Browsing by Author "Frisoni, Giovanni B"
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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
- ItemAssociation of blood pressure and genetic background with white matter lesions in patients with mild cognitive impairment.(2008-05-30) Galluzzi, Samantha; Geroldi, Cristina; Benussi, Luisa; Ghidoni, Roberta; Testa, Cristina; Borsci, Genoveffa; Bonetti, Matteo; Manfellotto, Dario; Romanelli, Giuseppe; Zulli, Roberto; Binetti, Giuliano; Frisoni, Giovanni BBackground White matter lesions WMLs may contribute to cognitive deficits in patients with mild cognitive impairment MCI but their pathogenesis is complex Fluctuations of blood pressure BP over 24 hours and genetic predisposition to develop vascular damage have been implicated Methods In 63 MCI patients 65 years old or older BP was measured both clinically and with ambulatory BP monitoring Patients were classified in two groups no very mild n 34 and mild to severe n 29 WMLs based on a visual scale on magnetic resonance mean age 71 8 4 7 vs 74 6 5 1 and female gender 53 vs 66 respectively The volume of WMLs was measured by a semi automatic method separately for periventricular caps and rim periventricular confluent subcortical punctate and subcortical confluent Polymorphisms of cystatin C CST3 and cholesterol 24 hydroxylase CYP46 genes putative risk factors for cerebrovascular disease were determined Results The prevalence of cerebrovascular risk factors was similar in the two MCI groups of different WML severity as well as clinic and ambulatory BP In patients with mild to severe but not in those with no very mild WMLs the volume of periventricular confluent WMLs increased with increasing daytime systolic BP regression coefficient 47 95 confidence interval CI 13 to 71 vs 02 95 CI 32 to 36 p 003 for the difference between slopes The volume of other WML subtypes was not associated with ambulatory BP Participants carrying both CST3 B and CYP46 T alleles were overrepresented in the MCI group with mild to severe WMLs 43 vs 17 p 03 Conclusions BP and gene putative risk factors for cerebrovascular disease are differentially associated with WMLs in two MCI groups of different WML severity WMLs might develop for the convergence of innate with acquired factors
- ItemBiomarker-based diagnosis of mild cognitive impairment due to Alzheimer's disease: how and what to tell. A kickstart to an ethical discussion.(2014-03-28) Porteri, Corinna; Frisoni, Giovanni BNew criteria for the diagnosis of Alzheimer s disease AD based on biomarker results have recently been developed and are currently undergoing extensive validation The next few years may represent a time window where the diagnostic validity of biomarkers will be studied in highly specialized research settings Biomarkers results will be used to direct clinical diagnosis and whenever appropriate therapy and management This piece aims to stimulate discussion by identifying the ethical challenges involved in the use of biomarkers to make a diagnosis of mild cognitive impairment due to AD and disclose it to patients At the individual level these challenges are related to i the ethical appropriateness of implementing an ecological diagnostic research protocol ii the related informed consent process and iii the diagnostic disclosure We justify the ethical legitimacy of implementing a research diagnostic protocol by referring to the respect of patients subjectivity and autonomy and we suggest guidelines for informed consent development and diagnostic disclosure All of the above points are discussed in light of the unique features of AD currently scanty treatment options and knowledge and uncertainties regarding the diagnostic value of biomarkers
- 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
- ItemBrain perfusion correlates of medial temporal lobe atrophy and white matter hyperintensities in mild cognitive impairment.(2007-08-31) Caroli, Anna; Testa, Cristina; Geroldi, Cristina; Nobili, Flavio; Guerra, Ugo P; Bonetti, Matteo; Frisoni, Giovanni BTo assess the association of Medial Temporal lobe Atrophy MTA and White Matter Hyperintensities WMHs with gray matter perfusion in Mild Cognitive Impairment MCI
