide economic cost of dementia was $818 billion in 2015, which is a massive burden for patients with dementia, their families, and the community (Wimo et al., 2017). Prevention of dementia in the aging society is important as there is no cure, only treatments to slow the progression of dementia after it occurs.

Physical activity is known to reduce the risk of dementia; however, controversial results have been reported. Some researchers have indicated that physical activity had no association with dementia risk (Mehlig et al., 2014; Sabia et al., 2017), whereas other researchers have shown associations with reduced dementia risk (Heser et al., 2014; Llamas-Velasco, Contador, Villarejo-Galende, Lora-Pablos, & Bermejo-Pareja, 2015). Conflicting findings might be related to physical activity types, frequency, or intensity. Considering types of physical activity, a previous study found that older adults who participated in gardening had a 34% lower dementia risk than those who did no physical activity (McCallum, Simons, Simons, & Friedlander, 2007).

A recent meta-analysis reported an inverse association between leisure time physical activities and all-cause dementia and Alzheimer's disease (AD), but no association with vascular dementia (Xu et al., 2017). When a leisure time physical activity session was increased by 500 kcal or 10 Metabolic Equivalent of Task-hours, the risks of all-cause dementia and AD decreased by 10% and 13%, respectively (Xu et al., 2017). A limitation of the previous meta-analysis was that the study considered only caloric energy expended by physical activity.

Older adults incur a loss of physical strength and a reduction in physical function with aging. These factors might affect their ability to participate in physical activities, which may lead to lower amounts and intensity of physical activity compared to younger adults. To provide more practical guidelines regarding physical activity recommendations for older adults, the association between physical activity and dementia risk should consider factors such as physical activity types, activity session time periods, performance frequency, and intensity. Thus, the purpose of the current meta-analysis was to investigate the relationship between physical activity and all-cause dementia, AD, and vascular dementia based on physical activity type, amount, and intensity.

Method

Study Search

The current meta-analysis followed the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines in the selection process for identifying eligible studies (Liberati et al., 2009). Embase and Medline databases were used to search for eligible studies published in English from January 1990 to December 2017. Two researchers (J.L. and another) searched for relevant studies independently. Any procedural issues or conflicts discovered during the process were discussed and resolved to both researchers' satisfaction. Several search terms were used: physical activity, exercise, dementia, Alzheimer's disease, vascular dementia, and risk. All selected studies were evaluated by guidelines for the Meta-Analysis of Observational Studies in Epidemiology (Stroup et al., 2000). In addition, both researchers reviewed reference lists from the potentially relevant studies and the reviewed articles to find relevant studies. The Newcastle-Ottawa Quality Assessment Scale was used to evaluate the quality of the selected studies (Wells, 1948).

Eligibility Criteria and Data Extraction

The eligibility criteria required that a selected study must provide a prospective cohort study and include the relative risks (RRs) of dementia according to older adults' participation in physical activity. Basic information collected from the selected studies included: name of the first author, country in which the study took place, design of the study, publication year, sample size, years the study was conducted, follow-up years, dementia diagnosis criteria, measurements of physical activity (i.e., type, frequency, intensity, and time), RR with 95% confidence interval [CI], and adjustment factors. Disqualifying criteria were: any case-control, cross-sectional, meta-analysis, or review study; article not written in English; not within date range; and any study that did not provide RRs.

Statistical Analysis

Directly extracted RRs from each selected study were used to calculate a summary of RRs. The Q-statistic was used to determine the statistical heterogeneity within the sampled studies. In performing the Q-statistic analysis, if the p value was <0.05, a fixed-effect model was used; if the p value was ≥0.05, a random-effect model was used. Inconsistency across the sampled studies was determined by the I2 statistic. If the p value from the I2 statistic was >0.10, the summary was considered heterogeneous homogeneous. If the p value from the I2 statistic was ≤0.10, the summary was considered homogeneous. Publication bias within the sampled studies was inspected visually using a funnel plot. Statistical significance was indicated when p was <0.05. The Comprehensive Meta-Analysis Version 1.25 software program was used to perform all statistical meta-analyses.

Results

Literature Search

The process for selecting studies is presented in Figure 1. A total of 1,229 studies were identified from the initial keyword-based searching steps. Screening continued by reviewing titles and abstracts of the identified studies, reading the literature review, and confirming that the study met additional criteria for inclusion in a meta-analysis; from these steps, 1,104 studies were excluded. The full-text versions of the remaining 125 studies were carefully reviewed in their entirety to determine whether the studies fit all eligibility criteria for this study. Eighty-one studies were subsequently eliminated because they did not provide the RRs of dementia according to physical activity and were not prospective cohort studies. A total of 44 studies were selected for the meta-analysis (Table A, available in the online version of this article).

Process for selecting studies for the current meta-analysis.

Figure 1.

Process for selecting studies for the current meta-analysis.

Characteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia RiskCharacteristics of Selected Studies: Physical Activity, and Dementia Risk

Table A:

Characteristics of Selected Studies: Physical Activity, and Dementia Risk

Study Characteristics

From the 44 studies selected for the meta-analysis, there was a total population of 258,138 participants. Thirty-six studies were conducted in America and Europe, seven studies were conducted in Asia, and one study was conducted in Africa. The average time for follow up was 9.51 years. Each study used a unique set of adjustments, with factors that included age, body mass index, and education. Older adults were divided into three groups depending on their physical activity levels. The first group, comprising older adults who rarely participated in physical activity or participated in physical activity for <1 hour per week, was the inactive group (Batty, Russ, Starr, Stamatakis, & Kivimaki, 2014; Bowen, 2012; Chang et al., 2010; de Bruijn et al., 2013; Elwood et al., 2013; Fabrigoule et al., 1995; Fenesi et al., 2017; Lee et al., 2015; Luck et al., 2014; McCallum et al., 2007; Mehlig et al., 2014; Morgan et al., 2014; Simons, Simons, McCallum, & Friedlander, 2006; Soni et al., 2017; Tolppanen et al., 2015; Tomata et al., 2017; Verghese et al., 2003; Yoshitake et al., 1995; Zhou, Fu, Hong, Wang, & Fang, 2017). The second group, the moderate physical activity group, participated in a total of >1 hour of physical activity over the course of two sessions per week (Abbott et al., 2004; Carlson et al., 2008; Karp et al., 2006; Laurin, Verreault, Lindsay, MacPherson, & Rockwood, 2001; Llamas-Velasco et al., 2015; Sabia et al., 2017; Sumic, Michael, Carlson, Howieson, & Kaye, 2007; Wang, 2002). The third group comprised individuals who participated in a high amount of physical activity, participating in a total of >2 hours of physical activity over the course of three sessions per week (Akbaraly et al., 2009; Annweiler et al., 2012; Buchman et al., 2012; Gureje, Ogunniyi, Kola, & Abiona, 2011; Hebert et al., 2000; Heser et al., 2014; Hessler et al., 2016; Kishimoto et al., 2016; Larson et al., 2006; Lindsay et al., 2002; Neergaard et al., 2016; Podewils et al., 2005; Ravaglia et al., 2008; Rovio et al., 2005; Rovio et al., 2007; Scarmeas et al., 2009; Verdelho et al., 2012). Based on the types of physical activity identified in the selected studies, a summary of RRs for four types of physical activity was calculated: walking, gardening, leisure time physical activity, and regular exercise. Physical activity intensity, type, and amount were measured by physical activity questionnaires or by interview. Leisure time physical activity was a self-reported answer that included physical activities such as tennis, swimming, bicycling, team games, and walking for exercise.

Total Amount of Physical Activity and Dementia Risks

Older adults who participated in a high amount of physical activity experienced a 22% decrease in all-cause dementia risk (odds ratio [OR] = 0.78, 95% CI [0.74, 0.81], p < 0.05), a 28% decrease in AD risk (OR = 0.72, 95% CI [0.66, 0.80], p < 0.05), and a 46% decrease in vascular dementia risk (OR = 0.54, 95% CI [0.42, 0.69], p < 0.05) compared to older adults who did not participate in physical activity (Figure A, available in the online version of this article). In addition, the association between moderate amounts of physical activity and dementia risk had an inverse association with all-cause dementia (OR = 0.77, 95% CI [0.75, 0.79], p < 0.05), AD (OR = 0.68, 95% CI [0.60, 0.77], p < 0.05), and vascular dementia (OR = 0.72, 95% CI [0.54, 0.97], p < 0.05). There was no statistically significant heterogeneity across the sampled studies. No publication biases were revealed, as tested using a funnel plot and the trim and fill method.

High and moderate amounts of physical activity and dementia riskHigh and moderate amounts of physical activity and dementia riskHigh and moderate amounts of physical activity and dementia risk

Figure A.

High and moderate amounts of physical activity and dementia risk

Intensity of Physical Activity and Dementia Risks

Regarding the intensity of physical activity, the current meta-analysis was conducted only for vigorous physical activity in comparison to low-intensity physical activity for all-cause dementia risk due to the limited numbers of studies available, as shown in Figure 2. The vigorous intensity physical activity group had a 28% decreased association with all-cause dementia (OR = 0.72, 95% CI [0.59, 0.86], p < 0.05). No statistically significant heterogeneity among the sampled studies existed. There was no publication bias, as tested using a funnel plot and the trim and fill method.

Physical activity intensity and all-cause dementia risk.

Figure 2.

Physical activity intensity and all-cause dementia risk.

Types of Physical Activity and Dementia Risks

An additional analysis was conducted in the current meta-analysis to examine physical activity types that included walking, gardening, leisure time physical activity, and regular exercise (Figure 3). Participation in gardening (OR = 0.59, 95% CI [0.50, 0.70], p < 0.05), leisure time physical activity (OR = 0.79, 95% CI [0.72, 0.88], p < 0.05), and regular exercise (OR = 0.58, 95% CI [0.47, 0.72], p < 0.05) each indicated a reduced association with all-cause dementia risks. However, that association was not found for individuals who participated in walking (OR = 0.86, 95% CI [0.72, 1.04], p > 0.05). Ten studies were used to analyze leisure time physical activity, seven for regular exercise, three for gardening, and four for walking. There was no statistically significant heterogeneity among the sampled studies. There was no publication bias, as tested using a funnel plot and the trim and fill method.

Physical activity types and all-cause dementia risk.

Figure 3.

Physical activity types and all-cause dementia risk.

