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Exercise and dementia prevention
  1. Jane Alty,
  2. Maree Farrow,
  3. Katherine Lawler
  1. Wicking Dementia Research and Education Centre, College of Health and Medicine, University of Tasmania, Hobart, Tasmania, Australia
  1. Correspondence to Dr Jane Alty, Wicking Dementia Research and Education Centre, University of Tasmania, Hobart, Tasmania 7000, Australia; jane.alty{at}utas.edu.au

Abstract

Ageing, genetic, medical and lifestyle factors contribute to the risk of Alzheimer’s disease and other dementias. Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, smoking and hypertension. With the rising prevalence and lack of neuroprotective drugs, there is renewed focus on dementia prevention strategies across the lifespan. Neurologists encounter many people with risk factors for dementia and are frequently asked whether lifestyle changes may help. Exercise has emerged as a key intervention for influencing cognition positively, including reducing the risk of age-related cognitive decline and dementia. This article focuses on the current evidence for physical inactivity as a modifiable dementia risk factor and aims to support neurologists when discussing risk reduction.

  • dementia
  • risk reduction
  • Alzheimer’s
  • exercise
  • physical activity

https://doi.org/10.1136/practneurol-2019-002335

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    Introduction

    ‘Dementia is the greatest global challenge for health and social care in the 21 st century’ Lancet Commission 2017.1

    An estimated 50 million people worldwide are living with dementia at great personal and societal costs, and 10 million people develop dementia every year. The worldwide prevalence is expected to triple to 152 million in the next 30 years, driven by rising numbers of older adults.2 3 Alzheimer’s disease and vascular dementia account for 80% of cases.2 The biggest risk factor for cognitive decline is ageing, with 90%–98% of people with dementia being aged over 65 years.4 5 Approximately 10% of adults aged over 65 years have dementia and a further 20% have mild cognitive impairment.2 5

    12 324 52 5

    With the rising prevalence and lack of neuroprotective drugs, there is renewed focus on strategies that prevent or delay the onset of dementia. Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, smoking, hypertension and obesity (figure 1). The cognitive symptoms of dementia pathology manifest late, after many years of neurodegeneration, so a lifelong approach to risk reduction is recommended. Any delay in clinical manifestations would reduce dementia prevalence at the population level and may delay symptom onset and functional decline in the individual. Two important recent publications have summarised the current evidence for modifiable dementia risk factors—the 2019 WHO guidelines on risk reduction of cognitive decline and dementia4 and the 2017 Lancet Commission.1 Dementia risk information is not yet well known: half of adults cannot identify any modifiable dementia risk factors, a fifth assume dementia is inevitable with ageing,6 and clinicians also report a lack of knowledge about dementia risk factors.7

    Figure 1
    Figure 1

    Life-course model of contribution of modifiable risk factors to dementia. Numbers are rounded to nearest integer. Figure shows potentially modifiable and non-modifiable risk factors (figure and legend are reproduced from The Lancet with permission)1

    Physical inactivity is a central modifiable dementia risk factor. There is good evidence that increased levels of exercise and general physical activity in cognitively healthy adults are associated with reduced risk of dementia, and some, although weaker, evidence that it may potentially slow down cognitive impairment once mild cognitive impairment and dementia are established.1 8 9 This article briefly outlines the modifiable risk factors for dementia and then focuses specifically on current evidence for exercise and dementia.

    Relevance for neurologists

    As neurologists, we are ideally placed to discuss dementia risk reduction with our patients and their families, and it is not uncommon to be asked about modifying lifestyle factors (boxes 1 and 2). Regarding primary prevention, we consult with many young, middle-aged and older people who present with unrelated neurological symptoms and are cognitively healthy but happen to have multiple risk factors for dementia, such as inactivity, smoking, diabetes or depression. A brief discussion about managing these risk factors proactively (just as we regularly do for stroke and cardiovascular risk) and an onward referral if necessary, has the potential to reduce dementia rates in future decades. Targeted secondary or tertiary prevention strategies are also relevant to our patients with mild cognitive impairment or dementia, to help slow disease progression and maintain quality of life.

    Box 1

    Case study

    Mr B, 70-years old, attended the neurology clinic with his wife, Mrs B, who is 65-years old. He was recently diagnosed with Alzheimer’s disease; she is healthy with no comorbidities. Their general practitioner 'prescribed parkrun’* for them both but Mrs B asked for the neurologist’s opinion on whether this could slow down the progression of Mr B’s dementia.

    Key points in the neurologist’s response:

    • There is evidence that regular exercise can reduce the risk of dementia (for Mrs B) but the evidence about exercise slowing the progression of established dementia is unclear.

