Introduction

Dementia is a leading cause of dependence and disability worldwide ¹1. Nichols E, Szoeke CEI, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. Global, regional, and national burden of Alzheimer's disease and other dementias, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet Neurol 2019; 18:88-106.^,22. World Health Organization. Global action plan on the public health response to dementia 2017-2025. https://www.who.int/publications/i/item/global-action-plan-on-the-public-health-response-to-dementia-2017---2025 (accessed on 09/Jun/2024).
https://www.who.int/publications/i/item/... ^,33. World Health Organization. Dementia: a public health. priority. https://apps.who.int/iris/handle/10665/75263 (accessed on 09/Jun/2024).
https://apps.who.int/iris/handle/10665/7... . The number of dementia cases worldwide is projected to increase from 57.4 million in 2019 to 152.8 million by 2050, with a new case of dementia being diagnosed every three seconds ⁴4. Global Burden of Diseases. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health 2022; 7:e105-25.^,55. Wortmann M. Dementia: a global health priority-highlights from an ADI and World Health Organization report. Alzheimers Res Ther 2012; 4:40.. In the last four decades, a great and continuous effort has led to the discovery of different pharmacological treatments to attenuate the symptoms and slow disease progression. For example, aducanumab and lecanemab are monoclonal antibodies directed against aggregated amyloid beta approved by the FDA (U.S. Food and Drug Administration), with findings indicating a reduction in amyloid-beta accumulation and slower cognitive decline through follow-up ⁶6. Budd Haeberlein S, Aisen PS, Barkhof F, Chalkias S, Chen T, Cohen S, et al. Two randomized phase 3 studies of aducanumab in early Alzheimer's disease. J Prev Alzheimers Dis 2022; 9:197-210.^,77. van Dyck CH, Swanson CJ, Aisen P, Bateman RJ, Chen C, Gee M, et al. Lecanemab in early Alzheimer's disease. N Engl J Med 2022; 388:9-21.. However, these treatments are largely unavailable at the population level due to their high estimated annual cost ⁸8. Sinha P, Barocas JA. Cost-effectiveness of aducanumab to prevent Alzheimer's disease progression at current list price. Alzheimers Dementia (N Y) 2022; 8:e12256..

A robust body of literature has established an association between physical activity and reduced risk of cognitive decline and dementia ⁹9. López-Ortiz S, Lista S, Valenzuela PL, Pinto-Fraga J, Carmona R, Caraci F, et al. Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses. J Neurol 2023; 270:711-25.^,1010. Blondell SJ, Hammersley-Mather R, Veerman JL. Does physical activity prevent cognitive decline and dementia? A systematic review and meta-analysis of longitudinal studies. BMC Public Health 2014; 14:510.^,1111. Guure CB, Ibrahim NA, Adam MB, Said SM. Impact of physical activity on cognitive decline, dementia, and its subtypes: meta-analysis of prospective studies. Biomed Res Int 2017; 2017:9016924.^,1212. Yin S, Nie H, Xu Y. Physical activity and dementia: a meta-analysis of prospective studies. J Chem Pharm Res 2013; 5:235-9.^,1313. Lee J. The relationship between physical activity and dementia: a systematic review and meta-analysis of prospective cohort studies. J Gerontol Nurs 2018; 44:22-9.^,1414. Xu W, Wang HF, Wan Y, Tan C-C, Yu J-T, Tan L. Leisure time physical activity and dementia risk: a dose-response meta-analysis of prospective studies. BMJ Open 2017; 7:e014706.^,1515. Iso-Markku P, Kujala UM, Knittle K, Polet J, Vuoksimaa E, Waller K. Physical activity as a protective factor for dementia and Alzheimer's disease: systematic review, meta-analysis and quality assessment of cohort and case-control studies. Br J Sports Med 2022; 56:701-9.. Consequently, governmental and nongovernmental organizations have advocated the role of physical activity in mitigating the risk of dementia ¹⁶16. Chen Y, Hou L, Li Y, Lou Y, Li W, Struble LM, et al. Barriers and motivators to promotion of physical activity participation for older adults with mild cognitive impairment or dementia: an umbrella review. Int J Nurs Stud 2023; 143:104493.. For example, the World Health Organization’s (WHO) global action plan on dementia ²2. World Health Organization. Global action plan on the public health response to dementia 2017-2025. https://www.who.int/publications/i/item/global-action-plan-on-the-public-health-response-to-dementia-2017---2025 (accessed on 09/Jun/2024).
https://www.who.int/publications/i/item/... recommends a minimum of 150 minutes of physical activity per week to prevent dementia. Similarly, national dementia plans, which are designed to reduce the current and projected burden of dementia in each country, endorse the role of physical activity as an essential preventive strategy. However, few studies have addressed the extent to which physical activity is recommended as a complementary treatment for dementia.

