Keywords: Behavior - Dementia - Exercise - Medication Adherence
Palavras-chave: Comportamento - Demência - Exercício Físico - Adesão à Medicação
INTRODUCTION
Dementia is a group of conditions characterized by cognitive and behavioral decline
with functional impact, commonly related to neurodegenerative processes[1 ]. Mild cognitive impairment (MCI) can represent the prodromal phase of dementia,
in which patients usually have cognitive complaints with relatively preserved functions
daily living[2 ].
Ageing, female gender, degree and type of dementia, as well as the APOE (apolipoprotein
E) epslion-4 allele influence the occurrence of neuropsychiatric symptoms (NPS) in
dementia[3 ]. Behavioral and psychological symptoms in dementia (BPSD) are described as a heterogeneous
group of symptoms including disturbances in thinking content, mood and behavior that
frequently manifest in people with dementia[4 ].
At least one type of behavioral and/or psychological symptom is expected at any stage
of dementia, especially in mild to moderate stages[5 ]. The manifestation of BPSD can be observed as behavioral changes such as physical
or verbal aggression, agitation, wandering, and sexual disinhibition that are usually
accompanied by anxiety, depression, apathy and psychosis (hallucinations and delusions)[6 ].
The presence of BPSD negatively affects patients’ quality of life, resulting in deterioration
of cognitive abilities, caregiver burden, early institutionalization, and increased
treatment costs[5 ]. For example, in the United States, about US$ 228 billion was estimated for the
care of patients with dementia in 2018[7 ], while in Brazil, in a tertiary center, the cost was estimated at approximately
US$ 1,683.18 per patient/month[8 ].
The practice of physical activity has shown promising results in improving agitation
in patients with dementia[9 ]. Non-pharmacological approaches, such as frequent practice of exercise are known
to be the most effective alternative in the treatment of these symptoms[10 ]. Exercise is considered a subcategory of physical activity being performed in a
planned, structured, repetitive and intentional way, to improve or maintain one or
more components of physical activity and health in general[11 ]. Studies indicate that aerobic exercises, if practiced over a certain period of
time, are capable of containing symptoms of depression and anxiety in elderly people
with dementia[12 ]. Aerobic exercise (15 min) combined with resistance training three times a week
for 3 weeks reduced agitation in elderly with severe cognitive impairment in one study[13 ]. Other study reported that sedentary elderly had more neuropsychiatric symptoms[14 ]. In patients with MCI, exercise training (6 months) is likely to improve cognitive
ability[2 ].
Previous studies addressing this theme have presented results of physical activity
combined with various interventions[9 ],[15 ],[16 ]. On the other hand, studies that evaluate the effects of exercise alone on behavioral
symptoms are scarce and existing studies lack methodological quality[15 ]. Little is known about which type of exercise is more appropriate, as well as the
exercise parameters, such as intensity and frequency, that are able to promote significant
results in such population.
Our hypothesis is that the practice of regular physical exercises under supervision
and with appropriate protocols could reduce BPSD in elderly with MCI and dementia.
This paper aimed to investigate whether the participation of elderly people in physical
exercise programs is effective in reducing behavioral and psychological symptoms of
dementia, in order to contribute to the decision-making process of healthcare professionals
based on scientific evidence, and helping them to better manage these symptoms.
METHODS
A systematic review of the literature was carried out to answer the initial question:
does physical exercise reduce behavioral and psychological symptoms in elderly people
with mild cognitive impairment and dementia? This review was conducted in accordance
with the recommendations of the “Preferred Reporting Items of Systematic Reviews”
(PRISMA)[17 ].
Eligibility criteria
The PICOS strategy (Population, Intervention, Control, Outcomes, Settings) was used
in order to establish the inclusion and exclusion criteria. The eligible studies were
randomized clinical trials involving elderly people with mild cognitive impairment
(MCI) or dementia (any disease stage), which measured neuropsychiatric and psychological
symptoms as a primary or secondary outcome and comprised physical exercise as an intervention
compared to a control group. Studies in animals, studies involving only caregivers
and those that did not evaluate behavioral and psychological symptoms were excluded.
Search strategy
Two independent researchers conducted an electronic search in MEDLINE (PubMed), SciELO,
Web of Science, Scopus and SPORTDiscus databases in July 2020. The filters applied
included clinical trials published in the last 10 years, without language restriction.
