L e a r n i n g O b j e c t i v e s
2
1) Understand the response of the end stage Alzheimer’s patient from the pre-published case review on Aquatic Therapy and End-Stage Dementia
2)Recognize the importance of an “enriched environment” and its crucial relationship to the continuum of care for all client populations.
3)Use clinical reasoning to defend the physiological, behavioral and cognitive responses of immersion in patients with moderate to severe cognitive impairments.
4) Identify aquatic treatment options for the minimally responsive patient population with focus on modifications of methods such as Halliwick, Water Specific Therapy, Watsu and Sensory Integration.
Aquatic Therapy inEarly & End-Stage Dementia
3
Aquatic Therapy inEarly & End-Stage Dementia
International AquaCongressComprehensive Aquatic Therapy
put into Practice
Querétaro, MexicoSaturday, October 29, 2016
Stacy Lynch, PTA, CLT, CPT, Aq,GAq Di rector o f ProgrammingIner t ia Therapy Serv ices
7
Stacy Lynch,PTA, CLT, CPT, Aq,GAq
Di rector o f ProgrammingIner t ia Therapy Serv ices
Aquatic Therapyin
Early & End-Stage Dementia
8
Stacy Lynch,PTA, CLT, CPT, Aq,GAq
Di rector o f ProgrammingIner t ia Therapy Serv ices
Aquatic Therapyin
End-Stage Dementia
10
IncreasedResponsiveness
Autism Spectrum DisorderCerebral Vascular Accident
Traumatic Brain InjuryPost Traumatic Stress Disorder
Dementia
➲
14
The Link Between Physical Activity and Cognitive Dysfunction in
Alzheimer Disease.Phillips, C., Akif Baktir, M., Das, D., Lin, B., & Salehi, A. (2015). Physical
Therapy, 95(7), 1046-1060.
http://dx.doi.org/10.2522/ptj.20140212
15
!
The Link Between Physical Activityand Cognitive Dysfunction inAlzheimer DiseaseCristy Phillips, Mehmet Akif Baktir, Devsmita Das, Bill Lin, Ahmad Salehi
Alzheimer disease (AD) is a primary cause of cognitive dysfunction in the elderlypopulation worldwide. Despite the allocation of enormous amounts of funding andresources to studying this brain disorder, there are no effective pharmacologicaltreatments for reducing the severity of pathology and restoring cognitive function inaffected people. Recent reports on the failure of multiple clinical trials for AD havehighlighted the need to diversify further the search for new therapeutic strategies forcognitive dysfunction. Thus, studies detailing the neuroprotective effects of physicalactivity (PA) on the brain in AD were reviewed, and mechanisms by which PA mightmitigate AD-related cognitive decline were explored. A MEDLINE database searchwas used to generate a list of studies conducted between January 2007 and Septem-ber 2014 (n!394). These studies, along with key references, were screened toidentify those that assessed the effects of PA on AD-related biomarkers and cognitivefunction. The search was not limited on the basis of intensity, frequency, duration,or mode of activity. However, studies in which PA was combined with anotherintervention (eg, diet, pharmacotherapeutics, ovariectomy, cognitive training, behav-ioral therapy), and studies not written in English were excluded. Thirty-eight animaland human studies met entry criteria. Most of the studies suggested that PA attenuatesneuropathology and positively affects cognitive function in AD. Although the litera-ture lacked sufficient evidence to support precise PA guidelines, convergent evi-dence does suggest that the incorporation of regular PA into daily routines mitigatesAD-related symptoms, especially when deployed earlier in the disease process. Herethe protocols used to alter the progression of AD-related neuropathology and cog-nitive decline are highlighted, and the implications for physical therapist practice arediscussed.
C. Phillips, PT, EdD, Departmentof Physical Therapy, ArkansasState University, PO Box 910,Jonesboro, AR 72467 (USA).Address all correspondence to DrPhillips at: [email protected].
M. Akif Baktir, MD, Department ofPhysiology, School of Medicine,Erciyes University, Kayseri, Turkey;VA Palo Alto Health Care System,Palo Alto, California; and Cardio-vascular Medicine, Department ofMedicine, School of Medicine,Stanford University, Palo Alto,California.
D. Das, MD, MPH, VA Palo AltoHealth Care System and Depart-ment of Psychiatry and BehavioralSciences, School of Medicine,Stanford University.
