Impaired Social Cognition in Mild Alzheimer Disease

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Journal of Geriatric Psychiatry and Neurology

DOI: 10.1177/0891988709332939 2009; 22; 130 originally published online Mar 25, 2009; J Geriatr Psychiatry Neurol

Alain Vighetto and Pierre Krolak-Salmon Benoit Bediou, Ilham Ryff, Bernadette Mercier, Maud Milliery, Marie-Anne Hénaff, Thierry D'Amato, Marc Bonnefoy,

Impaired Social Cognition in Mild Alzheimer Disease

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Impaired Social Cognition in MildAlzheimer Disease

Benoit Bediou, PhD, Ilham Ryff, MSc, Bernadette Mercier, MSc,Maud Milliery, MSc, Marie-Anne Henaff, MSc,Thierry D’Amato, MD, PhD, Marc Bonnefoy, MD, PhD,Alain Vighetto, MD, PhD, and Pierre Krolak-Salmon, MD, PhD

Abnormal decoding of social information has beenassociated with the conversion from prodromalAlzheimer’s disease (AD) to dementia. Since the dis-tributed neural networks involved in face processingare differentially affected in prodromal and dementiastates of AD and in Fronto-Temporal Dementia (FTD),we hypothezed a differential impairment in face pro-cessing in these populations. Facial expression, genderand gaze direction decoding abilities were examined inpatients with probable amnesic Mild Cognitive Impair-ment (aMCI, N ¼ 10) fulfilling criteria for prodromalAD, in patients with mild and moderate AD (N ¼ 10)

as well as in FTD patients (N ¼ 10) and in a groupof age- and sex-matched healthy comparison subjects(N ¼ 10). Gender recognition was preserved in allgroups. Compared to controls, patients with mild ormoderate AD were impaired in expression recognitionand FTD patients were impaired in expression and gazedirection determination, whereas MCI patients werenot impaired at all.

Keywords: social cognition; face processing; Alzheimerdisease; frontotemporal dementia; mild cognitiveimpairment; temporal lobe

Introduction

The ability to accurately decode facial emotionalexpressions is probably one of the most powerful vec-tors of nonverbal communication, involving a complex

neural circuitry. An impairment of that function maylead to interpersonal miscomprehension and socialdysfunction.1 Neurodegenerative diseases affectingneural networks involved in facial expression process-ing may thus be marked by an early and disproportion-ate impairment in social life. Indeed, Parkinson andHuntington diseases affecting dopaminergic networksand basal ganglia involved in negative emotion andreward processing associated with abnormal decodingof negative facial expressions.2-4 Likewise, frontotem-poral dementia (FTD), affecting temporal and frontalparts of the face processing networks, is also charac-terized by early social dysfunction and early facialexpression decoding impairment.5

Social cognition, and particularly face processingabilities, has rarely been explored in mild Alzheimerdisease (AD) and has yielded inconsistent results.6,7

Hence, the social dysfunction described at milddementia states of AD is poorly understood. In par-ticular, it remains unclear how early the neurodegen-erative processes leading to dementia of Alzheimertype alter the ability to process basic social signals

Received December 18, 2007. Revised received June 18, 2008.Accepted for publication June 25, 2008.

From the Universite de Lyon, EA 4166 Lyon, France (BB, TD);Centre Hospitalier « Le Vinatier », Bron, F-69677, France (BB,TD); Inserm U821, Centre hospitalier Le Vinatier, Bron,F-69677, France (M-AH, PK-S); Hospices Civils de Lyon, Hopitalneurologique, Service de Neurologie, Lyon, F-69003, France(IR, BM, MM, AV); Hospices Civils de Lyon, Centre HospitalierLyon Sud, Service de Medecine Geriatrique, Lyon, F-69003,France (MB, PK-S); Universite de Lyon, Lyon, F-69003, France(BB, TD, MB, AV, PK-S); and IFR19, Bron, F-69500, France(BB, M-AH, TD, MB, AV, PK-S).

There are no actual or potential conflicts of interest related tothis work.