Exercise as a prescription for people with dementia

Physical activity is a safe and effective nonpharmacological strategy to preserve cognition and functionality in people with intact cognitive function, mild cognitive impairment, and dementia ⁹9. López-Ortiz S, Lista S, Valenzuela PL, Pinto-Fraga J, Carmona R, Caraci F, et al. Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses. J Neurol 2023; 270:711-25.^,1717. Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci 2008; 9:58-65.^,1818. Erickson KI, Hillman C, Stillman CM, Ballard RM, Bloodgood B, Conroy DE, et al. Physical activity, cognition, and brain outcomes: a review of the 2018 physical activity guidelines. Med Sci Sports Exerc 2019; 51:1242-51.. In a rapid search on PubMed combining dementia, physical activity or exercise, and meta-analysis keywords, a total of 278 records were identified in November 2023. By searching only meta-analysis with randomized controlled trials (RCTs) employing physical activity protocols in people with dementia, 12 studies were found ¹⁹19. Livingston G, Kelly L, Lewis-Holmes E, Baio G, Morris S, Patel N, et al. A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia. Health Technol Assess 2014; 18:1.^,2020. Zhang S, Zhen K, Su Q, Chen Y, Lv Y, Yu L. The effect of aerobic exercise on cognitive function in people with Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials. Int J Environ Res Public Health 2022; 19:15700.^,2121. Karamacoska D, Butt A, Leung IHK, Childs RL, Metri NJ, Uruthiran V, et al. Brain function effects of exercise interventions for cognitive decline: a systematic review and meta-analysis. Front Neurosci 2023; 17:1127065.^,2222. Sun Y, Ji M, Leng M, Li X, Zhang X, Wang Z. Comparative efficacy of 11 non-pharmacological interventions on depression, anxiety, quality of life, and caregiver burden for informal caregivers of people with dementia: a systematic review and network meta-analysis. Int J Nurs Stud 2022; 129:104204.^,2323. Santiago JA, Potashkin JA. Physical activity and lifestyle modifications in the treatment of neurodegenerative diseases. Front Aging Neurosci 2023; 15:1185671.^,2424. Luo G, Zhang J, Song Z, Wang Y, Wang X, Qu H, et al. Effectiveness of non-pharmacological therapies on cognitive function in patients with dementia - a network meta-analysis of randomized controlled trials. Front Aging Neurosci 2023; 15:1131744.^,2525. Kouloutbani K, Venetsanou F, Karteroliotis KE, Politis A. Physical exercise as a nonpharmacological intervention for the treatment of neuropsychiatric symptoms in persons with dementia: a meta-analysis of randomized controlled trials. Alzheimer Dis Assoc Disord 2023; 37:73-81.^,2626. Huang X, Zhao X, Li B, Cai Y, Zhang S, Wan Q, et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis. J Sport Health Sci 2022; 11:212-23.^,2727. Ding Z, Leung PY, Lee T-L, Chan AS. Effectiveness of lifestyle medicine on cognitive functions in mild cognitive impairments and dementia: a systematic review on randomized controlled trials. Ageing Res Rev 2023; 86:101886.^,2828. Zeng Y, Wang J, Cai X, Zhang X, Zhang J, Peng M, et al. Effects of physical activity interventions on executive function in older adults with dementia: a meta-analysis of randomized controlled trials. Geriatr Nurs (Minneap) 2023; 51:369-77.^,2929. Yan J, Li X, Guo X, Lin Y, Wang S, Cao Y, et al. Effect of multicomponent exercise on cognition, physical function and activities of daily life in older adults with dementia or mild cognitive impairment: a systematic review and meta-analysis. Arch Phys Med Rehabil 2023; 104:2092-108.^,3030. de Almeida SIL, Gomes da Silva M, Marques ASPD. Home-based physical activity programs for people with dementia: systematic review and meta-analysis. Gerontologist 2020; 60:e600-8.. Also, three umbrella reviews of meta-analyses revealed that exercise could improve cognitive function in people with dementia ⁹9. López-Ortiz S, Lista S, Valenzuela PL, Pinto-Fraga J, Carmona R, Caraci F, et al. Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses. J Neurol 2023; 270:711-25.^,3131. Andrade A, Siqueira TC, D'Oliveira A, Dominski FH. Effects of exercise in the treatment of Alzheimer's disease: an umbrella review of systematic reviews and meta-analyses. J Aging Phys Act 2021; 30:535-51.^,3232. Demurtas J, Schoene D, Torbahn G, Marengoni A, Grande G, Zou L, et al. Physical activity and exercise in mild cognitive impairment and dementia: an umbrella review of intervention and observational studies. J Am Med Dir Assoc 2020; 21:1415-22.e6., with an effect size (ES) similar to that found by pharmacological studies (physical activity: standardized mean differences - SMD = 0.41, 95% confidence interval - 95%CI: 0.24-0.58; pharmacological studies: SMD ≤ 0.51, 95%CI: 0.35-0.67) ⁹9. López-Ortiz S, Lista S, Valenzuela PL, Pinto-Fraga J, Carmona R, Caraci F, et al. Effects of physical activity and exercise interventions on Alzheimer's disease: an umbrella review of existing meta-analyses. J Neurol 2023; 270:711-25.^,3333. Dou KX, Tan MS, Tan CC, Cao XP, Hou XH, Guo QH, et al. Comparative safety and effectiveness of cholinesterase inhibitors and memantine for Alzheimer's disease: a network meta-analysis of 41 randomized controlled trials. Alzheimers Res Ther 2018; 10:126.. The umbrella reviews acknowledged some limitations in the current evidence restricting our knowledge of the most effective exercise characteristics to improve physical and mental symptoms in people with dementia. However, there is sufficient evidence to state that older adults with dementia benefit from physical activity ²⁸28. Zeng Y, Wang J, Cai X, Zhang X, Zhang J, Peng M, et al. Effects of physical activity interventions on executive function in older adults with dementia: a meta-analysis of randomized controlled trials. Geriatr Nurs (Minneap) 2023; 51:369-77..