    • Physical activity such as walking has benefits for everyone, including better mood, cardiovascular health and metabolic health.

    • Getting started with exercise can often be difficult—doing something like parkrun can be a fun, social way to improve health.

    • More specific exercises can lead to improvements in strength, balance, mobility and endurance for a person with dementia45—and physiotherapy input may help.

    • *parkrun is a global organisation (mentioned in the WHO global action plan to promote physical activity 2018–2030) supporting free, weekly events in a local park where participants walk, jog or run for 5 km, or volunteer. For more information see parkrun.com.

    Box 2

    Primary prevention discussion

    Mr C, 35-years old, attended the neurology clinic with altered sensation in his hand and was diagnosed with carpal tunnel syndrome. During the consultation, the neurologist noted incidentally that he was a smoker and had depression and poorly controlled diabetes.

    The neurologist took the opportunity to briefly discuss reducing Mr C’s risk for developing heart disease, stroke and dementia in the future (ie, primary prevention). She advised that he stopped smoking, aimed for at least 10 min of physical activity twice a day (see figure 2) and made a general practitioner appointment to discuss management of his depression and diabetes. He then mentioned that his mother and grandfather both died from Alzheimer’s disease so he had assumed ‘it was inevitable’ he would get dementia when he was older. The neurologist explained that research has shown that there is a reduced risk of developing dementia in people who have a healthy lifestyle, even in groups of people with a higher genetic risk.15 He thanked her as he left the consultation saying that he felt ‘more empowered’ to change his lifestyle.

    Figure 2
    Figure 2

    Infographic summarising physical activity and dementia prevention, based on WHO 2019 guidelines (4)

    However, in busy neurology clinics and ward rounds, when there may not always be the time to have these discussions, it is important at least to signpost the patient to their general practitioner for further risk management. ‘Preventative neurology’ is an emerging concept, and looking to the future, it may be that dedicated dementia prevention interdisciplinary clinics, attended by physiotherapists, specialist nurses and physicians, take on this role. Research suggests that such clinics (similar to those already held for stroke and coronary heart disease) can successfully provide multidomain interventions that improve cognition and reduce dementia risk.10

    Modifiable dementia risk factors

    An estimated one-third of dementia cases worldwide can be attributed to modifiable risk factors. Figure 1 outlines the main dementia risk factors; it also shows the similarities with cardiovascular and cerebrovascular disease risk factors. Although ageing is the biggest risk, with an exponential rise in dementia incidence after the age of 65 years,5 11 dementia is not an inevitable part of ageing. There is good evidence that older adults who are physically active, do not smoke, drink alcohol only in moderation and eat a healthy diet have a lower risk of dementia.8 12–14 Importantly, there is evidence that genetic risks of dementia may also be offset: a study of almost 200 000 UK Biobank participants found that a healthy lifestyle was associated with reduced dementia incidence in all groups, including a 32% reduction in those with the highest genetic risk.15

    These are exciting results as it means that people can take a proactive approach to reduce their risk of dementia. The Lancet Commission (figure 1) emphasised the importance of a lifelong approach to dementia risk reduction, from childhood (increasing access and duration of education) through to older age (keeping physically and cognitively active). In particular, the authors emphasised the importance of mid-life interventions, as this is the period that most likely precedes the earliest stages of neurodegeneration. There is encouraging epidemiological evidence that risk reduction strategies are beginning to work—there has been an unexpected decline in age-specific dementia incidence in several countries including USA, UK, Netherlands and Canada.16–18 One explanation is that several decades of national cardiovascular risk management programmes have reduced the overlapping dementia risk factors too.

    A word about terminology: physical activity or exercise?

    Although most people tend to refer to ‘exercise’, there is a distinction in the medical literature with ‘physical activity’. We take a brief diversion to clarify these terms. Physical activity is defined as ‘the movement of skeletal muscles resulting in energy expenditure exceeding the resting state’, whereas exercise is ‘physical activity that is planned, structured and repetitive’.19 Therefore, exercise is a subtype of physical activity, but physical activity also includes everyday activities such as washing the car, carrying shopping and vacuuming. This means that recommending increased daily activities may reduce barriers for those people who wish to increase their physical activity levels but do not want to engage in exercise. Retrospective or longitudinal studies in dementia research tend to have a focus on physical activity whereas prospective studies with planned, structured protocols often investigate the role of exercise.