Address correspondence to: Benoit Bediou, Swiss Center forAffective Sciences, CISA, University of Geneva, Rue desBattoirs 7, 1205 Geneva, Switzerland; e-mail: [email protected].

130

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June 2009 130-140

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such as facial expressions. Alzheimer disease isindeed heralded by a progressive episodic amnesia,which has been related to medial temporal neurofi-brillary tangle (NT) pathology affecting entorhinalcortex and hippocampus.8 This stage of the diseaseusually corresponds to amnesic mild cognitiveimpairment (aMCI)9 or prodromal AD.10 The pro-gression of NT pathology toward neocortical areas,especially external temporal associative regions, ismarked by autonomy loss and social withdrawal thatare classically observed at the dementia stage.11 How-ever, the clinical detection of the conversion fromaMCI toward mild dementia states is often challen-ging, one main point being to diagnose an autonomyimpairment in domestic, social, or professional life.We investigated whether mild dementia stages ofAD and aMCI or prodromal stages are associated withreduced facial expression decoding abilities.

Face perception involves distributed neural sys-tems.12 In particular, several parts of the temporalassociative neocortex may be differentially involvedin the processing of distinct face features. Crucially,lateral temporal neocortical areas like the superiortemporal sulcus (STS) participating in the process-ing of socially meaningful variant face features suchas expressions and gaze are already affected at milddementia stages of AD.8 Conversely, more posteriorventral occipitotemporal areas involved in the pro-cessing of invariant face features like gender13 areaffected only at later stages of AD pathology.

The conversion from aMCI to mild dementiastate of AD being marked by progression of NTpathology from medial temporal lobe to associativeneocortical areas including the STS, we expectedfacial expression decoding to be impaired at mildand moderate stages of AD but not at prodromalAD, corresponding to aMCI state. Moreover, sucha deficit in facial expression processing may be dis-proportionately severe compared to the processingof invariant facial features like gender involving moreposterior areas not affected in AD. Frontotemporaldementia being characterized by more diffuse tem-poral lesions extending toward frontal cortex, we alsoexpected facial expression decoding to be altered inthese patients who may additionally be impaired ingaze processing. To address these hypotheses, weengaged patient with aMCI (prodromal AD) andmildly demented AD patients as well as patients withFTD and healthy comparison participants in faceprocessing tasks focusing on facial expression, facialgender, and gaze direction. To investigate whethersuch differential impairment can be observed in

relatively small samples, we used an innovative sti-mulating technique based on morphed faces as thistechnique has been shown sensitive enough to revealsubtle impairments in healthy populations at risk forschizophrenia.14

Methods

Participants

The study sample consisted of 10 patients withaMCI as diagnosed according to consensus criteria15

(5 men; mean age ¼ 73 + 9 years; mean MMS[MiniMental State] score ¼ 27 + 2), 10 patients withmild dementia related to AD16 (5 men; mean age:72 + 9 years; mean MMS score ¼ 21 + 2),10 patients with FTD17 (5 men; mean age: 67 +7 years; mean MMS score¼ 24 + 4), and 10 healthycontrols (5 men; mean age: 70 + 6; mean MMSscore¼ 30). Groups were matched in age and genderrepartition. All participants gave their informedconsent after detailed information regarding thestudy. The study was conducted in accordance withthe latest version of the Declaration of Helsinki andits design has been approved by the local ethicalcommittee.

Patients and controls were recruited at theNeurological Hospital of Lyon. All participants gavetheir informed consent and underwent structuredneurological interview and examination as well asneuropsychological testing to assess diagnosis cri-teria. Antipsychotic medication, previous history ofsevere medical or surgical illness, and other neurolo-gical or visual disorder were exclusion criteria in allgroups. All participants had normal or corrected tonormal visual acuity.