Physical Inactivity and Dementia Risks

Older adults who did not participate in physical activity had 1.51 times higher all-cause dementia risk (95% CI [1.27, 1.79], p < 0.05) compared to older adults who participated in a vigorous amount of physical activity, and a 1.32 times higher all-cause dementia risk (95% CI [1.10, 1.58], p < 0.05) compared to older adults who participated in a moderate amount of physical activity (Figure 4). No statistically significant heterogeneity among the sampled studies was found. There was no publication bias, as tested using a funnel plot and the trim and fill method.

Physical inactivity and all-cause dementia risk.

Figure 4.

Physical inactivity and all-cause dementia risk.

Discussion

A main finding of the current meta-analysis was the preventive effects of physical activity against dementia in older adults. Participation in physical activity, including high and moderate amounts of physical activity, was associated with decreases in all-cause dementia, AD, and vascular dementia in older adults. In addition, diverse physical activities including leisure time physical activity, regular exercise, and gardening showed a positive effect on dementia risk. However, physical inactivity may lead to an increase in dementia risk.

Older adults who participated in physical activities in high and moderate amounts had lower risks of all-cause dementia (22% and 23%, respectively), AD (28% and 32%, respectively), and vascular dementia (46% and 28%, respectively) compared to older adults who were physically inactive. These findings coincide with a previous meta-analysis that found an association between physical activity and dementia risk in older adults (Guure, Ibrahim, Adam, & Said, 2017). The greatest reduction (46%) was for vascular dementia in individuals with a high amount of physical activity. The larger reduction might be related to the impact of exercise on related risk factors that include diabetes mellitus, high blood pressure, high cholesterol, coronary heart disease, and peripheral artery disease, whereas AD risk factors are more likely associated with age, genetics, and general health (O'Brien & Markus, 2014).

Given the parameters of the source data regarding physical activity amounts, it is important to note that the cut-off for a high amount of physical activity in the current meta-analysis was a total of >2 hours of activity performed over the course of three sessions per week, and the cutoff for a moderate amount of physical activity was a total of >1 hour of activity performed over the course of two sessions per week. The minimum level of physical activity to have a positive effect against dementia is >1 hour per week performed over the course of two sessions per week. From these findings, the current meta-analysis suggests that participation in these amounts of physical activity helps prevent all-cause dementia, AD, and vascular disease.

A main finding of the current meta-analysis was that physical activity of vigorous intensity was inversely associated with all-cause dementia. That is, when older adults participated in vigorous intensity exercise, there was an associated 28% decrease in dementia risk, although only three studies were used in the meta-analysis to obtain this finding. An examination was not conducted for moderate intensity as associated with other subtypes of dementia, including AD and vascular dementia, as there was an insufficient amount of data to conduct a meta-analysis.

The sensitivity analysis of the current meta-analysis found that physical activity type influenced the risk of all-cause dementia. Gardening, which is considered more intense activity than moderate activity, was associated with a 41% decrease for all-cause dementia risk, but walking (likely of light intensity) did not have a statistically significant association with dementia risk. The current meta-analysis showed the importance of participation in regular exercise and leisure time physical activity against all-cause dementia risk. The association between intensity and types of physical activity and dementia needs further study. General comparisons to other similar studies (Kishimoto et al., 2016; Tomata et al., 2017) indicated that these findings were consistent in that moderate intensity physical activity and regular exercise would be more beneficial than light intensity physical activity and walking to produce a protective effect against dementia.

The current meta-analysis found that physical inactivity was associated with increased all-cause dementia. Older adults who did not participate in physical activity had 1.51 times the dementia risk than older adults who performed a high amount of physical activity (a total of >2 hours of activity performed over the course of three sessions per week). In addition, inactive older participants had 1.32 times the dementia risk as older adults who participated in a moderate amount of physical activity (a total of >1 hour of activity performed over the course of two sessions per week). These results coincide with previous studies that found that physical inactivity was related to increased incidence of other chronic diseases, including cancer, cardiovascular diseases, and metabolic disorders (Biswas & Alter, 2015). The current meta-analysis used six studies to determine the association between physical inactivity and all-cause dementia risk. Findings support participation in physical activity as an important step toward lowering dementia risk.

Three prominent mechanisms may explain how physical activity leads to a favorable physiological effect in reducing dementia risk. First, physical activity causes an increase in brain-derived neurotrophic factor and insulin-like growth factor that stimulate neurotransmitter functions and neuroprotection in the brain (Cotman, Berchtold, & Christie, 2007). Second, exercise helps maintain flow of blood and supply of oxygen and nutrients, promoting cerebrovascular integrity (Querido & Sheel, 2007) and inhibiting atrophy of the hippocampus volume that preserves memory (Smith et al., 2014). Third, regular physical activity tends to decrease the amount of cortisol in the bloodstream, leading to a reduction in symptoms of stress (Kalmijn et al., 1998).

Limitations

Several limitations of the current meta-analysis must be addressed. First, the amount and intensity of physical activity were heterogeneous. Measurements of physical activity amounts, intensity, and types were obtained by self-reported questionnaires. The current meta-analysis used the intensity categories directly from each original study to calculate a summary of RRs. Second, adjustment factors from each original study were unique to that study, and those unique differences could not be controlled. Third, the follow-up periods to determine the influence of exercise on dementia risk were different in each selected study.

