Unawareness of deficits in Alzheimer's disease: Role of the cingulate cortex

Department of Psychology, University of Turin, Via Verdi 10, 10123 Turin, Italy.
Brain (Impact Factor: 9.2). 03/2011; 134(Pt 4):1061-76. DOI: 10.1093/brain/awr020
Source: PubMed


Unawareness of deficits is a symptom of Alzheimer's disease that can be observed even in the early stages of the disease. The frontal hypoperfusion associated with reduced awareness of deficits has led to suggestions of the existence of a hypofunctioning prefrontal pathway involving the right dorsolateral prefrontal cortex, inferior parietal lobe, anterior cingulate gyri and limbic structures. Since this network plays an important role in response inhibition competence and patients with Alzheimer's disease who are unaware of their deficits exhibit impaired performance in response inhibition tasks, we predicted a relationship between unawareness of deficits and cingulate hypofunctionality. We tested this hypothesis in a sample of 29 patients with Alzheimer's disease (15 aware and 14 unaware of their disturbances), rating unawareness according to the Awareness of Deficit Questionnaire-Dementia scale. The cognitive domain was investigated by means of a wide battery including tests on executive functioning, memory and language. Neuropsychiatric aspects were investigated using batteries on behavioural mood changes, such as apathy and disinhibition. Cingulate functionality was assessed with functional magnetic resonance imaging, while patients performed a go/no-go task. In accordance with our hypotheses, unaware patients showed reduced task-sensitive activity in the right anterior cingulate area (Brodmann area 24) and in the rostral prefrontal cortex (Brodmann area 10). Unaware patients also showed reduced activity in the right post-central gyrus (Brodmann area 2), in the associative cortical areas such as the right parietotemporal-occipital junction (Brodmann area 39) and the left temporal gyrus (Brodmann areas 21 and 38), in the striatum and in the cerebellum. These findings suggest that the unawareness of deficits in early Alzheimer's disease is associated with reduced functional recruitment of the cingulofrontal and parietotemporal regions. Furthermore, in line with previous findings, we also found apathy and disinhibition to be prominent features of the first behavioural changes in unaware patients.

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    • "In particular, we have strengthened our previous hypothesis (Amanzio et al., 2010) by directly assessing action monitoring using the metacognitive version of the WCST (Koren et al., 2006). We have used a neurocognitive perspective in order to illustrate the link between a reduction in LIDself-awareness , brain dysfunction and concomitant mild cognitive disturbances (Amanzio et al., 2011; Palermo, Leotta, et al., 2014). The clinical group we evaluated was homogeneous in terms of disease duration and severity, pharmacological treatment and the cognitive and behavioral status was taken into consideration. "
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    ABSTRACT: The study analyzes the presence of dyskinesias-reduced-self-awareness in forty-eight patients suffering from Parkinson’s disease (PD). As the association with executive dysfunction is a matter of debate and we hypothesize it plays an important role in dyskinesias self-unawareness, we analyzed the role of dopaminergic treatment on the medial-prefrontal-ventral-striatal circuitry using a neurocognitive approach. Special attention was given to metacognitive abilities related to action-monitoring that represent a novel explanation of the phenomenon. PD patients were assessed using different rating scales that we devised to measure movement awareness disorders. In order to ascertain whether each variable measured at a cognitive-clinical level contributes to predicting the scores of the movement-disorder-awareness-scales, we conducted multiple logistic regression models using the latter as binary dependent variables. We used the Wisconsin Card Sorting Test-metacognitive-version to assess the executive functions of the prefrontal-ventral-striatal circuitry. Data showed that a reduction of self-awareness using the Dyskinesia rating scale was associated with global monitoring (p=.04), monitoring resolution (p=.04) and control sensitivity (p=.04). Patients failed to perceive their performance, distinguish between correct and incorrect sorts, be confident in their choice and consequently decide to gamble during the task. We did not find any association with executive functions using the Hypo-Bradykinesia rating scale. Our findings indicate that when the comparator mechanism for monitoring attentive performance is compromised at a prefrontal striatal level, patients lose the ability to recognize their motor disturbances that do not achieve conscious awareness. Key words: awareness of movement disorders, dyskinesias, Parkinson’s disease, self-awareness, metacognitive functions
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    • "The AD patients were assessed with a wide battery of neuropsychological and neuropsychiatric tasks. The MMSE enabled the selection of a homogeneous population (see Amanzio et al., 2011). In particular, only patients with scores between 19 and 24 were selected, as also previously "

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    • "The AD patients were assessed with a wide battery of neuropsychological and neuropsychiatric tasks. The MMSE enabled the selection of a homogeneous population (see Amanzio et al., 2011). In particular, only patients with scores between 19 and 24 were selected, as also previously "

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