Alzheimer disease: functional abnormalities in the dorsal visual pathway.

PURPOSE: To evaluate whether patients with Alzheimer disease (AD) have altered activation compared with age-matched healthy control (HC) subjects during a task that typically recruits the dorsal visual pathway. MATERIALS AND METHODS: The study was performed in accordance with the Declaration of Helsinki, with institutional ethics committee approval, and all subjects provided written informed consent. Two tasks were performed to investigate neural function: face matching and location matching. Twelve patients with mild AD and 14 age-matched HC subjects were included. Brain activation was measured by using functional magnetic resonance imaging. Group statistical analyses were based on a mixed-effects model corrected for multiple comparisons. RESULTS: Task performance was not statistically different between the two groups, and within groups there were no differences in task performance. In the HC group, the visual perception tasks selectively activated the visual pathways. Conversely in the AD group, there was no selective activation during performance of these same tasks. Along the dorsal visual pathway, the AD group recruited additional regions, primarily in the parietal and frontal lobes, for the location-matching task. There were no differences in activation between groups during the face-matching task. CONCLUSION: The increased activation in the AD group may represent a compensatory mechanism for decreased processing effectiveness in early visual areas of patients with AD. The findings support the idea that the dorsal visual pathway is more susceptible to putative AD-related neuropathologic changes than is the ventral visual pathway.

Anterior cingulum volumetry, auditory P300 in schizophrenia with negative symptoms.

The anterior cingulate cortex (ACC) is located at the rostum of the corpus callosum and involved in both cognitive and emotional brain processes. It has been suggested to be involved in P300 event-related potential generation. A large sample of schizophrenia inpatients and controls was examined in order to assess the potential relationship between ACC volumes and P300 characteristics in patients with more pronounced negative symptoms. In 50 male schizophrenia patients and 50 matched controls, auditory P300 and structural magnetic resonance imaging volume measurements of the ACC were obtained. Patients' negative symptoms were assessed using the PANSS (Positive and Negative Syndrome Scale). Volumetry of ACC subregions revealed a volume reduction in patients with schizophrenia compared with controls in right hemispheric rostral ACC subregions that were most pronounced in more negative schizophrenia patients. There was a positive correlation between PZ P300 amplitude and total ACC volume in the right hemisphere in schizophrenia patients with less negative symptoms. The results support the assumption that structural changes of the ACC are more pronounced in subgroups of schizophrenia patients with more negative psychopathology. In addition, while right hemisphere ACC volumes significantly differ between schizophrenia subgroups, combining measures of event-related potential (ERP) and ACC volumetry does not add additional information.

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease.

Magnetic resonance imaging (MRI)-based volumetry of medial temporal lobe regions is among the best established biomarker candidates of Alzheimer's disease (AD) to date. This study assessed the effect of multicentre variability of MRI-based hippocampus and amygdala volumetry on the discrimination between patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and on the association of morphological changes with ApoE4 genotype and cognition. We studied 113 patients with clinically probable AD and 150 patients with amnestic MCI using high-resolution MRI scans obtained at 12 clinical sites. We determined effect sizes of group discrimination and random effects linear models, considering multicentre variability. Hippocampus and amygdala volumes were significantly reduced in AD compared with MCI patients using data pooled across centres. Multicentre variability did not significantly affect the power to detect a volume difference between AD and MCI patients. Among cognitive measures, delayed recall of verbal and non-verbal material was significantly correlated with hippocampus and amygdala volumes. Amygdala and hippocampus volumes were not associated with ApoE4 genotype in AD or MCI. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for cross-sectional diagnostic studies, and they replicate essential findings from smaller scale monocentre studies.

Differences in hippocampal volume between major depression and schizophrenia: a comparative neuroimaging study.