The search strategy combined the following standardized descriptors according to MeSh/Decs:
(((dementia OR “Mild Cognitive Impairment”) AND (exercise) AND (“behavioral symptoms”
OR “neuropsychiatric symptoms”)).
Eligibility screening
The first stage of article selection was based the title and summary of articles.
The articles were screened and selected according to their relevance and inclusion
criteria, and were analyzed by two independent researchers. If different opinions
emerged, a third researcher would be consulted in order to make the final decision.
Data extraction
Data were extracted and entered in a spreadsheet to allocate the following variables:
author, year of publication, place where the study was developed, sample size and
characteristics, main outcomes analyzed, type of intervention and main conclusions,
as demonstrated in Tables [1 ] and [2 ]. The Physiotherapy Evidence Database (PEDro)[18 ] criteria were used to evaluate the methodological quality of the studies.
Table 1
Characteristics of studies that examined the effects of physical exercise on behavioral/neuropsychiatric
symptoms in elderly people with dementia.
Author (year)
Country
Sample, mean age
Characterization
Instruments
Ballard et al. (2016)[20 ]
United Kingdom
n=277 (G1: antipsychotic review=146; G2: no antipsychotic review=131), institutionalized
43 males/120 females 85.2 years old (IG: 86,9; CG: 86,4)
Mild to advanced stages of dementia Sedentary
NPI, CSDD, CMAI
Hoffmann et al. (2016)[23 ]
Denmark
n=200 (IG=107, CG=93), outpatient memory clinic 113 males/87 females 70.5 years old
(IG: 69.8; CG: 71.3)
Mild AD Physically active
NPI, HAM-D
Cancela et al. (2016)[22 ]
Spain
n=189 (IG=73, CG=116), institutionalized 63 males/126 females 81.7 years old (IG:
80.6; CG: 82.9)
Unespecified stage of dementia Sedentary
NPI, CSDD
Telenius et al. (2015)[24 ]
Norway
n=163 (IG=82, CG=81), institutionalized 43 males/120 females 86,7 years old (IG: 86.9;
GC: 86.4)
Mild to moderate AD Sedentary
NPI, CSDD
Öhman et al. (2017)[21 ]
Finland
n=179 (home-based exercises=63, group exercises=57, CG=59), voluntary 110 males/69
females 77.8 years old (G1: 77.4; G2: 77.9; CG: 78.1)
Mild to advanced AD NA
NPI, CSDD
Lamb et al. (2018)[25 ]
England
n=494 (IG=329, GC=165), memory clinics, general hospitals, community dementia services,
primary care 301 males/69 females 77 years old (IG: 76.9; GC: 78.4)
Mild to moderate dementia NA
NPI
Henskens et al. (2018)[19 ]
Netherlands
n=87 (G1: ADL+EX=22; G2: ADL=21 G3.EX=22 and CG =22), institutionalized 20 males/67
females 85.7 years old (ADL+EX: 86.9; ADL: 86.05; EX: 85.14: CG: 84.73)
MCI to advanced dementia NA
CMAI, CSDD, AES
AD: Alzheimer’s disease; NPI: Neuropsychiatric Inventory; CSDD: Cornell Scale for
Depression in Dementia; HAM-D: Hamilton’s Depression Rating Scale; ADCS-CGIC: Alzheimer’s
Disease Cooperative Study – Clinicians Global Impression of Change; CMAI: Cohen-Mansfield
Agitation Inventory; CG: control group; IG: intervention group; ADL: daily living
activity; EX: exercise; AES: Apathy Assessment Scale.
Table 2
Intervention and outcomes of studies that examined the effects of physical exercise
on behavioral/neuropsychiatric symptoms in elderly people with dementia.
