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Myotonic Dystrophy type 1 (DM1) is an autosomal dominant condition caused by expansion of the CTG triplet repeats within the myotonic dystrophy protein of the kinase (DMPK) gene. The central nervous system is involved in the disease, with multiple symptoms including cognitive impairment. A typical feature of DM1 is the presence of widespread white matter (WM) lesions, whose total volume is associated with CTG triplet expansion. The aim of this study was to characterize the distribution and pathological substrate of these lesions as well as the normal appearing WM (NAWM) using quantitative magnetization transfer (qMT) MRI, and comparing data from DM1 patients with those from patients with multiple sclerosis (MS). Twenty-eight patients with DM1, 29 patients with relapsing-remitting MS, and 15 healthy controls had an MRI scan, including conventional and qMT imaging. The average pool size ratio (F), a proxy of myelination, was computed within lesions and NAWM for every participant. The lesion masks were warped into MNI space and lesion probability maps were obtained for each patient group. The lesion distribution, total lesion load and the tissue-specific mean F were compared between groups. The supratentorial distribution of lesions was similar in the 2 patient groups, although mean lesion volume was higher in MS than DM1. DM1 presented higher prevalence of anterior temporal lobe lesions, but none in the cerebellum and brainstem. Significantly reduced F values were found within DM1 lesions, suggesting a loss of myelin density. While F was reduced in the NAWM of MS patients, it did not differ between DM1 and controls. Our results provide further evidence for a need to compare histology and imaging using new MRI techniques in DM1 patients, in order to further our understanding of the underlying disease process contributing to WM disease.

Aim: To investigate the cortical thickness in myotonic dystrophy type 1 (DM1) and its potential association with patients' genetic triplet expansion and social cognition deficits. Methods: Thirty patients with DM1 underwent the Social Cognition Battery Test and magnetic resonance imaging (MRI) scanning at 3 T. Twenty-five healthy subjects (HSs) were enrolled in the study to serve as a control group for structural MRI data. To assess changes in cortical thickness in DM1 patients, they were compared to HSs using a t-test model. Correlations were used to assess potential associations between genetic and clinical characteristics and social cognition performances in the patient group. Additionally, multiple regression models were used to explore associations between cortical thickness, CTG triplet expansion size, and scores obtained by DM1 patients on the Social Cognition Battery. Results: DM1 patients showed low performances in several subtests of the Social Cognition Battery. Specifically, they obtained pathological scores at Emotion Attribution Test (i.e., Sadness, Embarrassment, Happiness, and Anger) and at the Social Situations Test (i.e., recognition of normal situation, recognition of aberrant behavior). Significant negative correlations were found between CTG triplet expansion size and Embarrassment, and Severity of Aberrant Behavior. Similarly, a negative correlation was found between patients' MIRS scores and Sadness. DM1 patients compared to HSs showed reduced thickness in the right premotor cortex, angular gyrus, precuneus, and inferior parietal lobule. Significant associations were found between patients' CTG triplet expansion size and thickness in left postcentral gyrus and in the left primary somatosensory cortex, in the posterior cingulate cortex bilaterally, and in the right lingual gyrus. Finally, significant associations were found between cortical thickness and sadness in the superior temporal gyrus, the right precentral gyrus, the right angular gyrus

Background: Amnestic mild cognitive impairment (MCI) is a transitional stage between normal aging and Alzheimer's disease (AD). However, the clinical conversion from MCI to AD is unpredictable. Hence, identification of noninvasive biomarkers able to detect early changes induced by dementia is a pressing need. Purpose: To explore the added value of histogram analysis applied to measures derived from diffusion tensor imaging (DTI) for detecting brain tissue differences between AD, MCI, and healthy subjects (HS). Study Type: Prospective. Population/Subjects: A local cohort (57 AD, 28 MCI, 23 HS), and an Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort (41 AD, 58 MCI, 41 HS). Field Strength: 3T. Dual-echo turbo spin echo (TSE); fluid-attenuated inversion recovery (FLAIR); modified-driven-equilibrium-Fourier-transform (MDEFT); inversion-recovery spoiled gradient recalled (IR-SPGR); diffusion tensor imaging (DTI). Assessment: Normal-appearing white matter (NAWM) masks were obtained using the T1-weighted volumes for tissue segmentation and T2-weighted images for removal of hyperintensities/lesions. From DTI images, fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AXD), and radial diffusivity (RD) were obtained. NAWM histograms of FA, MD, AXD, and RD were derived and characterized estimating: peak height, peak location, mean value (MV), and quartiles (C25, C50, C75), which were compared between groups. Receiver operating characteristic (ROC) and area under ROC curves (AUC) were calculated. To confirm our results, the same analysis was repeated on the ADNI dataset. Statistical Tests: One-way analysis of variance (ANOVA), post-hoc Student's t-test, multiclass ROC analysis. Results: For the local cohort, C25 of AXD had the maximum capability of group discrimination with AUC of 0.80 for “HS vs. patients” comparison and 0.74 for “AD vs. others” comparison. For the ADNI cohort, MV of AXD revealed the maximum group discrimination capability with AUC o

This study investigates how cognitive reserve (CR) interacts with neurodegeneration (quantified by medial temporal atrophy, MTA) and macroscopic white matter lesions (WMLs) in delaying the conversion from amnestic mild cognitive impairment to Alzheimer's disease (AD). Forty-two amnestic mild cognitive impairment patients were consecutively recruited. They underwent magnetic resonance imaging and a comprehensive questionnaire to classify them as individuals with low or high CR. Patients were then clinically followed-up for 2 years. The patients' risk for conversion to AD because of CR was estimated by controlling for cognitive efficiency, MTA, and WMLs at baseline. Global cognition was the best predictor of conversion to AD in low CR patients. Conversely, in high CR patients only, WMLs (but not MTA) highly contributed in increasing the risk for conversion to AD. In conclusion, CR interacts with both patients' cognitive features and WMLs in modulating the impact of AD pathology. This seems relevant for clinical prognosis and therapeutic strategies.