Several studies have demonstrated that structural brain change is detectable in the hippocampus in both patients, with schizophrenia and major depression. Only few studies, however, compared both clinical disease entities directly and no larger study has tried to take different disease stages into account. The objectives of this study are to investigate whether hippocampal volumes are reduced in patients with schizophrenia and those with major depression with the same duration of illness compared to healthy controls and to assess further changes at different disease stages. A total of 319 inpatients and healthy controls were enrolled and investigated with magnetic resonance imaging (MRI). Hippocampal volumes were measured using the segmentation software BRAINS. Bilateral hippocampal volume reductions were detected in both schizophrenic and depressed patients compared to healthy control (HC) subjects. Although younger, schizophrenic (SZ) patients showed in their MRI scans significant bilaterally reduced hippocampal volumes compared to patients with major depression. Although the hippocampal reductions were similar at the onset of symptomatic manifestation of both diseases, there was a further significant reduction of the left hippocampus in the recurrently ill SZ subgroup. The data suggest rather dynamic structural brain alterations in schizophrenia compared to major depression. Here, the presented application of the comparative neuroscience approach, by the use of large neuroimaging MRI databases, seems highly valuable. In the field of psychiatry, with its still controversial operationalized descriptive diagnostic entities, the cross-nosological approach provides a helpful tool to better elucidate the still unknown brain pathologies and their underlying molecular mechanisms beyond a single nosological entity.

Functional neuroanatomy of CCK-4-induced panic attacks in healthy volunteers.

Experimental panic induction with cholecystokinin tetrapeptide (CCK-4) is considered as a suitable model to investigate the pathophysiology of panic attacks. While only a few studies investigated the brain activation patterns following CCK-4, no data are available on the putative involvement of the amygdala in the CCK-4 elicited anxiety response. We studied the functional correlates of CCK-4-induced anxiety in healthy volunteers by means of functional magnetic resonance imaging (fMRI) and region of interest (ROI) analysis of the amygdala. Sixteen healthy volunteers underwent challenge with CCK-4 compared with placebo in a single-blind design. Functional brain activation patterns were determined for the CCK-4-challenge, the placebo response and anticipatory anxiety (AA). CCK-4-induced anxiety was accompanied by a strong and robust activation (random effects analysis, P < 0.00001, uncorrected for multiple testing) in the ventral anterior cingulate cortex (ACC), middle and superior frontal gyrus, precuneus, middle and superior temporal gyrus, occipital lobe, sublobar areas, cerebellum, and brainstem. In contrast, random effects group analysis for placebo and AA using the same level of significance generated no significant results. Using a more liberal level of significance, activations could be observed in some brain regions such as the dorsal part of the ACC during AA (random effects analysis, P < 0.005). Overall functional responses did not differ between panickers and nonpanickers. Only 5 of 11 subjects showed strong amygdala activation. However, ROI analysis pointed towards higher scores in fear items in these subjects. In conclusion, while overall brain activation patterns are not related to the subjective anxiety response to CCK-4, amygdala activation may be involved in the subjective perception of CCK-4-induced fear.

Neuroanatomical correlates of different vulnerability states for psychosis and their clinical outcomes.

BACKGROUND: Structural brain abnormalities have been described in individuals with an at-risk mental state for psychosis. However, the neuroanatomical underpinnings of the early and late at-risk mental state relative to clinical outcome remain unclear. AIMS: To investigate grey matter volume abnormalities in participants in a putatively early or late at-risk mental state relative to their prospective clinical outcome. METHOD: Voxel-based morphometry of magnetic resonance imaging data from 20 people with a putatively early at-risk mental state (ARMS-E group) and 26 people with a late at-risk mental state (ARMS-L group) as well as from 15 participants with at-risk mental states with subsequent disease transition (ARMS-T group) and 18 participants without subsequent disease transition (ARMS-NT group) were compared with 75 healthy volunteers. RESULTS: Compared with healthy controls, ARMS-L participants had grey matter volume losses in frontotemporolimbic structures. Participants in the ARMS-E group showed bilateral temporolimbic alterations and subtle prefrontal abnormalities. Participants in the ARMS-T group had prefrontal alterations relative to those in the ARMS-NT group and in the healthy controls that overlapped with the findings in the ARMS-L group. CONCLUSIONS: Brain alterations associated with the early at-risk mental state may relate to an elevated susceptibility to psychosis, whereas alterations underlying the late at-risk mental state may indicate a subsequent transition to psychosis.