Author (year)
Intervention
Medication
Results
Ballard et al. (2016)[20 ]
IG (GEX): Type: aerobic training (outdoor or exercise bike), resistance training and
balance* Duration: 60 min/36 weeks Frequency: once a week Intensity: not specified
Antipsychotic
Reduced neuropsychiatric symptoms, except for agitation and depression NPI: T0: IG:
12.02/CG: 15.05; T1: IG: 11.73/CG: 14.89 Effect size: -3.59, p<0.05 CSDD: T0: IG:
4.16/CG: 4.86; T1: IG: 5.15/CG: 5.43 Effect size: -1.21, p=0.43 CMAI: T0: IG: 46.36/CG:
47.91; T1: IG: 46.94/CG: 50.75 Effect size: -1.76, p=0.47
CG: social interaction
Antipsychotic
Hoffmann et al. (2016)[23 ]
IG: Type: aerobic exercise: 3×10 min. on ergometer bicycle, cross trainer and treadmill
(2–5 min rest between) Duration: 60 min/16 weeks Frequency: three weekly sessions
Intensity: moderate to vigorous
Anti-dementia (acetylcholinesterase inhibitors and/or memantine) Antidepressant
Reduced neuropsychiatric symptoms, except for depression NPI: T0: IG: 10.0/CG: 9.4;
T1: IG: 8.8/CG: 11.4 Effect size: -3.,5, p=0.002 HAM-D: T0: IG: 1.9/CG: 2.0; T1:/IG:
1.7/CG: 1.8 Effect size: -0.1, p=0.791
CG: usual care
Anti-dementia (acetylcholinesterase inhibitors and/or memantine) Antidepressant
Cancela et al. (2016)[22 ]
IG: Type: aerobic training (recumbent bicycle) Duration: 15 min/60 weeks Frequency:
daily ** Intensity: self-selected
Anti-dementia (acetylcholinesterase inhibitors and/or memantine)
Reduced neuropsychiatric symptoms, except for depression NPI: T0: IG: 9.70/CG: 11.32;
T1: NA Effect size: NA, p=0.020 CSDD: T0: IG: 6.31/CG: 6.71; T1: NA Effect size: NA
CG: recreational activities (card games, reading and manual work)
Anti-dementia (acetylcholinesterase inhibitors and/or memantine)
Telenius et al. (2015)[24 ]
IG: Type: resistance training for lower limb muscles (12 MR) and 2 balance exercises
Duration: 50 to 60 min/12 weeks Frequency: twice weekly sessions Intensity: vigorous
NA
Reduced apathy and agitation, except for depression NPI: T0: IG: 5.8/CG: 4.8; T1:
IG: 5.1/CG: 5.4 Effect size: Apathy: 0.3, p=0.048 Agitation: 0.2, p=0.07 CSDD: T0:
IG: 4.7/CG: 4.9; T1: IG: 3.8/CG: 3.8 Effect size: 0.2, p=0.39
CG: mild physical activity, reading, games, talking, listening to music
NA
Öhman et al. (2017)[21 ]
IG (GE and HE): Type: aerobic training (Nordic walking and bike); resistance training;
balance and dual-task exercises (15 min for each modality) Duration: 60 min/52 weeks
Frequency: twice weekly sessions Intensity: gradually increased
1 in 4: Antidepressant 1 in 10: Antipsychotic
No improvements in neuropsychiatric symptoms NPI: T0: IG: (GE:12.05, HE: 13.45)/CG:
16.56; T1: NA Effect size: not significant/NA, p=0.41 CSDD: T0: IG: (GE:3.9, HE: 4.8)/CG:
5.9; T1: NA Effect size: not significant/NA, p=0.81
CG: usual care (physical therapy, if necessary)
NA
Lamb et al. (2018)[25 ]
IG: Type: aerobic training (static cycling) and resistance training (5 exercises for
arms and legs) Duration: 60–90-min/16 weeks Frequency: twice weekly sessions Intensity:
moderate to vigorous***
Anti-dementia (acetylcholinesterase inhibitors and/or memantine)
No improvements in neuropsychiatric symptoms NPI: T0: IG: 7.5/CG: 10; T1: IG: 12/CG:
9 Effect size: -2.1, p=0.14
CG: usual care (physical therapy when necessary)
Anti-dementia (acetylcholinesterase inhibitors and/or memantine)
Henskens et al. (2018)[19 ]
IG (GEX): Type: aerobic training (walk outdoors - 500mts or 1km), resistance training:
13 exercises for upper and lower extremities and the torso: 3 sets of 8 reps Duration:
30-45-min/24 weeks Frequency: three weekly sessions Intensity: gradually increased
NA
No improvements in depressive symptoms, apathy and agitation CSDD: T0: IG: 8.3/CG:
8.1; T1: IG: 8.6/CG: 6.7 Effect size: 0.1, p=0.89 CMAI: T0: IG: 51.8/CG: 52.3; T1:
IG: 53.4/CG: 52 Effect size: -4.3, p=0.11 AES: T0: IG:23.8/CG: 28.4; T1: IG: 25/CG:
24.8 Effect size: -0.1, p=0.91
CG: social interaction (drinking tea)/usual care
NA
AD: Alzheimer’s disease; NPI: Neuropsychiatric Inventory; UULL: upper limbs; LLLL:
lower limbs; CSDD: Cornell Scale for Depression in Dementia; HAM-D: Hamilton’s Depression
Rating Scale; ADCS-CGIC: Alzheimer’s Disease Cooperative Study – Clinicians’ Global
Impression of Change; CMAI: Cohen-Mansfield Agitation Inventory; CG: Control group;
IG: Intervention Group; ADL: daily living activity; GEX: exercise group; HE: tailored
home-based exercise; GE: group-based exercise; AES: Apathy Assessment Scale; MTS:
meters; KM: kilometer; REPS: repetitions; MR: maximum repetitions; T0: Baseline score
(mean); T1: Score after intervention (mean); NA: not available; *Walking was encouraged
as a routine activity, as were dancing, musical exercises, and chair volleyball; **It
was not specified whether the bicycle exercise was performed 5 or 7 times a week;