A network meta-analysis showed that aerobic, resistance, and mind-body exercises could improve cognitive function in people with mild cognitive impairment and dementia ²⁶26. Huang X, Zhao X, Li B, Cai Y, Zhang S, Wan Q, et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis. J Sport Health Sci 2022; 11:212-23.. The authors also showed that resistance training was the most effective intervention for people with dementia compared to aerobic, multicomponent, and mind-body exercises ²⁶26. Huang X, Zhao X, Li B, Cai Y, Zhang S, Wan Q, et al. Comparative efficacy of various exercise interventions on cognitive function in patients with mild cognitive impairment or dementia: a systematic review and network meta-analysis. J Sport Health Sci 2022; 11:212-23.. Moreover, another meta-analysis showed that home-based physical exercise could improve cognitive function (ES = 0.71; 95%CI: 0.43-0.99) and functional capacity (ES = 2.24; 95%CI: 1.80-2.68) and reduce neuropsychiatric symptoms (ES = 0.37; 95%CI: 0.17-0.57) and caregivers’ burden (ES = 0.63; 95%CI: 0.32-0.94) ³⁰30. de Almeida SIL, Gomes da Silva M, Marques ASPD. Home-based physical activity programs for people with dementia: systematic review and meta-analysis. Gerontologist 2020; 60:e600-8.. Finally, a systematic review with meta-analysis showed that aerobic (SMD = 0.24) and resistance (SMD = 0.18) training could improve physical function in older adults in residential care ³⁴34. Valenzuela PL, Saco-Ledo G, Morales JS, Gallardo-Gómez D, Morales-Palomo F, López-Ortiz S, et al. Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials. Lancet Healthy Longev 2023; 4:e247-56.. Moreover, a moderate-to-high effect was observed in studies including older adults with cognitive impairment (SMD = 0.44), with dependence in activities of daily living (SMD = 0.40), and in older adults with pre-frailty or frailty (SMD = 0.65) ³⁴34. Valenzuela PL, Saco-Ledo G, Morales JS, Gallardo-Gómez D, Morales-Palomo F, López-Ortiz S, et al. Effects of physical exercise on physical function in older adults in residential care: a systematic review and network meta-analysis of randomised controlled trials. Lancet Healthy Longev 2023; 4:e247-56..

Although evidence supports the benefits of exercise for people with dementia, it is essential to acknowledge specific gaps in our understanding. For example, the significant heterogeneity observed in meta-analyses concerning exercise interventions and sample characteristics limits our knowledge regarding the most effective exercise program in intensity, frequency, and type. A recent meta-analysis suggested two to three weekly sessions of multi-component and aerobic training, each session lasting 60 minutes, to improve cognitive and physical capacity in people with dementia ³⁵35. Li Z, Guo H, Liu X. What exercise strategies are best for people with cognitive impairment and dementia? A systematic review and meta-analysis. Arch Gerontol Geriatr 2024; 124:105450..

