Abstract
Semantic cues in the Free and Cued Selective Reminding Test (FCRST) play a key role in the neuropsychological diagnosis of Amnesic Mild Cognitive Impairment due to Alzheimer’s Disease (MCI-AD); however, the neural bases of their impact of recall abilities are only partially understood. Here, we thus decided to investigate the relationships between brain metabolism and the FCSRT Index of Sensitivity of Cueing (ISC) in patients with MCI-AD and in healthy controls (HC). Materials: Thirty MCI-AD patients (age: 74.7 ± 5.7 years; education: 9.6 ± 4.6 years, MMSE score: 24.8 ± 3.3, 23 females) and seventeen HC (age: 66.5 ± 11.1 years; education: 11.53 ± 4.2 years, MMSE score: 28.4 ± 1.14, 10 females) who underwent neuropsychological evaluation and brain F-18 fluorodeoxyglucose Positron Emission Tomography (FDG-PET) were included in the study. Results: ISC was able to differentiate HC from MCI-AD subjects as shown by a ROC analysis (AUC of 0.978, effect size Hedges’s g = 2.89). MCI-AD subjects showed significant hypometabolism in posterior cortices, including bilateral inferior Parietal Lobule and Precuneus and Middle Temporal gyrus in the left hemisphere (VOI-1) compared to HC. ISC was positively correlated with brain metabolism in a single cluster (VOI-2) spanning the left prefrontal cortex (superior frontal gyrus) and anterior cingulate cortex (ACC) in the patient group (R2 = 0.526, p < 0.001), but not in HC. Mean uptake values of VOI-2 did not differ between HC and MCI-AD. The structural connectivity analysis showed that VOI-2 is connected with the temporal pole, the cingulate gyrus and the posterior temporal cortices in the left hemisphere. Conclusion: In MCI-AD, the relative preservation of frontal cortex metabolic levels and their correlation with the ISC suggest that the left frontal cortices play a significant role in maintaining a relatively good memory performance despite the presence of posterior hypometabolism in MCI-AD.
Highlights
Formal assessment of memory is a key step to correctly identify subjects with Mild Cognitive Impairment due to Alzheimer’s Disease (MCI-AD) [1] and to define subjects with subjective memory complaints as well as to stratify asymptomatic subjects at risk for AD [2]
We evaluated the neural bases of Index of Sensitivity of Cueing (ISC) using a newly validated, robust version of the Free and Cued Selective Reminding Test (FCSRT) together with fluorodeoxyglucose Positron Emission Tomography (FDG-PET) imaging, focusing on a group of well characFigure 4
Structural connectievriitzyeodfMthCeVI-OAID-2.sTuhbejeVctOs.I-2 is connected with the temporal pole, the cingulate gyrustiavnedctohrereploasttieornioorfteISmCpowriatlhcborrtaicinesminettahbeolelifstmheimnitshpehVerOe.I-2 that includes the anterior cingulate and the superior frontal gyrus in the left hemisphere in MCI-AD patients
Summary
Formal assessment of memory is a key step to correctly identify subjects with Mild Cognitive Impairment due to Alzheimer’s Disease (MCI-AD) [1] and to define subjects with subjective memory complaints as well as to stratify asymptomatic subjects at risk for AD [2]. Even if the FCRST allows the computation of several indices of immediate and delayed recall, it makes it possible to evaluate the impact of semantic cues on recall This easyto-compute score (i.e., the Index of Sensitivity of Cueing (ISC) is clinically relevant as the presence of recall deficits with a limited effect of semantic cue is highly suggestive of a hippocampal syndrome, which represents a typical presentation of typical AD [3,8,9,10]. The ISC is partially altered in the first clinical stage of AD and it declines with the progression of the disease without suffering by the floor effect even at the moderate stage of the disease [11] It is one of the best indexes to estimate the risk of conversion from MCI to AD [5,7]
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