Homotaurine Effects on Hippocampal Volume Loss and Episodic Memory in Amnestic Mild Cognitive Impairment.

Homotaurine supplementation may have a positive effect on early Alzheimer's disease. Here, we investigated its potential neuroprotective effect on the hippocampus structure and episodic memory performances in amnestic mild cognitive impairment (aMCI). Neuropsychological, clinical, and neuroimaging assessment in 11 treated and 22 untreated patients were performed at baseline and after 1 year. Magnetic resonance data were analyzed using voxel-based morphometry to explore significant differences (Family Wise Error corrected) between the two groups over time. Patients treated with homotaurine showed decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex which was associated with improved short-term episodic memory performance as measured by the recency effect of the Rey 15-word list learning test immediate recall. Thus, homotaurine supplementation in individuals with aMCI has a positive effect on hippocampus atrophy and episodic memory loss. Future studies should further clarify the mechanisms of its effects on brain morphometry.

Unraveling predictors affecting compliance to MRI in Parkinson's disease.

INTRODUCTION: Magnetic resonance imaging (MRI) is a sensitive, noninvasive and widely available technique for studying Parkinson's disease (PD) from both research and clinical perspective. Several issues may physically impede execution of MRI. Moreover, the severity of motor or non-motor symptoms of PD might reduce compliance to MRI. Here we investigated predictors affecting compliance to MRI in PD patients. METHODS: Two-hundred-thirty-six PD patients underwent clinical, neuropsychological and neuropsychiatric investigations. Accordingly to their ability/inability to perform MRI scan, they were divided into 3 groups. Forty-two patients had physical incompatibility to MRI (PI); 51 patients refused to undergo scan during the MRI evaluation session (RR); 143 patients accepted to undergo and successfully completed MRI (SP). Multivariate/Univariate Analyses of Variance, followed by Bonferroni's post-hoc comparisons, were used to assess differences among groups. To identify predictors of compliance to MRI scan in the whole PD sample (SP vs. RR + PI) we carried out a logistic regression analysis. RESULTS: PI subjects were significantly older, had higher UPRDRS-III score, received lower daily dopamine agonist doses, and displayed worse cognitive performances than SP. RR subjects had significantly higher anxiety severity than SP. Lower daily dopamine agonist equivalents and higher anxiety scores were the significant whole predictors of not compliance to MRI in the logistic regression analysis. CONCLUSIONS: These results show that demographic, neuropsychological and neuropsychiatric features may limit compliance to MRI in PD, and provide valuable aid for setting and interpreting research and clinical MRI studies in PD.

Corpus Callosum Structure is Topographically Correlated with the Early Course of Cognition and Depression in Alzheimer's Disease.

Corpus callosum (CC) abnormalities may cause cognitive and neuropsychiatric complications due to reduced hemispheric integration. Over a one-year period, we investigated whether the CC structure of 20 patients with mild Alzheimer's disease (AD) was linked to the evolution of cognitive and neuropsychiatric symptoms. We also investigated whether this anatomical-clinical relationship was localized topographically on the CC by combining voxel-based morphometry and diffusion tensor imaging approaches. We assessed patients' global cognitive deterioration and neuropsychiatric symptoms with the Mini-Mental State Examination and the Neuropsychiatric Inventory. Increased global cognitive deterioration during the early course of AD was significantly related to reduced white matter density (p = 0.004) and fractional anisotropy (FA) (p = 0.012) and increased mean diffusivity (MD) (p = 0.017) at the level of the CC isthmus/splenium. Further, increased depression severity was significantly related to reduced FA (p = 0.008) and increased MD (p = 0.018) at the level of the CC rostrum. These results indicate that changes in early myelinated CC fibers, which subserve the lateral temporal and parietal cortices and are less vulnerable to damage, may be related to cognitive impairment. Furthermore, changes in late myelinated CC fibers, which connect the orbitofrontal cortices and are more vulnerable to damage, may be related to the earliest neuropsychiatric symptoms of AD, such as depression.