Decreased activation along the dorsal visual pathway after a 3-month treatment with galantamine in mild Alzheimer disease: a functional magnetic resonance imaging study.

Visual perception has been shown to be altered in Alzheimer disease (AD) patients, and it is associated with decreased cognitive function. Galantamine is an active cholinergic agent, which has been shown to lead to improved cognition in mild to moderate AD patients. This study examined brain activation in a group of mild AD patients after a 3-month open-label treatment with galantamine. The objective was to examine the changes in brain activation due to treatment. There were 2 tasks to visual perception. The first task was a face-matching task to test the activation along the ventral visual pathway, and the second task was a location-matching task to test neuronal function along the dorsal pathway. Brain activation was measured using functional magnetic resonance imaging. There were 5 mild AD patients in the study. There were no differences in the task performance and in the cognitive scores of the Consortium to Establish a Registry for Alzheimer's Disease battery before and after treatment. In the location-matching task, we found a statistically significant decrease in activation along the dorsal visual pathway after galantamine treatment. A previous study found that AD patients had higher activation in the location-matching task compared with healthy controls. There were no differences in activation for the face-matching task after treatment. Our data indicate that treatment with galantamine leads to more efficient visual processing of stimuli or changes the compensatory mechanism in the AD patients. A visual perception task recruiting the dorsal visual system may be useful as a biomarker of treatment effects.

Influence of trait anxiety on inhibitory control in alcohol-dependent patients: simultaneous acquisition of ERPs and BOLD responses.

Alcohol-dependence is often associated with comorbid psychiatric symptoms. However, the results concerning the influence of these symptoms on cognitive functioning in alcoholism are still inconsistent. The aim of this study was to determine performance monitoring in healthy volunteers and alcohol-dependent patients, and to assess the influence of trait anxiety on these processes. Sixteen healthy volunteers and 16 detoxified alcohol-dependent patients completed an auditory go/nogo paradigm. Functional magnetic resonance imaging, event-related potentials and behavioral data were acquired simultaneously. The patients were classified by median split based on level of self-rated trait anxiety (state-trait anxiety inventory; STAI). The results showed no significant differences regarding inhibition-associated electrophysiological and behavioral responses between alcohol-dependent patients with high-trait anxiety scores and alcohol-addicts with low-STAI scores. However, the functional MRI data revealed elevated activations during the response inhibition task especially in the middle frontal gyrus (BA 6/9), the superior frontal gyrus (BA 6/8/9) and the right inferior frontal gyrus, as well as temporo-parietal brain regions in patients with high-trait anxiety compared to non-anxious alcohol-addicts. Patients and healthy controls showed comparable results with regard to neural and behavioral responses. These results suggest that inhibitory control capacities of alcohol-dependent patients are not consistent: alcohol-addicts with high-trait anxiety ratings showed elevated neural responses compared to patients without any comorbid psychiatric symptoms. This may indicate that comorbid psychiatric symptoms need to be considered when assessing brain responses in alcohol-dependent patients.

Association of the brain-derived neurotrophic factor Val66Met polymorphism with reduced hippocampal volumes in major depression.

