Abstract
The occurrence of clinically significant changes in empathy is a matter of debate in Alzheimer’s disease (AD). Altered empathic mechanisms observed in AD may be a consequence of cognitive impairment, more specifically of reduced mental flexibility and self-regulation. The present study explored possible changes in empathy for subjects in the prodromal phase of AD, namely mild cognitive impairment (MCI) due to AD, and of their neural substrates. Eighteen MCI patients and 20 healthy controls (HC) were included in the study. The Interpersonal Reactivity Index (IRI) questionnaire was administered to each participant. The IRI encompasses four factors: Perspective Taking; Fantasy; Empathic Concern; Personal Distress. MCI patients underwent a magnetic resonance imaging structural examination and were compared to 30 healthy controls (HC-MRI). A limited number of cortical and subcortical regions involved in social cognition was selected as regions of interest (ROIs). MCI individuals obtained lower scores than HC in the Perspective Taking and Fantasy subscales of the IRI, whereas they obtained higher scores on Empathic Concern. Regarding neuroimaging data, a significant correlation emerged between IRI scores and the neural measurements of different regions involved in empathy, especially covering the temporoparietal junction, which is a critical region engaged in both affective and cognitive dimensions of empathy. The results of the present study suggest that a subtle impairment in regulatory mechanisms of empathy may occur very early during the course of AD, possibly as a consequence of neuropathological changes occurring in brain regions involved in social cognition.
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References
Abu-Akel, A., & Shamay-Tsoory, S. (2011). Neuroanatomical and neurochemical bases of theory of mind. Neuropsychologia, 49(11), 2971–2984. https://doi.org/10.1016/j.neuropsychologia.2011.07.012
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., Snyder, P. J., Carrillo, M. C., Thies, B., & Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association, 7(3), 270–279. https://doi.org/10.1016/j.jalz.2011.03.008
Alladi, S., Ch, S., Mekala, S., Santhoshi, C., Nigam, R., & Kaul, S. (2011). Empathy and frontal behavioral patterns discriminate between vascular dementia, Alzheimer’s disease and frontotemporal dementia. Alzheimers & Dementia: The Journal of the Alzheimer’s Association, 7. https://doi.org/10.1016/j.jalz.2011.09.185
Backhausen, L. L., Herting, M. M., Tamnes, C. K., & Vetter, N. C. (2022). Best practices in structural neuroimaging of neurodevelopmental disorders. Neuropsychology Review, 32(2), 400–418. https://doi.org/10.1007/s11065-021-09496-2
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society: Series B (Methodological), 57(1), 289–300. https://doi.org/10.1111/j.2517-6161.1995.tb02031.x
Binney, R. J., Henry, M. L., Babiak, M., Pressman, P. S., Santos-Santos, M. A., Narvid, J., Mandelli, M. L., Strain, P. J., Miller, B. L., Rankin, K. P., Rosen, H. J., & Gorno-Tempini, M. L. (2016). Reading words and other people: A comparison of exception word, familiar face and affect processing in the left and right temporal variants of primary progressive aphasia. Cortex; a Journal Devoted to the Study of the Nervous System and Behavior, 82, 147–163. https://doi.org/10.1016/j.cortex.2016.05.014
Bird, G., & Viding, E. (2014). The self to other model of empathy: Providing a new framework for understanding empathy impairments in psychopathy, autism, and alexithymia. Neuroscience and Biobehavioral Reviews, 47, 520–532. https://doi.org/10.1016/j.neubiorev.2014.09.021
Buhle, J. T., Silvers, J. A., Wager, T. D., Lopez, R., Onyemekwu, C., Kober, H., Weber, J., & Ochsner, K. N. (2014). Cognitive reappraisal of emotion: A meta-analysis of human neuroimaging studies. Cerebral Cortex (New York, N.Y.: 1991), 24(11), 2981–2990. https://doi.org/10.1093/cercor/bht154.