    ‘Two a day’ of moderate physical activity

    The WHO’s global recommendations on physical activity for adults is at least 150 min of moderate aerobic activity per week or at least 75 min of more vigorous activity.4 This may be more memorable if considered as roughly ‘two a day’ bursts of at least 10 min of moderate physical activity.20 Figure 2 gives some examples of ‘moderate’ activity—both in the forms of exercise and daily tasks. ‘Some is good, more is better’ was emphasised in the 2019 UK Chief Medical Officers’ Physical Activity Guidelines—highlighting that while specific targets may help some people aiming for a behavioural goal, ‘there is no minimum amount of physical activity required to achieve some health benefits’.21 The WHO also recommends muscle strengthening activities at least twice a week and, for older adults, activities to improve balance and reduce falls. We recommend giving specific examples of activities to patients, trying to tailor these to their mobility, neurological impairment, and their hobbies and interests, thereby incorporating personalised medicine and 'social prescribing' principles. When people cannot do the recommended amounts of physical activity due to health conditions, they should be as physically active as their abilities and conditions allow.4 21

    ‘Social prescribing’ has not been widely implemented in clinical practice and so there is little information available from the patient’s perspective. However, early research suggests that it is generally well received, with patients perceiving this as an opportunity to take back some control over their health. Factors associated with long-term behavioural change include prescribing an individualised intervention, and aiming for steady improvements rather than sudden changes.22

    Summary of the evidence

    There is strong evidence from large observational prospective studies with long follow-up periods, and meta-analyses of these studies, that physically active adults with normal cognition are less likely to develop cognitive decline or dementia, when compared with inactive people.23–25 The highest levels of exercise seem to be the most protective.23 24 For example, a meta-analysis of 16 studies with almost 164 000 participants reported a relative risk of 0.72 (95% CI 0.6 to 0.86) for all type dementia in the groups with highest levels of physical activity.24 The relative risk for developing specifically Alzheimer’s was even lower at 0.55 (95% CI 0.36 to 0.84). Similarly, another large meta-analysis of 15 prospective cohort studies comprising over 33 000 people found a hazard ratio of 0.62 (95% CI 0.54 to 0.7).23

    Individual randomised controlled trials evaluating the effects of exercise on cognition have reported less consistent results than the longitudinal studies—some have reported no improvement, and others have shown small improvements in limited cognitive domains. However, increasing sample size by meta-analyses of the pooled results has provided some supportive evidence that exercise reduces the risk of cognitive decline in healthy adults, and mixed evidence that physical activity may improve cognition in people already diagnosed with mild cognitive impairment or dementia.

    Evidence appears to be stronger for aerobic exercise but there is also some supportive evidence for resistance training and other forms of exercise. For example, a large meta-analysis of 36 studies comprising more than 2000 adults aged over 50 years, found that aerobic exercise, tai chi and resistance training improved cognition regardless of the participant’s cognitive status.26 A meta-analysis of 18 randomised controlled trials comprising 802 people with dementia found that physical activity interventions were associated with improvements on cognitive scores, with an overall standardised mean difference of 0.42 (95% CI 0.23 to 0.62) and greatest benefits for interventions including aerobic exercise.27 Regarding those with mild cognitive impairment, a meta-analysis of seven studies with 635 participants found a consistent beneficial effect of aerobic exercise, resistance training or multimodal exercise on global cognition with standard mean difference 0.3 (95% CI 0.1 to 0.49).28 These findings are not entirely consistent though and another meta-analysis of almost 3000 older adults from five randomised controlled trials found no significant effects of long term exercise for reducing the risk of dementia or mild cognitive impairment.29

    Potential mechanisms

    Exercise is postulated to have a neuroprotective effect through several mechanisms. First, there is evidence it can ‘buffer’ the gradual loss of neurones and synapses associated with ageing. Cognitive ageing manifests in most adults from the age of about 50 years, with subtle changes in memory and executive function, but rates of decline differ: some adults remain cognitively high functioning until advanced old age and others decline more rapidly with increased risk of dementia.30 It is important to note that cognitive trajectories are not always matched by pathology, and some cognitively healthy adults have dementia pathologies found at post-mortem, demonstrating that the brain, even when aged and/or with pathology, may compensate.31

    Exercise may strengthen compensatory mechanisms. For example, animal studies, such as those comparing rodents in empty cages to those with a running wheel, have consistently found that exercise is associated with increased neurogenesis, synaptic connections and capillary growth, and improved memory and learning.32 33 35 34 Human studies have shown that higher levels of exercise in mid-life are associated with greater preservation of cortical grey matter in older age.36 Even in those adults carrying the APOE e4 gene (and therefore at higher risk of developing dementia) there are lower levels of beta-amyloid, less reduction in hippocampal volume and less decline in cognitive functions in the physically active adults.37 Other potential mechanisms include promoting release of brain-derived neurotrophic factor; reducing oxidative stress, cortisol and other inflammatory processes; and modifying insulin and glucose signalling.32 38 39

    Physical activity has additional indirect mechanisms on brain health through reducing vascular disease risk (improving diabetes, hypertension, hypercholesterolaemia and obesity) as well as reducing depression, sleep disturbance and social isolation. The question of whether inactivity is an independent risk factor, or merely acting via overall vascular risk, was investigated recently in the Harvard Ageing Brain cohort. Physical activity, measured using a pedometer in 182 cognitively healthy older adults over roughly 6 years, was compared with serial cognitive assessments and amyloid and structural imaging. Higher levels of physical activity attenuated the association between beta-amyloid burden and cognitive decline and neurodegeneration, independently of the effects of vascular risk; this points towards physical activity having a separate protective effect, on top of indirect vascular disease risk reduction in delaying the manifestations of Alzheimer’s disease.40

    Never too little or too late

    Although it is optimal to take a lifelong approach to dementia risk reduction, there is emerging evidence that even the oldest brains, or those with dementia, may still benefit from physical activity. Even small increases in physical activity have benefits on brain structure and cognition and ‘there are no absolute thresholds’21—for example, a randomised controlled trial of walking for 40 min three times a week (compared with stretching exercises alone) showed increased hippocampal size and memory function in healthy adults aged 55–80 years.41 Physical activity leads to other benefits in people with and without dementia, including improved balance, reduced falls, improved mood and increased survival.42 43 For example, a longitudinal study of over 12 000 older men found that 150 min of vigorous physical activity per week was associated with a lower hazard ratio (0.74; 95% CI 0.68 to 0.81) of death over the 12-year follow-up period.44

    What we do not know

    Although meta-analyses have generally reported the highest levels of exercise were associated with the lowest risk of cognitive decline,23 heterogeneity between studies makes it difficult to draw firm conclusions about the minimum duration, frequency, type and intensity of exercise required to improve cognition. In the era of precision medicine, it is important to look at other individual factors that may modify the effects of exercise too. A recent meta-analysis of randomised controlled trials in older adults found that exercise had greater effect size on executive function in studies with higher proportions of women46, but we still know little about interactions with gender, ethnicity and comorbidities. Most of the studies relating to dementia evaluated people with Alzheimer’s, vascular and mixed dementias and it remains uncertain whether the benefits extend to other rarer dementias.

    Summary

    Exercise and other physical activity are important for brain health. Increasing physical activity is a promising non-pharmacological intervention to delay the cognitive manifestations of ageing and to reduce the risk of dementia. Large meta-analyses of longitudinal studies have consistently reported a reduced risk for developing dementia in those who regularly exercise. There is also some evidence of reduced rates of cognitive decline in those with mild cognitive impairment and dementia. Randomised controlled trials have provided less consistent results, however. There are additional health benefits of exercise including improved balance, reduced falls, improved cardiovascular health and reduced mortality.

    Key points

    • Take a proactive lifelong approach to dementia risk reduction.

    • Exercise in cognitively healthy people is associated with reduced risk of dementia.

    • There is weak evidence that exercise may slow progression of mild cognitive impairment.

    • Aerobic and resistance training are both associated with reduced risk of dementia, but there is more evidence for aerobic training.

    • Exercise has benefits beyond cognition, including improving mood, balance and physical function, and addressing cardiovascular risk factors.

    Acknowledgments

    We thank the Lancet for permission to reproduce figure 1. We are very grateful to Oliver Freeman from the Wicking Dementia Research and Education Centre for assistance in producing figure 2. The Wicking Dementia and Education Centre is supported by the J.O. and J.R. Wicking Trust (Equity Trustees)

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    Footnotes

    • Twitter Jane Alty @janealty1 and Katherine Lawler @KateLawlerPT

    • Contributors All authors contributed to the manuscript. JA conceived the idea, wrote the first draft and revised subsequent drafts, devised Box 2, contributed to Figure 2 development and obtained permission for Figure 1 reproduction; MF reviewed and revised the first and subsequent drafts; KL reviewed and revised the first and subsequent drafts, devised Box 1 and contributed to Figure 2 development.

    • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

    • Competing interests None declared.

    • Patient consent for publication Not required.

    • Provenance and peer review Commissioned. Externally peer reviewed by Monica Busse, Cardiff, UK, and Cath Mummery, London, UK.

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