Conclusion

Participation in physical activity was associated with a decreased risk of dementia, whereas physical inactivity was associated with an increased risk. Physical activity performed for at least 1 hour twice per week has been shown to reduce risk of dementia. Other amounts of regular exercise as well as gardening also help decrease dementia risk. The practical implication of the current meta-analysis is that participation in physical activity is an important factor in preventing dementia. The meta-analysis indicated that a total of 2 hours of exercise per week, performed three times per week, results in better outcomes for reducing dementia risk. Older adults would significantly benefit from participation in diverse activities such as leisure time physical activity, regular exercise, and gardening. Engaging in physical activity as a routine for older individuals should be recommended for preventing all-cause dementia, including AD and vascular dementia.

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Characteristics of Selected Studies: Physical Activity, and Dementia Risk

First author (year), name of study, study design, countrySample size study, recruitment period, ageFollow-up period (year)Dementia assessmentExercise assessment, exercise unitesRR (95% CI)Physical activityAdjustments
Abbott (2004), a prospective cohort study, Japan (Abbott et al., 2004)2,257 (1991–1999), 71–93 yearsAverage 25 yearsCognitive functionPhysical activity interview, walking mile per dayWalking (miles/day)All-cause DementiaAge, presence of apolipoprotein, baseline Cognitive Abilities Screening Instrument Score, decline in physical activity, education, body mass index, heart dieses, total cholesterol, prevalence coronary, diabetes, hypertension, HDLC
  >21
  2-11.33(0.73, 2.45)
  0.5–11.75(1.03, 2.99)
  <0.251.93(1.11, 3.34)
Alzheimer Dementia
  >21
  2-11.88(0.87, 4.40)
  0.5–11.86(0.91, 3.79)
  <0.252.21(1.06, 4.57)
Vascular Dementia
  >21
  2-10.16(0.02, 1.36)
  0.5–11.21(0.45, 3.22)
  <0.251.17(0.42, 3.27)
Mixed & other Dementia
  >21
  2-12.00(0.36, 11.01)
  0.5–12.84(0.62, 12.92)
  <0.252.83(0.59, 13.55)

Akbaraly (2009), a prospective community study, France (Akbaraly et al., 2009)5,698 (1991–2001), over 65 years old4 yearsDSM-IVPhysical Activity QuestionnaireLeisure activates (tertile)All-cause Dementia: PAVascular risk factors, depressive symptoms, physical functioning, other leisure activities
  Low1
  Mild0.83(0.55, 1.25)
  High1.08(0.74, 1.57)
Alzheimer Dementia
  Low1
  Mild0.87(0.52, 1.47)
  High1.45(0.92, 2.28)
Mixed/Vascular Dementia
  Low1
  Mild0.76(0.34, 1.71)
  High0.67(0.30, 1.53)

Annweiler (2012), a prospective multicenter cohort study, France (Annweiler et al., 2012)7,598 (1992–1994), average 78 years old7 yearsMini-Mental State ExaminationPhysical Activity QuestionnaireLeisure PA (hours/week)All-cause DementiaAge, body mass index, short portable mental state, high education level, disability, sun exposure at midday, chronic diseases, hypertension, depression, psychoactive drugs, dietary vitamin D intakes
  None1
  Light0.83(0.47, 1.46)
Alzheimer Dementia
  None1
  Light0.79(0.44, 1.42)

Batty (2014), a prospective cohort study, UK (Batty et al., 2014)103,764 (2003–2008), average 47 years old8 yearsICD-9 & 10Physical Activity QuestionnaireInactivity (sessions/week)All-cause Dementia:Age, parity, age at menarche, menopausal status/postmenopausal hormone use, tubal ligation, smoking status
  <51.17(0.72, 1.91)
  ≥51

Bowen (2012), a prospective cohort study, U.S.A. (Bowen, 2012)808 (1999–2005), average 71 years oldMedina 5 yearsCognitive Status interviewPhysical Activity QuestionnaireVigorous PAAll-cause Dementia (times/week)Smoking, drinking, body mass index, health condition
  None1.17(0.72, 1.91)
  Vigorous0.75(0.62, 0.92)

Buchman (2012), a prospective cohort study, U.S.A. (Buchman et al., 2012)716 (1997–2005), average 81.6 years old4 yearsStroke Alzheimer's Disease and Related Disorders AssociationActigraphs and daily physical activity questionnaireDaily PA (counts/day)Alzheimer DementiaAge, sex, education
  None1
  Active0.47(0.27, 0.83)

Carlson (2008), a prospective study, U.S.A. (Carlson et al., 2008)147 (1917–2005), over 70 years old15 yearsDSM-III-RPhysical Activity questionnaireTotal PA (times/week)All-cause DementiaAge at date of activity assessment
  None1
  Active0.99(0.73, 1.33)

Chang (2010), a longitudinal population-based study, Europe (Chang et al., 2010)4,945 (1907–2002), 76 years old26 yearsMini-Mental State ExaminationPhysical Activity InterviewSports & exercise (hours/week)All-cause DementiaAge, sex, education
  None1
≤ 50.59(0.40, 0.87)
  >50.74(0.34, 1.62)

de Bruijn (2013), a prospective cohort study, U.S.A. (de Bruijn et al., 2013)4,406 (1997–1999), average 81.8 years old4 yearsMini-Mental State Examination and Geriatric Mental ScheduleZutphen Physical Activity QuestionnaireAll-cause Dementia: PA (hours/week)Age, sex, score on MMSE, low educational level, smoking, APOE carrier status, hypertension, body mass index, diabetes, total cholesterol, HDL-cholesterol
  Low1
  High0.84(0.73, 0.97)
Alzheimer Dementia
  Low1
  High0.89(0.76, 1.03)

