Skip to main content Accessibility help

Theory of Mind in Mild Cognitive Impairment – Relationship with Limbic Structures and Behavioural Change

  • Johannes C. Michaelian (a1) (a2) (a3) (a4), Loren Mowszowski (a1) (a2) (a3), Adam J. Guastella (a1) (a5), Julie D. Henry (a6), Shantel Duffy (a2) (a4) (a5), Donna McCade (a1) and Sharon L. Naismith (a1) (a2) (a3) (a4)...



Older adults presenting with mild cognitive impairment (MCI) have a higher risk of developing dementia and also demonstrate impairments in social cognition. This study sought to establish whether in people with MCI, poorer theory of mind (ToM) was associated with volumetric changes in the amygdala and hippocampus, as well as early changes in behaviour.


One hundred and fourteen people with MCI and fifty-two older adult controls completed the Reading the Mind in the Eyes Test (RMET), while close informants (e.g., spouse/family member/friend/carer) described any current behavioural changes using the Revised Cambridge Behavioural Inventory (CBI-R). A subsample of participants completed structural magnetic resonance imaging (MRI).


The MCI group showed poorer performance on all neuropsychological tests administered, and moderate reductions on the RMET compared to the control group (d = .44), with greater reduction observed in those with amnestic compared to non-amnestic MCI (p = .03). While a robust correlation was identified between poorer RMET performance and smaller hippocampal volume in the control group (ρ = .53, p = .01), this relationship was not apparent in the MCI group (ρ = .21, p = .11). In the MCI group, poorer RMET performance was associated with poorer everyday skills (ρ = −.26, p = .01) assessed by the CBI-R.


Our findings cross-validate previous reports that social cognitive deficits in ToM are a feature of MCI and also suggest that disruptions to broader neural networks are likely to be implicated. Furthermore, ToM deficits in MCI are associated with a decline in everyday skills such as writing or paying bills.


Corresponding author

Correspondence and reprint requests to: Sharon Naismith, Healthy Brain Ageing Program, Brain and Mind Centre, The University of Sydney, 94 Mallett St, Camperdown, NSW 2050, Australia. E-mail:


Hide All
Adolphs, R. (2010). What does the amygdala contribute to social cognition? Annals of the New York Academy of Sciences, 1191, 4261.
Alexopoulos, P., Grimmer, T., Perneczky, R., Domes, G., & Kurz, A. (2006). Progression to dementia in clinical subtypes of mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 22(1), 2734.
Allison, T., Puce, A., & McCarthy, G. (2000). Social perception from visual cues: Role of the STS region. Trends in Cognitive Sciences, 4(7), 267278.
Baglio, F., Castelli, I., Alberoni, M., Blasi, V., Griffanti, L., Falini, A., Nemni, R, & Marchetti, A. (2012). Theory of mind in amnestic mild cognitive impairment: An FMRI study. Journal of Alzheimer’s Disease, 29(1), 2537.
Baron-Cohen, S., Wheelwright, S., Hill, J., Raste, Y., & Plumb, I. (2001). The “Reading the Mind in the Eyes” test revised version: A study with normal adults, and adults with asperger syndrome or high-functioning autism. Journal of Child Psychology and Psychiatry, 42(2), 241251.
Bediou, B., Ryff, I., Mercier, B., Milliery, M., Henaff, M.A., D’Amato, T., Bonnefoy, M., Vighetto, A., & Krolak-Salmon, P. (2009). Impaired social cognition in mild Alzheimer disease. Journal of Geriatric Psychiatry and Neurology, 22(2), 130140.
Beer, J.S. & Ochsner, K.N. (2006). Social cognition: A multi level analysis. Brain Research, 1079(1), 98105.
Bell-McGinty, S., Lopez, O.L., Meltzer, C., Scanlon, J.M., Whyte, E.M., Dekosky, S.T., & Becker, J.T. (2005). Differential cortical atrophy in subgroups of mild cognitive impairment. Archives of Neurology, 62(9), 13931397.
Benton, A.L., Sivan, A.B., Hamsher, S., Varney, N.R., & Spreen, O. (1994). Contributions to Neuropsychological Assessment: A Clinical Manual (2nd ed.). New York: Oxford University Press.
Berridge, K.C. & Kringelbach, M.L. (2013). Neuroscience of affect: Brain mechanisms of pleasure and displeasure. Current Opinion in Neurology, 23(3), 294303.
Bogdanova, Y., Yee, M.K., Ho, V.T., & Cicerone, K.D. (2016). Computerized cognitive rehabilitation of attention and executive function in acquired brain injury: A systematic review. The Journal of Head Trauma Rehabilitation, 31(6), 419433.
Bora, E. & Yener, G.G. (2017). Meta-analysis of social cognition in mild cognitive impairment. Journal of Geriatric Psychiatry and Neurology, 30(4), 206213.
Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., & Del Tredici, K. (2006). Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathologica, 112(4), 389404.
Brayne, C., Ince, P.G., Keage, H.A.D., McKeith, I.G., Matthews, F.E., Polvikoski, T., & Sulkava, R. (2010). Education, the brain and dementia: Neuroprotection or compensation? EClipSE Collaborative Members. Brain, 133(8), 22102216.
Brodaty, H. (1997). Caregivers and behavioral disturbances: Effects and interventions. International Psychogeriatrics, 8(S3), 455458.
Cacciotti-Saija, C., Langdon, R., Ward, P.B., Hickie, I.B., Scott, E.M., Naismith, S.L., Moore, L., Alvares, G.A., Redoblado-Hodge, M.A., & Guastella, A.J. (2015). A double-blind randomized controlled trial of oxytocin nasal spray and social cognition training for young people with early psychosis. Schizophrenia Bulletin, 41(2), 483493.
Calder, A.J., Keane, J., Manly, T., Sprengelmeyer, R., Scott, S., Nimmo-Smith, I., & Young, A.W. (2003). Facial expression recognition across the adult life span. Neuropsychologia, 41(2), 195202.
Carton, J.S., Kessler, E.A., & Pape, C.L. (1999). Nonverbal decoding skills and relationship well-being in adults. Journal of Nonverbal Behavior, 23(1), 91100.
Chalah, M.A., Kauv, P., Lefaucheur, J.-P., Hodel, J., Créange, A., & Ayache, S.S. (2017). Theory of mind in multiple sclerosis: A neuropsychological and MRI study. Neuroscience Letters, 658, 108113.
Delis, D.C., Kaplan, E., & Kramer, J.H. (2001). Delis–Kaplan Executive Function System (D-KEFS): Examiner’s Manual. San Antonio, TX: The Psychological Corporation.
Duffy, S.L., Lagopoulos, J., Hickie, I.B., Diamond, K., Graeber, M.B., Lewis, S.J., & Naismith, S.L. (2014). Glutathione relates to neuropsychological functioning in mild cognitive impairment. Alzheimers & Dementia, 10(1), 6775.