Neuropsychological Testing

The neuropsychological evaluation consisted inexploration of global cognition with the Mini MentalState Examination (MMSE),18 of episodic memorywith the RL/RI-16 test controlling semantic encod-ing, storage, and retrieval19 and memory efficiencytest,20 of executive functions with the Trail MakingTest—Part B21 and with verbal fluencies,22 of lan-guage with a 36 picture naming task. Mood was eval-uated with the Beck’s scale.23 Table 1 shows theneuropsychological performance for each patientgroup and correlation with facial expression recogni-tion performance. The coefficients of correlationsbetween cognitive performance and emotion

Face Processing in Dementia / Bediou et al 131



recognition performance are also provided for thewhole group; no significant correlation emerged.However, these results should be interpreted cau-tiously given that correlations could not be calcu-lated separately for each group and therefore onlyincluded a small number of participants with differ-ent performance at cognitive and emotion tasks.

Tasks and Stimuli

The participants were involved in 3 different tasksrequiring detection of faces depicting variousdegrees of emotion expression, gender, or various eyegaze angles. Examples of face stimuli are presentedat the bottom of Figure 1 for facial expressions,Figure 2 for gaze directions, and Figure 3 for gen-ders. The same timing and sequence of events wasapplied; each face appeared in the center of a com-puter screen for 1 second and was preceded by a fixa-tion cross (500 milliseconds) and followed by a list ofexpression labels (response screen) that lasted untilparticipant’s response. A more detailed descriptionof the tasks can be found elsewhere.14,24,25

Facial Expression Task

Face photographs of 2 females and 2 males depicting4 basic emotions (happiness, fear, anger, and dis-gust) morphed with a neutral face in 20% steps fora total of 96 photographs were randomly presented.Each trial consisted of the following events: a fixa-tion cross (500 milliseconds) followed by a face(1000 milliseconds) and then the choice list (untilresponse). Participants were asked to decide which

of 5 labels (neutral, happy, angry, fearful, or dis-gusted) best described facial expression shown usinga forced-choice paradigm.

Facial Gender Task

Face photographs of 8 females and 8 males morphedwith an average face in 20% steps for a total of 96photographs were randomly presented. All faces hada neutral expression. Face presentation was based onsimilar parameters: fixation cross (500 milliseconds),face (1000 milliseconds), and choice list (untilresponse). A forced-choice task (man or woman) wasused to assess participant ability to determine facegender.

Eye Gaze Direction Task

Face photographs of 4 females and 4 males lookingtoward the right or to the left by 5�, 10�, 15�, 20�,25�, or 30� of visual angle for a total of 96 imageswere randomly presented. Similar timing of eventswas used: 500 milliseconds fixation cross, 1000milliseconds face, and choice screen until response.The task was to determine eye gaze direction using aforced-choice task (left or right).

Statistical Analyses

Because of small sample sizes in the current experi-ment (N ¼ 10 per group), nonparametric statisticaltests were used to test our effects of interest. We firstinvestigated whether the 4 groups were differentiallyimpaired on the 3 face processing tasks. This was

Table 1. Neuropsychological Performance and Pearson’s Coefficients of Correlation With Emotion Recognitionfor the 3 Patient Groupsa

aMCI Mild AD Dementia FTD Correlation With Emotion Recognition

Mean (SD)/N Mean (SD)/N Mean (SD)/N Pearson (p)/N

MMSE 27.0 (1.7)/10 21.1 (1.6)/10 24.1 (3.8)/10 .12 (.52)/30RL/RI16 36.2 (2.5)/9 28.3 (8.6)/7 42.9 (3.1)/8 –.23 (.27)/24TMT-B 222.1 (33.9)/8 262.5 (30.5)/8 241.2 (35.7)/6 –.18 (.43)/22Verbal fluency (alpha) 17.1 (8.3)/9 13.7 (3.2)/8 11.4 (7.3)/8 .28 (.18)/24Verbal fluency (categ) 23.5 (3.6)/8 16.3 (5.2)/8 14.6 (6.7)/8 .29 (.18)/24Denomination 35.6 (1.1)/8 34.9 (1.7)/8 30.1 (5.8)/8 .22 (.31)/24BECK 3.4 (2.3)/10 4.6 (2.6)/10 4.8 (2.7)/10 .14 (.47)/30

NOTES: AD ¼ Alzheimer’s disease; alpha ¼ alphabetical; BECK ¼ Beck’s scale23; categ ¼ categorical verbal fluencies22; denomi-nation ¼ 36 picture naming task; aMCI ¼ amnestic mild cognitive impairment; FTD ¼ frontotemporal dementia; MMSE ¼ MiniMental State Examination18; N¼ number of participants included in the calculation of the mean, standard deviation, and correlation;P¼ statistical significance (2-tailed); RL/RI-16 episodic memory test (sum of total scores) controlling semantic encoding, storage andretrieval19; SD, standard deviation; TMT-B ¼ Trail Making Test-Part B21.a Not all participants could perform all the tasks.

