1. Alzheimer Hellas

2. 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Greece

1. Alzheimer Hellas

2. 3rd Department of Neurology, Medical School, Aristotle University of Thessaloniki, Greece

Longitudinal cognitive training changes the conversion’s rate of

Mild Cognitive Impairment to dementia

Kounti, F.1, Poptsi, E.1, Agogiatou, C.1, Bakoglidou, E. 1, Soumpourou A. 1, Zafeiropoulos, S. 1, Batsila G. 1, Nikolaidou,

E. 1, Vasiloglou, M. 1, Ouzouni, F. 1, Markou N. 1, Zafeiropoulou, M. 1, Tsolaki, M. 1, 2

Mild Cognitive Impairment

Mild Cognitive Impairment

MCI represents a transitional state between the cognitive changes of aging and the earliest clinical features of dementia

(Petersen, 2003; Petersen et al., 2001)

MCI patients are at increased risk for the development of dementia

(Bruscoli & Lovestone, 2004; Petersen, 2004)

MCI represents a transitional state between the cognitive changes of aging and the earliest clinical features of dementia

(Petersen, 2003; Petersen et al., 2001)

MCI patients are at increased risk for the development of dementia

(Bruscoli & Lovestone, 2004; Petersen, 2004)

MCI patients progress to dementia at very different

rates

MCI patients progress to dementia at very different

rates

aMCImd patients appear to be at greatest risk for future dementia(Di Carlo et al., 2007; Palmer et al., 2008; Tabert et al., 2006 Ravaglia et al., 2006)

Less than 20% of patients with aMCImd revert to normal aging (Loewenstein, et al., 2009)

Others remain stable upon retest(Bickel et al., 2006)

aMCImd patients appear to be at greatest risk for future dementia(Di Carlo et al., 2007; Palmer et al., 2008; Tabert et al., 2006 Ravaglia et al., 2006)

Less than 20% of patients with aMCImd revert to normal aging (Loewenstein, et al., 2009)

Others remain stable upon retest(Bickel et al., 2006)

Neurogenesis in aging (hippocampus)

Neurogenesis in aging (hippocampus)

ChEIs and Mild Cognitive Impairment

ChEIs and Mild Cognitive Impairment

ChEIs in patients with MCI are not associated with any delay in the onset of dementia The risks associated with ChEIs are not negligible(Raschetti et al., 2007)

It is important to study the possibility of cognitive training to improve cognitive and functional performance

ChEIs in patients with MCI are not associated with any delay in the onset of dementia The risks associated with ChEIs are not negligible(Raschetti et al., 2007)

It is important to study the possibility of cognitive training to improve cognitive and functional performance

Aims of non pharmacological

therapies

Aims of non pharmacological

therapiesAim of cognitive therapy:

Cognitive improvementDelay of conversion rate to dementia

Expected results:Reactivation of atrophic neurons in patients with MCI(Swabb, 1994) Maintenance of regenerated neurons after cognitive training for a long period of time

Aim of cognitive therapy:Cognitive improvementDelay of conversion rate to dementia

Expected results:Reactivation of atrophic neurons in patients with MCI(Swabb, 1994) Maintenance of regenerated neurons after cognitive training for a long period of time

The studyThe study

aMCImd patients

Non pharmacological therapy (cognitive training)

64 sessions (in a period of 2 years)

2 groups (experimental and control)

aMCImd patients

Non pharmacological therapy (cognitive training)

64 sessions (in a period of 2 years)

2 groups (experimental and control)

Study hypothesesStudy hypotheses

Experimental group:Improvement of targeted cognitive abilities (attention - parameters of executive function) Generalization of cognitive benefit in other cognitive domains through the consolidation of new learningDelay of conversion rate to dementia

Control Group:Stability of cognitive performance, a slight deterioration or a slight improvement, two years after the initial assessment

Experimental group:Improvement of targeted cognitive abilities (attention - parameters of executive function) Generalization of cognitive benefit in other cognitive domains through the consolidation of new learningDelay of conversion rate to dementia

Control Group:Stability of cognitive performance, a slight deterioration or a slight improvement, two years after the initial assessment

ParticipantsParticipants

Inclusion criteria:60 years of age

Subjective cognitive complaints

aMCImd diagnosis (Petersen’s criteria 2001)

MMSE: 26-30 points

Spared language skills(speech comprehension or production)

Inclusion criteria:60 years of age

Subjective cognitive complaints

aMCImd diagnosis (Petersen’s criteria 2001)

MMSE: 26-30 points

Spared language skills(speech comprehension or production)

ParticipantsParticipants

Exclusion criteria:Diagnosis of dementia

(NINCDS-ADRDA criteria-McKahnn et al., 1984)Severe psychotic traits (untreated depression, agitation or behavioral problems) Other neurological disorders (stroke or ischemic lesions)AntipsychoticsChEIsDifficulties in sensory abilities