Caffarra, P., Vezzadini, G., Dieci, F., Zonato, F., & Venneri, A. (2002a). Rey-Osterrieth complex figure: Normative values in an Italian population sample. Neurology Science, 22(6), 443–447. https://doi.org/10.1007/s100720200003
Caffarra, P., Vezzadini, G., Dieci, F., Zonato, F., & Venneri, A. (2002b). Una versione abbreviata del test di Stroop: Dati normativi nella popolazione italiana. Nuova Rivista di Neurologia, 12(4), 111–115.
Caffarra, P., Vezzadini, G., Dieci, F., Zonato, F., & Venneri, A. (2004). Modified card sorting test: Normative data. Journal of Clinical and Experimental Neuropsychology, 26(2), 246–250. https://doi.org/10.1076/jcen.26.2.246.28087
Carlesimo, G. A., Caltagirone, C., Gainotti, G., Fadda, L., Gallassi, R., Lorusso, S., Marfia, G., Marra, C., Nocentini, U., & Parnetti, L. (1996). The mental deterioration battery: Normative data, diagnostic reliability and qualitative analyses of cognitive impairment. European Neurology, 36(6), 378–384. https://doi.org/10.1159/000117297
Cerami, C., Dodich, A., Iannaccone, S., Marcone, A., Lettieri, G., Crespi, C., Gianolli, L., Cappa, S. F., & Perani, D. (2015). Right limbic FDG-PET hypometabolism correlates with emotion recognition and attribution in probable behavioral variant of frontotemporal dementia patients. PLoS One, 10(10), e0141672. https://doi.org/10.1371/journal.pone.0141672
Cohen, J. (2009). Statistical power analysis for the behavioral sciences (2nd edn, reprint). Psychology Press.
Dale, A. M., Fischl, B., & Sereno, M. I. (1999). Cortical surface-based analysis. I. Segmentation and surface reconstruction. NeuroImage, 9(2), 179–194. https://doi.org/10.1006/nimg.1998.0395
Davis, M. H. (1983). Measuring individual differences in empathy: Evidence for a multidimensional approach. Journal of Personality and Social Psychology, 44(1), 113.
Davis, M. H. (2018). Empathy: A social psychological approach. Routledge.
Decety, J., & Jackson, P. L. (2004). The functional architecture of human empathy. Behavioral and Cognitive Neuroscience Reviews, 3(2), 71–100. https://doi.org/10.1177/1534582304267187
Decety, J., & Lamm, C. (2007). The role of the right temporoparietal junction in social interaction: How low-level computational processes contribute to meta-cognition. The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 13(6), 580–593. https://doi.org/10.1177/1073858407304654
Dermody, N., Wong, S., Ahmed, R., Piguet, O., Hodges, J. R., & Irish, M. (2016). Uncovering the neural bases of cognitive and affective empathy deficits in Alzheimer’s disease and the behavioral-variant of frontotemporal dementia. Journal of Alzheimer’s Disease, 53(3), 801–816. https://doi.org/10.3233/JAD-160175
Desikan, R. S., Ségonne, F., Fischl, B., Quinn, B. T., Dickerson, B. C., Blacker, D., Buckner, R. L., Dale, A. M., Maguire, R. P., Hyman, B. T., Albert, M. S., & Killiany, R. J. (2006). An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. NeuroImage, 31(3), 968–980. https://doi.org/10.1016/j.neuroimage.2006.01.021
Destrieux, C., Fischl, B., Dale, A., & Halgren, E. (2010). Automatic parcellation of human cortical gyri and sulci using standard anatomical nomenclature. NeuroImage, 53(1), 1–15. https://doi.org/10.1016/j.neuroimage.2010.06.010
Diekhof, E. K., Geier, K., Falkai, P., & Gruber, O. (2011). Fear is only as deep as the mind allows: A coordinate-based meta-analysis of neuroimaging studies on the regulation of negative affect. NeuroImage, 58(1), 275–285. https://doi.org/10.1016/j.neuroimage.2011.05.073
Eisenberg, N., & Eggum, N. D. (2009). Empathic responding: Sympathy and personal distress. In J. I. W. e. Decety (Ed.), The social neuroscience of empathy. (pp. 71–83). MIT Press.
