Anosognosia in Alzheimer's disease associated with tau accumulation and hypometabolism in frontal areas: Neuropsychiatry and behavioral neurology/Neuropsychiatry.

Background: Impaired insight in cognitive deficits (anosognosia) in Alzheimer's disease (AD) is frequent and problematic, but pathophysiological mechanisms are not fully understood. So far, several regions such as the cingulate cortex or frontotemporal regions have been identified as crucial. The aim of the present study was to explore the neural substrates of anosognosia in AD by applying 18‐F fluorodeoxyglucose (FDG) and 18‐F‐AV‐1451 (Tau) positron emission tomography (PET). Method: Seventy‐four AD‐patients with mild cognitive impairment (MCI) or dementia were included in this study. Anosognosia was assessed by a clinician, based on a structured interview compared to patient's subjective cognitive impairment. Cognition was examined applying the Consortium to Establish a Registry for AD (CERAD‐Plus) neuropsychological assessment battery. All patients underwent FDG‐PET. Additionally, 29 patients received a Tau‐PET. Glucose metabolism and 18‐F‐AV‐1451 binding were analyzed in a whole brain approach by comparing patients with and without anosognosia. Imaging analyses were controlled for age and sex. Result: Of the 74 patients, 28 had anosognosia and 46 were aware of their deficits. Patients with anosognosia were significantly older and less depressed. The number of MCI/dementia patients was similar between groups (MCI+/‐anosognosia 11/25, dementia +/‐anosognosia 17/21, p=.209). Neuropsychological results showed a significantly more impaired verbal fluency in patients with anosognosia (p=.025). When FDG‐PET images were analyzed, patients with anosognosia had a significantly lower glucose metabolism in the inferior frontal gyrus, rectal gyrus and medial frontal gyrus including the anterior cingulate cortex (cluster level, p‐uncorrected<0.001, FWE‐corrected p=.006). Tau‐PET analyses showed a significant higher tracer binding in patients with anosognosia in the inferior and medial frontal gyrus (cluster level, p‐uncorrected=.003, FWE‐corrected p=.048). Conclusion: This is the first study examining FDG‐ and Tau‐PET in AD patients with and without anosognosia. Anosognosia was not only associated with reduced glucose metabolism but also with increased tau accumulation in inferior and medial frontal regions. We speculate that tau‐induced hypometabolism in regions related to self‐referential processes leads to anosognosia. [ABSTRACT FROM AUTHOR]