Sociodemographic, neuropsychiatric and cognitive characteristics of pathological gambling and impulse control disorders NOS in Parkinson's disease.

Despite of previous evidence supporting the association between impulse control disorder (ICD) and several demographic, clinical and therapeutic features in Parkinson's disease (PD), the relationships between pathological gambling (PG) or other variants of ICD (ICD-NOS) and specific neuropsychiatric or cognitive domains are not entirely defined. In this study, 155 PD patients without dementia or cognitive impairment underwent: i. the ICD diagnoses, using the Questionnaire for Impulsive-Compulsive Disorders, ii. the mood and anxiety disorders diagnoses, according to the DSM-IV-TR criteria, and iii. a comprehensive battery for measuring severity of psychopathology and neuropsychology domains. Patients were divided in those with pathological gambling (PG), ICDs not otherwise specified (ICD-NOS), or the lack of ICD (No-ICD). There was a progression in age and age at onset from the younger PG subjects throughout ICD-NOS to No-ICD. PG and ICD-NOS subjects had longer disease duration and were taking significantly higher dosages of antiparkinsonian drugs than No-ICD ones. PG subjects had significantly higher severity of depressive and anxious symptoms with respect to the other 2 groups. Both PG and ICD-NOS subjects suffer from increased severity of psychotic symptoms than No-ICD ones. The 3 groups did not differ in any cognitive measure. Our results support the concept that the different sociodemographic and neuropsychiatric profiles of PD patients are associated with different ICDs. Moreover, we clearly demonstrate the lack of relationship between ICD and cognitive performances in undemented PD patients.

Neuroanatomical correlates of awareness of illness in patients with amnestic mild cognitive impairment who will or will not convert to Alzheimer's disease.

BACKGROUND: Awareness of cognitive deficits may be reduced in mild cognitive impairment (MCI). This may have a detrimental effect on illness course and may be a predictor of subsequent conversion to AD. Although neuropsychological correlates have been widely investigated, no evidence of a neuroanatomical basis of the phenomenon has been reported yet. This study was aimed at investigating the neuroanatomical correlates of deficit awareness in amnestic MCI to determine whether they constitute risk factors for conversion to AD. METHOD: A sample of 36 first-diagnosis amnestic MCI patients were followed for five years. At the first diagnostic visit they were administered an extensive diagnostic and clinical procedure and the Memory Insight Questionnaire (MIQ), measuring a total index and four sub-indices, to investigate awareness of deficits in dementia; they also underwent a high resolution T1-weighted Magnetic Resonance Imaging (MRI) investigation. Grey matter brain volumes were analysed on a voxel-by-voxel basis using Statistical Parametric Mapping 8. Data of 10 converter patients (CONV) and those of 26 non converter patients (NOCONV) were analysed using multiple regression models. RESULTS: At baseline, self-awareness of memory deficits was poorer in CONV compared to NOCONV. Furthermore, reduced awareness of cognitive deficits in CONV correlated with reduced grey matter volume of the anterior cingulate (memory deficit awareness), right pars triangularis of the inferior frontal cortex (memory deficit awareness) and cerebellar vermis (total awareness), whereas in NOCONV it correlated with reduced grey matter volume of left superior (total awareness) and middle (language deficit awareness) temporal areas. Further, at baseline self-awareness of memory deficits were poorer in CONV than in NOCONV. CONCLUSIONS: Defective awareness of cognitive deficits is underpinned by different mechanisms in CONV and NOCONV amnestic MCI patients. Our data support the hypothesis that poor awareness of cognitive deficit is a predictor of subsequent conversion to AD.

White matter hyperintensities segmentation: a new semi-automated method.

