Differential medial temporal lobe morphometric predictors of item- and relational-encoded memories in healthy individuals and in individuals with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION:Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS:Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS:Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION:Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent

The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects

Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R2 = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI

Development and Cross-Validation of the UPSA Short Form for the Performance-Based Functional Assessment of Patients With Mild Cognitive Impairment and Alzheimer Disease

Functional capacity includes basic and complex behaviors necessary to independently live in the community. It has been found that patients with cognitive impairment have daily living functional skills altered at very early stages of illness. 1) To develop and validate a brief scale derived from the University of California, San Diego, performance-based skills assessment (UPSA); 2) to cross-validate this new UPSA short form with an independent healthy elderly sample. Fifty-one healthy elderly subjects, 26 mild cognitive impairment (MCI) subjects defined per Petersen's criteria, and 22 probable Alzheimer Disease (AD) subjects according to National Institute of Neurological and Communicative Disorders and Stroke–AD and Related Disorders Association criteria were included. For cross-validation purpose, a comparison group of 108 older healthy subjects with Mini-Mental scores of 25 or greater was also recruited. A modified four-functional domain version of the UPSA was administered. Communication and comprehension/planning domains accounted for almost 90% of the variance (R2 = 0.89) and in all models entered first and second, respectively. An UPSA short form using these two domains was significantly correlated with the full UPSA scale in all the groups examined: 0.86 for healthy controls; 0.87 for MCI; and 0.88 for AD. Acceptable sensitivity and specificity values for the UPSA short form were found in receiver operating characteristic (ROC) analysis. A correlation of 0.80 was found between the short and the full UPSA scales in the cross-validation sample. The UPSA short form is a rapid, reliable, and efficient measure of functional capacity that is able to detect performance impairment in an ecologically valid setting in much less time compared with the extended form of the scale. Furthermore, it demonstrated adequate discriminative properties among healthy subjects, MCI patients, and AD patients

Differential medial temporal lobe morphometric predictors of item- and relational-encoded memories in healthy individuals and in individuals with mild cognitive impairment and Alzheimer's disease.

INTRODUCTION:Episodic memory processes are supported by different subregions of the medial temporal lobe (MTL). In contrast to a unitary model of memory recognition supported solely by the hippocampus, a current model suggests that item encoding engages perirhinal cortex, whereas relational encoding engages parahippocampal cortex and the hippocampus. However, this model has not been examined in the context of aging, neurodegeneration, and MTL morphometrics. METHODS:Forty-four healthy subjects (HSs) and 18 cognitively impaired subjects (nine mild cognitive impairment [MCI] and nine Alzheimer's disease [AD] patients) were assessed with the relational and item-specific encoding task (RISE) and underwent 3T magnetic resonance imaging. The RISE assessed the differential contribution of relational and item-specific memory. FreeSurfer was used to obtain measures of cortical thickness of MTL regions and hippocampus volume. RESULTS:Memory accuracies for both item and relational memory were significantly better in the HS group than in the MCI/AD group. In MCI/AD group, relational memory was disproportionately impaired. In HSs, hierarchical regressions demonstrated that memory was predicted by perirhinal thickness after item encoding, and by hippocampus volume after relational encoding (both at trend level) and significantly by parahippocampal thickness at associative recognition. The same brain morphometry profiles predicted memory accuracy in MCI/AD, although more robustly perirhinal thickness for item encoding (R2 = 0.31) and hippocampal volume and parahippocampal thickness for relational encoding (R2 = 0.31). DISCUSSION:Our results supported a model of episodic memory in which item-specific encoding was associated with greater perirhinal cortical thickness, while relational encoding was associated with parahippocampal thickness and hippocampus volume. We identified these relationships not only in HSs but also in individuals with MCI and AD. In the subjects with cognitive impairment, reductions in hippocampal volume and impairments in relational memory were especially prominent

Extension and refinement of the predictive value of different classes of markers in ADNI: Four-year follow-up data

BACKGROUND: This study examined the predictive value of different classes of markers in the progression from Mild Cognitive Impairment (MCI) to Alzheimer’s disease (AD) over an extended 4 year follow-up in ADNI. METHODS: MCI patients assessed on clinical, cognitive, MRI, PET-FDG, and CSF markers at baseline, and followed on a yearly basis for four years to ascertain progression to AD. Logistic regression models were fitted in clusters including demographics, APOE genotype, cognitive markers, and biomarkers (morphometric, PET-FDG, CSF Abeta and tau). RESULTS: The predictive model at four years revealed that two cognitive measures, an episodic memory measure and a clock drawing screening test, were the best predictors of conversion (AUC= 0.78). CONCLUSIONS: This model of prediction is consistent to the previous model at two years, thus highlighting the importance of cognitive measures in progression from MCI to AD. Cognitive markers were more robust predictors than biomarkers

Table_1_The Age-Related Perfusion Pattern Measured With Arterial Spin Labeling MRI in Healthy Subjects.DOCX

<p>Aim: To analyze age-related cerebral blood flow (CBF) using arterial spin labeling (ASL) MRI in healthy subjects with multivariate principal component analysis (PCA).</p><p>Methods: 50 healthy subjects (mean age 45.8 ± 18.5 years, range 21–85) had 3D structural MRI and pseudo-continuous ASL MRI at resting state. The relationship between CBF and age was examined with voxel-based univariate analysis using multiple regression and two-sample t-test (median age 41.8 years as a cut-off). An age-related CBF pattern was identified using multivariate PCA.</p><p>Results: Age correlated negatively with CBF especially anteriorly and in the cerebellum. After adjusting by global value, CBF was relatively decreased with aging in certain regions and relatively increased in others. The age-related CBF pattern showed relative reductions in frontal and parietal areas and cerebellum, and covarying increases in temporal and occipital areas. Subject scores of this pattern correlated negatively with age (R² = 0.588; P < 0.001) and discriminated between the older and younger subgroups (P < 0.001).</p><p>Conclusion: A distinct age-related CBF pattern can be identified with multivariate PCA using ASL MRI.</p