B. Lin, BS, VA Palo Alto HealthCare System.
A. Salehi, MD, PhD, VA Palo AltoHealth Care System and Depart-ment of Psychiatry and BehavioralSciences, School of Medicine,Stanford University.
[Phillips C, Akif Baktir M, Das D,et al. The link between physicalactivity and cognitive dysfunctionin Alzheimer disease. Phys Ther.2015;95:1046–1060.]
© 2015 American Physical TherapyAssociation
Published Ahead of Print:January 8, 2015
Accepted: January 2, 2015Submitted: May 6, 2014
Perspective
Post a Rapid Response tothis article at:ptjournal.apta.org
1046 f Physical Therapy Volume 95 Number 7 July 2015 at APTA Member on July 14, 2015http://ptjournal.apta.org/Downloaded from
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
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Table 2.Effects of Physical Activity on Cognitive Outcomes in People With Alzheimer Disease (AD)a
AD InterventionSample
(n)
Dementia Severityas Determined by
MMSE Age (y) Sex Modality Frequency and Duration Assessment Study
Randomized control 14 14.3 76.8 5 men, 9 women Walking, strengthening, flexibility,balance training, agility
1-h session ! 3 sessions/wk ! 24 wk
2 Severity of sleepdisturbances
Nascimento et al,98
2014
Randomized control 32 "23 81.8 4 men, 12 women Walking 1-h session ! 3 sessions/wk ! 15 wk
Positive correlationwith ERFC
Kemoun et al,101
2010
Randomized control 27 !10 74–76.5 8 men, 19 women Walking Single session daily ! 12 wk 7 MMSE Steinberg et al,105
2009
Randomized control 21 5–15 84.0 30 men, 5 women Walking 30-min session ! 4 sessions/wk ! 24 wk
2 Rate of declinein MMSE
Venturelli et al,106
2011
Randomized control 40 10–28 51–89 16 men, 24 women Walking, strengthening, balancetraining
1-h session/wk ! 6 wk 1 MMSE;1 ADAS-cog
Vreugdenhil et al102
2012
Randomized control 27 12–29 72.0 11 men, 16 women Brain Gym Exercise Protocol 1-h session/wk ! 6 wk 1 Cantab-Expedio Yaquez et al,103
2011
Nonrandomizedcontrol
30 19.4 77.0 6 men, 24 women Aerobic training, strengthening,flexibility, balance training
1-h session ! 5 sessions/wk ! 16 wk
1 MCE de Andrade et al,104
2013
Randomized control 27 19 77.5 Not reported Aerobic training, strengthening,flexibility, balance training,agility, cognitive activities
1-h session ! 3 sessions/wk ! 16 wk
1 Executivefunctions,including FAB
Coelho et al,72
2013
Randomized control 21 Not applicable 76.0 Not reported Treadmill 1 session starting at 4 km/hwith slope of 3% andincreasing slope by 1%every 3 min until heartrate reached 85% ofmaximum capacity
1 Plasma BDNF incontrols andcases with AD
Coelho et al,129
2014
a Among the cognitive assessments used in these studies were Cantab-Expedio, which measures sustained attention and visual memory; the Montreal Cognitive Assessment (MCE), which assesses frontalcognitive function, attention, and language; and the Mini-Mental State Examination (MMSE), which is an objective measure of cognitive function that examines several parameters (including orientationwith regard to time and place, registration [eg, repeating prompts], attention and calculation [eg, backward spelling task], recall, language, and repetition [eg, verbalizing names of objects and complexcommands]). Mini-Mental State Examination scores ranging from 0 to 9 indicate severe cognitive impairment, those ranging from 10 to 18 indicate moderate impairment, and those ranging from 19 to24 suggest mild cognitive impairment. The Brain Gym Exercise Protocol consists of fine motor, balance, and eye-hand coordination activities. ERFC#Rapid Evaluation of Cognitive Functions Test,ADAS-cog#Alzheimer’s Disease Assessment Scale–cognitive subscale, FAB#Frontal Assessment Battery, BDNF#brain-derived neurotrophic factor.
