Large-Scale Functional Networks, Cognition and Brain Structures Supporting Social Cognition and Theory of Mind Performance in Prodromal to Mild Alzheimer's Disease.
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SUBMITTER: Valera-Bermejo JM
PROVIDER: S-EPMC8636093 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPatients suffering from Alzheimer's dementia develop difficulties in social functioning. This has led to an interest in the study of "theory of mind" in this population. However, difficulty has arisen because the associated cognitive demands of traditional short story theory of mind assessments result in failure per se in this population, making it challenging to test pure theory of mind ability.MethodsSimplified, traditional 1st and 2nd order theory of mind short story tasks and a battery of alternative theory of mind cartoon jokes and control slapstick cartoon jokes, without memory components, were administered to 16 participants with mild-moderate Alzheimer's dementia, and 11 age-matched healthy controls.ResultsNo significant differences were detected between participants with Alzheimer's dementia and controls on the 1st or 2nd order traditional short story theory of mind tasks (p = 0.155 and p = 0.154 respectively). However, in the cartoon joke tasks there were significant differences in performance between the Alzheimer participants and the control group, this was evident for both theory of mind cartoons and the control 'slapstick' jokes.ConclusionIt remains very difficult to assess theory of mind as an isolated phenomenon in populations with global cognitive impairment, such as Alzheimer's dementia, as the tasks used to assess this cognition invariably depend on other cognitive functions. Although a limitation of this study is the small sample size, the results suggest that there is no measurable specific theory of mind deficit in people with Alzheimer's dementia, and that the use of theory of mind representational models to measure social cognitive ability may not be appropriate in this population.
| S-EPMC4269983 | biostudies-literature
Project description:Successful episodic memory calls upon a number of different cognitive processes that are supported by the coordination of several large-scale cortical networks. Previous work from our group has demonstrated dissociable anatomic substrates at different stages of memory in patients with dementia due to Alzheimer's disease (AD). The aim of the current study was to extend the understanding of brain-behavior associations underlying a commonly administered neuropsychological assessment of verbal episodic memory (Rey Auditory Verbal Learning Test; RAVLT) by determining the cortical network contributions to the performance at early vs. late stages of list learning, delayed recall, and retention, in 235 very mild biomarker positive (A+/T+/N+) individuals diagnosed with amnestic mild cognitive impairment (aMCI; MMSE = 27.7). We measured cortical atrophy in four large-scale cortical networks impacted by AD: default mode (DMN), dorsal attention (DAN), frontoparietal (FPN), and language (LN) networks. We also evaluated the role of hippocampal atrophy at each stage of memory performance. Partial correlation analyses controlling for age, sex, and education and corrected for multiple comparisons revealed that early learning was most strongly associated with cortical thickness in the DAN, while late learning was most strongly associated with hippocampal volume, but also related to cortical thickness in the DAN, FPN, DMN, and LN. Delayed recall was associated most strongly with hippocampal volume, but was also related to cortical thickness in the FPN and DMN, while retention was associated only with hippocampal volume. These findings are consistent with prior models of the neural substrates of different stages of verbal list learning and retrieval, provide new insights into the cortical networks undergoing neurodegeneration even at very mild stages of prodromal AD, and inform our thinking about the networks and regions being interrogated by this kind of neuropsychological assessment of episodic memory.
| S-EPMC6571167 | biostudies-literature
Project description:Aggressive, violent behaviour is a major burden and challenge for society. It has been linked to deficits in social understanding, but the evidence is inconsistent and the specifics of such deficits are unclear. Here, we investigated affective (empathy) and cognitive (Theory of Mind) routes to understanding other people in aggressive individuals. Twenty-nine men with a history of legally relevant aggressive behaviour (i.e. serious assault) and 32 control participants were tested using a social video task (EmpaToM) that differentiates empathy and Theory of Mind and completed questionnaires on aggression and alexithymia. Aggressive participants showed reduced empathic responses to emotional videos of others' suffering, which correlated with aggression severity. Theory of Mind performance, in contrast, was intact. A mediation analysis revealed that reduced empathy in aggressive men was mediated by alexithymia. These findings stress the importance of distinguishing between socio-affective and socio-cognitive deficits for understanding aggressive behaviour and thereby contribute to the development of more efficient treatments.