Elwood (2013), a prospective cohort study, U.K. (Elwood et al., 2013)2,235 (1979–2004), over 70 years old30 yearsClinical Dementia RatingPhysical activity QuestionnaireRegular exercise (vigorous, miles/day)All-cause DementiaAge, social class
  Non1
  Exercise0.41(0.22, 0.77)

Fabrigoule (1995), a prospective cohort study, France (Fabrigoule et al., 1995)2,040 (1987–1990), at least 65 years old3 yearsMini-Mental State ExaminationPhysical activity interviewAll-cause DementiaSportsAge
  No1
  Yes0.24(0.09, 0.64)
Gardening
  No1
  Yes0.26(0.14, 0.49)

Fenesi (2017), a population-based study, Europe (Fenesi et al., 2017)1,646 (1996–1997), ≥65 years old5 yearsMini-Mental State ExaminationPhysical activity QuestionnaireExercise (times/week)All-cause DementiaAge, years of education
  None1
  Exercise0.77(0.46, 1.31)

Gureje (2011), a prospective cohort study, Nigeria (Gureje et al., 2011)1,408 (2003–2006), 65 years old3 yearsDSM-IVInternational Physical activity questionnaireTotal PA (scoring)All-cause DementiaAge, sex, education
  Vigorous1
  Middle1.00(0.40, 2.70)
  Low1.50(0.50, 4.60)

Heser (2014), a prospective multi-Centre study, German (Heser et al., 2014)1,131 (2003–2008), over 75 years old1.5–3yearsMini-Mental State Examination (MMSE)Physical Activity QuestionnaireLeisure (scoring)All-cause DementiaAge, sex, education, ApoE4, MMSE, Instrumental Activity of daily living (IADL)
  Inactive1
  Active0.62(0.47, 0.80)
Alzheimer Dementia
  Inactive1
  Active0.59(0.43, 0.82)

Hebert (2000), a prospective case-control study, Canada (R. Hebert et al., 2000)8,623 (1991–1996), over 65 years old5 yearsDSM-III-R, NINCDS-ADRDA, ICD-10QuestionnairesRegular exerciseVascular DementiaAge, region
Men
  Inactive1
  Active1.24(0.57, 2.94)
Women
  Inactive1
  Active0.46(0.25, 0.82)

Hessler (2016), a prospective cohort study, German (Hessler et al., 2016)3,547 (2001–2008), over 55 years old2.59 yearsMini-Mental State ExaminationPhysical activity questionnaireVigorous PA (times/week)All-cause DementiaAge, sex, education
  Inactive1.81(1.32, 2.47)
  1–21.38(1.52, 1.81)
  ≥ 31

Karp (2006), a prospective cohort study, Sweden (Karp et al., 2006)776 (1987–1996), 75 years old6 yearsMini-Mental State ExaminationPhysical activity interviewTotal PA (scoring)All-cause DementiaAge, sex, education, baseline MMSE score, comorbidity, physical functioning
  01
  10.55(0.34, 0.89)
  2–30.61(0.38, 0.99)
  ≥ 40.51(0.26, 0.99)
  Higher0.57(0.40, 0.81)

Kishimoto (2016), a longitudinal population-based study, Japan (Kishimoto et al., 2016)803 (1998–2005), over 65 years old17 yearsDiagnostic and Statistical manual of Mental DisordersPhysical activity questionnaireLeisure PA (times/week)All-cause DementiaAge, sex, low education level, systolic blood pressure, antihypertensive agents, diabetes, total cholesterol, body mass index, electrocardiogram abnormalities, history of stroke at entry, smoking habits, alcohol consumption
  Inactive1
  Active0.78(0.60, 1.01)
Alzheimer Dementia
  Inactive1
  Active0.59(0.41, 0.84)
Vascular Dementia
  Inactive1
  Active0.74(0.47, 1.16)
Other Dementia
  Inactive1
  Active1.42(0.79, 2.56)

Larson (2006), a prospective cohort study, U.S.A. (Larson et al., 2006)1,740 (1994–2003), over 85 years old6.2 yearsDSM-IV & NINCD-ADRDAPhysical activity questionnaireRegular exercise (times/week)All-cause DementiaAge, sex
  Inactive1
  Active0.62(0.44, 0.86)
Alzheimer Dementia
  Inactive1
  Active0.64(0.43, 0.96)

Laurin (2001), a prospective cohort study, Canada (Laurin et al., 2001)6,434 (1991–1997), Medians 72 years old11 yearsModified Mini-Mental State ExaminationPhysical activity questionnaireAll-cause Dementia (scoring, times/week)Age, sex, education level
  None1
  Low0.64(0.41, 1.02)
  Moderate0.69(0.51, 0.95)
  High0.63(0.40, 0.98)
Alzheimer Dementia
  None1
  Low0.67 (0.39, 1.14)
  Moderate0.67(0.46, 0.98)
  High0.50(0.28, 0.90)
Vascular Dementia
  None1
  Low0.54(0.20, 1.44)
  Moderate0.70(0.37, 1.31)
  High0.63(0.27, 1.44)