Eramudugolla, R., Huynh, K., Zhou, S., Amos, J. G., & Anstey, K. J. (2022). Social cognition and social functioning in MCI and dementia in an epidemiological sample. Journal of the International Neuropsychological Society, 28(7), 661–672. https://doi.org/10.1017/S1355617721000898
Etkin, A., Egner, T., & Kalisch, R. (2011). Emotional processing in anterior cingulate and medial prefrontal cortex. Trends in Cognitive Sciences, 15(2), 85–93. https://doi.org/10.1016/j.tics.2010.11.004
Fischer, A., Landeira-Fernandez, J., Sollero de Campos, F., & Mograbi, D. C. (2019). Empathy in Alzheimer’s disease: Review of findings and proposed model. Journal of Alzheimer’s Disease, 69(4), 921–933. https://doi.org/10.3233/JAD-180730
Fischl, B., Salat, D. H., Busa, E., Albert, M., Dieterich, M., Haselgrove, C., van der Kouwe, A., Killiany, R., Kennedy, D., Klaveness, S., Montillo, A., Makris, N., Rosen, B., & Dale, A. M. (2002). Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain. Neuron, 33(3), 341–355. https://doi.org/10.1016/s0896-6273(02)00569-x
Fischl, B., Sereno, M. I., & Dale, A. M. (1999). Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. NeuroImage, 9(2), 195–207. https://doi.org/10.1006/nimg.1998.0396
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), 189–198.
Gainotti, G. (2019). Emotions and the right hemisphere: Can new data clarify old models? The Neuroscientist: A Review Journal Bringing Neurobiology, Neurology and Psychiatry, 25(3), 258–270. https://doi.org/10.1177/1073858418785342
Hatfield, E., Cacioppo, J. T., & Rapson, R. L. (1993). Emotional contagion. Cambridge University Press.
Hodges, S. D., & Klein, K. J. K. (2001). Regulating the costs of empathy: The price of being human. The Journal of Socio-Economics, 30(5), 437–452. https://doi.org/10.1016/S1053-5357(01)00112-3
Hsieh, S., Irish, M., Daveson, N., Hodges, J. R., & Piguet, O. (2013). When one loses empathy: Its effect on carers of patients with dementia. Journal of Geriatric Psychiatry and Neurology, 26(3), 174–184. https://doi.org/10.1177/0891988713495448
Isernia, S., Cabinio, M., Pirastru, A., Mendozzi, L., Di Dio, C., Marchetti, A., Massaro, D., & Baglio, F. (2020). Theory of mind network in multiple Sclerosis: A double disconnection mechanism. Social Neuroscience, 15(5), 544–557. https://doi.org/10.1080/17470919.2020.1766562
JASP Team. (2020). JASP (Version 0.14) [Computer software].
Kalenzaga, S., & Clarys, D. (2013). Self-referential processing in Alzheimer’s disease: Two different ways of processing self-knowledge? Journal of Clinical and Experimental Neuropsychology, 35(5), 455–471. https://doi.org/10.1080/13803395.2013.789485
Katz, S., Ford, A. B., Moskowitz, R. W., Jackson, B. A., & Jaffe, M. W. (1963). Studies of illness in the aged. The index of ADL: A standardized measure of biological and psychosocial function. JAMA, 185, 914–919. https://doi.org/10.1001/jama.1963.03060120024016
Krall, S. C., Rottschy, C., Oberwelland, E., Bzdok, D., Fox, P. T., Eickhoff, S. B., Fink, G. R., & Konrad, K. (2015). The role of the right temporoparietal junction in attention and social interaction as revealed by ALE meta-analysis. Brain Structure & Function, 220(2), 587–604. https://doi.org/10.1007/s00429-014-0803-z
Lamm, C., Decety, J., & Singer, T. (2011). Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. NeuroImage, 54(3), 2492–2502. https://doi.org/10.1016/j.neuroimage.2010.10.014
Langford, D. J., Crager, S. E., Shehzad, Z., Smith, S. B., Sotocinal, S. G., Levenstadt, J. S., Chanda, M. L., Levitin, D. J., & Mogil, J. S. (2006). Social modulation of pain as evidence for empathy in mice. Science, 312(5782), 1967–1970. https://doi.org/10.1126/science.1128322
Lanooij, S. D., Eisel, U. L. M., Drinkenburg, W. H. I. M., van der Zee, E. A., & Kas, M. J. H. (2023). Influencing cognitive performance via social interactions: a novel therapeutic approach for brain disorders based on neuroanatomical mapping? Molecular Psychiatry, 28(1), 28–33. https://doi.org/10.1038/s41380-022-01698-1
Lawton, M. P., & Brody, E. M. (1969). Assessment of older people: Self-maintaining and instrumental activities of daily living. The Gerontologist, 9(3), 179–186.
Leiberg, S., & Anders, S. (2006). The multiple facets of empathy: A survey of theory and evidence. Progress in Brain Research, 156, 419–440. https://doi.org/10.1016/S0079-6123(06)56023-6
Lenzi, D., Serra, L., Perri, R., Pantano, P., Lenzi, G. L., Paulesu, E., Caltagirone, C., Bozzali, M., & Macaluso, E. (2011). Single domain amnestic MCI: A multiple cognitive domains fMRI investigation. Neurobiology of Aging, 32(9), 1542–1557. https://doi.org/10.1016/j.neurobiolaging.2009.09.006
Marra, C., Gainotti, G., Scaricamazza, E., Piccininni, C., Ferraccioli, M., & Quaranta, D. (2013). The multiple features target cancellation (MFTC): An attentional visual conjunction search test. Normative values for the Italian population. Neurology Science, 34(2), 173–180. https://doi.org/10.1007/s10072-012-0975-3
Mars, R. B., Sallet, J., Schüffelgen, U., Jbabdi, S., Toni, I., & Rushworth, M. F. S. (2012). Connectivity-based subdivisions of the human right “temporoparietal junction area”: Evidence for different areas participating in different cortical networks. Cerebral Cortex (New York, N.Y.: 1991), 22(8), 1894–1903. https://doi.org/10.1093/cercor/bhr268.
Miceli, G., Laudanna, A., Burani, C., & Capasso, R. (1994). Batteria per l’Analisi del deficit Afasico. BADA [BADA A battery for the assessment of aphasic disorders].
Monaco, M., Costa, A., Caltagirone, C., & Carlesimo, G. A. (2013). Forward and backward span for verbal and visuo-spatial data: Standardization and normative data from an Italian adult population. Neurological Sciences, 34(5), 749–754. https://doi.org/10.1007/s10072-012-1130-x
Narme, P., Mouras, H., Roussel, M., Devendeville, A., & Godefroy, O. (2013). Assessment of socioemotional processes facilitates the distinction between frontotemporal lobar degeneration and Alzheimer’s disease. Journal of Clinical and Experimental Neuropsychology, 35(7), 728–744. https://doi.org/10.1080/13803395.2013.823911
Pernigo, S., Gambina, G., Valbusa, V., Condoleo, M. T., Broggio, E., Beltramello, A., Moretto, G., & Moro, V. (2015). Behavioral and neural correlates of visual emotion discrimination and empathy in mild cognitive impairment. Behavioural Brain Research, 294, 111–122. https://doi.org/10.1016/j.bbr.2015.07.047
Preston, S. D., & de Waal, F. B. M. (2002). Empathy: Its ultimate and proximate bases. The Behavioral and Brain Sciences, 25(1), 1–20discussion 20-71. https://doi.org/10.1017/s0140525x02000018
Quaranta, D., Caprara, A., Piccininni, C., Vita, M. G., Gainotti, G., & Marra, C. (2016). Standardization, clinical validation, and typicality norms of a new test assessing semantic verbal fluency. Archives of Clinical Neuropsychology, 31(5), 434–445. https://doi.org/10.1093/arclin/acw034
Quesque, F., & Brass, M. (2019). The role of the temporoparietal junction in self-other distinction. Brain Topography, 32(6), 943–955. https://doi.org/10.1007/s10548-019-00737-5
Rankin, K. P., Gorno-Tempini, M. L., Allison, S. C., Stanley, C. M., Glenn, S., Weiner, M. W., & Miller, B. L. (2006). Structural anatomy of empathy in neurodegenerative disease. Brain: A Journal of Neurology, 129(Pt 11), 2945–2956. https://doi.org/10.1093/brain/awl254
