Annalena Venneri

Publications of Annalena Venneri

• Translocation of the embodied self without visuospatial neglect.

  Authors: Annalena Venneri, Roberta Pentore, Milena Cobelli, Paolo Nichelli, Michael F Shanks

  Neuropsychologia. 02/2012; 50(5):973-8.

  This is the case report of RB, a 68-year-old retired woman who, following an extensive right sided ischaemic stroke, showed hemiplegia, anosognosia and allochiria, but no somato-sensory deficits andThis is the case report of RB, a 68-year-old retired woman who, following an extensive right sided ischaemic stroke, showed hemiplegia, anosognosia and allochiria, but no somato-sensory deficits and no visuospatial neglect. A high resolution 3D MRI structural scan of her brain was acquired to define the structural damage in detail. Morphometric analyses of grey and white matter data revealed a large lesion which involved most of her right parietal, temporal, and mesial frontal cortex, with partial sparing of the right dorsolateral prefrontal cortex and part of the posterior corpus callosum. Detailed examination showed that RB attributed sensory stimuli, both on the left and on the right, to the opposite side of her body. This mirror reversed representation of her body caused misattribution of items even in the absence of stimulation, as for instance when the patient spontaneously reported pain in her right knee while pointing to her left knee. RB's neuropsychological profile showed normal or borderline performance on most cognitive tasks. Language comprehension was intact and she could tell left from right without difficulty in all instances except for those referable to her soma. To our knowledge this is the first description of severe allochiria for body representation in the absence of neglect. The evidence from this case supports the developing concept that the body representation is not simply a systematic registration of proprioceptive inputs, but that the brain has a more sophisticated high level representation of one's body map which is updated on the basis of multimodal information.

• Reduced grey matter in the posterior insula as a structural vulnerability or diathesis to addiction.

  Authors: Simona Gardini, Annalena Venneri

  Brain research bulletin. 12/2011; 87(2-3):205-11.

  A number of neuroimaging studies have shown that drug addiction is associated with morphological differences in several brain areas, including orbito-frontal and limbic structures. Most of theseA number of neuroimaging studies have shown that drug addiction is associated with morphological differences in several brain areas, including orbito-frontal and limbic structures. Most of these studies have investigated patients with addiction to cocaine. The neurobiological mechanisms which play a role in drug addiction are not fully understood, however, and the causal factors remain under investigation. The present study investigated morphological differences between patients with history of cocaine (N=14) and heroin (N=24) abuse and healthy matched controls (N=24). A 3D T1W MRI scan was acquired for all participants and the grey matter images of each patient group compared with those of controls. A direct comparison of the two addiction groups was also carried out. When compared with controls cocaine dependent patients had lower grey matter values in the left middle occipital gyrus, right putamen and insula, whereas heroin abusers had lower grey matter values in the right insula. The direct comparison between the two addiction groups showed that cocaine abusers had less grey matter in the right posterior cingulate, medio-temporal and cerebellar regions, whereas heroin abusers showed less grey matter in parietal regions on both sides, including postcentral gyrus and inferior parietal lobule. Reduced right posterior insular cortex was commonly found in both cocaine and heroin dependent patients. This morphological difference might represent a structural marker of addiction, which is independent of the discrete regional effects of each psychotropic substance of abuse, and might constitute a possible neurobiological vulnerability or diathesis to addiction. Equally, the discrete structural differences emerging from the direct comparison of cocaine and heroin abusers might reflect the effects of differential drug binding in the brain and/or express a form of neurobiological vulnerability which might explain individual drug choice.

• Suggested visual hallucination without hypnosis enhances activity in visual areas of the brain.

  Authors: William J McGeown, Annalena Venneri, Irving Kirsch, Luca Nocetti, Kathrine Roberts, Lisa Foan, Giuliana Mazzoni

  Consciousness and cognition. 11/2011; 21(1):100-16.