- ItemClinical and neuropsychological features associated with structural imaging patterns in patients with mild cognitive impairment.(2007-02-22) Rossi, Roberta; Geroldi, Cristina; Bresciani, Lorena; Testa, Cristina; Binetti, Giuliano; Zanetti, Orazio; Frisoni, Giovanni BTo describe the clinical and neuropsychological features of mild cognitive impairment MCI patients with medial temporal atrophy MTA white matter hyperintensities WMH both and neither and to assess whether the rate of progression differs among groups
- ItemCognitive rehabilitation for severe dementia: critical observations for better use of existing knowledge.(2006-02-06) Boccardi, Marina; Frisoni, Giovanni BCognitive rehabilitation for severely demented patients is a hard job for a number of reasons The most recent evidence based strategies such as the cued recall or the spaced retrieval techniques aim to improve cognitive function at initial stages of the disease while in more severe stages interventions such as validation therapy are used which are traditionally adopted but lack a solid scientific rationale and often even a consistent evidence based efficacy Many studies have been carried out to try demonstrate the effect of these therapies or to project new interventions while little attention has been given to the fact that simple neuropsychological principles keeping into account the nature of the pathological aging observed in dementia can be fruitfully adopted to improve and personalize different kinds of intervention A rational use of current neuropsychological concepts optimizes the patient s benefit as well as the operator s efforts A rehabilitative intervention based on current neuropsychological concepts and on awareness of the mechanisms of pathological ageing of cognition provides the possibility of tailored treatments for many different patients an important reduction of burn out in the personnel and clinically relevant outcomes such as an implicit orientation for the patient with beneficial effects on mood and behavior
- ItemDelphi definition of the EADC-ADNI Harmonized Protocol for hippocampal segmentation on magnetic resonance.(2014-08-18) Boccardi, Marina; Bocchetta, Martina; Apostolova, Liana G; Barnes, Josephine; Bartzokis, George; Corbetta, Gabriele; DeCarli, Charles; deToledo-Morrell, Leyla; Firbank, Michael; Ganzola, Rossana; Gerritsen, Lotte; Henneman, Wouter; Killiany, Ronald J; Malykhin, Nikolai; Pasqualetti, Patrizio; Pruessner, Jens C; Redolfi, Alberto; Robitaille, Nicolas; Soininen, Hilkka; Tolomeo, Daniele; Wang, Lei; Watson, Craig; Wolf, Henrike; Duvernoy, Henri; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B; ,This study aimed to have international experts converge on a harmonized definition of whole hippocampus boundaries and segmentation procedures to define standard operating procedures for magnetic resonance MR based manual hippocampal segmentation
- ItemDrug prescription in mild cognitive impairment: the physicians' perspective in Italy.(2006-10-30) Frisoni, Giovanni B; Canu, Elisa; Geroldi, Cristina; Zanetti, Orazio; Zacchi, ValeriaToday there are no data on the type of drugs prescribed to MCI patients nor the prevalence of their prescription The aim of this study was to describe which drugs were prescribed in 2004 for cognitive and non cognitive disturbances of patients with MCI in a sizable group of Italian expert centers for the diagnosis and treatment of Alzheimer s disease
- ItemThe EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance: Evidence of validity.(2014-09-30) Frisoni, Giovanni B; Jack, Clifford R; Bocchetta, Martina; Bauer, Corinna; Frederiksen, Kristian S; Liu, Yawu; Preboske, Gregory; Swihart, Tim; Blair, Melanie; Cavedo, Enrica; Grothe, Michel J; Lanfredi, Mariangela; Martinez, Oliver; Nishikawa, Masami; Portegies, Marileen; Stoub, Travis; Ward, Chadwich; Apostolova, Liana G; Ganzola, Rossana; Wolf, Dominik; Barkhof, Frederik; Bartzokis, George; DeCarli, Charles; Csernansky, John G; deToledo-Morrell, Leyla; Geerlings, Mirjam I; Kaye, Jeffrey; Killiany, Ronald J; Lehéricy, Stephane; Matsuda, Hiroshi; O'Brien, John; Silbert, Lisa C; Scheltens, Philip; Soininen, Hilkka; Teipel, Stefan; Waldemar, Gunhild; Fellgiebel, Andreas; Barnes, Josephine; Firbank, Michael; Gerritsen, Lotte; Henneman, Wouter; Malykhin, Nikolai; Pruessner, Jens C; Wang, Lei; Watson, Craig; Wolf, Henrike; deLeon, Mony; Pantel, Johannes; Ferrari, Clarissa; Bosco, Paolo; Pasqualetti, Patrizio; Duchesne, Simon; Duvernoy, Henri; Boccardi, Marina; ,An international Delphi panel has defined a harmonized protocol HarP for the manual segmentation of the hippocampus on MR The aim of this study is to study the concurrent validity of the HarP toward local protocols and its major sources of variance
- ItemEffect of memantine on resting state default mode network activity in Alzheimer's disease.(2011-02-21) Lorenzi, Marco; Beltramello, Alberto; Mercuri, Nicola B; Canu, Elisa; Zoccatelli, Giada; Pizzini, Francesca B; Alessandrini, Franco; Cotelli, Maria; Rosini, Sandra; Costardi, Daniela; Caltagirone, Carlo; Frisoni, Giovanni BMemantine is an approved symptomatic treatment for moderate to severe Alzheimer s disease that reduces the excitotoxic effects of hyperactive glutamatergic transmission However the exact mechanism of the effect of memantine in Alzheimer s disease patients is poorly understood Importantly the default mode network DMN which plays a key role in attention is hypoactive in Alzheimer s disease and is under glutamatergic control
- ItemEffect of the XbaI polymorphism of estrogen receptor alpha on postmenopausal gray matter.(2008-03-24) Boccardi, Marina; Scassellati, Catia; Ghidoni, Roberta; Testa, Cristina; Benussi, Luisa; Bonetti, Matteo; Bocchio-Chiavetto, Luisella; Gennarelli, Massimo; Binetti, Giuliano; Frisoni, Giovanni BThe frequent polymorphism XbaI A351G in the estrogen receptor alpha ERalpha gene has been associated with some postmenopausal pathologies risk such as Alzheimer s disease AD or cognitive decline In the present study we explored whether the XbaI polymorphism leads to different gray matter volumes using voxel based morphometry VBM on 20 magnetic resonance images of healthy postmenopausal women Subjects carrying the less common XbaI X allele were contrasted to non carriers in groups well balanced by relevant confounding variables The XbaI X allele carriers displayed clusters ranging from 9 to 28 of tissue reductions in the cerebellar cluster size z stereotactic coordinates 16 mm 3 3 17 14 94 38 and cerebral cortex in particular in the occipital lobe 272 mm 3 3 76 38 68 16 in the middle frontal gyrus 192 mm 3 3 71 38 12 38 and in the middle temporal gyrus while the opposite comparison was negative The XbaI X allele in ERalpha gene is associated to smaller gray matter volumes of the cerebral and cerebellar cortex This allele might increase the susceptibility for senile neurodegenerative conditions being associated to smaller cerebral reserve
- ItemThe effect of white matter lesions on cognition in the elderly--small but detectable.(2007-11-05) Frisoni, Giovanni B; Galluzzi, Samantha; Pantoni, Leonardo; Filippi, MassimoThe extent to which white matter changes affect brain function in elderly individuals is a matter for debate Although there is a consensus that large confluent white matter lesions WMLs can be attributed to small vessel disease and might denote anatomical damage to axons the clinical effect of WMLs with regard to cognitive impairment is less certain In this Review we argue that WMLs are associated with greater detectable progressive cognitive deterioration than is normal aging but other causes of progressive cognitive deterioration such as Alzheimer s disease are associated with greater cognitive decline than are WMLs This view has important implications for the development of drugs for the treatment and prevention of cognitive impairment and dementia
- ItemEffects of hormone therapy on brain morphology of healthy postmenopausal women: a Voxel-based morphometry study.(2006-08-09) Boccardi, Marina; Ghidoni, Roberta; Govoni, Stefano; Testa, Cristina; Benussi, Luisa; Bonetti, Matteo; Binetti, Giuliano; Frisoni, Giovanni BEstrogens are known to be protective in age associated cognitive changes in humans and in neurodegeneration in animal models The aim of this study was to evaluate the potential effects of estrogen therapy ET on human gray matter volume in vivo