CONTEXT: Brain-derived neurotrophic factor (BDNF) modulates hippocampal plasticity, which is believed to be altered in patients with major depression. OBJECTIVE: To examine the effect of the BDNF Val66Met polymorphism on hippocampal and amygdala volumes in patients with major depression and in healthy control subjects. DESIGN: Cross-sectional comparison between patients and controls. SETTING: Inpatients with major depression from the Department of Psychiatry and Psychotherapy and healthy controls from the community were recruited. PARTICIPANTS: The study population of 120 subjects included 60 patients with major depression and 60 healthy controls. MAIN OUTCOME MEASURES: Using a combined strategy, hippocampal and amygdala volumes were estimated on high-resolution magnetic resonance images, and genotyping was performed for the BDNF Val66Met polymorphism. RESULTS: Patients had significantly smaller hippocampal volumes compared with controls (P = .02). Significantly smaller hippocampal volumes were observed for patients and for controls carrying the Met-BDNF allele compared with subjects homozygous for the Val-BDNF allele (P = .006). With respect to amygdala volumes, no significant differences between patients and controls and no significant main effects for the BDNF Val66Met polymorphism were observed. CONCLUSIONS: These genotype-related alterations suggest that Met-BDNF allele carriers might be at risk to develop smaller hippocampal volumes and may be susceptible to major depression. This study supports findings from animal studies that the hippocampus is involved in brain development and plasticity.

Effect of hippocampal and amygdala volumes on clinical outcomes in major depression: a 3-year prospective magnetic resonance imaging study.

OBJECTIVE: According to the stress-toxicity hypothesis of depression, hippocampal volumes may diminish as the disease progresses. We sought to examine the changes in hippocampal and amygdala volumes at baseline and at 3 years after an acute depressive episode, and the impact of reduced hippocampal volumes on the outcome. METHODS: In a prospective, longitudinal study, we examined the hippocampus and amygdala of 30 inpatients with major depression from the Department of Psychiatry and Psychotherapy and 30 healthy participants from the community (control group) using high-resolution magnetic resonance images at baseline and after 3 years. Psychopathology was assessed at baseline, weekly during the inpatient phase and then after 1, 2 and 3 years. RESULTS: During the 3-year follow-up period, neither hippocampal nor amygdala volumes changed significantly among patients or participants in the control group. However, in the subgroup of patients who took antidepressants over the full 3 years, the left hippocampal volumes increased significantly. Patients with small hippocampal volumes and previous depressive episodes had a worse clinical outcome compared with patients with large hippocampal volumes and previous depressive episodes. CONCLUSION: Overall, our results suggest that a relatively small hippocampal volume may be a vulnerability factor for a bad treatment response in major depression. Subtle changes in hippocampal volumes may be detectable during continuous antidepressant therapy. Such changes may be the result of neuroplastic processes.

Involvement patterns in myotilinopathy and desminopathy detected by a novel neuromuscular whole-body MRI protocol.

Whole-body MRI (WB-MRI) has been successfully applied for oncologic and cardiovascular diagnostics, whereas imaging in myopathies usually employs dedicated protocols restricted to areas of specific interest. In this study, we propose a comprehensive neuromuscular WB-MRI protocol. Eighteen patients with degenerative and inflammatory muscle diseases were included. Whole-body imaging was performed on a 1.5-T MR system using parallel imaging. Examination time was 41:26 min. Coronal and axial T1-weighted and coronal short tau inversion recovery (STIR) sequences of the whole body were acquired. Images were analysed by two radiologists. With this protocol we could detect characteristic involvement patterns in different myofibrillar myopathies (MFMs): Patients with myotilinopathy showed frequent involvement of the rhomboid muscles (4/5), the erector spinae (5/5), the biceps femoris and the semimembranosus (5/5), while the semitendinosus was relatively spared (2/5). In contrast, in desminopathy patients the ilipsoas (3/4), the sartorius, (3/4), the gracilis (3/4) and the semitendinosus (3/4) were frequently involved, while the semimembranosus was spared (1/4). As shown for MFMs, WB-MRI is an appropriate modality to detect fatty infiltration and oedema in skeletal muscles. WB-MRI could be more useful than dedicated examinations for differential diagnosis, muscle biopsy planning and noninvasive follow-up examinations.

