Neuroanatomical correlates of the behavioral and psychiatric symptoms in Alzheimer's disease: A voxel-based morphometry study

Abstract

Background: Self-referential processing of personality trait words is generally associated with better remembering compared to words processed in a semantic condition, an effect called self-reference effect (SRE). Previous works suggest that SRE is subserved by neural activity during encoding in several cortical areas including the medial prefrontal cortex (MPFC). Alzheimer’s disease (AD) is characterized by early memory deficits and Ab deposits that predominate in the prefrontal cortex. The goal of the present study was to assess whether SREwas altered in AD and to highlight the neural basis of this effect using fMRI in mild cognitive impairment (MCI) and AD patients with Ab deposits. Methods: We used an fMRI event-related self-referential paradigm in 16 patients (8 MCI and 8 AD) with a florbetapir-positive scan and 27 healthy elderly with a florbetapir-negative scan. The neural activity associated with self-reference processing compared to a semantic control condition during both encoding and retrieval was compared between groups and correlated with behavioral measures of memory and SRE. Results are reported at p 0.05; condition x group interaction p1⁄40.01). In both groups, self-related processing was associated with increased activity during encoding in a common brain network involving midline cortical structures. Memory performance correlated with selfrelated activity in the hippocampus during both encoding and retrieval in the patients. SRE score was related to MPFC activity during encoding in controls. In patients, no such relationship was found with SRE, and self-related activity during encoding was decreased in theMPFC and posterior cingulate cortex (PCC) compared to controls.Conclusions:While the PCC and the hippocampus may have a more general role in self and memory processes, the positive effect of self-reference processing on memory appears to be subserved by increased activity in the MPFC. In AD patients, this effect is lost as self-reference processing does not improve memory performance, and this abnormality seems to be due to impaired MPFC activity.