PhysicalActivity
inA
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July2015
at APTA Mem
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Downloaded from
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
PhysicalActivity
inA
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Disease
1050f
PhysicalTherapyVolum
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July2015
at APTA Mem
ber on July 14, 2015http://ptjournal.apta.org/
Downloaded from
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysic
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ease
10
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fPh
ysic
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://ptjo
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysical
Activity
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Alzh
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ysicalTh
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysic
al
Activ
ity
inA
lzh
eim
er
Dis
ease
10
50
fPh
ysic
alTh
erap
yV
olu
me
95
Num
ber
7Ju
ly2
01
5 a
t AP
TA
Mem
ber o
n J
uly
14, 2
015
http
://ptjo
urn
al.a
pta
.org
/D
ow
nlo
aded fro
m
!
Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysical
Activity
in
Alzh
eim
er
Disease
10
50
fPh
ysicalTh
erap
yV
olum
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5N
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7July
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ber on July 14, 2015
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Dow
nloaded from
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysical
Activity
in
Alzh
eim
er
Disease
10
50
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ysicalTh
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yV
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e9
5N
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7July
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Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysic
al
Activ
ityin
Alz
heim
er
Dise
ase
1050
fPh
ysic
alTh
era
py
Volu
me
95
Num
ber
7Ju
ly2015
at A
PT
A M
em
be
r on
July 1
4, 2
01
5h
ttp://p
tjou
rna
l.ap
ta.o
rg/
Do
wn
loa
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d fro
m
!
Table 1.Effects of Physical Activity on Cognitive Function and Alzheimer Disease (AD)–Related Neurobiological Features in Rodent Models of Alzheimer Diseasea
Rodent ModelTargeted
Geneb Age (mo) Modality Frequency and DurationCognitive Assessment
and Outcome
AD-RelatedNeurobiological
Outcome Study
ICV injection of A! NA 2–4 Resistance exercise(swimming withtail weights)
5 d/wk ! 8 wk 1 Exploratory behavior (openfield)
2 Inflammatory markers Souza et al,85 2013
SAMP8 NA 10 Running wheel Free access ! 24 wk NA 1 BDNF gene expression Alvarez-Lopez et al,117
2013
APP695/PS1A246 APP/PS1 24 Treadmill 5 d/wk ! 5 wk 1 Spatial learning (MWM) 2 A! deposition Ke et al,21 2011
NSE/hTAU23 TAU 16 Treadmill 1 h/d ! 5 d/wk ! 12 wk NA 2 Inflammatory markers Leem et al,84 2011
ICV injection ofstreptozotocin
NA 3 Treadmill Daily ! 5 d/wk ! 5 wk 1 Spatial learning (MWM) 1 Antioxidant molecules;2 oxidative stress
Rodrigues et al,118
2010
APP23 APP 6 and 18 Running wheel Free access ! 10 d NA 2 A! deposition in18-mo group; 1neurogenesis in 18-mogroup
Mirochnic et al,119
2009
ICV injection ofA!25-35
NA 2 Running wheel Free access ! 12 d 1 Spatial learning (Y maze) 1 Synaptogenesis Wang et al,120 2013
APP/PS1 APP/PS1 3 Treadmill 30 min/d ! 5 d/wk ! 20 wk NA 2 A! deposition; 2 Tauphosphorylation
Liu et al,121 2013
PS2 mutant PS2 24 Treadmill 60 min/d ! 5 d/wk ! 12 wk 1 Spatial learning (MWM) 2 A! deposition;2 A!42; 2inflammatory markers
Kang et al,20 2013
ICV injection of A!1-42
NA Adult (age notspecified)
Treadmill 2 sessions/d (15 min each) !2/wk progressing to 3sessions/d ! 5 d ! 2 wk
1 Spatial learning (RAWM) 1 BDNF protein Dao et al,122 2013
CRND8 APP 2.5 Running wheel Free access ! 10 wk 7 Spatial learning (Barnesmaze); 2 stereotypicbehavior (eg, jumping,climbing, and bar chewing)
7 A! deposition; 7 stresshormones
Richter et al,123 2008
Tg2576 APP 15–19 Running wheel Free access ! 3 wk 1 Spatial learning (RAWM) 7 A! deposition; 1 levelsof immune system–related protectivemolecules
Parachikova et al,22
2008
Damaged cholinergicneurons
NA Age notspecified
Treadmill 60 min/d ! 7 d/wk ! 8 wk 1 Spatial learning (MWM) NA Hoveida et al,124
2011
Tg2576 APP 5 Running wheel 60 min/d ! 5 d/wk ! 12 wk 7 Novel object discrimination 2 A! plaques Yuede et al,125 2009
3!AD APP, TAU,PS1
1 and 9 Running wheel 1 mo old: free access ! either4 or 36 wk; 9 mo old: freeaccess ! 44 wk
7 Spatial learning (MWM) 7 BDNF; 7 A!; 7 pTau Marlatt et al,52 2013
(Continued)
Ph
ysic
al
Activ
ityin
Alz
heim
er
Dise
ase
10
50
fPh
ysic
alTh
era
py
Volu
me
95
Num
ber
7Ju
ly2015
at A
PT
A M
em
be
r on
July 1
4, 2
01
5h
ttp://p
tjou
rna
l.ap
ta.o
rg/
Do
wn
loa
de
d fro
m
19
21
1974-RudolfJaenischFirstgene4callyengineeredmouse
1960-HarryHarlowRecognizedchangesinthebehavioralandcogni4vedevelopmentofRhesusmonkeysduetomaternalandsocialdepriva4on
1947-DonaldO.HebbRatsraisedaspetssolvedproblemsbeEerthanratsraisedincages
1960-MarkRosenzweigBeganstudyingcogni4vebenefitsofusingtoysladdersandtunnelsoverbeingisolatedincages
35
Aquarobics group’s response:Significant increases in:
Cardio-respiratory endurance, muscle endurance, flexibility, balance, nimbleness.
