A REVIEW OF THREE STUDIES

DESPINA MORA ITOU & G EORG IA PA PA NTONIOU

A RISTOTLE UN IVERSITY OF THESSALONIKIUN IVERSITY OF IOA N N INA

Cognitive Control & Theory of Mind in Mild Cognitive Impairment

and Dementia

IntroductionMild Cognitive Impairment (MCI)

General term most commonly used to define a subtle butmeasurable memory impairment.

Clinical and Cognitive Criteria:

1. Subjective report of memory problems2. Greater than normal memory impairment detected with

standard memory assessment tests3. Normal general thinking and reasoning skills4. Ability to perform typically the daily activities

(American Academy of Neurology, 2001)

IntroductionAlzheimer’s Disease (AD) AD is a progressive, degenerative disorder that attacks

the brain's neurons, resulting in loss of memory,thinking and language skills and behavioral changes.

Clinical Criteria:A.1 Memory impairmentA.2 one (or more) of Aphasia / Apraxia / Agnosia / executive dysfunctionC. gradual onset and continuing cognitive declineD. A1 and A2 are not due to any of the following: central nervous system

diseases, Parkinson’s & Huntigton’s disease, systemic conditions thatare known to cause dementia (e.g., hypothyroidism), substance –induced conditions

E. Deficits don’t occur during the course of deliriumF. is not better accounted for by another Axis I disorder (DSM-5, 2013)

IntroductionFrontotemporal Dementia (FTD)

Cluster of syndromes which result from the frontal andtemporal lobe degeneration

Main clinical characteristics: progressive personality and behavioral changes or/and language deficits

Includes three clinical variants:1. Progressive non-fluent Aphasia (PNFA)2. Semantic Dementia (SD)3. behavioral or frontal variant of FTD (fvFTD)

(Adenzato et al., 2010; Gregory et al., 1999; Schroeter et al., 2007)

IntroductionfvFrontotemporal Dementia (fvFTD)

Main Clinical Diagnostic Features of fvFTD:

Marked changes in personality Dramatic alteration in social functioning Socially inappropriate and disinhibited behavior Lack of empathy or concern for others Apathy

(Gregory et al., 2002; Brune et al., 2006)

Brain areas mainly affected during early stages are theventromedial PFC, left and right anterior mPFC, medialorbitofrontal cortex, right anterior insula, and anteriorcingulate.

(Adenzato et al., 2010)

Introduction

Vascular Dementia (VaD) a group of dementias associated with vascular

brain lesions which can cause ischemic injuriesand hemodynamic disorders. Vascular lesions canbe either diffused or focal and can influencecognitive skills.

(Ballogiannis, 2012; Korczyn, Vakhapova, & Grinberg, 2012; Reilly, Rodriguez, Lamy, & Nells-Strunjas, 2010)

New term => major Vascular Neurocognitive Disorder(mVNCD)

DSM-5 (2013)

Introduction

Vascular Dementia (VaD) Clinical Diagnostic Features of VaD:

significant cognitive decline from a previous level ofperformance in one or more cognitive domains

clinical evidence which is consistent with a vascularetiology

sufficient evidence of cerebrovascular disease derivedfrom history, physical examination and/or neuroimagingmethods

cognitive deficits which are not better explained byanother organic or cerebral disease

IntroductionVascular hypothesis of cognitive aging

Risk factors for the emergence of vascular disease, such as

hypertension, hyperlipidemia, and diabetes mellitus, affect

cognitive functions that are supported by the frontal brain

regions

(Anstey, 2008; Gauthier et al., 2015; Lindeboom & Weinstein, 2004; Zhong et al., 2014)

IntroductionExecutive Functions (EF) or Cognitive control (Cc)

• cognitive processes that control thought and action• supported primarily by the prefrontal cortex

(Miller & Cohen, 2001; Miller & Wallis, 2009; Miyake et al., 2000)

1. Inhibitory control2. Task/rule switching/Shifting3. Planning

Introduction

Theory of Mind (ToM)

a complex mental function that refers to the abilityto attribute mental states to oneself and others

(Premack & Woodruff, 1978)

two types: cognitive and affective(Brothers & Ring, 1992)

prefrontal cortex (orbital frontal regions and themedial prefrontal cortex)

(Shamay-Tsoory & Aharon-Peretz, 2007)

Aim

The common aim of each of the three studiespresented was the examination of the level of

main dimensions of Cc specific ToM abilities the interconnections between Cc & ToM

in MCI, AD, or fvFTD, or VaD older-adult-patients,compared to community dwelling older adultshaving or not Vascular Risk Factors (VRF)

Participants (study 1)

Gender: χ2(2)=4.85, p>.05 Educational level: χ2(4)=2.85, p>.05 Age: F(2, 53)=.09, p>.05; age-range: 65-85 years MMSE: F(2, 54)=28.31, p<.001 (VRF & MCI vs. AD)

Total Sample

VRF group (n=22)

MCI group(n=17)

AD group(n=15)

Method

Participants (study 2)

Groups 1 and 2 were both consisted of cognitively healthy adults Participants of VRF and fvFTD groups were matched for: gender [x2(1) = .279, p > .05] age [t(28) = .561, p > .05], age-range: 50-88 years educational level [x2(2) = .00, p > .05]

Total Sample

Healthy controls (n=13)

VRF group(n=15)

fvFTD group(n=15)

Method

Participants (study 3)

Participants of VRF and VaD groups did not differ significantly in: age [t(38) = .81, p > .05] gender [t(38) = .94, p > .05] educational level [t(38) = .20, p > .05]

Total Sample

Young-adult controls (n=20)

VRF group(n=20)

VaD group(n=20)

Method

Measures

Cc => 4 testsD-KEFS Color-Word Interference Test (C-WIT)

(Delis, Kaplan, & Cramer, 2001): 4 conditions

Color Naming (90΄΄) Word Reading ((90΄΄)

Inhibitory Control (180΄΄): verbal inhibition. Cognitive flexibility [Inhibitory Control & Task

Switching (180΄΄)]

Measures

D-KEFS Verbal Fluency Test (VFT) (Delis, Kaplan, &

Cramer, 2001): 3 conditions

Letter Fluency (60΄΄): initiation, inhibition. Category Fluency (60΄΄): initiation, inhibition. Category Switching (60΄΄): cognitive flexibility

(initiation, inhibition, & rule switching).

Measures

D-KEFS Design Fluency Test (DFT) (Delis, Kaplan, &

Cramer, 2001): 3 conditions

Filled Dots (60΄΄): initiation, simultaneousprocessing , nonverbal creativity.

Empty Dots Only (60΄΄): added demand ofinhibitory control.

Dot Switching (60΄΄): added demands of cognitiveshifting (cognitive flexibility as inhibitorycontrol & switching).

Measures

D-KEFS Tower Test (TT) (Delis, Kaplan, & Cramer, 2001):

9 conditions

Objective => to move disks varying in size acrossthree pegs to build a “tower” in the fewestnumber of moves possible and by followingtwo rules.

EF tapped => Spatial Planning + Rule Learning +Inhibitory Control + Working Memory

MeasuresTASIT – Emotion Evaluation Test (EET)

(McDonald, Flanagan, & Rollins, 2001)

Examines a person’s ability to identify six basic emotions,namely happiness, pleasant surprise, sadness,anger, anxiety, disgust and discriminate these fromneutral expressions.

28 alternative forms of a series of short videotapedvignettes of people (actors) interacting in ‘everyday’situations.

Administration => with the sound turned off, so as to focuson the ability to read dynamic visual cues.

MeasuresToM: indirect speech understandingTASIT – Social Inference (SI-m) (McDonald,

Flanagan, & Rollins, 2001)

examines the viewer’s ability to determine thespeaker’s meaning and intentions based upon thedialogue, emotional expression, and otherparalinguistic cues.

Three types of exchanges (in 15 scenes): Sincere: the text and the cues are consistent Simple sarcastic: it needs to read the paralinguistic

cues of the sarcastic speaker Paradoxical sarcastic: the dialogue does not make

sense unless it is understood that one is beingsarcastic

Cognitive Control Theory of Mind

Main constructs measured

Inhibitory Control (IC)

Cognitive Flexibility [IC & Switching(S)]

Planning(IC & S & WM)

Emotion Recognition

Indirect Speech Understanding

SimpleSarcasm

ParadoxicalSarcasm

Procedure

All participants participated voluntary All participants signed an “Informed Consent” formThey were examined on an individual basisTesting took place over three sessionsThe tests were administered in random order, to

avoid sequence effects.

Statistical AnalysesSPSS 22

Mixed ANOVAs To explain possible interaction effects:

ANOVAsRepeated Measures ANOVAs MANOVAs

EQS 6.1 (Bentler, 2005)Multi-group Path Analyses

Robust Maximum Likelihood estimationprocedureIndices of good fit of the SEM models (Brown,2012):

RMSEA < .05 (close fit), .06 - .08 (good fit)CFI > .90 (reasonably good fit)Non-significant χ2

Results

Study 1: differences between VRF & MCI groups Cc Tower Test=> group differences, F(8, 98)=4.02, p<.001, ηp

2 =.25;

n of problems administered => VRF vs. MCI & AD,F(2, 51)=12.93, p<.001, ηp

2 =.34; MVRF=8.2, MMCI=6.8, MAD=6.5;

n of moves => VRF vs. MCI & AD, F(2, 51)=21.04, p<.001, ηp2

=.45; MVRF=107, MMCI=37.7, MAD=22.6;

Move accuracy ratio => VRF vs. MCI & AD, F(2,51)=15.36, p<.001, ηp

2 =.37; MVRF=1.4, MMCI=0.8, MAD=0.6;

Emotion recognition & ToM:no differences

Study 1: VRF & MCI vs. AD groupCc: C-WIT Inhibitory control => AD vs. VRF & MCI, F(4, 92)=3.74, p<.05, ηp

2 =.14;

Inhibitory control & task switching => AD attritionMostly, non-corrected errors => AD vs. VRF & MCI groups

Cc: VFT Category fluency =>AD vs. VRF & MCI groups, F(6, 100)=4.47, p<.001, ηp

2

=.21:

Switching (n) => AD vs. VRF (MVRF=11.3, MMCI=9.8, MAD=6.6; F(2, 51)=6.76,p<.005, ηp

2 =.21)

Cc: TTAll measures => AD vs. VRF & MCI groups

Total TT achievement score => VRF & MCI vs. AD, F(2, 51)=5.05,p<.01, ηp

2 =.17; MVRF=12, MMCI=9.4, MAD=7.8;

Emotion recognition & ToM: no differences

Results[VRF vs. MCI vs. AD] Τhe effects of planning (TT) on social inference X2(4)=2.08, p>.05, CFI=1.00, RMSEA < .001 (90%CI: .00-.15);

VRF Total score

.71(.70)

.34(.94)

.69(.73)

.53

Simple sarcasm

Paradoxical sarcasm .56

MCI Total score

Simple sarcasm

Paradoxical sarcasm

AD Simple sarcasm AD Paradoxical sarcasm

Study 1: Conclusions

MCI patients display a lower level of complex Cc abilities,such as planning, compared to older adults with VRF.

AD patients display the lowest level of Cc, compared tothe other two groups. Even the simpler Cc abilities appearto be degraded in this group.

Older adults with VRF recruit Cc abilities for specificdimensions of complex ToM tasks.

MCI patients recruit the same Cc abilities more globally,perhaps for compensation reasons.

AD patients appear unable to apply Cc abilities to ToMtasks.

Results

Study 2: differences between HC, VRF & fvFTDgroups

there were no significant differences between theHC and VRF groups in all measures

Cc: fvFTD: impaired in comparison to HC & VRF in somemeasures of:

Inhibitory control Planning

Emotion recognition: fvFTD: impairment in: decoding of all emotions (except happiness) decoding of the neutral condition

Results

Study 2: differences between HC, VRF & fvFTD groupsToM => fvFTD impairment in:

Sincere exchanges understanding Intention recognition Meaning understanding Beliefs understanding Emotion recognition

Simple sarcasm understanding Intention recognition Beliefs understanding

Paradoxical sarcasm understanding Meaning understanding Emotion recognition

ResultsModels (n=9) of Cc & SC relationships

C-WIT (inhibitory control) effects on emotion recognitionx2(1)=.40, p>.05, CFI=1.00, RMSEA=.00 (90%CI: .00-.41)

-.59(.80)VRFInhibitory control

(total error score)

Emotion Recognition

fvFTDInhibitory control

(total error score)Emotion

Recognition

Study 2: ConclusionsMain deficits in fvFTD

Emotion recognition Sincere exchanges Sarcasm (indirect speech) understanding

Cognitive control and social cognition relationshipin the early fvFTD

fvFTD patients’ fail to activate any EF during ToM tasksand, consequently, it seems that the interconnectionsamong Cc and SC are impaired

Results

Study 3: differences between YC, VRF & VaD groupsthere were significant differences among the YC

and VRF and VaD groups in the most of themeasures

Cc: VaD: impaired in comparison to YC & VRF in:C-WIT Inhibitory control & task switching => VaD attritionTT Planning => VaD impairment in all measures

Emotion recognition & ToM: no differences

Study 3: ConclusionsDeficits in complex or/and combined executive functionsare more prominent in VaD patients, compared to basicabilities of cognitive control.

Cognitive planning is considerably affected by VaDprogression even in the very first stages.

The performance of older adults with VaD was significantlyaffected by precision in movements. According to Delis etal. (2001), a close-to-zero ratio in precision in movementsand a low total achievement score indicate one’s

inability to find correct problem-solving strategies

VaD patients systematically presented this behavioralpattern.

Conclusions

Cc and ToM abilities’ impairment differs indifferent types of dementia. Hence, aneuropsychological battery that includes simpleand more complex measures of both of themshould be used as a diagnostic tool.

At the empirical level, more research is needed, inorder to reveal the prototype of theinterconnections of Cc and ToM abilities in MCIand dementia.

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