Rascovsky, K., Hodges, J. R., Knopman, D., Mendez, M. F., Kramer, J. H., Neuhaus, J., van Swieten, J. C., Seelaar, H., Dopper, E. G., Onyike, C. U., & others. (2011). Sensitivity of revised diagnostic criteria for the behavioural variant of frontotemporal dementia. Brain: A Journal of Neurology, 134(9), 2456–2477. https://doi.org/10.1093/brain/awr179
Roheger, M., Brenning, J., Riemann, S., Martin, A., Flöel, A., & Meinzer, M. (2022). Progression of socio-cognitive impairment from healthy aging to Alzheimer’s dementia: A systematic review and meta-analysis. Neuroscience and Biobehavioral Reviews, 140. https://doi.org/10.1016/j.neubiorev.2022.104796
Saxe, R., & Powell, L. J. (2006). It’s the thought that counts: Specific brain regions for one component of theory of mind. Psychological Science, 17(8), 692–699. https://doi.org/10.1111/j.1467-9280.2006.01768.x
Schulte-Rüther, M., Markowitsch, H. J., Fink, G. R., & Piefke, M. (2007). Mirror neuron and theory of mind mechanisms involved in face-to-face interactions: A functional magnetic resonance imaging approach to empathy. Journal of Cognitive Neuroscience, 19(8), 1354–1372. https://doi.org/10.1162/jocn.2007.19.8.1354
Shamay-Tsoory, S. G. (2011). The neural bases for empathy. The Neuroscientist, 17(1), 18–24. https://doi.org/10.1177/1073858410379268
Spunt, R. P., & Adolphs, R. (2019). The neuroscience of understanding the emotions of others. Neuroscience Letters, 693, 44–48. https://doi.org/10.1016/j.neulet.2017.06.018
Sturm, V. E., Yokoyama, J. S., Seeley, W. W., Kramer, J. H., Miller, B. L., & Rankin, K. P. (2013). Heightened emotional contagion in mild cognitive impairment and Alzheimer’s disease is associated with temporal lobe degeneration. Proceedings of the National Academy of Sciences of the United States of America, 110(24), 9944–9949. https://doi.org/10.1073/pnas.1301119110
Sugranyes, G., Kyriakopoulos, M., Corrigall, R., Taylor, E., & Frangou, S. (2011). Autism spectrum disorders and schizophrenia: Meta-analysis of the neural correlates of social cognition. PLoS One, 6(10), e25322. https://doi.org/10.1371/journal.pone.0025322
Synn, A., Mothakunnel, A., Kumfor, F., Chen, Y., Piguet, O., Hodges, J. R., & Irish, M. (2018). Mental states in moving shapes: Distinct cortical and subcortical contributions to theory of mind impairments in dementia. Journal of Alzheimer’s Disease, 61(2), 521–535. https://doi.org/10.3233/JAD-170809
Valera-Bermejo, J. M., De Marco, M., Mitolo, M., Cerami, C., Dodich, A., & Venneri, A. (2021). Large-scale functional networks, cognition and brain structures supporting social cognition and theory of mind performance in prodromal to mild Alzheimer’s disease. Frontiers in Aging Neuroscience, 13, 766703. https://doi.org/10.3389/fnagi.2021.766703
Van Overwalle, F., & Baetens, K. (2009). Understanding others’ actions and goals by mirror and mentalizing systems: A meta-analysis. NeuroImage, 48(3), 564–584. https://doi.org/10.1016/j.neuroimage.2009.06.009
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Quaranta, D., Di Tella, S., Cassano, V. et al. Neural correlates of empathy in mild cognitive impairment. Cogn Affect Behav Neurosci 24, 171–183 (2024). https://doi.org/10.3758/s13415-023-01146-9
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DOI: https://doi.org/10.3758/s13415-023-01146-9