Dunn, C.J., Duffy, S.L., Hickie, I.B., Lagopoulos, J., Lewis, S.J., Naismith, S.L., & Shine, J.M. (2014). Deficits in episodic memory retrieval reveal impaired default mode network connectivity in amnestic mild cognitive impairment. NeuroImage: Clinical, 4, 473480.
Elcombe, E.L., Lagopoulos, J., Duffy, S.L., Lewis, S.J., Norrie, L., Hickie, I.B., & Naismith, S.L. (2015). Hippocampal volume in older adults at risk of cognitive decline: The role of sleep, vascular risk, and depression. Journal of Alzheimer’s Disease, 44(4), 12791290.
Elferink, M.W., van Tilborg, I., & Kessels, R.P. (2015). Perception of emotions in mild cognitive impairment and Alzheimer’s dementia: Does intensity matter? Translational Neuroscience, 6(1), 139149.
Fan, Y., Duncan, N.W., de Greck, M., & Northoff, G. (2011). Is there a core neural network in empathy? An fMRI based quantitative meta-analysis. Neuroscience & Biobehavioral Reviews, 35(3), 903911.
Finger, E.C., MacKinley, J., Blair, M., Oliver, L.D., Jesso, S., Tartaglia, M.C., Borrie, M., Wells, J., Dziobek, I., Pasternak, S., & Mitchell, D.G. (2015). Oxytocin for frontotemporal dementia: A randomized dose-finding study of safety and tolerability. Neurology, 84(2), 174181.
Folstein, M.F., Folstein, S.E., & McHugh, P.R. (1975). “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189198.
Fujie, S., Namiki, C., Nishi, H., Yamada, M., Miyata, J., Sakata, D., Sawamoto, N., Fukuyama, H., Hayashi, T., & Murai, T. (2008). The role of the uncinate fasciculus in memory and emotional recognition in amnestic mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 26(5), 432439.
Gamer, M. & Buchel, C. (2009). Amygdala activation predicts gaze toward fearful eyes. The Journal of Neuroscience, 29(28), 91239126.
Gauthier, S., Reisberg, B., Zaudig, M., Petersen, R.C., Ritchie, K., Broich, K., Belleville, S., Brodaty, H., Bennett, D., Chertkow, H., & Cummings, J.L. (2006). Mild cognitive impairment. The Lancet, 367(9518), 12621270.
Goodglass, H., Kaplan, E., & Weintraub, S. (1983). Boston Naming Test. Philadelphia, PA: Lea & Febiger.
Guastella, A.J., Einfeld, S.L., Gray, K.M., Rinehart, N.J., Tonge, B.J., Lambert, T.J., & Hickie, I.B. (2010). Intranasal oxytocin improves emotion recognition for youth with autism spectrum disorders. Biological Psychiatry, 67(7), 692694.
Guastella, A.J. & MacLeod, C. (2012). A critical review of the influence of oxytocin nasal spray on social cognition in humans: Evidence and future directions. Hormones and Behavior, 61(3), 410418.
Guastella, A.J., Mitchell, P.B., & Mathews, F. (2008). Oxytocin enhances the encoding of positive social memories in humans. Biological Psychiatry, 64(3), 256258.
Guastella, A.J., Ward, P.B., Hickie, I.B., Shahrestani, S., Hodge, M.A., Scott, E.M., & Langdon, R. (2015). A single dose of oxytocin nasal spray improves higher-order social cognition in schizophrenia. Schizophrenia Research, 168(3), 628633.
Heitz, C., Noblet, V., Phillipps, C., Cretin, B., Vogt, N., Philippi, N., Kemp, J., de Petigny, X., Bilger, M., Demuynck, C., Martin-Hunyadi, C., Armspach, J.P., & Blanc, F. (2016). Cognitive and affective theory of mind in dementia with Lewy bodies and Alzheimer’s disease. Alzheimer’s Research & Therapy, 8, 10.
Henry, J.D., Ruffman, T., McDonald, S., O’Leary, M.A., Phillips, L.H., Brodaty, H., & Rendell, P.G. (2008). Recognition of disgust is selectively preserved in Alzheimer’s disease. Neuropsychologia, 46(5), 13631370.
Henry, J.D., von Hippel, W., Molenberghs, P., Lee, T., & Sachdev, P.S. (2016). Clinical assessment of social cognitive function in neurological disorders. Nature Reviews Neurology, 12, 28.
Hosmer, Jr , D.W., Lemeshow, S., & Sturdivant, R.X. (2013). Applied Logistic Regression, Vol. 398. Hoboken, NJ: John Wiley & Sons.
Hunderfund, A.L., Roberts, R.O., Slusser, T.C., Leibson, C.L., Geda, Y.E., Ivnik, R.J., Tangalos, E.G., & Petersen, R.C. (2006). Mortality in amnestic mild cognitive impairment: A prospective community study. Neurology, 67(10), 17641768.
Immordino-Yang, M.H. & Singh, V. (2013). Hippocampal contributions to the processing of social emotions. Human Brain Mapping, 34(4), 945955.
Isaacowitz, D.M., Lockenhoff, C.E., Lane, R.D., Wright, R., Sechrest, L., Riedel, R., & Costa, P.T. (2007). Age differences in recognition of emotion in lexical stimuli and facial expressions. Psychology and Aging, 22(1), 147159.