132 Journal of Geriatric Psychiatry and Neurology / Vol. 22, No. 2, June 2009



0%

20%

40%

60%

80%

100%

120%

20% 40% 60% 80% 100% Overall

Cor

rect

Res

pons

es

CTL aMCI Mild AD dementia FTDCTL aMCI Mild AD dementia FTD

Disgust

Happiness

Anger

Fear

cccbb

cce

bbcce

cce

cce

Figure 1. Correct responses (%) in emotion recognition as a function of intensity and overall performance averaged acrossintensities (each point corresponds to averaged performance across different expressions). Significant difference comparedwith controls (Mann-Whitney tests): aMCI versus CTL, a ¼ P < .05, aa ¼ P < .01; mild AD dementia versus CTL, b ¼ P < .05, bb ¼P < .01; FTD versus CTL, c ¼ P < .05, cc ¼ P < .01; aMCI versus mild AD dementia, d ¼ P < .05, dd ¼ P < .01; mild AD dementiaversus FTD, e ¼ P < .05, ee ¼ P < .01. Examples of 4 different morphed faces depicting various intensities of each emotionalexpression are shown at the bottom of the figure. AD indicates Alzheimer disease; aMCI ¼ amnestic mild cognitive impairment;CTL ¼ healthy controls; FTD ¼ frontotemporal dementia.




tested by submitting the overall percentage of correctresponses in each task to Kruskal-Wallis analysisof variance (ANOVA) examining the factors group(mild AD dementia, aMCI, FTD, and controls;between participants) and task (emotion, gender, andgaze direction; within participants). For tasks associ-ated with significant group effects, Mann-Whitneytests were used to further assess between-group dif-ferences. Then, the factor intensity on one hand and

the factors expression category (happy, angry, fearful,or disgusted), gender category (male or female), andgaze direction (left or right) on the other hand, wereanalyzed separately.

For tasks associated with a significant groupeffect, Kruskal-Wallis analyses of variance furtherexamined the factors group (between participants)and intensity (within participants) separately for eachtask (ie, emotion, gaze, or gender discrimination).

0%

20%

40%

60%

80%

100%

120%

5º 10º 15º 20º 25º 30º Overall

Cor

rect

Res

pons

es

CTL aMCI Mild AD dementia FTDCTL aMCI Mild AD dementia FTD

Left

Right

cceecc

ee

ccee

ccee

ccee

ccee

ccceee

Figure 2. Correct responses (%) in gaze direction determination as a function of gaze angle and overall performance averagedacross various the whole set of angles (each point corresponds to averaged performance across both gaze directions). Significantdifference compared with controls (Mann-Whitney tests): aMCI versus CTL, a ¼ P < .05, aa ¼ P < .01; mild AD dementia versusCTL, b¼ P < .05, bb¼ P < .01; FTD versus CTL, c¼ P < .05, cc¼ P < .01; aMCI versus mild AD dementia, d¼ P < .05, dd¼ P < .01;mild AD dementia versus FTD, e ¼ P < .05, ee ¼ P < .01. At the bottom of the figure are shown examples of morphed faces depictingvarious gaze directions and angles. AD indicates Alzheimer disease; aMCI ¼ amnestic mild cognitive impairment; CTL ¼ healthycontrols; FTD ¼ frontotemporal dementia.




Please, note here that the factor intensity refers eitherto the percentage of emotional morph, to the percent-age of gender morph, or to the eye gaze visual angledepending on the task. The other (within participant)factors were examined separately for each task withgroup� expression, group� gender, and group� gazedirection Kruskal-Wallis analyses of variance assessingpotential selective deficits in the discrimination of a

particular level of emotion, gender, or gaze direction.Significant effects were further addressed forbetween-group comparisons with Mann-Whitney tests.Exact probabilities (permutation-based P values) arereported instead of Z approximations as they are moreadapted to small samples (N ¼ 10).