White matter hyperintensities (WMH) are brain areas of increased signal on T2-weighted or fluid-attenuated inverse recovery magnetic resonance imaging (MRI) scans. In this study we present a new semi-automated method to measure WMH load that is based on the segmentation of the intensity histogram of fluid-attenuated inversion recovery images. Thirty patients with mild cognitive impairment with variable WMH load were enrolled. The semi-automated WMH segmentation included removal of non-brain tissue, spatial normalization, removal of cerebellum and brain stem, spatial filtering, thresholding to segment probable WMH, manual editing for correction of false positives and negatives, generation of WMH map, and volumetric estimation of the WMH load. Accuracy was quantitatively evaluated by comparing semi-automated and manual WMH segmentations performed by two independent raters. Differences between the two procedures were assessed using Student's t-tests and similarity was evaluated using linear regression model and Dice similarity coefficient (DSC). The volumes of the manual and semi-automated segmentations did not statistically differ (t-value = -1.79, DF = 29, p = 0.839 for rater 1; t-value = 1.113, DF = 29, p = 0.2749 for rater 2), were highly correlated [R (2) = 0.921, F (1,29) = 155.54, p < 0.0001 for rater 1; R (2) = 0.935, F (1,29) = 402.709, p < 0.0001 for rater 2] and showed a very strong spatial similarity (mean DSC = 0.78, for rater 1 and 0.77 for rater 2). In conclusion, our semi-automated method to measure the load of WMH is highly reliable and could represent a good tool that could be easily implemented in routinely neuroimaging analyses to map clinical consequences of WMH.

Neuropsychiatric symptoms and interleukin-6 serum levels in acute stroke.

The role of interleukin-6 (IL-6) as a risk factor for developing depressive symptoms, neuropsychological impairment, and related functional and neurological symptom severity during the acute phase of ischemic stroke is still underexplored. Here, the authors assessed this issue, in 48 patients without significant clinical history for major medical illnesses or other factors that promote inflammation, 72 hours after a first-ever acute ischemic stroke. In the acute phase of ischemic stroke, increased IL-6 plays a key role in the onset of depressive disorders, apathy/amotivation, somatic symptoms of depression, and neurological/functional symptoms, resulting in higher disability and poor outcome of stroke patients.

Cognitive Performance following Carotid Endarterectomy or Stenting in Asymptomatic Patients with Severe ICA Stenosis.

Background. Endarterectomy (CEA) or stenting (CAS) of a stenotic carotid artery is currently undertaken to reduce stroke risk. In addition removal of the arterial narrowing has been hypothesized to improve cerebral hemodynamics and provide benefits in cognitive functions, by supposedly resolving a "hypoperfusion" condition. Methods. In this study we sought to test whether resolution of a carotid stenosis is followed by measurable changes in cognitive functions in 22 subjects with "asymptomatic" stenosis. Results. A main finding of the study was the statistically significant pre-post difference observed in the performance of phonological verbal fluency and Rey's 15-word immediate recall. Remarkably, there was a significant interaction between phonological verbal fluency performance and side of the carotid intervention, as the improvement in the verbal performance, a typical "lateralized" skill, was associated with resolution of the left carotid stenosis. Conclusion. The results reflect a substantial equivalence of the overall performance at the before- and after- CEA or CAS tests. In two domains, however, the postintervention performance resulted improved. The findings support the hypothesis that recanalization of a stenotic carotid could improve brain functions by resolving hypothetical "hypoperfusion" states, associated with the narrowing of the vessels.

Rapid-onset apathy may be the only clinical manifestation after dorsal striatum hemorrhagic lesion: a case report.

Apathy is a common clinical feature of stroke patients and it is often correlated with cognitive deficits, functional impairment and depression. Here we report the case of a 70-year-old woman with no history of neuropsychiatric disorders who showed abrupt onset of pure apathy after the onset of a right brain vascular lesion located in the head of the caudate nucleus, the anterior part of the putamen, and the genu and the anterior limb of the internal capsule. A complete neuropsychological and neurological examination did not show deficits. A comprehensive neuropsychiatric assessment focusing on the post-stroke hospitalization period showed severe motor, cognitive and affective apathy with no depression or other neuropsychiatric symptoms. This case highlights the key role of the dorsal striatum in the development of pure apathy, possibly due to its function in regulating approach-attachment behavior, affect and initiative, which are the emotional, cognitive and motor dimensions of apathy.