Kanwisher, N. & Yovel, G. (2006). The fusiform face area: A cortical region specialized for the perception of faces. Philosophical Transactions of the Royal Society B: Biological Sciences, 361(1476), 21092128.
Kohler, C.G., Anselmo-Gallagher, G., Bilker, W., Karlawish, J., Gur, R.E., & Clark, C.M. (2005). Emotion-discrimination deficits in mild Alzheimer disease. The American Journal of Geriatric Psychiatry, 13(11), 926933.
Laisney, M., Bon, L., Guiziou, C., Daluzeau, N., Eustache, F., & Desgranges, B. (2012). Cognitive and affective Theory of Mind in mild to moderate Alzheimer’s disease. Journal of Neuropsychology, 7(1), 107120.
Laurita, A.C. & Nathan Spreng, R. (2017). The hippocampus and social cognition. In Hannula, D.E. & Duff, M.C. (Eds.), The hippocampus from cells to systems: structure, connectivity, and functional contributions to memory and flexible cognition, (pp. 537558). Cham: Springer International Publishing.
LeDoux, J.E. (2000). Emotion circuits in the brain. Annual Review of Neuroscience, 23, 155184.
Lezak, M.D. (1995). Neuropsychological Assessment. New York: Oxford University Press.
Markesbery, W.R. (2010). Neuropathologic alterations in mild cognitive impairment: A review. Journal of Alzheimer’s Disease, 19(1), 221228.
Mars, R.B., Neubert, F.-X., Noonan, M.P., Sallet, J., Toni, I., & Rushworth, M.F.S. (2012). On the relationship between the “default mode network” and the “social brain”. Frontiers in Human Neuroscience, 6, 189.
Martinez, M., Multani, N., Anor, C.J., Misquitta, K., Tang-Wai, D.F., Keren, R., Fox, S., Lang, A.E., & Tartaglia, M.C. (2018). Emotion detection deficits and decreased empathy in patients with Alzheimer’s disease and Parkinson’s disease affect caregiver mood and burden. Frontiers in Aging Neuroscience, 10, 120.
McCade, D., Savage, G., Guastella, A., Hickie, I.B., Lewis, S.J., & Naismith, S.L. (2013a). Emotion recognition deficits exist in mild cognitive impairment, but only in the amnestic subtype. Psychology and Aging, 28(3), 840852.
McCade, D., Savage, G., Guastella, A., Hickie, I.B., Lewis, S.J., & Naismith, S.L. (2013b). Emotion recognition in mild cognitive impairment: Relationship to psychosocial disability and caregiver burden. Journal of Geriatric Psychiatry and Neurology, 26(3), 165173.
McCade, D., Savage, G., & Naismith, S.L. (2011). Emotion recognition in mild cognitive impairment. Dementia and Geriatric Cognitive Disorders, 32(4), 257266.
McDonald, S., Bornhofen, C., Shum, D., Long, E., Saunders, C., & Neulinger, K. (2006). Reliability and validity of The Awareness of Social Inference Test (TASIT): A clinical test of social perception. Disability and Rehabilitation, 28(24), 15291542.
Montagrin, A., Saiote, C., & Schiller, D. (2018). The social hippocampus. Hippocampus, 28(9), 672679.
Moreau, N., Rauzy, S., Bonnefoi, B., Renié, L., Martinez-Almoyna, L., Viallet, F., & Champagne-Lavau, M. (2015). Different patterns of theory of mind impairment in mild cognitive impairment. Journal of Alzheimer’s Disease, 45(2), 581597.
Paradise, M., McCade, D., Hickie, I.B., Diamond, K., Lewis, S.J.G., & Naismith, S.L. (2015). Caregiver burden in mild cognitive impairment. Aging and Mental Health, 19(1), 7278.
Perry, D., Hendler, T., & Shamay-Tsoory, S.G. (2011). Projecting memories: The role of the hippocampus in emotional mentalizing. Neuroimage, 54(2), 16691676.
Petersen, R.C. (2004). Mild cognitive impairment as a diagnostic entity. Journal of Internal Medicine, 256(3), 183194.
Petersen, R.C. & Negash, S. (2008). Mild cognitive impairment: An overview. CNS Spectrums, 13(1), 4553.
Petersen, R.C., Parisi, J.E., Dickson, D.W., Johnson, K.A., Knopman, D.S., Boeve, B.F., Jicha, G.A., Ivnik, R.J., Smith, G.E., Tangalos, E.G., Braak, H., & Kokmen, E. (2006). Neuropathologic features of amnestic mild cognitive impairment. Archives of Neurology, 63(5), 665672.
Phillips, L.H., Scott, C., Henry, J.D., Mowat, D., & Bell, J.S. (2010). Emotion perception in Alzheimer’s disease and mood disorder in old age. Psychology and Aging, 25(1), 3847.