***Participants were asked to exercise at home for an additional hour each week.
RESULTS
The literature search resulted in 129 articles after duplicates were removed. All
were examined for title and abstract, and 109 of them were excluded because they were
not related to the theme or had a study design not contemplated in the present study.
The remaining 20 articles were fully read and, at this stage, 13 articles were excluded.
The remaining seven articles met the inclusion criteria and were used for analysis.
[Figure 1 ] summarizes the literature search process.
Figure 1 Flowchart of studies included for qualitative synthesis.
Tables [1 ] and [2 ] summarizes the main information of the studies included in this review. The included
articles were published between 2015 and 2020, all in English language, and the mean
age of participants varied from 70.5 to 86.7 years old.
All studies used cognitive measurement scales (e.g. Mini Mental State Examination
— MMSE, Cognitive Subscale of Alzheimer’s Disease Assessment Scale — ADA-Cog), functionality
(e.g. Sit-to-stand test, 6-minute walk test, Timed up and go — TUG, Katz index), quality
of life (e.g. Quality of life in Alzheimer’s disease scale — QoL-AD, European quality
of life - 5 dimensions — EQ-5D), neuropsychiatric symptoms (Neuropsychiatric Inventory
— NPI), as well as depression, apathy and agitation (Hamilton Depression Rating Scale
— HAM-D, Cohen-Mansfield Agitation Inventory — CMAI, Cornell Scale for Depression
in Dementia — CSDD, Apathy Evaluation Scale - AES).
Overall, studies focused on early to moderate stages of dementia. In three studies,
MCI[16 ] and advanced phase were also included[19 ],[20 ],[21 ], while one study did not specify the disease stage[22 ]. Dementia stage was classified by the CDR (clinical dementia rating) in 4 of the
7 studies. Female participants represented the majority of subjects in most studies.
Moreover, the degree of sedentarism was specified in only 3 of the 7 studies included
for analysis.
Physical exercise interventions consisted mainly of strength, resistance and balance
trainings, as well as aerobic exercises. Resistance exercises focused on improving
muscle bulk of upper limbs, lower limbs, and trunk (squats, knee extension, pull,
elevation and pulley exercises etc.). Balance training often included simple steps
involved in dancing or tandem walking. Double-task exercises consisted of speaking
while walking, singing during training, and performing manual tasks simultaneously
while counting up, and aerobic exercises were performed in the bicycle or treadmill
devices.
The period of the intervention ranged from 2 to 60 weeks, 2 to 5 times a week, with
sessions duration ranging from 15 to 90 minutes. Exercise intensity ranged from moderate
to vigorous, with the exception of the study by Cancela et al.[22 ] in which participants could modulate the intensity themselves. For control groups,
the activities included usual care, manual work, music therapy, reading, and social
interaction. The seven studies that met the eligibility criteria are summarized below.
Ballard et al.[20 ] carried out a cluster randomized clinical trial and evaluated the impact of an antipsychotic
review, social interaction, and exercise associated with person-centered care on NPS
of 277 individuals with mild to advanced dementia who lived in nursing homes in the
UK. The effect of an exercise training program (stretching, muscle strengthening,
aerobic and balance exercises), once a week for 36 weeks was sufficient to significantly
reduce general NPS according to the measured scales (NPI), except for agitation and
depressive symptoms.
Hoffmann et al.[23 ] examined 200 individuals with a clinical diagnosis of mild Alzheimer’s Disease (AD),
according to the NINDS-ADRDA Alzheimer’s criteria, recruited from an outpatient memory
clinic in Denmark. Participants were randomized into two treatment groups (IG: aerobic
and strengthening exercises; CG: usual care). The exercise program was conducted in
a group of 3 to 5 participants. Throughout the first four weeks, the aim was to adapt
participants to the training and improve the strength of their lower limbs (twice
a week); in the remaining twelve weeks, the patients underwent aerobic training (stationary
bike, cross-training, and treadmill) three times a week in a moderate to vigorous
intensity. The results pointed to the benefits of exercise training for controlling
NPS, with significant reduction of symptoms according to the measured scales (NPI).
Nevertheless, no effects on depressive symptoms were reported.
Cancela et al.[22 ] developed a randomized clinical trial with 188 institutionalized patients with dementia,
according to the Diagnostic and Statistical Manual of Mental Disorders, unspecified
stage. The experimental group undertook daily bicycle exercise for 15 minutes, alone
or in pairs, for 60 weeks with self-selected intensity, while the control group performed
sedentary recreational activities. Significant improvements were observed in the reduction
of neuropsychiatric disorders according to the measured scales (NPI), with no improvement
in depression.
According to the study by Telenius et al.[24 ] vigorous-intensity lower limb strengthening and balance exercises (12 repetitions
maximum), twice a week, with a 50 to 60 minutes of duration was sufficient to significantly
reduce apathy and agitation in institutionalized men and women with mild to moderate
dementia, with an mean age of 86.9±7 years old. The NPI was used to assess the severity
of common behavioral and neuropsychiatric symptoms in dementia. Each symptom is assessed
as present or absent; if present, the severity is classified as mild, moderate or
severe. NPI subscales were also used. The subscales consisted of: 1) agitation: items
of agitation/aggression, irritability and disinhibition (minimum score: 0, maximum:
9); 2) affective: items of depression and anxiety (minimum score: 0, maximum: 6);
3) apathy: symptom analyzed solely.
Ohman et al.[21 ] randomized elderly people with mild to advanced AD (mean age 77.8 years old) into
three groups that performed different types of treatment (G1: home-based exercises;
G2: exercises in daycare centers; CG: usual care). For both exercise groups, the sessions
consisted of 60 minutes comprising multicomponent training sessions (aerobic exercise,
strength, balance, and dual-task exercises) twice a week with progressively increasing
intensity. After 48 weeks, a small decrease in irritability levels in the daycare
exercise group was observed, with a -0.49 score (95%CI 0.99–0.54, p=0.03). When examining
the effects in NPS subgroups, the effect sizes remained below statistical significance.
To assess the NPS, the NPI was used, an instrument that assesses symptoms commonly
observed in dementia: agitation, dysphoria, delusions, aberrant motor behavior, euphoria,
dis-inhibition, anxiety, apathy, irritability, hallucinations, sleep disturbances,
besides appetite and eating abnormalities. Regarding depressive symptoms, CSDD was
used to assess depression and its changes over 12 months, which were modest: in G1:
1.35 (95%CI 0.14–2.66), in G2: 0.5 (95%C: 0.67–1.54), and in G3: 0.04 (95%CI 1.56–1.40).
The scale contains 19 items with a maximum score of 38 and a score >10 indicates depression.
Lamb et al.[25 ] randomized 494 individuals with mild to moderate dementia recruited from memory
clinics, general hospitals, community dementia services, and primary care in England.
Behavioral symptoms were measured by NPI after 12 weeks of aerobic training (stationary
bike) and resistance training (upper and lower limbs), performed in a moderate to
high intensity twice a week. This intervention, however, did not promote a reduction
in NPS.
Henskens et al.[19 ] randomized 87 elderly people with MCI to advanced dementia who lived in psychogeriatric
wards in the Netherlands into three intervention groups (G1: activities of daily-living
(ADL); G2: exercise; G3: ADL+exercise). Participants in the control group drank tea
three times per week with the nursing team to control the social aspect. Depressive
symptoms were measured by the CSDD and the Apathy Evaluation Scale-10 was used to
measure patients’ apathetic behavior (scores from 0 to 40; higher scores indicate
more apathetic behavior). The CMAI was used to measure the frequency of agitated behavior.
The exercise program consisted of aerobic (outdoor walking) and strength training
(upper and lower limbs and trunk) sessions, performed in groups (4–6 participants),
three times a week, and the intensity was progressively increased in both groups.
The reports obtained on exercise intensity suggested that there were some deviations
in the intended exercise protocol: for example, two sets of repetitions were performed
instead of the intended three sets and, regarding aerobic exercise, the participants
did not always reach a distance of 500 m or 1 km due to time restrictions. After 24
weeks, no significant effect of exercise was found on depressive symptoms, apathy,
and agitation when compared to the sedentary group.
All randomized clinical trials demonstrated good methodological quality (over 6 points)
according to the criteria of internal validity and statistical description of the
PEDro Scale ([Table 3 ]). On this scale, each article receives a score ranging from 0 to 10. All trials
used randomization methods with secret allocation; besides, participants had similar
baseline characteristics, comparisons were carried out between groups, and they have
included means and variability of results. Due to the nature of the research, none
of the studies could blind the participants or therapists. Most evaluators were blinded
with regards to the analysis of the results (5 studies), measuring key outcomes in
more than 85% of the participants (4 studies), and analyzed the data according to
the intention to treat principles (5 studies).
Table 3
PEDro scale items and scores of the included studies.
Criteria/study
Ballard et al.[20 ]
Hoffmann et al.[23 ]
Cancela et al.[22 ]
Telenius et al.[24 ]
Öhman et al.[21 ]
Lamb et al.[25 ]
Henskens et al.[19 ]
Random allocation
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Blinding of allocation
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Similar groups
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Blinding of participants
No
No
No
No
No
No
No
Blinding of therapists
No
No
No
No
No
No
No
Blinding of evaluators
Yes
Yes
No
Yes
No
Yes
Yes
<15% loss sample
No
Yes
No
Yes
Yes
Yes
No
Analysis by intention to treat
Yes
Yes
Yes
Yes
No
Yes
No
Difference between groups
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Trend measurements central and variability
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Total (0–10)
7
8
6
8
6
8
6
DISCUSSION
The systematic review of the 7 randomized clinical trials provided substantial information
regarding the benefits of physical exercises in controlling BPSD. Of the seven articles,
four[20 ],[22 ],[21 ],[22 ],[23 ],[24 ] indicated improvements, while three demonstrated less[21 ] or no benefit[19 ],[25 ].
Previous reviews had generalist approaches, combining studies that associated exercise
with other activities, addressing different outcomes: cognition, antipsychotic drugs
usage, falls, ADLs, and mortality[9 ],[15 ],[16 ]. However, our review avoided heterogeneity of studies and sought to include articles
that presented at least one group with systematic physical exercise interventions
and their relationship with BPSD. In this way, we tried to elucidate the evidence
avoiding masking the results by overlapping different interventions.
Only two articles combined other interventions with exercise[19 ],[20 ]. Nevertheless, they presented an intervention with only exercise, not associated
with other interventions, meeting the eligibility criteria of this review. The study
conducted by Ballard et al.[20 ] analyzed the effects of antipsychotic, exercise, and social interaction, and indicated
a positive effect in reducing NPS; while the study carried out by Henskens et al.[19 ] included 3 groups (exercise, ADLs training, and ADLs combined with ADLs training),
not showing benefits in BPSD.
Regarding the effects of exercise, it is worth mentioning that the study conducted
by Öhman et al.[21 ] demonstrated a small reduction in BPSD and this result may be related to the fact
that patients had already started the program with a low total NPI, since almost all
of them were using antipsychotics for AD. Similarly, in the study by Henskens et al.[19 ], the authors stated that no absolute conclusions could be drawn regarding the effectiveness
of the exercise intervention because there was a moderate (55%) adherence to treatment
and a limited number of intensity reports. Another study[9 ],[26 ] reported higher adherence rates (>75%), and multicomponent exercise reduced depression
and agitation levels. In the study by Lamb[25 ], despite a large sample size with relatively high doses of exercise and good compliance,
no significant differences were observed in cognitive or neuropsychiatric measures.
