Tsolaki

www.alzheimer-hellas.gr

Physical activities and Cognitive function

Magda Tsolaki, MD, PhDNeuropsychiatrist

Professor of Aristotle University of Thessaloniki

Chair of Greek Alzheimer Federation

Age is #1 Dementia Risk Factor

04/08/23

Numbers in Greece

1.Prevalence , 9% in subjects more than 70 in Pylea, Thessaloniki2. In Great Alexander municipality

3,6% >65 Tsolaki M. et al, AJAD, 1999 Tsolaki M. et al, ADI2010

Family Ε4 (11% vs 32%) Olive oil

MINDMINDYOUR BODYYOUR BODY

and YOUR BRAINand YOUR BRAIN

Alzheimer Disease Progression Deterioration

Time in years

Mooddisturbances

Cognitiveimpairments

Impaired activities of daily living ADL

Behaviouraldisturbances

Motordisorders

From S GAUTHIER 1996

Clinical Phase

?

LITERATURE

• Participation in both aerobic and resistance training exercises alone, and in combination, leads to sustained improvements in cognitive performance, particularly for executive control tasks

(MEDICINE & SCIENCE IN SPORTS & EXERCISE, 2009; 1510-1530)

Guidelines for Physical Activities

Physical Exercise:Mechanisms of action

1.CNS neuronal apoptosis is a consequence of exercise in the adult rat and suggests that this process is a potential mediator of rapid exercise-induced plasticity. Exercise in mouse models causes neurogenesis in the dentate gyrus.

Alzheimers Res Ther. 2011 Feb

Physical Exercise:Mechanisms of action

2.Exercise engages arousal mechanisms in the reticular-activating system, which involves a big number of neurotransmitter systems.

3. Exercise, also, disengages the higher-order functions of the prefrontal cortex.

4. Improvement of blood circulation and brain oxygen supply J. Am Geriatr. Soc., 38, 123-128, 1990.

Πιθανή επίδραση των παρεμβάσεων στην καθυστέρηση της εμφάνισης της νόσου Alzheimer

1997 2007 2017 2027 2037 2047

Year

ΗΠΑΕπιπολασμός

της ΝΑ(εκατ)

ΝΑ = Alzheimer’s Disease.Brookmeyer R et al. Am J Public Health. 1998;88:1337-1342.

Καθυστέρηση(χρόνια)

00.51.0

2.05.0

8

6

4

2

0

Possible effect of interventions which delay the onset of dementia

Prevalence in USA

Delay (years)

ANIMAL MODELS (Combination of

physical and cognitive exercise )

NBBMBNMBNMBSSS

Other MECHANISMS The current experiment assessed levels

of apoptosis, angiogenesis, and neurogenesis during the first week of an exercise regimen in the adult rat. The results indicate that exercise rapidly induces these processes in the hippocampus and cerebellum

Behav Neurosci. 2011 Feb

TRIALS IN HUMANS(ONLY PHYSICAL EXERCISE)

ACSM (American College of Sports Medicine), 2009

• At least 3 times a week for two weeks• ~ 1 hour

• Warm-up period 5-10 min. Warm-up period 5-10 min. • Main Part 40-50 min.Main Part 40-50 min.

1.1. Stretching 8-10 min.Stretching 8-10 min.2.2. Strength (upper body) 10-15 minStrength (upper body) 10-15 min3.3. Flexibility - Aerobic 8-10 min.Flexibility - Aerobic 8-10 min.4. Balance – Strength (lower body) 15 min.

• Cool down period 5 min

FFA, FFA, Scientific issuesScientific issues Organized interventions

of Increased difficulty

Assessment

Subjective criteria:Heart rate and blood pressure

Subjective criteria: Borg Scale

Borg Scale

Physical exercise and cognitive function

Multiple results of physical exercise on cognitive function3 reviews -meta-analysis and 7 studies

Principles

Scientific model of improvement of cognitive functions – clear methodology and targetSeverity of exercise according the abilities of participants. – step by step changes of exercisesEvery patient can do different activities Balance between duration of exercise and frequency

Physical exercise and Cognitive function

Principles of body exerciseMedical follow upOrganization of the program according abilitiesUse of experienceEncourage of independence

Characteristics of exercise:Simple, preparation– main part- relaxationSocialization

Physical exercise and Cognitive function

SuggestionsDuration (31 – 45 mins)Bigger improvement (more than 6 months). Moderate aerobic exercise

Authors Year Participants Intervention Results

Molloy et al 1988 N=15,

MMSE: 24

1st group: mild aerobic exercise 45΄/ once a week for two

weeks

2nd group: no intervention

Improvement in verbal fluency

Mulrow et al 1994 N=194,

MMSE: 21

1st group ασκήσεις ενδυνάμωσης, ισορροπίας,

κινητικότητας.2η ομάδα: φιλικές

επισκέψεις.45΄/ 3 φορές την

εβδομάδα/ 16 εβδομάδες

Moderate motor improvement

Baum et al 2003 N=20

MMSE: 21

1η ομάδα: εύρος κινητικότητας

καθισμένου2η ομάδα:

