Review Article

Role of physical activity in ameliorating

neuropsychiatric symptoms in Alzheimer’s disease.
Group 2

Lorna Schaefer, Jacob Mlynarczyk, Joe Maisano, Ashley Canida

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Objective

The aim of this review is to evaluate the impact of

physical activity on NPs in patients with AD.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Alzheimer’s Disease

● Loss of function in neurons

- Atrophy of the brain as neurons die.
- Build up of protein causing plaques.
● Chronic Inflammation
- Microglia fail to clear waste.
- Breakdown of the blood-brain-barrier.

What Happens to the Brain in Alzheimer's Disease? 2017.

 Symptoms of Alzheimer Disease

● Deterioration in mood, thought, perception and behavior.

● Classified into 4 clusters:

- Hyperactivity cluster: agitation and aggression.

- Psychosis cluster: hallucinations and delusions.

- Mood liability cluster: depression and anxiety.

- Instinctual cluster: appetite and sleep disturbance.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Methods

● Articles on PA in the treatment of NPs were used.

● Studies were excluded if they did not include

patients with AD.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Physical Activity

● Walking.

● Aerobic and endurance activities:

- Aerobic exercise classes.
- Ballroom dance classes.
- Cycling.
● Strength-Balance exercises.
● Memory training.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

Does physical activity reduce NPs?

● Lack of PA is an independent predictor of

depression in patients with AD.
● Longer duration of weekly walks are associated
with better sleep quality.
● Moderate to high intensity activity reduced NP
clusters in a 16-week program.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Results

● The regulation of levels of dopamine in the brain

following PA may ameliorate NPs.

● Norepinephrine may participate in the up‐regulation

of brain derived neurotrophic factor in response to
PA and, which, in turn, can reduce NPs in patients
with AD.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Results Cont.

● PA reduces oxidative stress and inflammation.

● Moderate PA resulted in increased blood flow to the

brain and higher glucose uptake in the brain.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

 Conclusion

● PA ameliorates depression and sleep disturbances.

● PA can be considered as an add-on treatment to

reduce or prevent NP onset or recurrence.

● Further research is needed.

Veronese et al, International Journal of Geriatric Psychiatry, 2018.

Effect of a Multimodal Exercise
Program on Sleep Disturbances
and Instrumental Activities of
Daily Living Performance on
Parkinson’s and Alzheimer’s
Disease Patients

Nascimento et
al.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Purpose

● Assess the contribution of a multimodal exercise

program on sleep disturbances (SD) and on the
performance of instrumental activities daily living
(IADL) in patients with a clinical diagnosis of AD.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Participants

● 35 Patients with AD
- Trained n=19
- Control n=16

● Male and female

● Ages: 70-83 years old

Nascimento et al. Geriatrics Geronto. Int., 2014

 Methods

● Recruited from the Laboratory Databases in Brazil.

● Participant Eligibility:
- Regular medication.
- No PA programs in the last year.
- Clinical Diagnosis according to DSM-IV-TR.
- Stages between mild and moderate according to
Clinical Dementia Rating.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Methods Cont.

● The MiniMental State Examination (MMSE) and the

clock drawing test evaluate cognitive function.

● Neuropsychiatry Inventory.

● The Brazilian validated version of The Pfeffer

Instrumental Activities Questionnaire (PIAQ)
- Assesses patient deficits.
- Max score is a 30, a 5 means functionally
impaired.
Nascimento et al. Geriatrics Geronto. Int., 2014
 Methods Cont.

● Sleep disturbances assessed with Brazilian Mini-Sleep

Questionnaire (MSQ), 10 items scored 1-7.
- 10-24 = good sleep
- 25-27 = mild sleep disorder
- 28-30 = moderate sleep disorder
- 30+ = Severe sleep disorder

● Heart Rate (HR) Monitor/Chest Pulsometer used to

control intensity via HR.
- Karvonen’s formula to determine maximal HR.
- Patients instructed to exercise at 60-80% maximal HR.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Methods Cont.

Warm Up Gentle Walking and stretching exercises

Muscular Calisthenic exercises: bars, medicine balls,
Resistance thera-bands, bobath balls, ankle weights and barbells
were progressively included. Volume overload also
was applied during the phases.

Balance and Recreational/rhythmic activities aimed at stimulating

Motor the visual, somatosensorial, and vestibular systems
Coordinatio
n
Aerobic Circuits designed with an array of equipment including
Fitness hoops, steps, hopes, and mini trampolines to
encourage a walking gait up to a light run
Nascimento et al. Geriatrics Geronto. Int., 2014
 Methods Cont.
● Evaluated at baseline and 24 weeks after program
- Single-blinded, psychiatrist evaluated both times.
● Three 1-hour sessions per week
- 12 sessions per phase, 6 phases total.
- Ending each phase with an overload.
- Control group patients did not exercise.
● Program administered by physical educators
experienced with AD.
● 70% adherence required.
Nascimento et al. Geriatrics Geronto. Int., 2014
 Results

● Participants dropped
- Trained n=19 → 14
- Control n=16

Nascimento et al. Geriatrics Geronto. Int., 2014

 Results Cont.
● Shapiro-Wilks Test
- Variables were normally distributed
- One-way ANOVA test

● PIAQ and MSQ

- Two-way ANCOVA Test

Nascimento et al. Geriatrics Geronto. Int., 2014

Results Cont.

Nascimento et al. Geriatrics Geronto. Int., 2014

Results Cont.

Nascimento et al. Geriatrics Geronto. Int., 2014

Results Cont.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Strengths/Limitations

● Strengths
- Builds from previous recommendations.
- Low cost of program.
- Variables were normally distributed.

● Limitations
- Small sample size.
- Self-Report Bias.
- No intermediary data to show change.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Summary

● Sleep is altered with age.

- Plays a major role in normal mental function.

● Few studies currently exist.

● Exercise reduces SD and improves performance of

IADL.
● Significance was found in data.

● Larger sample size in future.

Nascimento et al. Geriatrics Geronto. Int., 2014

 Patients with Alzheimer’s disease have
reduced activities in midlife compared with
healthy control-group members

Does reduced physical activity midlife lead to Alzheimer’s

disease?

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Participants

● Subjects were participants in the alzheimer’s disease

Case-control Study at Case Western Reserve
University.
● N= 193 with Alzheimer’s Disease (case group).
● N= 358 control group.
● Alzheimer’s participants were in a clinical setting at
University hospitals of Cleveland.
● Midlife defined as 2o-60 years old.
● Men and Women.

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Methods

● Case-Control Study.
● Study was initiated in 1991.
● Control group were friends or neighbors of Patients
● Case group was required to have AD symptoms.
within 5 years of evaluation to prevent premorbid
features.
● Analysis of covariance using ANCOVA.

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Methods

● Diversity defined as the sum of total numbers of

activities participated in at least once per month per
category, divided by the total number of activities
making up an activity category.
● Intensity defined as the sum of total hours devoted
per month to each activity type.
● Percentage intensity defined as percent of total

activity hours per month devoted to each category.

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Methods

● Diversity score were calculated to separate univariate

ANOVAs and ANCOVAs- control group shows larger
diversity.

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Procedures

● Study uses Questionnaire.

● Studied 26 different activities.
● Data from 26 activities divided into 3 sub groups.
- Passive **activities not stated, available upon request**
- Intellectual
- Physical
● One-way ANOVA used between case/ control.

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
Results

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
Results

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
Results

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Strengths

● Results in accord with studies:

- Hultsch et al.
- A longitudinal study performed to display cognitive

decline with intellectual activity as intervention.

● Results remained consistent after controlling for
covariates amongst case and control.
● Obtained information for case group members using
surrogates because case group members cannot self
report.
Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Limitations

● Confounding factors.
- Early life environmental factors
- Stress
- Occupation
● Case and control group members not random.
● Self-report bias.

Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Summary

1. Results conclude that patients with AD are less active

in midlife in all 3 subgroups compared to control
group.
2. Diversity of intellectual, passive, and physical
activities were protective against development of AD.
3. Results indicate lower participation in activities
midlife in addition to lower education and
occupational achievement is a risk factor.
Friedland et al., Proceedings of the National Academy of Sciences of the United States of America , 2001
 Moderate-to-High Intensity
Physical Exercise in Patients
with Alzheimer’s Disease: A
Randomized Control Trial
Hoffman et
al.

What are the effects of moderate-high

intensity aerobic exercise program in
patients with Alzheimer’s Disease
(AD)?

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Background

● Studies of Physical Activity (PA) in patients with AD

are few and results are inconsistent.

● First study investigating benefits of supervised,

mod-to-high intense aerobic exercise.
- Cognition, neuropsychiatric & depressive
symptoms, QOL, & ADL in patients with mild AD

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Study Design

● The Preserving Cognition, Quality of Life, Physical

Health and Functional Ability in Alzheimer’s
Disease: The Effect of Physical Exercise (ADEX)

● Multi-center, single-blind, randomized trial

- Jan ‘12-June ‘14

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Participants

● 200 patients with

mild AD

● Outpatient
memory clinics in
Denmark

● Age range: 50-90

years

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Procedures

● Control Group:
- Treatment as usual with access to memory clinic
staff.