  This functional Magnetic Resonance Imaging (fMRI) study investigated high and low suggestible people responding to two visual hallucination suggestions with and without a hypnotic induction.This functional Magnetic Resonance Imaging (fMRI) study investigated high and low suggestible people responding to two visual hallucination suggestions with and without a hypnotic induction. Participants in the study were asked to see color while looking at a grey image, and to see shades of grey while looking at a color image. High suggestible participants reported successful alterations in color perception in both tasks, both in and out of hypnosis, and showed a small benefit if hypnosis was induced. Low suggestible people could not perform the tasks successfully with or without the hypnotic induction. The fMRI results supported the self report data, and changes in brain activity were found in a number of visual areas. The results indicate that a hypnotic induction, although having the potential to enhance the ability of high suggestible people, is not necessary for the effective alteration of color perception by suggestion.

• Italian norms for the Freedman version of the Clock Drawing Test.

  Authors: Paolo Caffarra, Simona Gardini, Fabrizio Zonato, Letizia Concari, Francesca Dieci, Sandra Copelli, Morris Freedman, Andrea Stracciari, Annalena Venneri

  Journal of clinical and experimental neuropsychology. 11/2011; 33(9):982-8.

  The Clock Drawing Test (CDT) is a valid screening tool for the evaluation of cognitive decline. This study aimed to compute standardized norms for the Freedman version of the CDT in a population ofThe Clock Drawing Test (CDT) is a valid screening tool for the evaluation of cognitive decline. This study aimed to compute standardized norms for the Freedman version of the CDT in a population of 248 healthy Italian individuals aged from 20 to 89 years. The effects of age, education, and gender on performance were assessed. Three conditions were administered: free-drawn clock (FD), which required participants to draw the contour, numbers, hands, and center of the clock; predrawn clock (PD), in which numbers, hands, and center had to be included in a predrawn contour; examiner-drawn clock (ED), in which only hands and center had to be inserted in a template including a predrawn contour and numbers. Scores for each of the single conditions and a total score were calculated. Age had no effect on the FD condition, whereas a significant effect of age was found for the PD and ED conditions and the total score. Gender and education had no influence on any of the scores. Correction grids, cutoffs, and equivalent scores were computed. Standardized norms for the Freedman version of the CDT were collected in a large sample of healthy individuals. No adjustments were required for scores on the free-drawn condition, whereas raw scores on the predrawn and examiner-drawn conditions and the total score needed adjustments to account for age effects. The availability of standardized norms for this version of the CDT could increase the use of this comprehensive tool in the detection of dementia.

• Combining neuropsychological and structural neuroimaging indicators of conversion to Alzheimer's disease in amnestic mild cognitive impairment.

  Authors: Annalena Venneri, Giovanni Gorgoglione, Cristian Toraci, Luca Nocetti, Patrizia Panzetti, Paolo Nichelli

  Current Alzheimer research. 11/2011; 8(7):789-97.

  Morphometric and neuropsychological retrospective studies of amnestic mild cognitive impairment (MCI) have demonstrated that regional atrophies and cognitive impairments may differentiate stable fromMorphometric and neuropsychological retrospective studies of amnestic mild cognitive impairment (MCI) have demonstrated that regional atrophies and cognitive impairments may differentiate stable from progressing MCI. No measure has proved helpful prospectively. In this study, twenty five amnestic MCI patients and 25 healthy controls underwent structural MRI and comprehensive neuropsychological assessment. The groups' grey matter volumes were compared with voxel based morphometry and were also correlated with scores obtained on paired associates learning and category fluency tasks. MCI patients had significantly reduced grey matter volume in left mediotemporal and other neocortical regions compared with controls. Atrophy in perirhinal and anterior inferior temporal cortex was associated with poor scores on both category fluency and paired associates learning tasks. After 36 months, 44% of the MCI sample converted to dementia. Converter and non-converter MCI subgroups differed in paired associates learning and in category fluency scores, and showed limited differences in grey matter loss in the hippocampal complex. Variable atrophy in the hippocampus was not a relevant element in the converter/non converter distinction, but converters had significant volumetric reductions in the perhirinal cortex and in other anterior temporal and frontal neocortical areas. A high proportion of converters (91%) could be identified from baseline data using a combination of measures of regional atrophy in left temporal association cortex and poor scores on paired associates learning and category fluency tasks. This combined approach may offer a better option than using each measure alone to prospectively identify individuals at more immediate risk of conversion to dementia in the MCI population. The clinical advantage of this combination of structural MRI and neuropsychological measures in predicting conversion to dementia will need additional prospective validation.