Morphological substrate of face matching in healthy ageing and mild cognitive impairment: a combined MRI-fMRI study.

Functional MRI during face matching shows activation of the ventral visual stream, including the ventral temporal lobes and fusiform gyrus. In contrast, a location-matching task activates the dorsal visual stream, compromising parietal lobe areas. The morphological basis of the functional coupling between brain regions may be related to the distribution of neuron numbers and neuropil density, but has not yet been demonstrated in the living human brain. Regional neuron density can indirectly be assessed in vivo using structural MRI. The progression of Alzheimer's disease pathology along specific functional systems provides an in vivo lesion model to determine the interaction between reduced neuron numbers and reduced neuronal activation. In this study, we determined correlations between activation of the fusiform gyrus in fMRI during face matching and cortical grey matter density derived from structural MRI in 17 healthy elderly subjects (mean age = 67.5 years, SD = 4.5 years, 10 women) and 16 patients with amnestic mild cognitive impairment (MCI) (mean age = 69.9 years, SD = 8.0 years, 8 women), a predementia stage of Alzheimer's disease. Independently of diagnosis, stronger activation of the fusiform gyrus was correlated with larger grey matter density in the fusiform gyrus, inferior and middle temporal gyrus, parahippocampal gyrus and dorsolateral prefrontal cortex. In contrast, smaller activation of the fusiform gyrus was associated with larger grey matter density in the inferior parietal lobule, post-central gyrus and dorsolateral prefrontal cortex. Compared to controls, MCI patients had more pronounced positive correlations in the ventral temporal lobes and more pronounced negative correlations in the parietal lobes. Our data suggest that fusiform activation is positively correlated with cortical grey matter density of brain areas belonging to the ventral visual stream and negatively correlated with grey matter density of brain areas belonging to the dorsal visual stream and that, these effects are more pronounced in MCI patients than in controls. These findings support the notion that the functional segregation within the visual system is based on the distribution of cortical grey matter volumes, possibly reflecting the spatial distribution of neuron density.

Anterior cingulate cortex does not differ between patients with major depression and healthy controls, but relatively large anterior cingulate cortex predicts a good clinical course.

The anterior cingulate cortex (ACC) is involved in the regulation of emotion processing, and its volume has been found to be reduced in patients with major depression. Furthermore, larger ACC volumes have been associated with faster symptom improvement under therapy. The aims of the study were to examine whether volumes of the anterior cingulate cortex are altered and are related to the clinical course of major depression. Subjects comprised 78 inpatients with major depression and 78 age-, gender- and handedness- matched healthy volunteers, who were investigated with structural magnetic resonance imaging (MRI). The ACC was subdivided into the subgenual, pre-callosal, rostral-anterior and caudal-anterior ACC. No significant differences were observed for ACC volumes between patients and healthy controls. Left ACC volumes showed a significant negative correlation with the number of hospitalizations. These findings suggest that ACC volumes are not altered in patients with major depression, but that patients with larger ACC have a better clinical outcome than patients with smaller ACC.

Functional abnormalities of the visual processing system in subjects with mild cognitive impairment: an fMRI study.

Subjects with mild cognitive impairment (MCI) have a higher risk of developing Alzheimer's disease compared with healthy controls (HC). Sensory impairment can contribute to the severity of cognitive impairment. We measured the activation changes in the visual system between MCI and HC subjects. There were 16 MCI subjects with either amnestic MCI or multiple-domain+amnestic MCI and an HC group of 19 subjects. There were two tasks: (a) a face matching and (b) a location matching task. Brain activation was measured using functional magnetic resonance imaging. There were no differences in task performance. The HC group selectively activated the ventral and dorsal pathways during the face and location matching tasks, respectively, while the MCI group did not. The MCI group had greater activation than the HC group in the left frontal lobe during the location matching task. There were no areas of increased activation in the HC group compared with the MCI group. The MCI group, as a compensatory mechanism, activated both visual pathways and increased activation in the left frontal lobe during the location matching task compared with the healthy controls. To our knowledge, this is the first study that has examined visual processing in MCI.

