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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The present study analyzed the awareness of deficits in 117 mild Alzheimer's disease participants. Since few studies have examined the cognitive and behavioral domains of reduced awareness in detail, we performed a domain-specific assessment using the Awareness of deficit Questionnaire - Dementia scale with the novel aim of describing the relationship with everyday executive dysfunction. Through the use of the subtests of the Behavioral Assessment of the Dysexecutive Syndrome, we hypothesized that executive cognitive functions may play an important role in the reduced awareness of deficits. We also considered other variables of interest to provide a novel comprehensive explanation of this phenomenon. Our first approach to the study was a factor analysis considering the role of these variables in the awareness of deficits; subsequently, regression analysis models were used to define which variables were associated with a reduction of awareness in cognitive and behavioral domains. In particular, the factors retained from the factor analysis, in terms of inhibition, self-monitoring, set-shifting, and mood orientation changes, appear to be important skills for awareness of instrumental activities of daily living (R(2) = .32). We also found hypo manic mood orientation and a tendency through apathy to be prominent indications of reduced behavioral awareness (R(2) = .13).

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