• Influence of APOE Status on Lexical-Semantic Skills in Mild Cognitive Impairment.

  Authors: Roberta Biundo, Simona Gardini, Paolo Caffarra, Letizia Concari, Davide Martorana, Tauro Maria Neri, Michael F Shanks, Annalena Venneri

  Journal of the International Neuropsychological Society : JINS. 03/2011;

  This study characterized the relationship between apolipoprotein E (APOE) status and residual semantic abilities in amnestic mild cognitive impairment (MCI). APOE status (ε4 carrier/non ε4 carrier)This study characterized the relationship between apolipoprotein E (APOE) status and residual semantic abilities in amnestic mild cognitive impairment (MCI). APOE status (ε4 carrier/non ε4 carrier) was determined in 30 amnestic MCIs and in 22 healthy matched non ε4 carrier controls. The lexical characteristics (age of acquisition, typicality, familiarity) of words produced in a category fluency task were determined. MCIs produced fewer words than controls and these were also earlier acquired and more familiar. The words produced by MCI ε4 carriers were earlier acquired than those of non ε4 carriers. Analyses limited to the first 10 words produced by patients and controls showed similar findings and also revealed that MCI subgroups retrieved first more typical words than controls. Follow up showed higher conversion to Alzheimer's disease (AD) in MCI ε4 carriers than in non ε4 carriers. These findings show that a significant proportion of phenotype variability in performance on category fluency in people at increased AD risk is influenced by genetic factors. These findings explain why category fluency deficits, together with episodic memory deficits, are the only consistent early deficits in MCI patients who convert to AD. (JINS, 2011, 17, 1-8).

• Visuo-spatial imagery impairment in posterior cortical atrophy: a cognitive and SPECT study.

  Authors: Simona Gardini, Letizia Concari, Salvatrice Pagliara, Caterina Ghetti, Annalena Venneri, Paolo Caffarra

  Behavioural neurology. 01/2011; 24(2):123-32.

  This study investigated the cognitive profile and the cerebral perfusion pattern in a highly educated 70 year old gentleman with posterior cortical atrophy (PCA). Visuo-perceptual abilities, spatialThis study investigated the cognitive profile and the cerebral perfusion pattern in a highly educated 70 year old gentleman with posterior cortical atrophy (PCA). Visuo-perceptual abilities, spatial memory, spatial representation and navigation, visuo-spatial mental imagery, semantic and episodic-autobiographical memory were assessed. Regional cerebral blood flow (rCBF) was imaged with SPECT. Cognitive testing showed visual-perceptual impairment, apperceptive visual and landmark agnosia, topographical disorientation with way-finding deficits, impaired map learning and poor mental image generation. Semantic memory was normal, while episodic-autobiographical memory was impaired. Reduced rCBF was found mainly in the right hemisphere, in the precentral gyrus, posterior cingulate and middle temporal gyri, cuneus and precuneus, in the left superior temporal and lingual gyri and in the parahippocampus bilaterally. Hypoperfusion in occipito-parietal regions was associated with visuo-spatial deficits, whereas deficits in visuo-spatial mental imagery might reflect dysfunction related to hypoperfusion in the parahippocampus and precuneus, structures which are responsible for spatial and imagery processing. Dissociating performance between preserved semantic memory and poor episodic-autobiographical recall is consistent with a pattern of normal perfusion in frontal and anterior temporal regions but abnormal rCBF in the parahippocampi. The present findings indicate that PCA involves visuo-spatial imagery deficits and provide further validation to current neuro-cognitive models of spatial representation and topographical disorientation.

