Hyperconnectivity Associated with Anosognosia Accelerating Clinical Progression in Amnestic Mild Cognitive Impairment

The incidence and prevalence of anosognosia are highly variable in amnestic mild cognitive impairment (aMCI) patients. The study aims to explore the neuropathological mechanism of anosognosia in aMCI patients using two different but complementary technologies, including ¹⁸F-flortaucipir positron emission tomography and resting state functional magnetic resonance imaging. The study found that anosognosia was related to higher tau accumulation in the left medial orbitofrontal cortex (OFC), left posterior cingulate cortex, and right precuneus in aMCI patients. Intrinsic functional connectivity analyses found significant correlations between anosognosia index and hypoconnectivity between the left medial OFC and left middle temporal gyrus (MTG), right precuneus and left lingual gyrus. Longitudinally, the connectivity of these brain regions as well as the right precuneus and right cuneus showed hyperconnectivity in aMCI patients with anosognosia. The anosognosia index was also correlated with AD pathological markers (i.e., Aβ, t-tau, and p-tau) and brain glucose metabolism in aMCI patients. In conclusion, anosognosia in aMCI patients is associated with the dysfunction of medial OFC-MTG circuit and the precuneus-visual cortex circuit and accelerates clinical progression to AD dementia.