ψυχαγωγικές δραστηριότητες60΄/ 3 φορές την

εβδομάδα/ 6 μήνες

Improvement in physical status and MMSE

Stevens et al 2006

N=75MMSE:9 - 23

1η ομάδα: σωματική άσκηση

2η ομάδα: κοινωνικές επισκέψεις

30΄/ 3 φορές την εβδομάδα/ 12

εβδομάδες2η ομάδα: καμία

παρέμβαση

Delay of cognitive and physical deterioration

Physical Exercise Proximal F/U

Hillman et al. Nature Reviews Neuroscience (2008)

RCT of PEx in MCI with Longitudinal FU

Lautenschlager et al. 2008

RCT of PEx in MCI with Longitudinal FU

RCT of PEx in MCI with Longitudinal FU

RCT of PEx in MCI with Longitudinal FU

PEx Reorganises Hippocampal Synaptic Connectivity

Joyce Siette In preparation

What about combining cBT and PEx?

TRIALS IN HUMAN(PROTECTIVE)

Can Physical Exercise Prevent Cognitive

Decline?

PHYSICAL EXERCISE AND DEMENTIA

Physical activity or exercise can prevent or delay the onset of age-related cognitive impairment or dementia (Middleton K.R., 2007)

Positive effects of physical activity on attention, memory, communication, executive functions and global mental functioning, in older people with dementia.

(Eggermont L., Swaab D., et al, 2005; Fang Yu, Kolanowski A. M., 2006)

TRIALS IN HUMAN(THERAPEUTIC)

OUR EXPERIENCE RHEA, a non pharmacological

cognitive training intervention in patients with Mild Cognitive Impairment (MCI): A Pilot Study

  Kounti F, 1, 2 Bakoglidou E, 1, 2

Agogiatou C, 1, 2 Emerson Lombardo NB,5 Serper LL,4 Tsolaki M1, 2, 3

PARTICIPANTS 58 MCI patients with MMSE=27.69,

assigned to 2 groups of 29 each (experimental, 20-weekly RHEA sessions, and no-therapy control), matched for age, gender, education, cholinesterase inhibitors, cognitive abilities.

NEUROPSYCHOLOGICAL TESTS• MMSE [Mini Mental State Examination-MMSE (Roth,

Huppert, Tum, & Mouthjoy, 1988)] • TEA [Test of Every Day Attention(Robertson et al.,

1989)] • RBMT [Rivermead Behavioural Memory Test (Wilson et

al.,1989)]

• ROCFT [Rey Osterreith Complex Figure Test (Rey,1941)]

NEUROPSYCHOLOGICAL TESTS

• FUCAS [Functional Cognitive Assessment Scale-FUCAS (Kounti, Efklides, Tsolaki, & Kiosseoglou, 2006)]

• WCST [Wisconsin Card Sorting Test (Berg, 1948)]

• ΧΣΑ [Verbal fluency (Kosmidis, Vlachou, Panagiotaki, & Kiosseoglou, 2004)]

• FRSSD [Functional Rating Scale of Symptoms of Dementia-FRSSD (Hutton, 1990)]

RHEA Intervention Design and Rationale

• The RHEA intervention was 90 minutes duration, once a week, for 20 weeks.

• The tasks are ecological. The stimuli that are used are shapes, colours, sizes, and numbers. The technical materials include wreath, boards with letters, cards with colours, shapes and numbers, corridors with numbers, balls, wands, rings, and cones.

RHEA Intervention Design and Rationale

• Each session includes 5 exercises lasting approximately 15 minutes each.

• The program has tasks with an increasing degree of difficulty varying according to the cognitive and kinetic performance of the participants

1st Exercise (Free movements)

1st Exercise (Free movements)

2nd Exercise: Walking

2nd Exercise (Walking)

3rd Exercise (Balance)

3rd Exercise (Balance)

4th Exercise (mild movement abilities)

4th Exercise (mild movement abilities)

5th Exercise (Free voluntary movements)

5th Exercise (Free voluntary movements)

Results (MCI)The benefit of the experimental group was in

Attention (p=0.002), Language(p=0.015), Visual-spatial (p=0.013), MMSE (p=0.047), ADL(p=0.009). Experimental participants improved cognitive and

functional performances while control participants remained stable.

OUR EXPERIENCE

EFFECTS OF AN EXERCISE INTERVENTION ON COGNITIVE FUNCTION OF ALZHEIMER’S DISEASE

PATIENTS

C.A. Mouzakidis, M.Tsolaki

METHODS

24 AD patients

Exercise Group (n=12). Mean Age = 65.70, SD = 7.73, Education = 9.33, SD = 2.90. Control Group (n=12). Mean Age = 68.50, SD = 3.87, Education = 8.92, SD = 4.72.

AssessmentCognitive Functions (MMSE)

Psychomotor Measures

Equipment• Colored easy controlled balls, sticks, hoops of different

sizes, plastic bottles, soda cans, tennis balls, chairs, dumbbells.