- ItemEstablishing magnetic resonance images orientation for the EADC-ADNI manual hippocampal segmentation protocol.(2014-09-08) Boccardi, Marina; Bocchetta, Martina; Apostolova, Liana G; Preboske, Gregory; Robitaille, Nicolas; Pasqualetti, Patrizio; Collins, Louis D; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B; ,An effort to define and validate a Harmonized Protocol for standard hippocampal segmentation is being carried out We wished to estimate the effect of magnetic resonance image MRI spatial orientation on manual hippocampal segmentations to define optimal standard orientation of MRIs for hippocampal volumetry
- ItemHarmonization of magnetic resonance-based manual hippocampal segmentation: a mandatory step for wide clinical use.(2011-03-18) Frisoni, Giovanni B; Jack, Clifford RHippocampal atrophy is a marker of disease state and progression in Alzheimer s disease The gold standard to measure hippocampal volume is through manual segmentation A number of protocols to measure hippocampal volume through manual segmentation have been developed but the marked heterogeneity of anatomical landmarks has given rise to wide variability of volume estimates With the aim of fostering the use of hippocampal volume in routine clinical settings an international task force is currently working on developing a harmonized protocol that will resolve and reduce the present heterogeneity The task force will then validate the harmonized protocol develop harmonized probabilistic hippocampal maps and develop illustrative and educational material on the use of the harmonized protocol and maps
- ItemHarmonized benchmark labels of the hippocampus on magnetic resonance: The EADC-ADNI project.(2014-09-16) Bocchetta, Martina; Boccardi, Marina; Ganzola, Rossana; Apostolova, Liana G; Preboske, Gregory; Wolf, Dominik; Ferrari, Clarissa; Pasqualetti, Patrizio; Robitaille, Nicolas; Duchesne, Simon; Jack, Clifford R; Frisoni, Giovanni B; ,A globally harmonized protocol HarP for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer s Disease Consortium EADC and Alzheimer s Disease Neuroimaging Initiative ADNI Our aim was to produce benchmark labels based on the HarP for manual segmentation
- ItemHippocampal and amygdalar local structural differences in elderly patients with schizophrenia.(2014-12-16) Prestia, Annapaola; Cavedo, Enrica; Boccardi, Marina; Muscio, Cristina; Adorni, Andrea; Geroldi, Cristina; Bonetti, Matteo; Thompson, Paul M; Frisoni, Giovanni BMorphological abnormalities have been reported for the hippocampi and amygdalae in young schizophrenia patients but very little is known about the pattern of abnormalities in elderly schizophrenia patients Here we investigated local structural differences in the hippocampi and amygdalae of elderly schizophrenia patients compared with healthy elderly subjects We also related these differences to clinical symptom severity
- 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
- ItemImaging as a biomarker in drug discovery for Alzheimer's disease: is MRI a suitable technology?(2014-12-08) Merlo Pich, Emilio; Jeromin, Andreas; Frisoni, Giovanni B; Hill, Derek; Lockhart, Andrew; Schmidt, Mark E; Turner, Martin R; Mondello, Stefania; Potter, William ZThis review provides perspectives on the utility of magnetic resonance imaging MRI as a neuroimaging approach in the development of novel treatments for Alzheimer s disease These considerations were generated in a roundtable at a recent Wellcome Trust meeting that included experts from academia and industry It was agreed that MRI either structural or functional could be used as a diagnostic for assessing worsening of disease status for monitoring vascular pathology and for stratifying clinical trial populations It was agreed also that MRI implementation is in its infancy requiring more evidence of association with the disease states test retest data better standardization across multiple clinical sites and application in multimodal approaches which include other imaging technologies such as positron emission tomography electroencephalography and magnetoencephalography