The authors discuss study limitations such as 1) lack of proper allocation masking,
2) measurement bias, and 3) a high number of people who declined to participate in
the trial with significant gender differences. They also hypothesize that high intensity
training in healthy humans can have negative short-term effects, including slow reoxygenation
of cortical areas with a transient reduction in executive function. However, the authors
did not discuss how this could apply to BPSD measures and it is our impression that
high intensity protocols do not fit all individuals and could lead to lower subjective
well-being.
Overall, regarding the types of protocol or specific modalities of exercise, 4 of
the 7 studies indicated significant improvements in BPSD. However, most reports did
not specify what type of BPSD benefited more from interventions. Telenius et al.[24 ] reported that their intervention of high-intensity exercises, along with balance
and resistance training, mostly reduced apathy with a tendency towards improving agitation
after 12 weeks. In the study by Hoffmann et al.[23 ] there were less severe neuropsychiatric symptoms after 16 weeks, but the intervention
did not reduce depressive symptoms. In most studies, symptoms of depression responded
poorly to interventions. This finding could be related to the low scores of depression
in baseline samples. In their study, Telenius et al.[24 ] observed that only 23% of participants scored above the cutoff value of eight points
in the Cornell Scale for Depression in Dementia (CSDD). Only one study included in
the analysis[19 ] reported a mean baseline CSDD of 8.3 in the intervention group compared to 8.1 in
controls. Moreover, we hypothesize that different strategies of social interaction
could interfere in the depression scores, as controls often had access to usual group
activities, while individuals in the intervention groups would often exercise under
individual supervision.
The majority of the studies were conducted in long-term facilities. These facilities
tend to house a large proportion of the elderly population with dementia, as this
is one of the main causes of institutionalization of the elderly[27 ]. The included studies analyzed different stages of dementia (MCI and advanced dementia).
Because of such heterogeneity in the samples, the results of the studies must be interpreted
with caution, as in advanced stages, the exercise may not be viable or may not generate
the same effects as in initial stages of the disease.
The studies included in our analysis did not explore in depth the mechanisms involved
in BPSD reduction and this is probably multifactorial. The brain has a high plasticity
and physical exercises could influence the production of neurotrophic factors leading
to improved network signaling, cell growth, and cell differentiation[28 ]. One recent traumatic brain injury study showed that ten days of moderate intensity
treadmill exercise reduced anxiety-like behavior, improved hippocampus-dependent spatial
memory, and promoted hippocampal proliferation and newborn neuronal survival in rodents[29 ]. In structural Magnetic Resonance Imaging studies, physical activity was associated
with larger brain volumes (less brain atrophy), specifically in brain regions vulnerable
to dementia, comprising the hippocampus, temporal, and frontal regions[30 ]. Physical activities can modulate brain maintenance and compensation, resulting
in improved resistance against degenerative pathologies[31 ]. Together with improvements in routine and social interaction and sleep and appetite
regulation, we believe that there could be a reasonable neural basis for changes in
BPSD following regular practice of physical exercise.
The benefits of regular physical activity in preventing dementias are already well
known, as is its protective role on cognition in patients with MCI[32 ]. On the other hand, the evidence of physical exercise in reducing behavioral symptoms
still needs further investigation and this systematic review reinforces the need for
more intervention studies with appropriate methods, larger populations, and that investigate
the effects of physical exercise as a single intervention.
We also highlight that non-pharmacological measures are currently the most effective
in managing behavioral symptoms[33 ]. Supervised physical exercise seem to be a highly cost-effective strategy because
of its low cost and additional benefits in terms of subjective well-being,[34 ] protection against falls, and prevention of sarcopenia[35 ],[36 ].
As a limitation of this review, we point out to the small number of studies found.
Besides, we are aware that the application of the PICOS strategy brings more rigor
to this area of scarce data. To our knowledge, and although some studies are secondary
analyzes, this is the first systematic review to include only randomized clinical
trials of interventions specifically focused on physical exercise and its relationship
with BPSD.
In conclusion, moderate to intense aerobic and muscle strengthening exercises may
have a potential benefit in the management of BPSD, but studies reached mixed conclusions.
This review demonstrated that further intervention and meta-analysis studies are needed
in the area, aiming to investigate the absolute effect of physical exercise and its
impact on the behavioral and psychological symptoms of elderly people with dementia,
especially in the early stages of the disease.