In-vivo topography of structural alterations of the anterior cingulate in patients with schizophrenia: new findings and comparison with the literature.

The anterior cingulate cortex (ACC) is part of the rostral limbic system and is involved in cognitive and affective processes that have been reported to be disturbed in schizophrenia. Despite the evidence for ACC abnormalities in schizophrenia indicated by functional imaging studies, structural magnetic resonance imaging (MRI) studies of this region of interest (ROI) have been relatively few and the results inconsistent. The aim of the present study was to examine the hypothesis that different subregions of the ACC are differentially affected by the disease process of schizophrenia, a circumstance that might contribute to contradictory results of earlier structural ACC studies. We investigated ACC volumes in 50 male and right-handed patients with schizophrenia according to ICD-10 and DSM-IV. The patients were individually matched for age, sex, handedness and education with 50 control subjects. ACC was subdivided into four parts: precallosal, subgenual, precommissural and postcommissural regions. Measurements were performed with a 1.5 T magnetom vision apparatus. Regions of interest were defined on consecutive coronal MRI-slices. The software program BRAINS was used for volumetry and segmentation into gray and white matter. We detected that ACC gray matter volume of the right precallosal region and right total ACC was significantly reduced in schizophrenic patients compared with control subjects. In addition, left ACC gray matter was selectively reduced in the subgenual region. These results confirmed our hypothesis that different ACC regions are differentially affected by structural alterations in schizophrenia, a circumstance that might explain in part the discrepant findings of former structural imaging studies of the ACC.

Hippocampal volume reduction and history of aggressive behaviour in patients with borderline personality disorder.

Disturbances of aggression and impulse control are important symptoms of borderline personality disorder (BPD). The hippocampus is part of the limbic system, which is involved in the control of these types of behaviour. The aim of our study was to investigate potential structural changes of the hippocampal formation in BPD and to evaluate if these are related to aggressive and impulsive behaviour. Twenty-five female and right-handed BPD patients (DSM-IV) and 25 healthy control subjects matched according to sex, age, handedness and educational status were examined. Magnetic resonance imaging (MRI) was performed using a 1.5-T Magnetom Vision system. The software program "BRAINS" was employed for segmentation and volumetry of the hippocampal formation. German versions of instruments were used to evaluate impulsive and aggressive behaviour. Hippocampal grey matter volume was significantly decreased in BPD patients: the reduction was more pronounced in patients with multiple hospitalizations. Hippocampal volume of the left hemisphere was inversely correlated with lifetime history of aggressive behaviour. However, no significant relationship was found between hippocampal volume and impulsive behaviour. Our study confirms previous results indicating a volume reduction of the hippocampal formation in BPD patients. Furthermore, this structural change might facilitate aggressive behaviour. Subsequent studies are required to clarify whether the reduction of hippocampal volume is a trait and risk factor for increased aggression.

Amygdala volume and depressive symptoms in patients with borderline personality disorder.

BACKGROUND: Borderline personality disorder (BPD) is characterized by a high prevalence of comorbid psychiatric disorders, including major depression (MD). The aim of this study was to examine whether a co-occurrence of MD is associated with structural changes in the amygdala of BPD patients. METHODS: Twenty-five right-handed, female patients with BPD and 25 matched healthy control subjects were examined. Diagnoses of BPD and MD were made according to DSM IV. Depressive symptomatology was determined with the Hamilton Depression Scale (HAMD). Magnetic resonance imaging scans were performed with 1.5 T Magnetom Vision (Siemens, Erlangen, Germany). The software program "BRAINS" was applied for brain volumetry and segmentation. The amygdala was delineated as "region of interest." RESULTS: Comparison of amygdala volumes between the whole group of BPD patients and control subjects revealed no significant difference. Amygdala volumes in both hemispheres were significantly larger in BPD patients with MD compared with those without MD. There was a significant correlation in BPD patients between left amygdala volume and depressive symptoms as measured by HAMD. CONCLUSIONS: Correlation of amygdala volume with depression in BPD patients might indicate a causal relationship. Future studies should clarify whether amygdala enlargement is a risk factor for MD in BPD patients or a consequence of the affective disorder.