Duration36 weeks (3

times/week)90 minutes/time

Description of Exercise Program• Warm up Period (30’). Aerobic & range of motion

exercises• Main Exercise Period (50’). flexibility, strength of upper

and lower limbs, endurance, dexterity, balance, agility, speed, attention and accuracy, co-ordination, orientation, memory, self-control, and co-operation

• Cool down Period (10’). Main purpose to allow the heart rate to return to normal and the body to relax.

RESULTS

The patients of the exercise group managed to maintain their cognitive and functional abilities, while the patients of the control group deteriorated.

Exercise Group (n = 12)

Control Group(n = 12)

BeforeMean (SD)

AfterΜean (SD)

BeforeΜean (SD)

AfterΜean (SD)

MMSE 18,50 (8,85) 18,33 (9,02) 16,25 (5,64) 12,83 (5,57)*

*p< 0.05

Soda Pop Test 12 16.50 (±11.79) 13.20 (±11.20) NS

Finger Dexterity 12 29.75 (±31.00) 25.85 (±23.26) NS

Hand Tapping 12 62.00 (±19.00) 70.00 (±11.67) NS

Reaction Time (cm) 12 38.50 (±15.51) 29.70 (±13.75) p = 0.001

Repetitive Arm and Hand Movements

Right Hand 12 3.21 (±0.97) 2.75 (±0.74) p = 0.001

Left Hand 12 3.44(±0.97) 3.00 (±0.78) p = 0.010

Grip Test (kg)

Right Hand 12 27.58 (±6.37) 30.00 (±7.29) p = 0.007

Left Hand 12 24.33 (±7.40) 26.50 (±8.10) p = 0.007

Sequential Arm and Hand Movements 12 1.75 (±2.05) 0.83 (±2.00) p = 0.050

Reeling String on a Stick 11 17.17 (±11.93) 15.22 (±11.00) p = 0.001

Bounce a Ball 12 2.17 (±2.21) 1.08 (±2.06) NS

Throw a Ball to a target 12 2.08 (±1.24) 0.92 (±1.24) p = 0.004

Bowling 12 2.17 (±2.33) 3.50 (±2.71) NS

Gait Control 11 0.45 (±1.21) 0.09 (±0.30) NS

Static Balance 12 25.17 (±22.61) 33.81 (±23.57) p = 0.008

Step Into and Out of a Hoop 12 0.83 (±1.64) 1.58 (±2.35) NS

Sit and Reach Test 12 49.25 (±13.50) 52.17 (±15.35) p = 0.006

Agility 12 7.00 (±4.26) 8.25 (±5.67) NSNS = non-significant

OUR EXPERIENCE (MCI) Tsolaki M, Kounti F, Agogiatou C, Poptsi E,

Bakoglidou E, Zafeiropoulou M, Soumbourou A, Nikolaidou E, Batsila G, Siambani A, Nakou S, Mouzakidis C, Tsiakiri A, Zafeiropoulos S, Karagiozi K, Messini C, Diamantidou A, Vasiloglou M.

Effectiveness of Nonpharmacological Approaches in Patients with Mild Cognitive Impairment. Neurodegener Dis. 2010 Dec 3

ΝΟΣΟΣ ΝΟΣΟΣ ALZHEIMERALZHEIMER

Μάγδα Τσολάκη,Μάγδα Τσολάκη, MD, PhD MD, PhDΝευρολόγος-Ψυχίατρος, Νευρολόγος-Ψυχίατρος,

Θεολόγος,Θεολόγος,Αναπληρώτρια Καθηγήτρια, Αναπληρώτρια Καθηγήτρια,

Α.Π.Θ.Α.Π.Θ.Πρόεδρος της Ελληνικής Πρόεδρος της Ελληνικής

Ομοσπονδίας Νόσου Ομοσπονδίας Νόσου AlzheimerAlzheimer

CLINICAL TRIALS(Combination of

physical and cognitive exercise )

What is LLM ?

• Long Lasting Memories (LLM) is an integrated ICT platform which:

combines state-of-the-art cognitive exercises with physical activityin the framework of an advanced ambient assisted living environment.

20112011

Component 1: Effects of Physical Exercise in the Elderly

• Regular physical exercise, significantly improves physical functioning of individuals at any age

• Engagement of elderly individuals in regular physical exercise programs has demonstrated improvement in

aerobic capacity, muscular strength, muscular endurance, flexibility, balance,

motor control and performance, skill acquisition, coordination, cognition and psychological well being

(www.who.int/hpr/ageing/heidelberg_eng.pdf)

20112011

LLM Design Idea

20112011

The PilotsPilots in 5 countries

Austria Spain France Greece Cyprus

20112011

2011

Expected Results

pre post

Cogn

itive

Fun

ctio

n

Theory Expected Results

Results from Konstanz:10 weeks physical training2 x 45 min/week

Hertzog et al., 2009

LLM

Control

ΓΙΑΤΙ ΟΧΙ AKOMH ΣΤΟ ΑΙΜΑ;

Thank you very much for your attention