| S-EPMC5429629 | biostudies-literature
Project description:BackgroundDelaying the transition from minimal cognitive impairment to Alzheimer's dementia is a major concern in Alzheimer's disease (AD) therapeutics. Pathological signs of AD occur years before the onset of clinical dementia. Thus, long-term therapeutic approaches, with safe, minimally invasive, and yet effective substances are recommended. There is a need to develop new drugs to delay Alzheimer's dementia. We have taken a nutritional supplement approach with genistein, a chemically defined polyphenol that acts by multimodal specific mechanisms. Our group previously showed that genistein supplementation is effective to treat the double transgenic (APP/PS1) AD animal model.MethodsIn this double-blind, placebo-controlled, bicentric clinical trial, we evaluated the effect of daily oral supplementation with 120 mg of genistein for 12 months on 24 prodromal Alzheimer's disease patients. The amyloid-beta deposition was analyzed using 18F-flutemetamol uptake. We used a battery of validated neurocognitive tests: Mini-Mental State Exam (MMSE), Memory Alteration Test (M@T), Clock Drawing Test, Complutense Verbal Learning Test (TAVEC), Barcelona Test-Revised (TBR), and Rey Complex Figure Test.ResultsWe report that genistein treatment results in a significant improvement in two of the tests used (dichotomized direct TAVEC, p = 0.031; dichotomized delayed Centil REY copy p = 0.002 and a tendency to improve in all the rest of them. The amyloid-beta deposition analysis showed that genistein-treated patients did not increase their uptake in the anterior cingulate gyrus after treatment (p = 0.878), while placebo-treated did increase it (p = 0.036). We did not observe significant changes in other brain areas studied.ConclusionsThis study shows that genistein may have a role in therapeutics to delay the onset of Alzheimer's dementia in patients with prodromal Alzheimer's disease. These encouraging results indicate that this should be followed up by a new study with more patients to further validate the conclusion that arises from this study.Trial registrationNCT01982578, registered on November 13, 2013.
| S-EPMC9635167 | biostudies-literature
Project description:See Coulthard and Knight (doi:10.1093/aww335) for a scientific commentary on this article.Individuals with mild cognitive impairment and Alzheimer's disease clinical diagnoses can display significant phenotypic heterogeneity. This variability likely reflects underlying genetic, environmental and neuropathological differences. Characterizing this heterogeneity is important for precision diagnostics, personalized predictions, and recruitment of relatively homogeneous sets of patients into clinical trials. In this study, we apply state-of-the-art semi-supervised machine learning methods to the Alzheimer's disease Neuroimaging cohort (ADNI) to elucidate the heterogeneity of neuroanatomical differences between subjects with mild cognitive impairment (n = 530) and Alzheimer's disease (n = 314) and cognitively normal individuals (n = 399), thereby adding to an increasing literature aiming to establish neuroanatomical and neuropathological (e.g. amyloid and tau deposition) dimensions in Alzheimer's disease and its prodromal stages. These dimensional approaches aim to provide surrogate measures of heterogeneous underlying pathologic processes leading to cognitive impairment. We relate these neuroimaging patterns to cerebrospinal fluid biomarkers, white matter hyperintensities, cognitive and clinical measures, and longitudinal trajectories. We identified four such atrophy patterns: (i) individuals with largely normal neuroanatomical profiles, who also turned out to have the least abnormal cognitive and cerebrospinal fluid biomarker profiles and the slowest clinical progression during follow-up; (ii) individuals with classical Alzheimer's disease neuroanatomical, cognitive, cerebrospinal fluid biomarkers and clinical profile, who presented the fastest clinical progression; (iii) individuals with a diffuse pattern of atrophy with relatively less pronounced involvement of the medial temporal lobe, abnormal cerebrospinal fluid amyloid-β1-42 values, and proportionally greater executive impairment; and (iv) individuals with notably focal involvement of the medial temporal lobe and a slow steady progression, likely representing in early Alzheimer's disease stages. These four atrophy patterns effectively define a 4-dimensional categorization of neuroanatomical alterations in mild cognitive impairment and Alzheimer's disease that can complement existing dimensional approaches for staging Alzheimer's disease using a variety of biomarkers, which offer the potential for enabling precision diagnostics and prognostics, as well as targeted patient recruitment of relatively homogeneous subgroups of subjects for clinical trials.
| S-EPMC5837514 | biostudies-literature
Project description:Many psychological theories posit foundational links between two fundamental constructs: (1) our ability to produce, perceive, and represent action; and (2) our ability to understand the meaning and motivation behind the action (i.e. Theory of Mind; ToM). This position is contentious, however, and long-standing competing theories of social-cognitive development debate roles for basic action-processing in ToM. Developmental research is key to investigating these hypotheses, but whether individual differences in neural and behavioral measures of motor action relate to social-cognitive development is unknown. We examined 3- to 5-year-old children's (N = 26) EEG mu-desynchronization during production of object-directed action, and explored associations between mu-desynchronization and children's behavioral motor skills, behavioral action-representation abilities, and behavioral ToM. For children with high (but not low) mu-desynchronization, motor skill related to action-representation abilities, and action-representation mediated relations between motor skill and ToM. Results demonstrate novel foundational links between action-processing and ToM, suggesting that basic motor action may be a key mechanism for social-cognitive development, thus shedding light on the origins and emergence of higher social cognition.