Significant reductions in:Tension, Depression, Anger, Fatigue, and Total Mood Disturbance (TMD)
The Long-Term Effect of Aquarobics Exercise Program on Physical Function and Mental Health in Elderly Women. IIl-Myeong Kim, Sung-Jin Kim, Hae-Ryoung Park, Ji-Hyang Lim, Sung-Woon Kim. Indian Journal of Science and Technology, Vol 8(26), IPL0499, October 2015.
36
Functional Assessment Staging of Alzheimer’s disease (FAST)Moderate to severe dementia range
Exploring the effect of aquatic exercise on behavior and psychological well-being in people with moderate to severe dementia: A pilot study of the Watermemories Swimming Club. Neville Christine, Henwood Tim, Beattie Elizabeth, and Fielding Elaine. Australian Journal on Ageing, Vol 33 No 2. June 2014, 124-127.
37
Psychological Well-Being in Cognitively Impaired Persons Scale (PW-BCIP)Patients showed a statistically significant increase in their psychological well-being
Revised Memory and Behavior Problems Checklist (RMBPC)Significant decrease in psychological symptoms of dementia towards
other residents as well as staff and family
Exploring the effect of aquatic exercise on behavior and psychological well-being in people with moderate to severe dementia: A pilot study of the Watermemories Swimming Club. Neville Christine, Henwood Tim, Beattie Elizabeth, and Fielding Elaine. Australian Journal on Ageing, Vol 33 No 2. June 2014, 124-127.
Becker, Bruce MD &Cole, Andrew MD
(2011)
ComprehensiveAquatic Therapy
3rd edition.
Pullman, WA
Washington State University Publishing
42
60% in thoracic blood volume 35% in cardiac stroke volumeREST = Land-basedcardiovascular activity
CirculatorySystem
43
44
StructureofEndothelialNitricOxideSynthase.DelkerSL,XueF,LiH,JamalJ,SilvermanRB,PoulosTL.
CirculatorySystem
&Nitric Oxide
Imageby:JamesHeilman,MD-thepicturewastakenwiththepaIent'spermission,CCBY-SA3.0,h[ps://upload.wikimedia.org/wikipedia/commons/7/70/Rheumatoid_ArthriIs.JPG
Land Treadmill participants had no increase in eNOS
Aquatic Treadmill participants had an average of 31% increase in eNOS 24 hours following their sessions.
47
CirculatorySystem
Aquatictreadmilltrainingreducesbloodpressurereactivitytophysicalstress.Lambert,etal.MSSE46:4,2014,809-816.
Link between endothelial dysfunction and Alzheimer disease.
Yi Chu, and Donald D. Heistad Circ Res. 2010;107:1400-1402
Copyright © American Heart Association, Inc. All rights reserved.
NO Answer to Alzheimer’s Disease?
48
NOAnswertoAlzheimer’sDisease?YiChu,DonaldD.Heistad.CirculationReserch.2010;107:1400-1402.doi:10.1161/CIRCRESAHA.110.234450
NitricOxide=Amyloid
49
Exercise=
Aquatic Exercise =
é
ê
éééNitricOxide
NitricOxideNeurotrophicFactors
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