Lee (2015), a observational study, China (Lee et al., 2015)15,589 (1994–2005), 65 years old6 yearsICD-10Physical activity questionnaireLeisure PAAll-cause DementiaAge, gender, other types of exercise, educational level, hypertension, diabetes, heart diseases, visual, hearing impairments, poor mobility, depression
  No1
  Yes0.53(0.34, 0.82)

Lindsay (2002), a prospective cohort study, Canada (Lindsay et al., 2002)6,434 (1991–1997), 0ver 65 years old5 yearsDiagnostic and Statistical Manual of Mental DisordersPhysical activity questionnaireTotal PAAlzheimer DementiaAge, sex, education
  No1
  Yes0.69(0.50, 0.96)

Llamas-Velasco (2015), a prospective study, Spain (Llamas-Velasco et al., 2015)5,278 (1994–1998), 65 years old3 yearsDiagnostic and Statistical Manual of Mental DisordersPhysical activity interviewTotal PA (classifying)DementiaAge, sex, education, alcohol consumption, stroke, hypertension, Charlson Index
  Inactive1
  Low0.53(0.34, 0.82)
  Moderate0.45(0.27, 0.76)
  High0.29(0.16, 0.52)

Luck (2014), a longitudinal study, German (Luck et al., 2014)6,619 (2003–2011), 81.1 years old1.5 yearsMini-Mental State ExaminationPhysical activity interviewTotal PA (times/week)DementiaAge, gender, education, alcohol consumption, smoking, MME score, mental activity, co-morbidity at follow-up
  None1
  Add0.79(0.75, 0.90)
Alzheimer Dementia
  None1
  Add0.81(0.69, 0.94)

Mehlig (2014), a prospective population study, Swedish (Mehlig et al., 2014)1,448 (1974–2002), 38–60 years old5–34 yearDiagnostic and Statistical Manual of Mental disordersPhysical activity questionnaireTotal Leisure time (hours/week)DementiaAge, education, smoking, consumption of alcohol, triglycerides, hypertension, parental history of diabetes
  Active1
  Inactive1.04(0.67, 1.61)
  Obese active0.98(0.51, 1.90)
  Obese inactive3.31(1.43, 7.66)

McCallum (2007), a longitudinal study, Australia (McCallum et al., 2007)1,805 (1988–2002), over 60 years old14 yearsICD-9, ICD-10QuestionnaireAll-cause DementiaGardening (hours/week)Marital status, education, prior history of stroke, activities of daily living
  Rarely1
  Daily0.64(0.50, 0.83)
Walking (hours/week)
  Rarely1
  Daily1.00(0.78, 1.28)

Morgan (2014), a prospective study, U.K. (R. J. Morgan, Jr., 2014)2,959 (1979–2004), 45–59 years old10 yearsCognitive Impairment not Dementia or DementiaPhysical activity questionnaireAll-cause DementiaWork-related (tertiles)Age, social class, national adult reading test score, smoking status, marital status, self-reported history of vascular disease, alcohol consumption, body mass index, common mental disorder, Spielberg's State-Trait Anxiety Index score
  Low1
  Moderate0.70(0.36, 1.39)
  High0.53(0.24, 1.19)
Leisure-time (tertiles)
  Low1
  Moderate0.57(0.28, 1.16)
  High1.16(0.61, 2.19)

Neergaard (2016), a prospective cohort study, Denmark (Neergaard et al., 2016)5,855 (1999–2001), average 70 years oldMean 11.9± 3.9 yearsICD-OD & ADPhysical activity questionnaireTotal PA (times/week)All-cause DementiaAge, education, body mass index, smoking, alcohol, vascular factors, neural disorders
  None1
  10.77(0.61, 0.96)
  20.80(0.61, 1.04)
  3+0.79(0.64, 0.97)
Alzheimer Dementia
  None1
  10.84 (0.58, 1.20)
  20.99(0.66, 1.47)
  3+1.00(0.73, 1.37)
Vascular Dementia
  None1
  10.55(0.24, 1.25)
  20.46(0.16, 1.35)
  3+0.42(0.19, 0.93)
Other Dementia
  None1
  10.79(0.56, 1.04)
  20.72(0.49, 1.05)
  3+0.71(0.53, 0.95)

Podewills (2005), a prospective cohort study, U.S.A. (Podewils et al., 2005)3, 375 (1992 (2000), ≥65 years or older5.4 yearsModified mini-mental state examinationMinnesota Leisure Time Activity QuestionnaireTotal PA (scoring)All-cause DementiaAge, educational level, gender, ethnicity, apolipoprotein E genotype, baseline modified Mini-Mental State Examination Score, magnetic resonance imaging white-matter-grade score, activities of daily living impairment, instrumental activities of daily living impairment, Lubben Social Network Score, Social support score
  0–11
  20.90(0.69,1.18)
  30.90(0.66,1.22)
  ≥ 40.58(0.41, 0.83)
Alzheimer Dementia
  0–11
  20.73(0.49,1.08)
  30.85(0.57,1.29)
  ≥ 40.55(0.34, 0.88)
Vascular Dementia
  0–11
  21.09(0.74,1.60)
  31.01(0.64,1.58)
  ≥ 40.65(0.39, 1.08)

Ravaglia (2008), a prospective population-based cohort, Italian (Ravaglia et al., 2008)749 (1999–2003), over 65 years oldOver 3.9±0.7 yearsDSM-IVPhysical activity questionnaireAll-cause DementiaWalking (Kcal/week)Cardiovascular disease, hypertension, hyperhomocysteinemia
  >2091
  209–4170.67(0.37, 1,09)
  >4170.60(0.33, 1.12)
Moderate (Kcal/week)
  <3,4551
  3,455–6,7490.51(0.28, 0.95)
  >6,7490.86(0.52, 1.42)
Vigorous (Kcal/week)
  No1
  Yes0.64(0.25, 1.62)
Total activity (Kcal/week)
  <4,7741
  4,774–8,0900.63(0.38, 1.05)
  >8,0900.52(0.29, 0.93)
Alzheimer DementiaWalking (Kcal/week)
  >2091
  209–4171.37(0.67, 2,83)
  >4170.60(0.45, 1.66)
Moderate (Kcal/week)
  <3,4551
  3,455–6,7491.53(0.79, 2.96)
  >6,7490.81(0.36, 1.82)
Vigorous (Kcal/week)
  No1
  Yes0.93(0.25, 2.68)
Total activity (Kcal/week)
  <4,7741
  4,774–8,0900.94(0.50,1.77)
  >8,0900.71(0.34, 1.49)
Vascular DementiaWalking (Kcal/week)
  >2091
  209–4170.27(0.12, 0,63)
Moderate (Kcal/week)
  <3,4551
  3,455–6,7490.29(0.12, 0.66)
Vigorous (Kcal/week)
  No1
  Yes0.36(0.05, 2.73)
Total activity (Kcal/week)
  <4,7741
  4,774–8,0900.24(0.11, 0.56)

Rovio (2005), a population-based study, Sweden (Rovio et al., 2005)1,449 (1972–1987), 65–70 years old21 yearsModified mini-mental state examinationPhysical activity questionnaireLeisure-timeAll-cause DementiaAge, sex, education, follow=up time locomotors symptoms, main occupation during life, income leisure time commuting physical activity, ApoE genotype, body mass index, blood pressure, cholesterol, history of myocardial infarction
  Inactive1
  Active0.45(0.24,0.85)
Alzheimer Dementia
  Inactive1
  Active0.34(0.15, 0.74)

Rovio (2007), a population-based study, Sweden (Rovio et al., 2007)1,449 (1972–1987), 65–70 years old21 yearsModified mini-mental state examinationPhysical activity questionnaireOccupational PAAll-cause DementiaAge, sex, education, follow=up time locomotors symptoms, main occupation during life, income leisure time commuting physical activity, ApoE genotype, body mass index, blood pressure, cholesterol, history of myocardial infarction
  None1
  Active1.45(0.66, 3.17)
Alzheimer Dementia
  None1
  Active1.90(0.73, 4.95)

Sabia (2017), Whitehall II prospective cohort study, U.S.A. (Sabia et al., 2017)10,308 (1985–1993), 35–55 years old27 yearsInternational Classification of Diseases (ICD-10)Physical activity questionnaireAll-cause DementiaTotal PA (hours/week)Age, sex, ethnicity, education, occupational position, marital status, smoking status, alcohol consumption, fruits and vegetable consumption, hypertension, diabetes, body mass index, general health questionnaire score, cardiovascular diseases, cardiovascular disease drugs
  ≤ 81
  8–120.97(0.72, 1.29)
  ≥ 121.05(0.82, 1.36)
  ≥ per 10.99(0.98, 1.01)
Mild PA
  <51
  5–91.21(0.98, 1.58)
  ≥ 90.98(0.74, 1.30)
  ≥ per 11.00(0.98, 1.01)
Moderate to vigorous PA
  ≤ 21
  2–41.01(0.76, 1.35)
  ≥ 41.08(0.82, 1.41)
  ≥ per 10.99(0.97, 1.02)
PA recommendation (MVPA)
  <2.51
  ≥ 121.07(0.86, 1.35)

Scarmeas (2009), a prospective cohort study, U.S.A. (Scarmeas, Honig, et al., 2009)1,908 (1992–2006), mean 77.2 years old3.4 yearsDiagnostic and Statistical Manual of Mental DisordersGodin leisure time exercise questionnaireTotal PA (MET)Alzheimer DementiaAge, sex, ethnicity, education, apolipoprotein, caloric intake, body mass index, smoking, depression, leisure activities, comorbidity index, baseline Clinical Dementia Rating score, time between first dietary, first physical activity assessment
  No1
  Some0.59(0.45, 0.78)
  Much0.50(0.39, 0.67)
  Trend (1–3)0.70(0.61, 0.82)

Simons (2006), a prospective cohort study, Australian (Simons et al., 2006)2,805 (1988–2004), 60 years old16 yearsICD-9 & 10Physical activity questionnaireAll-cause Dementia (times/week)GardeningAge, years of education
  None1
  Daily0.56(0.44, 0.71)
Walking
  None1
  Daily0.93(0.74, 1.18)

Soni (2017), a prospective cohort study, U.K. (Soni et al., 2017)11,391 (2002–2013), over 50 years old10 yearsInformant Questionnaire on Cognitive Decline in the ElderlyPhysical activity questionnaireAll-cause Dementia (scoring)Age, gender, education, wealth, cognitive function, physical function, smoking status, alcohol consumption, depression, mood problems, cardiovascular conditions, chronic disease
  Lower1
  Higher0.82(0.72, 0.94)

Sumic (2007), a prospective data, U.S.A. (Sumic et al., 2007)66 (1989–19992), mean age 88.54.7 yearsMini Mental State Examination, Clinical Dementia Rating ScalePhysical activity questionnaireExercise (hours/week)All-cause DementiaAge, education, apolipoprotein allele 4 states, cognitive function
Women
  ≤ 41
  >40.12(0.03, 0.41)
Men
  ≤ 41
  >40.91(0.25, 3.40)

Tomata (2017), a population-based cohort study, Japan (Tomata et al., 2017)6,909 (1994–2006), over 65 years old5.7 yearsLong-term Care Insurance (LTCI)Physical activity interviewAll-cause DementiaWalking (hours/day)Age, sex, body mass index, history of disease, education level, smoking, alcohol drinking, psychological distress score, pain, physical functioning level
  <0.51
  0.5–10.80(0.59, 1.10)
  ≥ 10.72(0.53, 0.97)

Tolppanen (2015), population-based random sample stud, Finland (Tolppanen et al., 2015)1,560 (1972 (2000), average 78.8 years old24.4 yearsNational Hospital Discharge Register, Special Reimbursement Register, Causes of Death RegisterPhysical activity surveyAlzheimer DementiaLeisure-time PA(weekly MET-hours)Age, living area, education family income, body mass index, tobacco smoking, alcohol dirking, parity, duration of lactation, oral contraceptive and HRT use, previous hysterectomy, menstrual periods and reason for amenorrhea, smoking and energy from diet
  High1
  Moderate1.45(1.06, 1.97)
  Low1.39(0.99, 1.95)
Strenuous sports (hours/week)
  Low(0)1
  Medium (<2)1.02(0.92, 3.60)
  High (≥2)0.33(0.14, 0.75)
Vigorous work (hours/week)
  Low (0)1
  Medium (≤20)0.88(0.53, 1.46)
  High (>20)0.73(0.41, 1.31)
Moderate activity (hours/week)
  Low (≤0)1
  Medium (11–30)0.65(0.35, 1.20)
  High (≥31)0.42(0.22, 0.81)
Activity-induced sweating
  Low (0)1
  Medium (1–2)0.59(0.31, 1.12)
  High (≥3)0.57(0.37, 0.84)

Verdelho (2012), a prospective cohort study, Europe (Verdelho et al., 2012)638 (1985–1992), 74.1 years3 yearsMini-Mental State ExaminationInterview physical activityTotal PA (hours/week)All-cause DementiaAge, education, white matter change severity, medial temporal atrophy, previous and incident stroke, diabetes
  Inactive1
  Active0.61(0.04, 0.38)
Alzheimer Dementia
  <101
  10–<301.93(0.82, 0.50)
Vascular dementia
  Never1
  <10.42(0.22, 0.80)

Verghese (2003), a prospective cohort study, U.S.A. (Verghese et al., 2003)469 (1983–1989), older than 75 years of age5.1 yearsDiagnostic and Statistical Manual of Mental DisordersPhysical activityLeisure PA score (points)All-cause DementiaAge, sex, educational level, presence or absence of chronic medical lionesses
  <91
  9–161.06(0.67, 1.65)
  >160.92(0.58, 1.45)

Wang (2002), a longitudinal population-based study, Sweden (W. Wang, Xie, Wan, & Wang, 2002)1,473 (1987–1996), over 75 years old6.4 yearsMini-Mental State ExaminationPhysical activity interviewAll-cause DementiaTotal PA (times/week)Age, sex, education, baseline Mini-Mental State Examination Score, comorbidity, depressive symptoms, physical functioning
  No1
  <70.97(0.42, 2.22)
  ≥ 70.41(0.13, 1.31)
Recreational PA
  No1
  <71.06(0.42, 2.45)
  ≥ 70.95(0.55, 1.63)

Yoshitake (1995), a prospective cohort study, Japan (Yoshitake et al., 1995)828 (1985–1992), over 65 years old7 yearsNINDS-AIREN & NINCD-ADRDAA standard questionnaireTotal PA (scoring)Vascular DementiaAge
  Inactive1
  Active0.81(0.42, 1.57)
Alzheimer Dementia
  <101
  10–<300.18(0.06, 0.61)

Zhou (2017), China, a nationwide longitudinal study, China (Y. L. Zhou, Liu, Yuan, & Lu, 2017)7,501 (2002–2012), over 65 years old9 yearsQuestionnairePhysical activity questionnaireExerciseAll-cause DementiaDemographic characteristics, lifestyle variables, health status variables
  Yes1
  No0.53(0.33, 0.85)
Authors

Dr. Lee is Assistant Professor, Sports Medicine and Science, KyungHee University, Gyeonggi-do, Republic of Korea.

The author has disclosed no potential conflicts of interest, financial or otherwise. The author thanks Dr. John Brobst for comments on a previous draft of this manuscript.

Address correspondence to Junga Lee, PhD, Assistant Professor, Sports Medicine and Science, KyungHee University, 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104, Republic of Korea; e-mail: junga613@gmail.com.

Received: January 05, 2018
Accepted: June 28, 2018

10.3928/00989134-20180814-01

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