How to understand it
Exercise and dementia prevention
Wicking Dementia Research and
Education Centre, College of
Health and Medicine, University
of Tasmania, Hobart, Tasmania,
Australia
Correspondence to
Dr Jane Alty, Wicking Dementia
Research and Education Centre,
University of Tasmania, Hobart,
Tasmania 7000, Australia; ​jane.​
alty@​utas.​edu.a​ u
Accepted 10 December 2019
© Author(s) (or their
employer(s)) 2020. No
commercial re-­use. See rights
and permissions. Published
by BMJ.
To cite: Alty J, Farrow M,
Lawler K. Pract Neurol Epub
ahead of print: [please include
Day Month Year]. doi:10.1136/
practneurol-2019-002335
Jane Alty ‍ ‍, Maree Farrow ‍
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.
Introduction
‘Dementia is the greatest global chal-
lenge for health and social care in the 21st
century’ Lancet Commission 2017.1
An estimated 50 million people world-
wide 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 symp-
toms of dementia pathology manifest late,
Alty J, et al. Pract Neurol 2020;0:1–7. doi:10.1136/practneurol-2019-002335
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‍, Katherine Lawler ‍ ‍
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 Commis-
sion.1 Dementia risk information is not yet
well known: half of adults cannot identify
Enseignement Superieur (ABES). Protected by copyright.
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
Physical inactivity is a central modifi-
able dementia risk factor. There is good
evidence that increased levels of exercise
and general physical activity in cogni-
tively healthy adults are associated with
reduced risk of dementia, and some,
although weaker, evidence that it may
potentially slow down cognitive impair-
ment once mild cognitive impairment and
dementia are established.1 8 9 This article
briefly outlines the modifiable risk factors
for dementia and then focuses specifi-
cally 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 proac-
tively (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.
1
How to understand it

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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 comorbid-
ities. 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 arkrun can be a fun, social way
to improve health.

Enseignement Superieur (ABES). Protected by copyright.

►► 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.

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

Box 2  Primary prevention discussion

Mr C, 35-­years old, attended the neurology clinic with

altered sensation in his hand and was diagnosed with
Figure 1  Life-­course model of contribution of modifiable risk carpal tunnel syndrome. During the consultation, the
factors to dementia. Numbers are rounded to nearest integer. neurologist noted incidentally that he was a smoker and
Figure shows potentially modifiable and non-­modifiable risk had depression and poorly controlled diabetes.
factors (figure and legend are reproduced from The Lancet with
The neurologist took the opportunity to briefly discuss
permission)1
reducing Mr C’s risk for developing heart disease, stroke
and dementia in the future (ie, primary prevention). She
Targeted secondary or tertiary prevention strategies
advised that he stopped smoking, aimed for at least 10 min
are also relevant to our patients with mild cognitive
of physical activity twice a day (see figure 2) and made a
impairment or dementia, to help slow disease progres-
general practitioner appointment to discuss management
sion and maintain quality of life.
of his depression and diabetes. He then mentioned that
However, in busy neurology clinics and ward
his mother and grandfather both died from Alzheimer’s
rounds, when there may not always be the time to have
disease so he had assumed ‘it was inevitable’ he would get
these discussions, it is important at least to signpost
dementia when he was older. The neurologist explained
the patient to their general practitioner for further risk
that research has shown that there is a reduced risk of
management. ‘Preventative neurology’ is an emerging
developing dementia in people who have a healthy life-
concept, and looking to the future, it may be that dedi-
style, even in groups of people with a higher genetic risk.15
cated dementia prevention interdisciplinary clinics,
He thanked her as he left the consultation saying that he
attended by physiotherapists, specialist nurses and
felt ‘more empowered’ to change his lifestyle.
physicians, take on this role. Research suggests that

2 Alty J, et al. Pract Neurol 2020;0:1–7. doi:10.1136/practneurol-2019-002335


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 cerebro-
vascular disease risk factors. Although ageing is the
biggest risk, with an exponential rise in dementia inci-
dence 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 associ-
ated 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) empha-
sised 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 inter-
ventions, as this is the period that most likely precedes
the earliest stages of neurodegeneration. There is
encouraging epidemiological evidence that risk reduc-
tion strategies are beginning to work—there has been
an unexpected decline in age-­specific dementia inci-
dence in several countries including USA, UK, Nether-
lands 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 ‘phys-
ical 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 ‘ phys-
ical 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 activ-
ities may reduce barriers for those people who wish
to increase their physical activity levels but do not
want to engage in exercise. Retrospective or longitu-
dinal 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.
Alty J, et al. Pract Neurol 2020;0:1–7. doi:10.1136/practneurol-2019-002335
How to understand it
‘Two a day’ of moderate physical activity
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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 activ-
ities to patients, trying to tailor these to their mobility,
neurological impairment, and their hobbies and inter-
ests, thereby incorporating personalised medicine and
Enseignement Superieur (ABES). Protected by copyright.
'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 partic-
ipants 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 devel-
oping 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 cogni-
tive domains. However, increasing sample size by
3
How to understand it
Figure 2  Infographic summarising physical activity and dementia prevention, based on WHO 2019 guidelines (4)
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 exer-
cise 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
4 Alty J, et al. Pract Neurol 2020;0:1–7. doi:10.1136/practneurol-2019-002335
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Enseignement Superieur (ABES). Protected by copyright.
found that physical activity interventions were associ-
ated 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 bene-
ficial effect of aerobic exercise, resistance training or
multimodal exercise on global cognition with stan-
dard 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 signif-
icant 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 capil-
lary 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 preser-
vation 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 neuro-
trophic 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, hypercholestero-
laemia 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 inves-
tigated 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 neuro-
degeneration, 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
Alty J, et al. Pract Neurol 2020;0:1–7. doi:10.1136/practneurol-2019-002335
How to understand it
in physical activity have benefits on brain structure and
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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 bene-
fits 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 conclu-
sions about the minimum duration, frequency, type and
Enseignement Superieur (ABES). Protected by copyright.
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 comor-
bidities. Most of the studies relating to dementia eval-
uated people with Alzheimer’s, vascular and mixed
dementias and it remains uncertain whether the bene-
fits 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 cogni-
tive manifestations of ageing and to reduce the risk of
dementia. Large meta-­analyses of longitudinal studies
have consistently reported a reduced risk for devel-
oping dementia in those who regularly exercise. There
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.
5
 How to understand it
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 addi-
tional health benefits of exercise including improved
balance, reduced falls, improved cardiovascular health
and reduced mortality.
Further reading
World Health Organisation. Risk reduction of cogni-
tive decline and dementia: WHO guidelines, 2019.
Livingston, G., et al., Dementia prevention, interven-
tion, and care. Lancet 2017;390(10113):2673–734.
Twitter Jane Alty @janealty1 and Katherine Lawler @
KateLawlerPT
Acknowledgements  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)
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.
ORCID iDs
Jane Alty http://​orcid.​org/​0000-​0002-​5456-​8676
Maree Farrow https://​orcid.​org/​0000-​0003-​0302-​9426
Katherine Lawler http://​orcid.​org/​0000-​0002-​1484-​1113
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