Following this statistical approach, data reportedin tables represent group performance averaged

0%

20%

40%

60%

80%

100%

120%

20% 40% 60% 80% 100% Overall

Cor

rect

Res

pons

es

CTL aMCI Mild AD dementiaFTD CTL aMCIMild AD dementia FTD

Male

Female

Figure 3. Gender recognition performance in the studied groups across the various intensities of gender morphs and overallperformance across the whole set of gender intensities (each point corresponds to averaged performance across both genders).Significant difference compared with controls (Mann-Whitney tests): aMCI versus CTL, a ¼ P < .05, aa ¼ P < .01; mild AD dementiaversus CTL, b ¼ P < .05, bb ¼ P < .01; FTD versus CTL, c ¼ P < .05, cc ¼ P < .01; aMCI versus mild AD dementia, d ¼ P < .05,dd ¼ P < .01; mild AD dementia versus FTD, e ¼ P < .05, ee ¼ P < .01. At the bottom of the figure are shown the morphed facesdepicting the various intensities of male and female gender morphs. AD indicates Alzheimer disease; aMCI ¼ amnestic mild cognitiveimpairment; CTL ¼ healthy controls; FTD ¼ frontotemporal dementia.




across the whole set of intensities for each condition(ie, expressions, genders, or gaze directions). Con-versely, data presented in figures represent perfor-mance averaged across the whole set of conditions(ie, expressions, genders or gaze directions) for eachintensity.

Results

Descriptive statistics are summarized in Table 2.

All Tasks

The group � task Kruskal-Wallis ANOVA showed asignificant main effect of group in the emotion task[H(3,40)¼ 19.71, P < .001] and in the gaze directiontask [H(3,40) ¼ 18.69, P < .001] but not in the gen-der task [H(3,40) ¼ 3.58, P > .3]. Between-groupcomparisons using Mann-Whitney tests showed thatmild AD demented patients performed worse thanhealthy participants in facial expression detection(U ¼ 23; Z ¼ 2.05; exact P < .05) and that patientswith FTD performed worse than healthy participantsin facial expression detection (U ¼ 2.5; Z ¼ 3.6;exact P < .001) and in gaze direction discrimination(U ¼ 3.5; Z ¼ 3.35; exact P < .001). Patients withFTD also differed from mild AD demented patientsin expression detection (U ¼ 16; Z ¼ 2.58; exactP < .01) and gaze discrimination (U ¼ 5; Z ¼ 3.41;

P < .001). In contrast, participants with aMCIshowed no impairment in any of the tasks in compar-ison to healthy participants.

The expression and gaze direction tasks beingassociated with significant group effects, the factorsintensity, expression category, and gaze directionwere further explored. Figures 1 and 2 show perfor-mance of the 4 groups in the expression and gazedirection tasks at various intensities of expressionand various gaze angles, respectively. Figure 3 showsperformance of the 4 groups in the gender task.

Expression Task

The group � expression category Kruskal-Wallis testshowed significant group differences in the detectionof disgust [H(3,40) ¼ 19.02, P < .001], happiness[H(3,40) ¼ 8.67, P < .05], and a trend toward groupdifferences for anger [H(3,40) ¼ 6.57, P < .09] butno group difference in the detection of fear[H(3,40) ¼ 4.75, P > .1]. Between-group compari-sons revealed a weak but significant deficit in angerdetection (U ¼ 24; Z ¼ 1.99; exact P < .05) and atrend toward worse detection of happiness (U ¼25.5; Z ¼ 1.88; exact P < .07) in mild AD dementedpatients compared with healthy participants. Patientswith FTD differed from healthy participants in detec-tion of disgust (U¼ 0; Z¼ 3.79; exact P < .001), hap-piness (U ¼ 20.5; Z ¼ 2.24; exact P < .05), and