• The neuroanatomical substrate of lexical-semantic decline in MCI APOE ε4 carriers and noncarriers.

  Authors: Annalena Venneri, William J McGeown, Roberta Biundo, Marco Mion, Paolo Nichelli, Michael F Shanks

  Alzheimer disease and associated disorders. 12/2010; 25(3):230-41.

  Lexical-semantic competency in mild cognitive impairment (MCI) ε4 carriers was used as an endophenotype, and gray matter volume in MCI ε4 carriers/noncarriers and in noncarrier controls was compared.Lexical-semantic competency in mild cognitive impairment (MCI) ε4 carriers was used as an endophenotype, and gray matter volume in MCI ε4 carriers/noncarriers and in noncarrier controls was compared. Residual gray matter volumes were correlated with age of acquisition values for words from a category fluency task, an index of semantic competency. MCI patients had significantly impoverished lexical-semantic output compared with controls, more marked in MCI ε4 carriers. Smaller volumes in the left hippocampus, bilateral regions of the uncus, and posterior cingulate cortex were associated with a tendency to retrieve earlier acquired words in the category fluency task in MCI ε4 carriers, whereas poor semantic performance in MCI noncarriers was associated with smaller volumes in the left uncus, bilateral regions of the parahippocampal gyrus, and hippocampus, and also in a large number of neocortical regions. There was a significant semantic competency by genotype interaction in the left perirhinal cortex, in a number of left frontal and temporal areas and in the right inferior parietal lobule and precuneus. MCI ε4 carriers, when compared with noncarriers, had lower gray matter volume values confined to the right precuneus and the cerebellum bilaterally, but the converse comparison showed that MCI noncarriers had lower values in extensive frontal, temporal, and parietal regions of the neocortex. Similar brain volumetric variations linked to genotype were found in minimal-to-mild AD. The results suggest a relatively specific impact of apolipoprotein E (APOE) ε4 burden and underline the value of linguistic assessment in preclinical diagnosis.

• Recovery from transient global amnesia following restoration of hippocampal and fronto - cingulate perfusion.

  Authors: Paolo Caffarra, Letizia Concari, Simona Gardini, Sabrina Spaggiari, Francesca Dieci, Sandra Copelli, Caterina Ghetti, Annalena Venneri

  Behavioural neurology. 01/2010; 22(3-4):131-9.

  A patient who suffered a transient global amnesia (TGA) attack underwent regional cerebral blood flow (rCBF) SPECT imaging and neuropsychological testing in the acute phase, after one month and afterA patient who suffered a transient global amnesia (TGA) attack underwent regional cerebral blood flow (rCBF) SPECT imaging and neuropsychological testing in the acute phase, after one month and after one year. Neuropsychological testing in the acute phase showed a pattern of anterograde and retrograde amnesia, whereas memory was within age normal limits at follow up. SPECT data were analysed with a within subject comparison and also compared with those of a group of healthy controls. Within subject comparison between the one month follow up and the acute phase detected increases in rCBF in the hippocampus bilaterally; further rCBF increases in the right hippocampus were detected after one year. Compared to controls, significant hypoperfusion was found in the right precentral, cingulate and medial frontal gyri in the acute phase; after one month significant hypoperfusion was detected in the right precentral and cingulate gyri and the left postcentral gyrus; after one year no significant hypoperfusion appeared. The restoration of memory was paralleled by rCBF increases in the hippocampus and fronto-limbic-parietal cortex; after one year neither significant rCBF differences nor cognitive deficits were detectable. In conclusion, these data indicate that TGA had no long lasting cognitive and neural alterations in this patient.

• Hypnotic induction decreases anterior default mode activity.

  Authors: William J McGeown, Giuliana Mazzoni, Annalena Venneri, Irving Kirsch

  Consciousness and cognition. 09/2009;

  The 'default mode' network refers to cortical areas that are active in the absence of goal-directed activity. In previous studies, decreased activity in the 'default mode' has always been associatedThe 'default mode' network refers to cortical areas that are active in the absence of goal-directed activity. In previous studies, decreased activity in the 'default mode' has always been associated with increased activation in task-relevant areas. We show that the induction of hypnosis can reduce anterior default mode activity during rest without increasing activity in other cortical regions. We assessed brain activation patterns of high and low suggestible people while resting in the fMRI scanner and while engaged in visual tasks, in and out of hypnosis. High suggestible participants in hypnosis showed decreased brain activity in the anterior parts of the default mode circuit. In low suggestible people, hypnotic induction produced no detectable changes in these regions, but instead deactivated areas involved in alertness. The findings indicate that hypnotic induction creates a distinctive and unique pattern of brain activation in highly suggestible subjects.

• Patterns of brain activity during a semantic task differentiate normal aging from early Alzheimer's disease.

  Authors: William Jonathan McGeown, Michael Fraser Shanks, Katrina Elaine Forbes-McKay, Annalena Venneri

  Psychiatry research. 09/2009;

  In a study of the effects of normal and pathological aging on semantic-related brain activity, 29 patients with Alzheimer's disease (AD) and 19 controls subjects (10 young and 9 older controls)In a study of the effects of normal and pathological aging on semantic-related brain activity, 29 patients with Alzheimer's disease (AD) and 19 controls subjects (10 young and 9 older controls) performed a version of the Pyramids and Palm Trees Test that had been adapted for use during functional magnetic resonance imaging (fMRI). Young and older controls activated the left inferior and middle frontal gyri, precuneus and superior parietal lobule. Right frontal and left temporal cortices were activated only in the young. The AD group activated only the left prefrontal and cingulate cortex. Separate analyses of high- and low-performing AD subgroups showed a similar pattern of activation in the left frontal lobe, although activiation was more widespread in low performers. High performers significantly deactivated anterior midline frontal structures, however, while low performers did not. When the older adult and AD groups were combined, there was a significant positive correlation between left frontal and parietal activation and Mini-Mental State Examination (MMSE) score (covarying for age), suggesting a disease effect. A significant negative correlation between activation in the left temporal cortex and age (covarying for MMSE score) reflected a possible age effect. These differential effects suggest that semantic activation paradigms might aid diagnosis in those cases for whom conventional assessments lack the necessary sensitivity to detect subtle changes.

• Individual differences in personality traits reflect structural variance in specific brain regions.

  Authors: Simona Gardini, C Robert Cloninger, Annalena Venneri

  Brain research bulletin. 07/2009; 79(5):265-70.

  Personality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic andPersonality dimensions such as novelty seeking (NS), harm avoidance (HA), reward dependence (RD) and persistence (PER) are said to be heritable, stable across time and dependent on genetic and neurobiological factors. Recently a better understanding of the relationship between personality traits and brain structures/systems has become possible due to advances in neuroimaging techniques. This Magnetic Resonance Imaging (MRI) study investigated if individual differences in these personality traits reflected structural variance in specific brain regions. A large sample of eighty five young adult participants completed the Three-dimensional Personality Questionnaire (TPQ) and had their brain imaged with MRI. A voxel-based correlation analysis was carried out between individuals' personality trait scores and grey matter volume values extracted from 3D brain scans. NS correlated positively with grey matter volume in frontal and posterior cingulate regions. HA showed a negative correlation with grey matter volume in orbito-frontal, occipital and parietal structures. RD was negatively correlated with grey matter volume in the caudate nucleus and in the rectal frontal gyrus. PER showed a positive correlation with grey matter volume in the precuneus, paracentral lobule and parahippocampal gyrus. These results indicate that individual differences in the main personality dimensions of NS, HA, RD and PER, may reflect structural variance in specific brain areas.

• Responders to ChEI treatment of Alzheimer's disease show restitution of normal regional cortical activation.

  Authors: Annalena Venneri, William J McGeown, Michael F Shanks

  Current Alzheimer research. 05/2009; 6(2):97-111.

  Clinical trials of cholinesterase inhibitor (ChEI) drugs, although generally reporting only minimal improvements in patients with Alzheimer's disease (AD), indicate that a subgroup of patients mayClinical trials of cholinesterase inhibitor (ChEI) drugs, although generally reporting only minimal improvements in patients with Alzheimer's disease (AD), indicate that a subgroup of patients may respond substantially to treatment. This study aimed to assess the clinically variable ChEI treatment effects in a group of patients with mild AD using a semantic association and an N-back light working memory activation paradigm. Twenty-six patients with probable mild AD treated with a ChEI for 20 weeks were retrospectively divided into responders and non-responders. Patients were classified as responders if their Clinician's Interview Based Impression of Change (CIBIC - Plus) score was four or less and if they had an increase of at least two points on the MMSE. These criteria resulted in two subgroups comprising nine responders and seventeen non responders. Nine healthy elderly age-matched controls were also recruited as a comparison group. ChEI treatment was accompanied by significant modulation of task induced activation increases in both fMRI tasks in AD responders. The effect of ChEI response was in effect a restoration of regional brain function in the same areas used by elderly controls when performing these tasks. In non-responders decrements in task related activation were observed and over time activation patterns appeared less like the elderly controls. Screening semantic fluency scores correlated negatively with activation increases at retest. In the paper, a tentative explanation is offered of why subgroups of patients with a similar clinical diagnosis and level of clinical severity show a different physiological response to ChE inhibition.

• Effects of cholinesterase inhibition on brain white matter volume in Alzheimer's disease.

  Authors: Annalena Venneri, Roger Lane

  Neuroreport. 03/2009; 20(3):285-8.

  Brain white matter volume changes were quantified by using voxel-based morphometry in 26 minimal-to-mild Alzheimer's disease patients receiving cholinesterase inhibitors over 20 weeks. PatientsBrain white matter volume changes were quantified by using voxel-based morphometry in 26 minimal-to-mild Alzheimer's disease patients receiving cholinesterase inhibitors over 20 weeks. Patients treated with rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, did not show those reductions in white matter volume that were observed in patients treated with acetylcholinesterase-selective agents, donepezil and galantamine. This is the first time that dual cholinesterase inhibition has been shown to influence white matter volume specifically. The findings are consistent with a thesis that dual cholinesterase inhibition may have neuroprotective potential. Attenuated loss of brain volumes and delayed/slower long-term clinical decline in patients treated with agents such as rivastigmine may be due to less extensive white matter damage and loss of corticosubcortical connectivity.

• Cognitive and neuronal processes involved in sequential generation of general and specific mental images.

  Authors: Simona Gardini, Cesare Cornoldi, Rossana De Beni, Annalena Venneri

  Psychological research. 12/2008;

  Mental image generation is a complex process mediated by dynamically interrelated components, e.g. image generation and image enrichment of details. This study investigated the cognitive and neuralMental image generation is a complex process mediated by dynamically interrelated components, e.g. image generation and image enrichment of details. This study investigated the cognitive and neural correlates of sequential image generation. An event-related fMRI experiment was carried out in which general and specific images had to be generated sequentially in two different positions. Participants had to generate either a general image first and then a specific one or a specific image first and then a general one, in response to the same word-stimulus. Generation times showed that specific images took shorter to be produced if they had been preceded by the generation of a general image. The fMRI results showed that position of generation and type of image was associated with different patterns of neurofunctional change. When an image was generated as first, areas of activation were found in the parahippocampal, fusiform and occipital regions. These are areas associated with memory retrieval and visual processing. When an image was generated as second, significant activations were found in superior temporal and precuneus areas, brain structures that are involved in the storage of visual memory for object shapes and imagery, respectively. The generation of a general image was supported by frontal areas and by the precuneus. The generation of a specific image involved frontal and thalamic areas (structures associated with visual processing of details) and the posterior cingulate cortex. When shifting from a specific image to a general one, a higher level of activity was found in the middle frontal gyrus involved in global visuo-spatial processing, suggesting that the generation of specific images required the retrieval of an object's global shape. Altogether, these data suggest that the sequential generation of different types of image is associated with discrete processes but also shares common cognitive and neural components.

• Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease.

  Authors: Peita D Bruen, William J McGeown, Michael F Shanks, Annalena Venneri

  Brain : a journal of neurology. 10/2008; 131(Pt 9):2455-63.

  Alzheimer's disease research has largely concentrated on the study of cognitive decline, but the associated behavioural and neuropsychiatric symptoms are of equal importance in the clinical profileAlzheimer's disease research has largely concentrated on the study of cognitive decline, but the associated behavioural and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. There is emerging evidence that regional differences in brain atrophy may align with variant disease presentations. The objective of this study was to identify the regions of decreased grey matter (GM) volume which were associated with specific neuropsychiatric behaviours in patients with mild Alzheimer's disease. Voxel-based morphometry was used to correlate GM derived from T(1)-weighted MRI images of 31 patients with mild Alzheimer's disease and specific neuropsychiatric symptoms and behaviours measured by the Neuropsychiatric Inventory. Delusions were associated with decreased GM density in the left frontal lobe, in the right frontoparietal cortex and in the left claustrum. Apathy was associated with GM density loss in the anterior cingulate and frontal cortex bilaterally, the head of the left caudate nucleus and in bilateral putamen. Agitation was associated with decreased GM values in the left insula, and in anterior cingulate cortex bilaterally. Neuropsychiatric symptoms of Alzheimer's disease seem to associate with neurodegeneration of specific neural networks supporting personal memory, reality monitoring, processing of reward, interoceptive sensations and subjective emotional experience. The study of neurodegenerative disorders such as Alzheimer's disease using voxel-based morphometry and other imaging modalities may further the understanding of the neural structures that mediate the genesis of abnormal behaviours.

• Prolonged cholinergic enrichment influences regional cortical activation in early Alzheimer's disease.

  Authors: William J McGeown, Michael F Shanks, Annalena Venneri

  Neuropsychiatric disease and treatment. 05/2008; 4(2):465-76.

  Neuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) indicate that the short and long term actions of ChEIs are dissimilar. fMRI studies of the ChEINeuroimaging studies of cholinesterase inhibitor (ChEI) treatment in Alzheimer's disease (AD) indicate that the short and long term actions of ChEIs are dissimilar. fMRI studies of the ChEI rivastigmine have focused on its short term action. In this exploratory study the effect of prolonged (20 weeks) rivastigmine treatment on regional brain activity was measured with fMRI in patients with mild AD. Eleven patients with probable AD and nine age-matched controls were assessed with a Pyramids and Palm Trees semantic association and an n-back working memory fMRI paradigm. In the patient group only, the assessment was repeated after 20 weeks of treatment. There was an increase in task-related brain activity after treatment with activations more like those of normal healthy elderly. Behaviorally, however, there were no significant differences between baseline and retest scores, with a range of performance probably reflecting variation in drug efficacy across patients. Variable patient response and drug dynamic/kinetic factors in small patient groups will inevitably bias (either way) the effect size of any relevant drug related changes in activation. Future studies should take drug response into account to provide more insight into the benefits of ChEI drugs at the individual level.

• Differential patterns of hypoperfusion in subtypes of mild cognitive impairment.

  Authors: Paolo Caffarra, Caterina Ghetti, Letizia Concari, Annalena Venneri

  The open neuroimaging journal. 02/2008; 2:20-8.

  In this study the regional cerebral blood flow (rCBF) pattern of three Mild Cognitive Impairment (MCI) subtypes was measured with SPECT in 60 patients (nineteen with an amnestic deficit, sixteen withIn this study the regional cerebral blood flow (rCBF) pattern of three Mild Cognitive Impairment (MCI) subtypes was measured with SPECT in 60 patients (nineteen with an amnestic deficit, sixteen with disexecutive deficits, and twenty five with mild multidomain deficits) and compared with that of 15 healthy matched older adults. The amnestic MCI subgroup showed significant hypoperfusion in the left hippocampus, parahippocampal gyrus and fronto-parieto-temporal areas. The disexecutive subgroup had significant hypoperfusion of the left superior, medial frontal and cingulate cortex. The multidomain subgroup had similar perfusion deficits to the amnestic subgroup, with an additional deficit in the left posterior cingulate gyrus. This study found differential patterns of hypoperfusion in MCI subtypes. Since all patients who progressed to dementia converted to probable Alzheimer's disease, the different rCBF patterns most likely reflect the neuropathological heterogeneity at onset and differences in disease stage.

• The anatomical bases of semantic retrieval deficits in early Alzheimer's disease.

  Authors: Annalena Venneri, William J McGeown, Heidi M Hietanen, Chiara Guerrini, Andrew W Ellis, Michael F Shanks

  Neuropsychologia. 02/2008; 46(2):497-510.

  Semantic abilities deteriorate early in patients with Alzheimer's disease (AD) and their residual language is characterised by strong lexical effects such as the age of acquisition of words and theirSemantic abilities deteriorate early in patients with Alzheimer's disease (AD) and their residual language is characterised by strong lexical effects such as the age of acquisition of words and their typicality. The anatomical bases of this early semantic degradation have not been fully explored. To clarify which neural structures, when atrophic, alter lexical-semantic function in patients with very mild AD, this study correlated the lexical attributes of words produced in a semantic fluency task with grey matter density values from 3D MRI scans of mild AD patients. The voxel-based analyses showed a significant correlation between the lexical attributes characterising residual linguistic production in early AD patients and the integrity of regions of the medial temporal lobes, especially in areas of the perirhinal and parahippocampal cortex. This correlation was present in both hemispheres. There were no correlations within these structures with scores on neuropsychological tests not involving semantic or episodic memory. The results have implications for the role of medial temporal structures in episodic and semantic retrieval and argue against a unitary function of these structures in respect of episodic and semantic memory processes. This evidence suggests that specialised regions within the hippocampal complex engage in processes of encoding and retrieval for both semantic and episodic memories.

• Imaging treatment effects in Alzheimer's disease.

  Authors: Annalena Venneri

  Magnetic resonance imaging. 08/2007; 25(6):953-68.

  Alzheimer's disease (AD) is the commonest form of degenerative dementia and is characterised by progressive cognitive decline. Despite extensive research, the cause of AD is unknown and there is noAlzheimer's disease (AD) is the commonest form of degenerative dementia and is characterised by progressive cognitive decline. Despite extensive research, the cause of AD is unknown and there is no cure at present. Of the deficits found in AD, that affecting the cholinergic neurotransmitter system is the best established and the only one translated into symptomatic treatment. Cholinergic enhancement with cholinesterase inhibitor (ChEI) drugs has been achieved and their efficacy and safety ascertained by conventional clinical trials. The mechanism of action of these drugs, however, is not well understood. Imaging with SPECT, PET, MRI and fMRI after treatment has clarified what happens in the brains of those AD patients treated with ChEI drugs. Studies with these techniques have identified increases in brain blood flow and glucose metabolism, restoration of nicotinic receptor function and re-establishment of task-related regional brain activation in response to cognitive stimulation after treatment. Structural MRI studies have explained, to some degree, why only a proportion of patients benefits from ChEI treatment and there is some evidence that some ChEI drugs might be neuroprotective. There are, however, many unsolved problems. Timing of treatment intervention to obtain maximum response and the determinants of treatment response are mostly unknown. It is also unclear whether administration of treatment in those patients who have no potential for response accelerates disease progression. These issues cannot be solved by conventional clinical trials. Pharmacoimaging studies could assist the development and refinement of drugs to treat those diseases, such as AD, which affect the central nervous system.