This study investigates whether different patterns of grey matter (GM) loss may account for the different neuropsychological profiles observed in patients with amnestic (a-) and non-amnestic (na-) mild cognitive impairment (MCI), and may predict patients' clinical evolution. Fifty-five consecutive individuals complaining of cognitive dysfunction (referred to specialist dementia clinics) were screened and included in the study if they met the diagnostic criteria for MCI on a neurodegenerative basis. After an extensive neuropsychological assessment, patients were classified as suffering from a-MCI or na-MCI. Twenty-eight healthy individuals were also recruited and served as controls. All participants underwent magnetic resonance imaging at 3T, including conventional images and volumetric scans. Volumetric data were processed using voxel-based morphometry to assess between-group differences in regional GM volumes and correlations with neuropsychological performances. When compared to controls, a-MCI patients showed prominent GM volume reductions in the medial temporal lobes, while those with na-MCI showed reduced GM volumes in the orbito-frontal cortex and basal ganglia. In a-MCI patients, significant associations were found between verbal long-term memory performance and GM volumes in the hippocampus. Conversely, in na-MCI patients, associations were found between scores at tests exploring executive functions and GM volumes in the orbito-frontal cortex. At one-year follow-up, conversions were recorded exclusively toward Alzheimer's disease (AD) in the a-MCI group, and toward non-AD dementia in the na-MCI group. This study confirms that MCI is a heterogeneous clinical identity including different neurodegenerative entities; specific patterns of regional GM loss appear to account for specific neuropsychological features and are likely to predict patients' clinical evolution.

This study investigates whether different patterns of grey matter (GM) loss may account for the different neuropsychological profiles observed in patients with amnestic (a-) and non-amnestic (na-) mild cognitive impairment (MCI), and may predict patients' clinical evolution. Fifty-five consecutive individuals complaining of cognitive dysfunction (referred to specialist dementia clinics) were screened and included in the study if they met the diagnostic criteria for MCI on a neurodegenerative basis. After an extensive neuropsychological assessment, patients were classified as suffering from a-MCI or na-MCI. Twenty-eight healthy individuals were also recruited and served as controls. All participants underwent magnetic resonance imaging at 3T, including conventional images and volumetric scans. Volumetric data were processed using voxel-based morphometry to assess between-group differences in regional GM volumes and correlations with neuropsychological performances. When compared to controls, a-MCI patients showed prominent GM volume reductions in the medial temporal lobes, while those with na-MCI showed reduced GM volumes in the orbito-frontal cortex and basal ganglia. In a-MCI patients, significant associations were found between verbal long-term memory performance and GM volumes in the hippocampus. Conversely, in na-MCI patients, associations were found between scores at tests exploring executive functions and GM volumes in the orbitofrontal cortex. At one-year follow-up, conversions were recorded exclusively toward Alzheimer's disease (AD) in the a-MCI group, and toward non-AD dementia in the na-MCI group. This study confirms that MCI is a heterogeneous clinical identity including different neurodegenerative entities; specific patterns of regional GM loss appear to account for specific neuropsychological features and are likely to predict patients' clinical evolution.

A previous preliminary investigation based on a novel MRI approach to map anatomical connectivity revealed areas of increased connectivity in Alzheimer's disease (AD) but not in mild cognitive impairment patients. This prompted the hypothesis tested here, that these areas might reflect phenomena of brain plasticity driven by acetylcholinesterase inhibitors (AChEIs). Thirty-eight patients with probable AD (19 under medication with AChEIs and 19 drug-naïve) were recruited together with 11 healthy controls. All subjects had MRI scanning at 3T, including volumetric and diffusion-weighted scans. Probabilistic tractography was used to initiate streamlines from all parenchymal voxels, and anatomical connectivity maps (ACMs) were obtained by counting, among the total number of streamlines initiated, the fraction passing through each brain voxel. After normalization into standard space, ACMs were used to test for between-group comparisons, and for interactions between the exposure to AChEIs and global level of cognition. Patients with AD had reduced ACM values in the fornix, cingulum, and supramarginal gyri. The ACM value was strongly associated with the AChEI dosage-x-duration product in the anterior limb (non-motor pathway) of the internal capsule. Tractography from this region identified the anterior thalamic radiation as the main white matter (WM) tract passing through it. The reduced connectivity in WM bundles connecting the hippocampi with the rest of the brain (fornix/cingulum) suggests a possible mechanism for the spread of AD pathology. An intriguing explanation for the interaction between AChEIs and ACM is related to the mechanisms of brain plasticity, partially driven by neurotrophic properties of acetylcholine replacement. Hum Brain Mapp, 2012. © 2012 Wiley Periodicals, Inc.