PROGETTI

PROGETTI

Istitutional research-Ricerca corrente 2001 Thematic research-Ricerca finalizzata Mild Alzheimer project

ISTITUTIONAL RESEARCH-RICERCA CORRENTE
2001

Morphometric cerebral correlates in behavioural disturbances in Alzheimer’s disease
Correlati di morfometria cerebrale dei disturbi comportamentali nella malattia di Alzheimer

Delusions are particularly common and distressing for patients and their caregivers. On the ground of results obtained in a study based on Neuroimaging, in which it was visualized an asymmetrical specific pattern of temporal and frontal atrophy in patients with mild Alzheimer’s disease showing delusions (Geroldi, et al., J Neurol Neurosurg Psychiatry 2000;69:187-91), we intend to investigate this feature, using our available datasets, which need specific management (particularly, SPECT and PET). At the present, we are analysing data.
About half of patients with Alzheimer’s disease and delusions, included in Mild Project doesn’t show a predominant right temporal atrophy. We are evaluating if other factors, such as caregivers’ stress o other coping strategies may have an interaction with right temporal atrophy in developing delusions.

Furthermore, a project with Psychiatric Opeative Unit of our Institute will be initiated. We will study the contribution of neurobiological damages on disability in instrumental activities in patient with cronic schizophrenia assessing psychopatological, pharmacologic, somatic and functional characteristics in a group of 20 patients with cronic schizophrenia with a prevalence of negative symptoms and 20 patients with a prevalence of positive symptoms, using a multidimentional battery and RM.

Guide lines for the use of neuroimaging in Alzheimer’s disease
Linee guida per l'uso del neuroimaging nella malattia di Alzheimer.

Although knowledge about Alzheimer’s disease and cognitive disturbances are improved in the last two decades, an important difference between development in research and clinical practice is still present. To formulate guide lines, useful in national clinical practice, we need to have a “photograph” showing modalities of diagnostic Imaging. In the present, these data are not available yet.
The aim of this project is taking data about "what", "when", "how" investigations are prescribed in the Alzheimer Assessment Unit (Unità di Valutazione Alzheimer- - U.V.A) of the Regione Lombardia (Italian Research Group for the Use of Diagnostic Imaging in Cognitive Disturbances - Gruppo Italiano di Studio per l'Uso dell'Imaging Diagnostico nei Disturbi Cognitivi). It will be necessary to collect e-mail addresses and formulate a questionaire to investigate when TAC, RM and SPECT are prescribed, for what kind of patients and how information is used. The results will be diffused using our web site.

Neuroimaging tools for the diagnosis of Alzheimer’s disease in clinical practice.
Strumenti di lettura delle indagini di neuroimmagine nella diagnosi di malattia di Alzheimer di utilizzo routinario e innovativi.

Atrophy index Medial temporal atrophy showed using functional Imaging is one of the most accurate markers of Alzheimer’s disease. Preliminary data indicate that a misure of medial temporal atrophy based on CT (width of the temporal horn, rWTH), is able to discriminate patients with Alzheimer’s disease from not demented subjects, with a sensibility of 93% and a specificity of 95%. These data could demonstrate that width of the temporal horn is an accurated marker to distinguish patients with Alzheimer’s disease from controls. To extend atrophy index in clinic setting is a key factor for its utility.
At the present, we are going on the validation of atrophy index with CT, extending it to patients with mild cognitive impairment and other kind of dementia, degenerative and not degenerative. A useful dataset is already available (Mild Project). Patients with particular diagnostic typology (mild cognitive impairment, degenerative and vascular, Lewy bodies dementia, frontotemporal degeneration and vascular subcortical dementia) will be included in this year and will be subjected to the same clinic protocol of Mild project. Furthermore, atrophy index will be developed in our web site and it will be used in the clinical daily practice of Alzheimer Operative Unit.

Vascularity Cerebrovascular disease has a key role in the genesis of cognitive and motor impairment, not only in patients with vascular dementia. First question to solve when association between vascular dementia and cognitive impairment is examined, is quantification of cerebrovascular lesions. We have built a new scale in which it’s assumed that different kind of lesions have a different weight in determining cognitive impairment: diffuse lesions in white matter have less weight, subcortical lesions have an intermediate weight and cortical lesions have greater weight. Within these valutations, severity is stimated to reflect this hierarchical order, to calculate a global score of vascular severity.
Preliminar data indicate that this scale is valid in a group of 105 subjects with cognitive impairment or mild dementia.
At the present, the development stage is going to be completed and we are collecting data about the validity of the vascular scale. We use the mild project dataset and we will include other patients with cognitive impairment of vascular type. Scale validity will be tested regards to variables associated with cerebral vascularity.
Furthermore, vascular scale will be develop in the web site and it will be used in the clinical daily practice of Alzheimer Operative Unit.