Exclusion criteria:Diagnosis of dementia

(NINCDS-ADRDA criteria-McKahnn et al., 1984)Severe psychotic traits (untreated depression, agitation or behavioral problems) Other neurological disorders (stroke or ischemic lesions)AntipsychoticsChEIsDifficulties in sensory abilities

ParticipantsParticipants

Outpatients of the memory and dementia clinic of “G.Papanikolaou” General Hospital and of the day care centers of Alzheimer HellasArea of Northern HellasPatients visited these sources voluntarily and signed an informed consent

Outpatients of the memory and dementia clinic of “G.Papanikolaou” General Hospital and of the day care centers of Alzheimer HellasArea of Northern HellasPatients visited these sources voluntarily and signed an informed consent

ParticipantsParticipants

ParticipantsParticipants

No statistically significant differences between the two groups at baseline

In age, education, gender, cognitive and functional performance

Controls did not take part in any kind of cognitive therapy

They continued their regular daily activities

No statistically significant differences between the two groups at baseline

In age, education, gender, cognitive and functional performance

Controls did not take part in any kind of cognitive therapy

They continued their regular daily activities

Sample CharacteristicsSample Characteristics

Characteristics/Cognitive/Functional Performance*M (SD)

Control Group (n=45)

Experimental Group (n=95)

p

Age 68.00

(8.62)

60.01 (7.34) .312

Gender (Male/Female) Fisher’s test .073

Education 10.40

(4.11)

11.17 (4.44) .117

Global cognitive function (Total MMSE) 28.28

(1.35)

27.71 (1.77) .046

Global cognitive function (Total MoCA) 23.23

(2.84)

23.05 (2.79) .328

ADL (Total FRSSD) 4.33 (1.73) 3.83 (1.92) .081

ADL (Total FUCAS) 43.00

(1.34)

43.34 (1.33) .060

Neuropsychological assessment

Neuropsychological assessment

1st assessment: at baseline

2nd assessment: 2 years later, at the end of the therapy

1st assessment: at baseline

2nd assessment: 2 years later, at the end of the therapy

Neuropsychological battery

Neuropsychological battery

MEMORYRivermead Behavioral Memory test (RBMT)Rey Auditory Verbal Learning Test (RAVLT)Rey – Osterrieth Complex figure Test (ROCFT)

ATTENTIONTest of Everyday Attention (TEA) WAIS-R (DIDIT SYMBOL)

LANGUAGEBoston Naming Test (BNT)Verbal fluency test (ΧΣΑ)

MEMORYRivermead Behavioral Memory test (RBMT)Rey Auditory Verbal Learning Test (RAVLT)Rey – Osterrieth Complex figure Test (ROCFT)

ATTENTIONTest of Everyday Attention (TEA) WAIS-R (DIDIT SYMBOL)

LANGUAGEBoston Naming Test (BNT)Verbal fluency test (ΧΣΑ)

EXECUTIVE FUNCTION Wisconsin Card Sorting Test (WCST)Trail-making Test Part B (TRAIL B)Stroop Color Word test (SCWT)Functional Cognitive Assessment Scale (FUCAS-EXECUTIVE FUNCTION)

GENERAL COGNITIVE FUNCTIONMini Mental State Examination (MMSE)Montreal Cognitive Assessment (MoCA)

ADLFunctional Rating Scale of Symptoms of Dementia (FRSSD)Functional Cognitive Assessment Scale (FUCAS-ADL)

EXECUTIVE FUNCTION Wisconsin Card Sorting Test (WCST)Trail-making Test Part B (TRAIL B)Stroop Color Word test (SCWT)Functional Cognitive Assessment Scale (FUCAS-EXECUTIVE FUNCTION)

GENERAL COGNITIVE FUNCTIONMini Mental State Examination (MMSE)Montreal Cognitive Assessment (MoCA)

ADLFunctional Rating Scale of Symptoms of Dementia (FRSSD)Functional Cognitive Assessment Scale (FUCAS-ADL)

Therapeutic techniquesTherapeutic techniques

Cognitive Training techniques of Attention and Cognitive Parameters of Executive Function through:Paper and pencil tasks Kinetic instructions Mental Imagery under Relaxation Musical Stimuli Reality Orientation in Currents EventsComputer softwareEach trainee took part in a specific therapeutic combination of techniques, related to his/her residual abilities and impaired functions

Cognitive Training techniques of Attention and Cognitive Parameters of Executive Function through:Paper and pencil tasks Kinetic instructions Mental Imagery under Relaxation Musical Stimuli Reality Orientation in Currents EventsComputer softwareEach trainee took part in a specific therapeutic combination of techniques, related to his/her residual abilities and impaired functions