Table 2. Correct Responses (%) for the Detection of Facial Expression, Gaze Direction, and Gender in the 4Groupsa

CTL (N ¼ 10) aMCI (N ¼ 10) Mild AD dementia (N ¼ 10) FTD (N ¼ 10)

Mean (SD) Mean (SD) Mean (SD) Mean (SD)

Emotion 56.8 (10) 53.6 (7.9) 47.0 (7.9)b,ee 34.9 (6.1)ccc,ee

Disgust 69 (8.8) 68 (14.4) 57.5 (14.4)ee 32.5 (15.1)ccc,ee

Anger 40 (14.5) 35.5 (17.1) 28 (17.1)b 25.5 (12.8)Happiness 77 (11.8) 74.5 (10.1) 70 (10.1) 55.5 (23.2)c

Fear 41 (17.1) 36.5 (16.5) 32.5 (16.5) 26.0 (10.2)c

Gaze direction 95 (4.1) 91.6 (8.9) 90.3 (8.9) 58.8 (19.9)ccc

Left 95.7 (3.3) 93.7 (7.5) 91.5 (7.5) 62.1 (21.9)ccc

Right 94.3 (5.5) 89.5 (11.4) 89.2 (11.4) 55.4 (21.5)ccc

Gender 77.2 (8.4) 78.1 (3.8) 75.5 (3.8) 70.01 (10.2)Female 83.3 (8.8) 84.5 (9.7) 76.2 (9.7) 69.4 (17.2)Male 76.2 (8.3) 71.8 (9.5) 74.9 (9.5) 70.67 (10.9)

NOTES: AD ¼ Alzheimer’s Disease; aMCI ¼ amnestic mild cognitive impairment; CTL ¼ healthy comparison group; FTD ¼ fronto-temporal dementia.a Significant difference compared with controls (Mann-Whitney tests): aMCI versus CTL, a ¼ P < .05, aa ¼ P < .01, aaa ¼ P < .001;mild AD dementia versus CTL, b¼ P < .05, bb¼ P < .01, bbb¼ P < .001; FTD versus CTL, c¼ P < .05, cc¼ P < .01, ccc ¼ P < .001;aMCI versus mild AD dementia, d ¼ P < .05, dd ¼ P < .01, ddd ¼ P < .001; mild AD dementia versus FTD, e ¼ P < .05, ee ¼ P < .01,eee ¼ P < .001. Significant differences compared to controls are shown in bold.




fear (U ¼ 23.5; Z ¼ 2.03; exact P < .05), whereas thedifference between FTD and healthy participantsfor anger detection only approached significance(U ¼ 24.5; Z ¼ 1.94; exact P < .06). Frontotemporaldementia also showed worse detection of disgustcompared to mild AD demented patients (U ¼ 15.5;Z ¼ 2.62; exact P < .01). No other between-group dif-ference was found (Table 2).

The group � intensity Kruskal-Wallis ANOVAshowed group differences in emotion detectionwith morphing intensities of 40% [H(3,40) ¼ 14.87,P < .01], 60% [H(3,40) ¼ 20.25, P < .001], 80%[H(3,40) ¼ 16.08, P < .01], and 100% [H(3,40) ¼14.41, P < .01]. Mild AD demented patients differedfrom healthy participants at 60% of morphing inten-sity only (U ¼ 14; Z ¼ 2.76; P < .01) and there wasa nonsignificant trend at 40% (U ¼ 27.5; Z ¼ 1.75;P < .09). Patients with FTD differed from healthy par-ticipants from 40% to 100% of morphing intensities(all P < .01) and they differed from mild AD dementedpatients from 40% to 100% (all P < .05).

Gaze Task

The group � gaze direction Kruskal-Wallis ANOVAshowed group differences in both gaze directions [leftgaze: H(3,40) ¼ 18.41, P < .001; right: H(3,40) ¼18.29, P < .001], reflecting impaired discriminationof left and right gaze orientations in patients with FTDcompared to healthy participants [left gaze: U ¼ 1;Z ¼ 3.72; P < .001; right: U ¼ 5; Z ¼ 3.41; P < .001].