| S-EPMC5332397 | biostudies-literature
Project description:BackgroundPrior research supports a strong link between Alzheimer's disease (AD) and metabolic dysfunction that involves a multi-directional interaction between glucose, glutamatergic homeostasis, and amyloid pathology. Elevated soluble amyloid-β (Aβ) is an early biomarker for AD-associated cognitive decline that contributes to concurrent glutamatergic and metabolic dyshomeostasis in humans and male transgenic AD mice. Yet, it remains unclear how primary time-sensitive targeting of hippocampal glutamatergic activity may impact glucose regulation in an amyloidogenic mouse model. Previous studies have illustrated increased glucose uptake and metabolism using a neuroprotective glutamate modulator (riluzole), supporting the link between glucose and glutamatergic homeostasis.ObjectiveWe hypothesized that targeting early glutamatergic hyperexcitation through riluzole treatment could aid in attenuating co-occurring metabolic and amyloidogenic pathologies with the intent of ameliorating cognitive decline.MethodsWe conducted an early intervention study in male and female transgenic (AβPP/PS1) and knock-in (APPNL - F/NL - F) AD mice to assess the on- and off-treatment effects of prodromal glutamatergic modulation (2-6 months of age) on glucose homeostasis and spatial cognition through riluzole treatment.ResultsResults indicated a sex- and genotype-specific effect on glucose homeostasis and spatial cognition with riluzole intervention that evolved with disease progression and time since treatment.ConclusionThese findings support the interconnected nature of glucose and glutamatergic homeostasis with amyloid pathology and petition for further investigation into the targeting of this relationship to improve cognitive performance.
| S-EPMC10357216 | biostudies-literature
Project description:A highly sensitive immunoassay, the immunomagnetic reduction, is used to measure several biomarkers for plasma that is related to Alzheimer's disease (AD). These biomarkers include Aβ-40, Aβ-42, and tau proteins. The samples are composed of four groups: healthy controls (n=66), mild cognitive impairment (MCI, n=22), very mild dementia (n=23), and mild-to-serve dementia, all due to AD (n=22). It is found that the concentrations of both Aβ-42 and tau protein for the healthy controls are significantly lower than those of all of the other groups. The sensitivity and the specificity of plasma Aβ-42 and tau protein in differentiating MCI from AD are all around 0.9 (0.88-0.97). However, neither plasma Aβ-42 nor tau-protein concentration is an adequate parameter to distinguish MCI from AD. A parameter is proposed, which is the product of plasma Aβ-42 and tau-protein levels, to differentiate MCI from AD. The sensitivity and specificity are found to be 0.80 and 0.82, respectively. It is concluded that the use of combined plasma biomarkers not only allows the differentiation of the healthy controls and patients with AD in both the prodromal phase and the dementia phase, but it also allows AD in the prodromal phase to be distinguished from that in the dementia phase.
| S-EPMC3867966 | biostudies-other
Project description:Human beings constantly engage in attributing causal explanations to one's own and to others' actions, and theory-of-mind (ToM) is critical in making such inferences. Although children learn causal attribution early in development, children with autism spectrum disorders (ASDs) are known to have impairments in the development of intentional causality. This functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) study investigated the neural correlates of physical and intentional causal attribution in people with ASDs. In the fMRI scanner, 15 adolescents and adults with ASDs and 15 age- and IQ-matched typically developing peers made causal judgments about comic strips presented randomly in an event-related design. All participants showed robust activation in bilateral posterior superior temporal sulcus at the temporo-parietal junction (TPJ) in response to intentional causality. Participants with ASDs showed lower activation in TPJ, right inferior frontal gyrus and left premotor cortex. Significantly weaker functional connectivity was also found in the ASD group between TPJ and motor areas during intentional causality. DTI data revealed significantly reduced fractional anisotropy in ASD participants in white matter underlying the temporal lobe. In addition to underscoring the role of TPJ in ToM, this study found an interaction between motor simulation and mentalizing systems in intentional causal attribution and its possible discord in autism.
| S-EPMC3871731 | biostudies-literature
Project description:Social cognition might be impaired in first degree relatives (FDR) of BD but existing research shows controversial results about social cognitive impairments in this population. The aim of this study was to assess Theory of Mind (ToM) and nonverbal sensitivity in FDR of BD and compare the results with those of two groups of persons with remitted bipolar disorder (BD), type I and II, and a control group. Social cognitive ability was examined in first degree relatives of BD, with a biological parent, offspring or sibling diagnosed with the disorder. For this study, 37 FDRs of bipolar patients, 37 BD I, 40 BD II and 40 control participants were recruited. Social cognition was explored by means of the Reading the Mind in the Eyes Test and the MiniPONS. Results showed a significant impairment in FDR of BD in the ToM task, but not in nonverbal sensitivity. Performance of FDRs in social cognition is better than that of BDs (either type I or type II) but worse when compared with that of healthy individuals without a family history of psychiatric disorders. Nevertheless, no differences were found between BD I and BD II groups. Males and older participants showed a worse performance in all groups. Group family therapy with FDRs of BD might include training in the recognition of nonverbal cues, which might increase the understanding of their familiars with BD, in order to modify communication abilities.
| S-EPMC7924770 | biostudies-literature