Amygdala and hippocampus volumetry and diffusivity in relation to dreaming.

Microstructural analyses by MRI brain scans and by DTI analysis of MR images were used to investigate the possible relationship between deep gray matter structures (amygdala and hippocampus) and dreaming in healthy subjects. Thirty-four subjects ranging in age 20s to 70s underwent to a MRI protocol for the assessment of volume and mean diffusivity (MD) in the amygdala and hippocampus and were asked to fill out a dream diary via audiotape recording upon morning awakening for two weeks. Multiple regression analyses evaluated the relationships between anatomical measures and quantitative and qualitative measures of the reported dreams. The main result points to a dissociation between some quantitative and qualitative aspects of dream reports. While the mean number of dreams recalled per day did not show any significant relationship with the neuroanatomical measures, significant associations with some qualitative features of the recalled dreams (emotional load, bizarreness, and vividness) and, to some extent, with the length of dream reports were observed. Particularly, a higher MD of the left amygdala, reflecting a decreased microstructural integrity, was associated with shorter dream reports and lower scores on emotional load. Bizarreness of dream reports was negatively correlated with the left amygdala volume and positively correlated with the right amygdala MD. Some specific, although weaker, relationships were also found between bizarreness and hippocampal measures. These findings indicate some direct relationships between volumetric and ultrastructural measures of the hippocampus-amygdala complex and specific qualitative features of dreaming.

White matter microstructure and apathy level in amnestic mild cognitive impairment.

In this study, we assess white matter microstructural deficit correlates of apathy level in 20 patients with amnestic mild cognitive impairment by means of diffusion tensor imaging. Mean diffusivity correlated positively with apathy level in the right temporal portion of the uncinate, middle longitudinal and inferior longitudinal fasciculi and in the parathalamic white matter, the fornix and the posterior cingulum of the right hemisphere. Fractional anisotropy results confirmed evidence of disconnection associated with apathy in all white matter areas except the middle longitudinal fasciculus. These results support the view that alterations in the neural mechanisms underlying apathy level occur in the early phase of degenerative dementias.

Disease outcome, alexithymia and depression are differently associated with serum IL-18 levels in acute stroke.

Stroke has been shown to lead to depressive disorders, anxiety disorders and other emotional consequences. Although the cause of these disorders is a subject of debate, stroke has clearly been shown to lead to the production of pro-inflammatory cytokines, which we hypothesized to play a role in the production of post-stroke emotional disorders. Thus we investigated here whether acute stroke might be associated with changes in the normal serum levels of IL-18 and if these changes were related to stroke severity, as well as to the presence and severity of alexithymia and depression. Thirty patients with a first-ever symptomatic ischemic stroke were included. Alexithymia (Toronto Alexithymia Scale; TAS-20), depression (Hamilton Depression Rating Scale; HDRS-17) and serum IL-18 were assessed. Stroke patients showed serum levels of IL-18 significantly related to stroke severity. Furthermore, a strong positive correlation was observed between IL-18 levels and severity of alexithymia, particularly among patients with right-hemisphere lesions. Specifically, circulating concentrations of IL-18 were significantly increased in patients with categorical alexithymia (TAS-20 score 61), as compared with both non alexithymic patients and control subjects. In addition, stroke was more severe in alexithymic patients, as compared to non alexithymic patients. Following multivariate regression, serum IL-18 levels appeared to be specifically associated with alexithymia rather than with stroke severity in patients with right-hemisphere lesions only. These results suggest that IL-18 might be specifically implicated in the pathogenesis of post-stroke alexithymia, ultimately contributing to impaired recovery from stroke.