The group � gaze intensity Kruskal-Wallis anal-ysis showed a main effect of group at all gaze angles(all P < .01). Post hoc Mann-Whitney tests showedthat these effects reflected worse gaze direction dis-crimination in patients with FTD compared withhealthy participants at all gaze angles (all P < .01).Similar effects were found when comparing patientswith FTD with mild AD demented patients (allP < .01; Figure 2).

Discussion

This study investigated whether impaired social mes-sage detection from faces is a hallmark of the conver-sion from prodromal AD to mild dementia states ofAD. Facial expression, gender, and gaze directiondecoding abilities were examined in patients affectedby aMCI and in patients with mild AD dementia incomparison to healthy controls and to patientsaffected by FTD. Mildly demented AD patients were

impaired in facial expression detection and patientswith FTD were impaired in facial expression detec-tion as well as in gaze direction determination,whereas patients with aMCI and healthy controls didnot differ significantly on any of the tasks. In accor-dance with our hypothesis, gender detection was pre-served in all groups.

Face processing models12,26 have disentangleddifferent neural systems involved in detection ofidentity, gender, age, eye gaze, lip movements, andemotional expression. Invariant facial features likeidentity, gender, and ethnicity may be mainly pro-cessed by posterior occipitotemporal areas,27 asopposed to variant facial features such as emotionalexpression, eye gaze, and lip movements, involvingmore anterior structures such as STS, amygdala,and orbitofrontal cortex.28-30 These latter variantfacial features are particularly important for socialcommunication.

The discrepancy between the aMCI group andthe mild AD dementia group in overall task perfor-mance for facial emotional expression detection,normal in the former group and impaired in the lat-ter, may reflect the progression of AD pathology fromentorhinal cortex and hippocampus toward lateraltemporal neocortex including the STS.31 Moreover,our finding that patients with aMCI were notimpaired relative to healthy participants in emotionalexpression, eye gaze, and gender discrimination inthe current study is consistent with an exclusivemedial temporal lobe involvement in the pathologi-cal processes leading to isolated amnesic disorders.In accordance with this, a recent study disclosed nor-mal performance in facial affect discrimination insingle-domain MCI, as opposed to multiple-domainMCI.32 Indeed, multiple-domain MCI is generallyassociated with more diffuse neuropathologicallesions and altered cognitive functioning.9

Crucially, in AD, the conversion from the aMCIstate to the mild dementia state coincides with theimpairment of daily life activities and social beha-vior.33 Our study shows that these behaviouralchanges are accompanied by an impairment of socialmessage detection, particularly facial emotionalexpression. Although it is not clear yet how this def-icit relates to their social functioning outside thelaboratory, impaired processing of emotional expres-sions may likely participate in early social behaviorchanges and in the impairment of patient autonomyand quality of life at the mild dementia stage ofAD.1,33 An impairment of facial expression detectionin AD has been previously observed at moderate or




severe stages34-36 (but see Ref 37). However, thepresence of a deficit at mild dementia stage remainedcontroversial.6,7 Our finding of an early impairmentin mild AD dementia for the processing of a variantfacial feature, for example, emotional expression,as compared to an invariant facial feature, for exam-ple, gender, is also consistent with an earlier altera-tion of lateral temporal lobe structures and a longerpreservation of occipital cortex. Interestingly, perfor-mance of participants with aMCI appeared similar tothat of mild AD demented patients when emotionalexpression was more subtle (until 40%), whereas itwas more comparable to that of controls at higherintensities of emotional expression (80%-100%; Fig-ure 1). However, the direct (exploratory) between-group comparison showed no significant differencein facial expression detection between aMCI andcontrols or between aMCI and mild AD dementia,suggesting that intermediate performance in facialexpression detection in aMCI may reflect an emer-ging deficit worsening with the progression of ADneuropathology toward STS, a progression that mayalso coincide with the appearance of social dysfunc-tion. Our results thus fit with the concept of a neu-ropathological and functional continuum betweenaMCI, suggestive of prodromal AD and dementiaof AD type.10