Novel splice site mutation in the caveolin-3 gene leading to autosomal recessive limb girdle muscular dystrophy.

Mutations in CAV3 gene encoding the protein caveolin-3 are associated with autosomal dominant limb girdle muscular dystrophy 1C, rippling muscle disease, hyperCKemia, distal myopathy, hypertrophic cardiomyopathy and rare autosomal recessive limb girdle muscular dystrophy phenotypes. In a 57-year-old patient with asymmetric limb girdle weakness, we detected a novel homozygous intronic mutation (IVS1 + 2T > C) of the CAV3 gene. This is the first splicing mutation reported for CAV3. These findings add to the clinical and genetic variability of CAV3 mutations.

Comprehensive dissection of the medial temporal lobe in AD: measurement of hippocampus, amygdala, entorhinal, perirhinal and parahippocampal cortices using MRI.

BACKGROUND: Early pathological involvement of specific medial temporal lobe areas is characteristic for Alzheimer's disease (AD). OBJECTIVE: To determine the extent of regional medial temporal lobe atrophy, including hippocampus, amygdala, and entorhinal, perirhinal, and parahippocampal cortices in mild AD patients and healthy controls, and to compare diagnostic accuracy across volumetric markers. METHODS: We studied 34 patients with clinically probable AD and 22 healthy elderly control subjects. Regional volumetric measures were obtained from volumetric T1-weighted MRI scans after accounting for global brain atrophy using affine transformation into standard space. RESULTS: Volumes of medial temporal lobe structures were significantly smaller in AD patients than in controls with exception of the left entorhinal cortex. The degree of atrophy was comparable between all structures. Diagnostic accuracy (number of correctly allocated cases divided by number of all cases) was highest for the right parahippocampal cortex with 85%, but only slightly lower for the right hippocampus and right entorhinal cortex with 82% and 84%. Using a linear combination of markers, the unilateral volumes of the right hippocampus, parahippocampal cortex and perirhinal cortex yielded an accuracy of 93%. CONCLUSION: Extent of atrophy is similar between the different regions of the medial temporal lobe in mild AD.Volume measurements of medial temporal lobe structures in addition to the hippocampus only yield improved diagnostic accuracy if a combination of these structures is used.

Effects of rivastigmine on visual attention in subjects with amnestic mild cognitive impairment: A serial functional MRI activation pilot-study.

A pilot study to investigate the effects of rivastigmine on the brain activation pattern due to visual attention tasks in a group of amnestic Mild Cognitive Impaired patients (aMCI). The design was an initial three-month double blind period with a rivastigmine and placebo arms, followed by a nine-month open-label period. All patients underwent serial functional magnetic resonance imaging (fMRI) at baseline, and after three and six months of follow-up. Primary endpoint was the effect of rivastigmine on functional brain changes during visual attention (face and location matching) tasks. There were five in the rivastigmine arm and two in the placebo arm. The face matching task showed higher activation of visual areas after three months of treatment but no differences compared to baseline at six months. The location matching task showed a higher activation along the dorsal visual pathway at both three and six months follow ups. Treatment with rivastigmine demonstrates a significant effect on brain activation of the dorsal visual pathway during a location matching task in patients with aMCI. Our data support the potential use of task fMRI to map specific treatment effects of cholinergic drugs during prodromal stages of Alzheimer's disease (AD).