Additionally, most RCTs have been conducted in high-income countries, requiring further studies in cognitively diverse populations to better comprehend the impact of exercise on cognitive function. Given the heterogeneity of disease stages observed across meta-analyses on exercise in people with dementia, exploring the effects of exercise for each stage of the disease may enhance our understanding.

Considering the evidence, governments are expected to promote physical activity as a complementary therapy for people with dementia via public health initiatives, including a national plan to combat dementia. Instead of generic recommendations, national plans to combat dementia can address dementia-related issues, respecting each country’s culture and sociodemographic characteristics.

We reviewed national plans to combat dementia worldwide to identify the presence of initiatives to promote physical activity for people with dementia. After retrieving the national plans, we systematically searched for any mention of physical activity as a nonpharmacological and complementary therapy for people with dementia. To keep focus on national plans that promote physical activity for people with dementia, we did not include documents in which physical activity was only mentioned as a preventive strategy. For national plans published in languages other than English, Spanish, or Portuguese, online tools were used to identify the most appropriate terms for physical activity, exercise, and walking.

From 194 countries, we identified 35 (18%) with national dementia plans: 20 (57.1%) in Europe, 10 (28.6%) in Asia, three (8.6%) in North America, and two (5.7%) in South America and the Caribbean (Figure 1). Only the following eight (22.9%) countries, all high-income countries, recommended physical activity for people with dementia: Chile, Denmark, France, Luxembourg, Norway, Singapore, Sweden, and the United States. For example, the Chilean plan reinforces the pivotal role of physical activity in preventing and managing disease ³⁶36. Ministerio de Salud. Plan Nacional de Demencia. https://www.minsal.cl/wp-content/uploads/2017/11/PLAN-DE-DEMENCIA.pdf (accessed on 25/Jun/2023).
https://www.minsal.cl/wp-content/uploads... . The Norwegian document ³⁷37. Norwegian Ministry of Health and Care Services. Dementia Plan 2025. https://www.regjeringen.no/contentassets/b3ab825ce67f4d73bd24010e1fc05260/dementia-plan-2025.pdf (accessed on 25/Jun/2023).
https://www.regjeringen.no/contentassets... also highlights the importance of good architecture and planning to stimulate physical activity. Also, starting in January 2020, cities should offer activities for people with dementia living at home, including physical activity, as part of an inclusion strategy that contributes to mastery, meaningfulness, and good experience for these individuals ³⁷37. Norwegian Ministry of Health and Care Services. Dementia Plan 2025. https://www.regjeringen.no/contentassets/b3ab825ce67f4d73bd24010e1fc05260/dementia-plan-2025.pdf (accessed on 25/Jun/2023).
https://www.regjeringen.no/contentassets... . The Singaporean dementia plan promoted the Peer-to-Peer Support Group, where Zoom videoconferences with music, social engagement, health education, and exercise were offered to minimize the harmful consequences of social distancing restrictions on health ³⁸38. Dementia Colabs. Towards a dementia-inclusive Singapore. https://www.aic.sg/resources/Documents/Brochures/Mental%20Health/Dementia%20Colabs%20Report.pdf (accessed on 26/Jun/2023).
https://www.aic.sg/resources/Documents/B... .

Generally, the literature indicates that physical activity is a safe and effective complementary therapy for people living with dementia. In contrast, only 35 high-income countries designed national dementia plans that recommend physical activity for this population. This finding mirrors the small number of RCTs with physical activity in people with dementia in low- and middle-income countries and those with varying cognitive reserves. We do not intend to imply that exercise or any form of physical activity can replace traditional and innovative therapeutic methods for dementia. Instead, we emphasize the importance of promoting physical activity for this population. Older individuals with mild cognitive impairment and dementia often bear multiple comorbidities, such as cardiovascular disease and diabetes. Therefore, prescribing physical activity as a therapeutic intervention can target various therapeutic goals while minimizing side effects, and it can be tailored to individual preferences, akin to pharmacotherapy.

Acknowledgments

N. Feter is supported by the Brazilian National Research Council (CNPq). J. Feter is supported by the Brazilian Coordination for the Improvement of Higher Education Personnel (CAPES). A. J. Rombaldi is supported by the CNPq (grant n. 307147/2022-3).

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