The direct between-group comparison allowedby our study shows that patients with FTD are dis-proportionately impaired in social message detec-tion, particularly variant facial features such asemotional expression and gaze direction, relative topatients with AD. This dramatic impairment of facialexpression recognition in FTD38-40 may be related togreater atrophy of the amygdala and prefrontal corti-cal regions.41,42 Consistent with this, eye gaze pro-cessing, which involves the amygdala,29,43 theSTS44 and the orbitofrontal cortex45 was alsoimpaired in the FTD population but not in mildAD dementia. However, it remains to be examinedwhether gaze processing is impaired at later stagesof AD pathology. Contrary to the decline in emotionrecognition observed with the progression of ADneuropathology, emotion recognition ability appearsrelatively stable in the course of FTD.39 Our resultsshow that the deficit observed in patients with FTDnot only affects the detection of negative emotions46

but it also affects the detection of happiness. Thisconsistent with a previous study5 suggesting thatpatients with frontal variant FTD were impaired inthe recognition of negative (sadness, anger, fear) aswell as positive (happiness) facial expressions, while

patients with temporal variant FTD showed impair-ment for negative emotions only. However, theabsence of deficit for happiness detection in somestudies47 may also reflect a ceiling effect that mightencourage the use of more sensitive and ecologicaltechniques using emotional expressions graded inintensity. Previous research suggests that the visualprocessing of the eyes region is particularly relevantto the recognition of facial expression.28,48 More-over, there is growing evidence that emotionalexpression and gaze direction are processed in over-lapping brain networks, especially the amygdala,49,50

which is particularly affected by FTD.41,42 One pos-sibility then is that patients with FTD do not focustheir gaze on the eye region, which is crucial for therecognition of facial expression.

Our study is original in dealing with several cru-cial issues. First, the study of mild AD dementedpatients and patients with aMCI compared to con-trols on the same tasks and paradigms suggests thatthe emotion processing deficit may be covariant withthe conversion from aMCI to mild AD dementia,concurring with the onset of social dysfunctions thatare critical in the diagnosis of mild dementia. Sec-ond, the direct comparison of mild AD dementedpatients with patients with FTD shows that the latterare more dramatically impaired in variant facial fea-ture detection, that is, emotional expression and eyegaze. Third, the differential impairment in the detec-tion of variant and invariant face features highly sug-gests that, unlike other facial features, processingemotional aspects of faces is particularly affectedin mild AD dementia. The high sensitivity of ourtechnique using morphed faces allowed disclosingthis impairment in relatively small groups ofpatients, where other studies using prototypicalexpressions have provided inconsistent results.6,7 Itis of particular note that, in our study, mild ADdemented patients did not differ significantly fromcontrols in facial expression detection with prototy-pical full intensity expressions (100%), whereas asignificant deficit was observed when using a moreecological method including a larger range of emo-tional expressions intensities. Such subtle deficitswould not be apparent using discrete facial stimuli(Figure 1).

Our results must be taken with caution becausethe small sample size in the current study (N ¼ 10per group) does not allow for a generalization of theresults before replication in larger groups. We alsodraw attention on the fact that analyses of perfor-mance for each intensity (or gaze angle) and for each




expression (or gaze direction or gender) wereexploratory (no correction applied, limited numberof trial per condition leading to limited power, andincreased risk for false positives); these analyseswere conducted to provide a complete picture of ourresults. However, the current discussion emphasizedessentially on the hypothesis-driven analysis of over-all task performance as this provides stronger (i.e.,more powerful and reliable) evidence for impairedfacial expression detection in mild AD dementia.Moreover, it is not clear yet how face processingimpairments relate to real-life social functioning inthese patients; this may be an area of interest forfuture research.

In conclusion, conversely to patients with aMCI,mild AD demented patients are impaired in facialemotional expression detection. Such a deficit mayparticipate in social behavior disorders that affectsocial life early in the course of AD. Investigationsof early social cognition changes associated withAD may represent a promising field for futureresearch as they may increase our understanding ofbehavioral modifications and should lead to specificcare. Future research examining the evolution offace processing abilities in the course of neurodegen-erative process is warranted.

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Impaired Social Cognition in Mild Alzheimer Disease