Poletti, M. & Bonuccelli, U. (2013). Alteration of affective theory of mind in amnestic mild cognitive impairment. Journal of Neuropsychology, 7(1), 121131.
Reitan, R.M. (1979). Manual for Administration of Neuropsychological Test Batteries for Adults and Children. Tucson, AZ: Neuropsychology Laboratory.
Roy, M., Shohamy, D., & Wager, T.D. (2012). Ventromedial prefrontal-subcortical systems and the generation of affective meaning. Trends in Cognitive Sciences, 16(3), 147156.
Ruff, R.M., Light, R.H., Parker, S.B., & Levin, H.S. (1996). Benton controlled oral word association test: Reliability and updated norms. Archives of Clinical Neuropsychology, 11(4), 329338.
Schilbach, L., Eickhoff, S.B., Rotarska-Jagiela, A., Fink, G.R., & Vogeley, K. (2008). Minds at rest? Social cognition as the default mode of cognizing and its putative relationship to the “default system” of the brain. Consciousness and Cognition, 17(2), 457467.
Schott, J.M., Kennedy, J., & Fox, N.C. (2006). New developments in mild cognitive impairment and Alzheimer’s disease. Current Opinion in Neurology, 19(6), 552558.
Serrano, C.M., Dillon, C., Leis, A., Taragano, F.E., & Allegri, R.F. (2013). Mild cognitive impairment: Risk of dementia according to subtypes. Actas Españolas de Psiquiatría, 41(6), 330339.
Sestieri, C., Corbetta, M., Romani, G.L., & Shulman, G.L. (2011). Episodic memory retrieval, parietal cortex, and the default mode network: Functional and topographic analyses. The Journal of Neuroscience, 31(12), 44074420.
Singer, T., Seymour, B., O’Doherty, J., Kaube, H., Dolan, R.J., & Frith, C.D. (2004). Empathy for pain involves the affective but not sensory components of pain. Science, 303(5661), 11571162.
Sodian, B. & Kristen, S. (2010). Theory of Mind. In Glatzeder, B., Goel, V., & Müller, A. (Eds.), Towards a theory of thinking: building blocks for a conceptual framework (pp. 189201). Berlin, Heidelberg: Springer Berlin Heidelberg.
Spoletini, I., Marra, C., Di Iulio, F., Gianni, W., Sancesario, G., Giubilei, F., Trequattrini, A., Bria, P., Caltagirone, C., & Spalletta, G. (2008). Facial emotion recognition deficit in amnestic mild cognitive impairment and Alzheimer disease. The American Journal of Geriatric Psychiatry, 16(5), 389398.
Tombaugh, T.N., Kozak, J., & Rees, L. (1999). Normative data stratified by age and education for two measures of verbal fluency: FAS and animal naming. Archives of Clinical Neuropsychology, 14(2), 167177.
Tsang, R.S., Diamond, K., Mowszowski, L., Lewis, S.J., & Naismith, S.L. (2012). Using informant reports to detect cognitive decline in mild cognitive impairment. International Psychogeriatrics, 24(6), 967973.
Van Overwalle, F. (2009). Social cognition and the brain: A meta-analysis. Human Brain Mapping, 30(3), 829858.
Wear, H.J., Wedderburn, C.J., Mioshi, E., Williams-Gray, C.H., Mason, S.L., Barker, R.A., & Hodges, J.R. (2008). The cambridge behavioural inventory revised. Dementia & Neuropsychologia, 2(2), 102107.
Wechsler, D. (1997). Manual for the Wechsler Adult Intelligence Scale - Third Edition. San Antonio, TX: The Psychological Corporation.
Wechsler, D. (2001). Wechsler Test of Adult Reading: WTAR. San Antonio, TX: Pearson Education, Inc.
Weiss, E.M., Kohler, C.G., Vonbank, J., Stadelmann, E., Kemmler, G., Hinterhuber, H. & Marksteiner, J. (2008). Impairment in emotion recognition abilities in patients with mild cognitive impairment, early and moderate Alzheimer disease compared with healthy comparison subjects. The American Journal of Geriatric Psychiatry, 16(12), 974980.
Winblad, B., Palmer, K., Kivipelto, M., Jelic, V., Fratiglioni, L., Wahlund, L.O., Nordberg, A., Bäckman, L., Albert, M., Almkvist, O., Arai, H., Basun, H., Blennow, K., de Leon, M., DeCarli, C., Erkinjuntti, T., Giacobini, E., Graff, C., Hardy, J., Jack, C., Jorm, A., Ritchie, K., van Duijn, C., Visser, P. & Petersen, R.C. (2004). Mild cognitive impairment--beyond controversies, towards a consensus: Report of the International Working Group on Mild Cognitive Impairment. Journal of Internal Medicine, 256(3), 240246.
Zigmond, A.S. & Snaith, R.P. (1983). The hospital anxiety and depression scale. Acta Psychiatrica Scandinavica, 67(6), 361370.



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed