Browsing by Author "Pievani, Michela"
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- ItemAPOE4 is associated with greater atrophy of the hippocampal formation in Alzheimer's disease.(2011-03-07) Pievani, Michela; Galluzzi, Samantha; Thompson, Paul M; Rasser, Paul E; Bonetti, Matteo; Frisoni, Giovanni BPrior studies reported that the hippocampal volume is smaller in Alzheimer s disease patients carrying the Apolipoprotein E 4 allele APOE4 versus patients who are non carriers of this allele This effect however has not been detected consistently possibly because of the regionally specific involvement of the hippocampal formation in Alzheimer s disease The aim of this study was to analyze the local effect of APOE4 on hippocampal atrophy in Alzheimer s disease patients Using high resolution T1 weighted images we investigated 14 patients heterozygous for the 4 allele age 72 8 SD years MMSE 20 4 SD and 14 patients not carrying the 4 allele age 71 10 MMSE 20 5 SD and 28 age sex and education matched controls age 71 8 MMSE 29 1 SD The hippocampal formation was outlined with manual tracing and 3D parametric surface models were created for each subject Radial atrophy was assessed on the whole hippocampal surface using the UCLA mapping technique E4 carriers and non carriers did not differ in their level of impairment in global cognition p 0 91 Mann Whitney test or memory p 0 29 Hippocampal surface analysis showed the typical pattern of CA1 and subicular tissue atrophy in both 4 carriers and non carriers compared with controls e4 carriers pUnder0 0002 4 non carriers pUnder0 01 permutation test The left hippocampal volume was significantly smaller in 4 carriers than non carriers p 0 044 Mann Whitney test the effect of APOE4 mapping to the subicular CA1 region p 0 041 permutation test Differences were not statistically significant in the right hippocampus p 0 20 permutation test These findings show that hippocampal atrophy is greater in APOE4 carriers in regions typically affected by pathology APOE4 may affect the structural expression of Alzheimer s disease
- ItemBrain connectivity in neurodegenerative diseases--from phenotype to proteinopathy.(2014-10-21) Pievani, Michela; Filippini, Nicola; van den Heuvel, Martijn P; Cappa, Stefano F; Frisoni, Giovanni BFunctional and structural connectivity measures as assessed by means of functional and diffusion MRI are emerging as potential intermediate biomarkers for Alzheimer disease AD and other disorders This Review aims to summarize current evidence that connectivity biomarkers are associated with upstream and downstream disease processes molecular pathology and clinical symptoms respectively in the major neurodegenerative diseases The vast majority of studies have addressed functional and structural connectivity correlates of clinical phenotypes confirming the predictable correlation with topography and disease severity in AD and frontotemporal dementia In neurodegenerative diseases with motor symptoms structural but to date not functional connectivity has been consistently found to be associated with clinical phenotype and disease severity In the latest studies the focus has moved towards the investigation of connectivity correlates of molecular pathology Studies in cognitively healthy individuals with brain amyloidosis or genetic risk factors for AD have shown functional connectivity abnormalities in preclinical disease stages that are reminiscent of abnormalities observed in symptomatic AD This shift in approach is promising and may aid identification of early disease markers establish a paradigm for other neurodegenerative disorders shed light on the molecular neurobiology of connectivity disruption and ultimately clarify the pathophysiology of neurodegenerative diseases
- ItemHippocampal atrophy in people with memory deficits: results from the population-based IPREA study.(2014-05-30) Ferrarini, Luca; van Lew, Baldur; Reiber, Johan H C; Gandin, Claudia; Galluzzo, Lucia; Scafato, Emanuele; Frisoni, Giovanni B; Milles, Julien; Pievani, Michela; ,Clinical studies have shown that hippocampal atrophy is present before dementia in people with memory deficits and can predict dementia development The question remains whether this association holds in the general population This is of interest for the possible use of hippocampal atrophy to screen population for preventive interventions The aim of this study was to assess hippocampal volume and shape abnormalities in elderly adults with memory deficits in a cross sectional population based study
- ItemThe in vivo topography of cortical changes in healthy aging and prodromal Alzheimer's disease.(2013-09-23) Prestia, Annapaola; Baglieri, Annalisa; Pievani, Michela; Bonetti, Matteo; Rasser, Paul E; Thompson, Paul M; Marino, Silvia; Bramanti, Placido; Frisoni, Giovanni BGray matter atrophy is regarded as a valid marker of neurodegeneration in Alzheimer s disease AD but few studies have investigated in detail the topographic changes associated with normal aging In addition few studies have compared the changes in the earliest clinical stage of AD prodromal AD pAD with those of healthy aging Here we aimed to investigate the topographical distribution of age related cortical atrophy and to compare it with that associated with prodromal and estabilished AD
- ItemInfluence of serotonin receptor 2A His452Tyr polymorphism on brain temporal structures: a volumetric MR study.(2006-03-23) Filippini, Nicola; Scassellati, Catia; Boccardi, Marina; Pievani, Michela; Testa, Cristina; Bocchio-Chiavetto, Luisella; Frisoni, Giovanni B; Gennarelli, MassimoSerotonin 5 HT receptors 2A are expressed in brain regions involved in memory and learning processes Recently a functional single nucleotide polymorphism in the 5 HT2A receptor gene leading to an amino acid substitution at residue 452 His452Tyr has been involved in memory performance persons with the rare 452Tyr allele showing poorer memory performance compared to His452His subjects To investigate a putative structural effect of this polymorphism on temporal areas typically involved in memory processes we performed voxel based morphometry VBM and region of interest ROI volumetric analysis on high resolution magnetic resonance images in 15 carriers and 61 noncarriers of the 452Tyr allele ROI volumetric analysis showed a significant reduction of the fractional volume of the temporal white matter in 452Tyr carriers 0 67 0 07 vs 0 73 0 08 P 0 007 VBM confirmed this finding and in addition showed reduced grey matter in the left hippocampus left inferior temporal gyrus and bilaterally in the middle and superior temporal gyrus A possible effect on synaptic plasticity or neurodevelopment might explain the influence of the His452Tyr polymorphism on temporal brain structures and this might be the basis for poorer memory performance in 452Tyr carriers These findings should be considered preliminary and future replication is needed
- ItemMedial temporal atrophy in early and late-onset Alzheimer's disease.(2014-06-10) Cavedo, Enrica; Pievani, Michela; Boccardi, Marina; Galluzzi, Samantha; Bocchetta, Martina; Bonetti, Matteo; Thompson, Paul M; Frisoni, Giovanni BLate onset and early onset Alzheimer s disease LOAD EOAD affect different neural systems and may be separate nosographic entities The most striking differences are in the medial temporal lobe severely affected in LOAD and relatively spared in EOAD We assessed amygdalar morphology and volume in 18 LOAD and 18 EOAD patients and 36 aged matched controls and explored their relationship with the hippocampal volume Three dimensional amygdalar shape was reconstructed with the radial atrophy mapping technique hippocampal volume was measured using a manual method Atrophy was greater in LOAD than EOAD 25 versus 17 in the amygdala and 20 versus 13 in the hippocampus In the amygdala LOAD showed significantly greater tissue loss than EOAD in the right dorsal central lateral and basolateral nuclei 20 30 loss p Under 0 03 all known to be connected to limbic regions In LOAD but not EOAD greater hippocampal atrophy was associated with amygdalar atrophy in the left dorsal central and medial nuclei r 0 6 p Under 0 05 also part of the limbic system These findings support the notion that limbic involvement is a prominent feature of LOAD but not EOAD
- ItemNeural signatures of the interaction between the 5-HTTLPR genotype and stressful life events in healthy women.(2014-07-08) Favaro, Angela; Manara, Renzo; Pievani, Michela; Clementi, Maurizio; Forzan, Monica; Bruson, Alice; Tenconi, Elena; Degortes, Daniela; Pinato, Claudia; Giannunzio, Valeria; Battista Frisoni, Giovanni; Santonastaso, PaoloA change in neural connectivity of brain structures implicated in the memory of negative life events has been hypothesized to explain the enhancement of memory encoding during the processing of negative stimuli in depressed patients Here we investigated the effects of the interaction between negative life events and the 5 HTTLPR genotype a polymorphism of the serotonin transporter gene on the functional and structural connectivity of the hippocampal area in 34 healthy women All participants were genotyped for the presence of the 5 HTTLPR short variant and for the A G single nucleotide polymorphism they underwent clinical assessment including structured diagnostic interviews to exclude the presence of psychiatric disorders and to assess the presence of stressful life events Resting state functional magnetic resonance imaging and diffusion tensor imaging scans were performed We found significant interactions between stressful events and the 5 HTTLPR genotype in both the functional connectivity of the parahippocampus with the posterior cingulate cortex and the structural connectivity between the hippocampus and both the amygdala and the putamen In addition we found several genotype related differences in the relationship between functional structural connectivity of the hippocampal area and the ability to update expectations or stress related phenotypes such as anxiety symptoms If confirmed by future studies these mechanisms may clarify the role of the 5HTTLPR genotype as a risk factor for depression in interaction with negative events
- ItemPattern of structural and functional brain abnormalities in asymptomatic granulin mutation carriers.(2014-10-24) Pievani, Michela; Paternicò, Donata; Benussi, Luisa; Binetti, Giuliano; Orlandini, Alberto; Cobelli, Milena; Magnaldi, Silvia; Ghidoni, Roberta; Frisoni, Giovanni BTo investigate the patterns of brain atrophy white matter WM tract changes and functional connectivity FC abnormalities in asymptomatic granulin GRN mutation carriers
- ItemThe topography of grey matter involvement in early and late onset Alzheimer's disease.(2007-03-09) Frisoni, Giovanni B; Pievani, Michela; Testa, Cristina; Sabattoli, Francesca; Bresciani, Lorena; Bonetti, Matteo; Beltramello, Alberto; Hayashi, Kiralee M; Toga, Arthur W; Thompson, Paul MClinical observations have suggested that the neuropsychological profile of early and late onset forms of Alzheimer s disease EOAD and LOAD differ in that neocortical functions are more affected in the former and learning in the latter suggesting that they might be different diseases The aim of this study is to assess the brain structural basis of these observations and test whether neocortical areas are more heavily affected in EOAD and medial temporal areas in LOAD Fifteen patients with EOAD and 15 with LOAD onset before and after age 65 Mini Mental State Examination 19 8 SD 4 0 and 20 7 SD 4 2 were assessed with a neuropsychological battery and high resolution MRI together with 1 1 age and sex matched controls Cortical atrophy was assessed with cortical pattern matching and hippocampal atrophy with region of interest based analysis EOAD patients performed more poorly than LOAD on visuospatial frontal executive and learning tests EOAD patients had the largest atrophy in the occipital 25 grey matter GM loss in the left and 24 in the right hemisphere and parietal lobes 23 loss on both sides while LOAD patients were remarkably atrophic in the hippocampus 21 and 22 loss Hippocampal GM loss of EOAD 9 and 16 to the left and right and occipital 12 and 14 and parietal 13 and 12 loss of LOAD patients were less marked In EOAD GM loss of 25 or more was mapped to large neocortical areas and affected all lobes with relative sparing of primary sensory motor and visual cortex and anterior cingulate and orbital cortex In LOAD GM loss was diffusely milder below 15 losses of 15 20 were confined to temporoparietal and retrosplenial cortex and reached 25 in restricted areas of the medial temporal lobe and right superior temporal gyrus These findings indicate that EOAD and LOAD differ in their typical topographic patterns of brain atrophy suggesting different predisposing or aetiological factors
- ItemTraining labels for hippocampal segmentation based on the EADC-ADNI harmonized hippocampal protocol.(2015-01-24) Boccardi, Marina; Bocchetta, Martina; Morency, Félix C; Collins, D Louis; Nishikawa, Masami; Ganzola, Rossana; Grothe, Michel J; Wolf, Dominik; Redolfi, Alberto; Pievani, Michela; Antelmi, Luigi; Fellgiebel, Andreas; Matsuda, Hiroshi; Teipel, Stefan; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B; ,The European Alzheimer s Disease Consortium and Alzheimer s Disease Neuroimaging Initiative ADNI Harmonized Protocol HarP is a Delphi definition of manual hippocampal segmentation from magnetic resonance imaging MRI that can be used as the standard of truth to train new tracers and to validate automated segmentation algorithms Training requires large and representative data sets of segmented hippocampi This work aims to produce a set of HarP labels for the proper training and certification of tracers and algorithms