Statistical analysis Statistical analysis

SPSS 17.0 software programKolmogorov-Smirnov Z-testNonparametric testsMann–Whitney test for 2 independent samples (Monte Carlo method) between groups comparisonsWilcoxon test for 2 related samples, within group comparisons

Bonferonni correction was used in order to make our significance criterion more conservative

SPSS 17.0 software programKolmogorov-Smirnov Z-testNonparametric testsMann–Whitney test for 2 independent samples (Monte Carlo method) between groups comparisonsWilcoxon test for 2 related samples, within group comparisons

Bonferonni correction was used in order to make our significance criterion more conservative

Study ResultsStudy Results

Between groups comparison

Between groups comparison

Experimental group in comparison to controls had better performance

in:

attention (p= .009)

visual memory (p= .043)

executive function (p≤ .000)

Experimental group in comparison to controls had better performance

in:

attention (p= .009)

visual memory (p= .043)

executive function (p≤ .000)

At the end of the intervention

(2 years period)

At the end of the intervention

(2 years period)

Ability Control Group *M (SD) (N=45) Experimental Group *M (SD) (N=95) p

Global cognitive function (Total MoCA) 23.64 (4.04) 24.29 (3.66) NS

ADL (Total FRSSD) 3.83 (2.02) 3.38 (1.42) NS

ADL (Total FUCAS) 43.71 (1.99) 43.14 (1.39) NS

ATTENTION

Inhibition interference (STROOP) -5.78 (9.00) -1.86 (7.40) NS

Digit symbol (WAIS - R) 29.36 (13.17) 30.43 (10.35) NS

Auditory sustained attention (MoCA) .82 (.38) .97 (.16) .009

VERBAL MEMORY

Learning ability (RAVLT) 10.97 (2.53) 11.30 (2.74) NS

Delayed recall (RAVLT) 8.27 (3.21) 11.30 (2.74) NS

Immediate story recall (RBMT) 12.23 (3.25) 13.12 (3.14) NS

Delayed story recall (RBMT) 11.42 (3.75) 12.40 (3.29) NS

VISUAL MEMORY 29.01 (6.29) 30.50 (4.54)

Complex figure delayed recall (ROCFT) 13.40 (6.86) 15.92 (7.00) .043

VISUAL CONSTRUCTIVE ABILITIES

Complex figure copy (ROCFT) 29.01 (6.29) 30.50 (4.54) NS

LANGUAGE

Naming without help (per cent %) (BNT) 79.65 (16.10) 78.88 (14.70) NS

EXECUTIVE FUNCTION

Phonemic verbal fluency (FAS) 9.82 (2.49) 11.95 (3.41) .000

Trail making part B (TRAIL B) 249.68 (138.18) 204.06 (96.45) NS

Planning (FUCAS) 6.20 (.45) 6.03 (.17) .004

Working memory (MoCA) 2.53 (.75) 2.81 (.42) NS

Within Group Comparisons between the 1st and the 2nd

assessment

Within Group Comparisons between the 1st and the 2nd

assessment

abilities of attention (p≤ .002) executive function (p≤ .008) verbal memory (p≤ .003) visual memory (p= .000)language (p= .000)

global cognitive performance (p= .028)

abilities of attention (p≤ .002) executive function (p≤ .008) verbal memory (p≤ .003) visual memory (p= .000)language (p= .000)

global cognitive performance (p= .028)

Experimental group

After two years’ participation in cognitive training

Experimental group

After two years’ participation in cognitive training

Has shown improvement in:

Ability Μ(SD)* 1st Assessment M (SD)* 2nd Assessment p

Global cognitive function (Total MoCA) 23.05 (2.79) 24.29 (3.66) .000

ADL (Total FRSSD) 3.83 (1.92) 3.38 (1.42) NS

ADL (Total FUCAS) 43.34 (1.33) 43.14 (1.39) NS

ATTENTION

Visual selective attention (TEA) 27.83 (10.07) 30.30 (9.53) .001

Speed of selective attention (multiple choices) (TEA) 5.16 (2.05) 4.81 (1.39) .003

Inhibition interference (STROOP) -4.57 (7.04) -1.86 (7.40) .002

Digit symbol (WAIS - R) 28.10 (9.50) 30.43 (10.35) .001

Auditory sustained attention (MoCA) .93 (.25) .97 (.16) NS

Digit span (RAVLT) 4.94 (2.07) 5.72 (2.22) .002

VERBAL MEMORY

Learning ability (RAVLT) 10.59 (2.75) 11.30 (2.74) .003

Delayed recall (RAVLT) 7.14 (3.56) 11.30 (2.74) .000

Immediate story recall (RBMT) 13.10 (3.18) 13.12 (3.14) NS

Delayed story recall (RBMT) 12.15 (3.57) 12.40 (3.29) NS

VISUAL MEMORY

Complex figure delayed recall (ROCFT) 12.11 (6.04) 15.92 (7.00) .000

VISUAL CONSTRUCTIVE ABILITIES

Complex figure copy (ROCFT) 29.71 (4.64) 30.50 (4.54) NS

LANGUAGE

Naming without help (per cent %) (BNT) 71.95 (15.14) 78.88 (14.70) .000

EXECUTIVE FUNCTION

Numbers of trials attempted (WCST) 91.97 (20.50) 88.61 (16.94) .005

Perseverative responses (WCST) 11.65 (8.81) 9.32 (6.38) .001

Phonemic verbal fluency (FAS) 9.57 (2.70) 11.95 (3.41) .000

Trail making part B (TRAIL B) 229.79 (97.17) 204.06 (96.45) .002

Planning (FUCAS) 6.03 (.17) 6.03 (.17) NS

Working memory (MoCA) 2.80 (.45) 2.81 (.42) NS

Within Group Comparisons between the 1st and the 2nd

assessment

Within Group Comparisons between the 1st and the 2nd

assessment

Significant improvement in:

visual memory (p= .006)attention (p= .007)

Significant deterioration in: executive function (p≤ .006)

The rest of the cognitive abilities remained stable

Significant improvement in:

visual memory (p= .006)attention (p= .007)

Significant deterioration in: executive function (p≤ .006)

The rest of the cognitive abilities remained stable

After two years

control group

has shown:

After two years

control group

has shown:

Ability Μ(SD)* 1st Assessment M (SD)* 2nd Assessment p

Global cognitive function (Total MoCA) 23.23 (2.84) 23.64 (4.04) NS

ADL (Total FRSSD) 4.33 (1.73) 3.83 (2.02) NS

ADL (Total FUCAS) 43.00 (1.34) 43.71 (1.99) NS

ATTENTION

Inhibition interference (STROOP) -3.98 (10.56) -5.78 (9.00) NS

Digit symbol (WAIS - R) 27.61 (11.51) 29.36 (13.17) NS

Auditory sustained attention (MoCA) .94 (.22) .82 (.38) NS

Digit span (RAVLT) 4.20 (1.50) 4.92 (2.10) .007

VERBAL MEMORY

Learning ability (RAVLT) 10.84 (2.28) 10.97 (2.53) NS

Delayed recall (RAVLT) 8.15 (3.23) 8.27 (3.21) NS

Immediate story recall (RBMT) 12.82 (3.33) 12.23 (3.25) NS

Delayed story recall (RBMT) 12.20 (3.25) 11.42 (3.75) NS

VISUAL MEMORY

Complex figure delayed recall (ROCFT) 11.31 (4.76) 13.40 (6.86) .006

VISUAL CONSTRUCTIVE ABILITIES

Complex figure copy (ROCFT) 29.64 (5.29) 29.01 (6.29) NS

LANGUAGE

Naming without help (per cent %) (BNT) 69.69 (14.17) 79.65 (16.10) NS

EXECUTIVE FUNCTION

Phonemic verbal fluency (FAS) 9.46 (2.13) 9.82 (2.49) NS

Trail making part B (TRAIL B) 205.29 (102.62) 249.68 (138.18) .000

Planning (FUCAS) 6.02 (.15) 6.20 (.45) NS

Working memory (MoCA) 2.86 (.34) 2.53 (.75) .006

Conversion to dementia

Conversion to dementia

6 patients (13.33%) out of the controls converted to dementia, as they fulfilled the dysfunction criteria for dementia (performance in FUCAS’ ADL ≥ 47)

NONE of the experimental group converted to dementia after two years of participation in cognitive training

6 patients (13.33%) out of the controls converted to dementia, as they fulfilled the dysfunction criteria for dementia (performance in FUCAS’ ADL ≥ 47)

NONE of the experimental group converted to dementia after two years of participation in cognitive training

Conclusions Conclusions

Cognitive training helped experimental patients to: Cognitive training helped experimental patients to:

Improve abilities of attention and executive functionGeneralize the cognitive benefit in visual memory, language & verbal memoryStabilize ADL Minimize the rate of conversion to dementia

Improve abilities of attention and executive functionGeneralize the cognitive benefit in visual memory, language & verbal memoryStabilize ADL Minimize the rate of conversion to dementia

Further studies are needed in order to examine the longitudinal effectiveness of cognitive training in MCI

Further studies are needed in order to examine the longitudinal effectiveness of cognitive training in MCI

Thank youThank you

Contact e-mail: elpida.alz@gmail.come.poptsi@alzheimer-hellas.gr

Contact e-mail: elpida.alz@gmail.come.poptsi@alzheimer-hellas.gr

for your attentio

n