● Intervention Group:
- 3 weekly, 60-min exercise sessions for 16 weeks.

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Intervention Group cont.

First 4 weeks: Last 12 weeks:

● strength of lower ● 3x10 min- ergometer
extremities (2x/wk) bicycle, cross
● aerobic exercise (once trainer, and
weekly)
treadmill (2-5 min
rest)
HR:
● 70-80% max HR (220-age)
● calculated for 3 time periods b/t weeks 4-8, 8-12,
and 12-16 (avg HR of all sessions in 4 wk pd/max
HR)

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Outcomes
● Primary outcome:
- Symbol Digit Modalities Test
(SDMT)

● Secondary outcomes:
- Alzheimer’s Disease Assessment Scale-Cognitive
Subscale (ADAS-Cog)
- Caregiver questionnaires
• Neuropsychiatric Inventory (NPI-12)
• European QOL-5 Dimensions (EQ-5D) health-related QOF
scale administered to caregiver and patient

Hoffman et al, Journal of Alzheimer’s Disease, 2016

Aaron Smith, Symbol Digits Modalities Test Manual, 2018
 Results
Table 2
Study measures at baseline and 16 weeks and between-group differences in the change from baseline

Hoffman et al, Journal of Alzheimer’s Disease, 2016

Fig.2
NPI
Difference in changes in neuropsychiatric symptoms between intervention and control group.

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Summary

● Aerobic exercise is a feasible and well-perceived

intervention for older adults with AD.

● Exercise may inhibit/delay emergence of more severe

neuropsychiatric symptoms with disease progression.

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Summary

● Potential positive-dose response on physical exercise

and cognition provided that high attendance and
intensity is maintained.

● No effects found on measures of ADL, depressive

symptoms, or health-related QOF.

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Strengths

● Randomized-trial

● Large number of patients

● Supervised exercise program

● High rate of adherence to intervention

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Weaknesses

● Lack of monitoring outside PA

● Protocol analysis may have been underpowered

● Selection bias

Hoffman et al, Journal of Alzheimer’s Disease, 2016

 Conclusion

● PA can be considered as an add-on treatment to

reduce or prevent NP onset or recurrence.

● Exercise reduces SD and improves QOL and ADL

● Inverse-dose response with exercise during midlife

and risk of AD with age

 Thank You

Questions?

Ashley Canida, Joe Maisano, Jacob

Mlynarczyk, Lorna Schaefer
 References
1. Veronese, N., Solmi, M., Basso, C., Smith, L., & Soysal, P. (2018). Role of physical activity in ameliorating
neuropsychiatric symptoms in Alzheimer disease: A narrative review. International Journal of Geriatric
Psychiatry.

2. What Happens to the Brain in Alzheimer's Disease? (2017, May 16). Retrieved from
https://www.nia.nih.gov/health/what-happens-brain-alzheimers-disease.

3. Hoffmann K. et al., Moderate-to-High Intensity Physical Exercise in Patients with Alzheimer’s Disease: A
Randomized Controlled Trial. Journal of Alzheimers Disease. 2015;50(2):443-453. doi:10.3233/jad-150817.
4. Nascimento, C.M.C.; Ayan, C.; Cancela, J.M.; Gobbi, L.T.B.; Gobbi, S.; Stella, F. Effect of a
multimodal exercise program on sleep disturbances and instrumental activities of daily living
performance on Parkinson’s and Alzheimer’s Disease patients. Geriatrics Gerontology Int.2014, 14,
259–266, doi:10.1111/ggi.12082

5. Robert P. Friedland, Thomas Fritsch, Kathleen A. Smyth, et al. Patients with Alzheimer’s Disease Have
Reduced Activities in Midlife Compared with Healthy Control-Group Members.

6. Mini-Mental State Examination (MMSE). MedWorks Media.

https://medworksmedia.com/product/mini-mental-state-examination-mmse/. Accessed November 12, 2018.

7. Hogrefe Ltd. BRIEF-A - Behaviour Rating Inventory of Executive Function, Adult – Hogrefe - Online
testing, psychometric test & training providers.
https://www.hogrefe.co.uk/shop/symbol-digit-modalities-test.html. Accessed November 12, 2018.