The Amnestic Syndrome of Hippocampal type in Alzheimer's Disease: An MRI Study

Abstract

The Free and Cued Selective Reminding Test (FCSRT) is a verbal episodic memory test used to identify patients with mild Alzheimer's disease (AD). The present study investigates the relationships between performance on FCSRT and grey matter atrophy assessed with structural MRI in patients with AD. Three complementary MRI-based analyses (VBM analysis, ROI-based analysis, and three-dimensional hippocampal surface-based shape analysis) were performed in 35 patients with AD to analyze correlations between regional atrophy and their scores for episodic memory using the FCSRT. With VBM analysis, the total score on the FCSRT was correlated with left medial temporal lobe atrophy including the left hippocampus but also the thalami. In addition, using ROI-based analysis, the total recall score on the FCSRT was correlated with the left hippocampal volume. With three-dimensional hippocampal surface-based shape analysis, both free recall and total recall scores were correlated with regions corresponding approximately to the CA1 field. No correlation was found with short term memory scores using any of these methods of analysis. In AD, the FCSRT may be considered as a useful clinical marker of memory disorders due to medial temporal damage, specially the CA1 field of the hippocampus.

Neuroanatomical Comparison of the “Word” and “Picture” Versions of the Free and Cued Selective Reminding Test in Alzheimer’s Disease

“…Nevertheless, clinical pathological studies suggested that NINCDS-ADRDA criteria are reliable for the diagnosis of AD [62]. Finally, even if most of AD patients included in our study are at the mild stage of AD, several subjects present with moderate AD and were severely impaired in the FCSRT, in line with previous studies with AD [19,63,64]. Indeed, a floor effect in some patients is also reported in previous studies and does not affect the VBM analysis.…”

“…Indeed, involvement of the hippocampus is a hallmark feature of AD and is considered to underlie the predominant amnesic syndrome [49]. Furthermore, previous studies reported correlation between scores of FCSRT free recall and atrophy in the left hippocampus and parahippocampus in AD and MCI subjects [19,20,22]. This finding is concordant with a recent study reporting that either the Rey Complex Figure delayed recall and the FCSRT delayed Recall, visual and a verbal episodic memory tests, are associated with total hippocampal volume in cognitively normal older adults [47].…”

“…PET studies have reported an association between free recall of the Word version of the FCSRT and right frontal perfusion, with cued recall associated instead with parahippocampal metabolism [17]. Furthermore, structural neuroimaging studies with the FCSRT Word version have exhibited an association between free recall and hippocampal volume measured with MRI-based volumetry in AD and MCI patients [18][19][20]. Free recall of the Picture version has been associated with left and right hippocampal volume, although the association was either stronger for left hippocampal, or only reported for the left hippocampal volume in AD patients and non-demented elderly people [21,22].…”

Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline

“…Using the available neuropsychological data on the ROS cohort (Supplemental Table 1), we focused on the relationship of neuronal insulin signaling and regulating molecules in CA1 to episodic memory, given the close association of CA1 atrophy in AD to this type of memory (72). Linear regression analyses revealed that, apart from Akt 2, basal activation states of insulin signaling and regulating molecules in CA1 were highly related to episodic memory ( Table 7).…”

“…Both these brain areas express the IR and IGF-1R (64,65), as well as insulin-sensitive GLUT4 (66)(67)(68)(69)(70). We then focused on the HF to study the causes and consequences of brain insulin resistance, since it is more directly involved in AD pathogenesis (61,63) and cognitive decline (71,72).…”