Istitutional research-Ricerca corrente 2001 Thematic research-Ricerca finalizzata

THEMATIC RESEARCH - RICERCA FINALIZZATA
2001

Italian normative archive of cerebral morphometry with magnetic resonance
Archivio normativo italiano di morfometria cerebrale con risonanza magnetica (età 40+)

Coordinating centre: Lab. of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio -FBF, Brescia (Giovanni B Frisoni) Patners:

U.O.2: Servizio di Neuroradiologia, Istituto Clinico Città di Brescia (Matteo Bonetti)
U.O.3: Unità Operativa Alzheimer, IRCCS S. Giovanni di Dio-FBF, Brescia (Cristina Geroldi)
U.O.4: Servizio di Neuroradiologia, Fondazione Centro San Raffaele Del Monte Tabor, Milano (Andrea Falini)
U.O.5: Servizio di Neurologia, Ospedale di Circolo e Fondazione Macchi/Università degli Studi dell'Insubria, Varese (Giorgio Bono)
U.O.6: Servizio di Neuroradiologia, Ospedale Maggiore, Verona (Alberto Beltramello)
U.O.7: Laboratorio di Neurobiologia, IRCCS S. Giovanni di Dio-FBF, Brescia (Luisa Benussi)
U.O.8: Sezione di Statistica Medica e Biometria, Dipartimento di Scienze Biomediche e Biotecnologiche, Università degli Studi di Brescia (Adriano Decarli)

Neuroimaging has a critical role in the diagnosis of aged-related diseases.
Some issues prevent the use of Magnetic Resonance (MR) imaging from being informative in clinical practice. First of all, most parameters used to measure atrophy and vascularity are aged-related, consequently the judgement about the presence of regional atrophy and vascularity have to be formulated on the basis of age-specific features.
Moreover, there are other factors, besides gender, that have an influence on cerebral morphometry. It was been demonstrated that allele e4 of Apolipoprotein E (apoE) is associated with a particular volumetric profile in medial temporal regions and, probably, in the frontal ones. (Geroldi et al., Neurology 1999;53:1825-32). Lastly, the site and the minimal extension of vascular lesions so that they can explain cognitive or motor impairment remain unclear.
It is necessary a series of data about regional volumetry and cerebral vascularity for different levels of age, gender and genotipe. This data base could be a landmark to judge how each patient is different from its own aged-, gender- and genotipe-specific level.
Health volunteers and patients making a MR not to evaluate cognitive impairment (to reach cerebral metabasis, cranial trauma, cephalalgia, vertigo, orbital syndromes hypophysis) will be admitted.

Mild Cognitive Impairment without dementia: pre-clinical stage of Alzheimer's disease and vascular dementia. Clinical, instrumental, genetic and neurobiological features and development of diagnostic criteria to be used in the Italian clinical practice.
Decadimento Cognitivo Lieve non dementigeno: stadio preclinico di malattia di Alzheimer e demenza vascolare. Caratterizzazione clinica, strumentale, genetica e neurobiologica e sviluppo di criteri diagnostici utilizzabili nella realtà clinica nazionale.

Coordinating Centre: U.O. Alzheimer, IRCCS S.Giovanni di Dio- FBF, Brescia (Cristina Geroldi)
Patner: Lab. of Epidemiology e Neuroimaging, IRCCS San Giovanni di Dio -FBF (Giovanni B. Frisoni)

Modern biomedical technologies allow to evaluate cerebral modifications before that dementia is clinically manifested with its typical syntomatology. Identifying dementia in a pre-clinic stage could consent to begin an anticipatory treatment, delaying the presence of disability.
The condition of Mild cognitive impairment (not dementing), Mild Cognitive Impairment, MCI; Petersen et al., 1999) is characterized by an isolated memory impairment, without any functional impact on daily activities, higher risk to develop dementia and increased mortality.
Mild cognitive impairment (not dementing) is a risk- factor in the development of dementia. The aim of this research is to recognize pre-clinical dementia and to describe the syntomatology associated to Alzhheimer’s disease and vascular dementia in a pre-clinic stage.
Furthermore, we would provide a sindromic definition of MCI of vascular type as regards to MCI of degenerative type and a series of diagnostic criteria, useful in Italian clinical practice.
It will be useful to describe subjects showing MCI, with a particular emphasis on behavioural, affective and biological aspects (risk-factors and Neuroimaging profile). We will study somatic comorbility in subjects affected by MCI and the possible interaction between MCI and chronic-degenerative pathology.
At the end of project, it will be available a database for the study of Mild cognitive impairment of degenerative and vascular type
Different methodological tools will be used and different Operative Unit will be included. 200 subjects with MCI will be admitted.
The Laboratory of Neuroimaging, with Alzheimer Operative Unit, will prepare the protocol for the clinical evaluation (cognitive, functional and behavioural), it will manage the instrumental examinations, the database (clinical and instrumental) and the quantitative analysis of instrumental data.

Studio degli effetti degli ormoni estrogeni sulle funzioni cognitive e nella malattia di Alzheimer
Study of the effects on oestrogens on cognitive functions and Alzheimer'disease

Coordinating Centre: IRCCS Centro San Giovanni-FBF, Brescia (Luisa Benussi)
Patner: Lab. of Epidemiology and Neuroimaging, IRCCS S.Giovanni di Dio- FBF, Brescia (Cristina Testa)

The aim of this project is to investigate the effects of oestrogenic stimulation (i) in experimental cellular and animal models, (ii) on cognitive functions in climacter women; (iii) to study the protective role of the oestrogens in neurodegenerative processes by estimating, with a case-control method, risk to develop Alzheimer’s disease, associated of a oestrogenic therapy and factors correlated to Alzheimer’s disease: (1) endocrinologic features; (2) oxydative stage; (3) biological markers (APOE, Cystatine C, ER alpha); (4) cerebral atrophy.
Laboratory of Neuroimaging will: (i) coordinate the execution of Magnetic Resonances, made by O.U. associated, Department of Neuroradiology of Borgo Trento hospital, Verona; (ii) manage images; (iii) make morphometric analysis; (iv) evaluate atrophy, comparing results with a standard of health elderly, already available.
When RM images will be made by O. U associated, all the contributes will be carry out in Laboratory of Neuroimaging, IRCCS S. Giovanni di Dio- FBF; (i) collection and filing: images will be transfer using internet (ii) morphometric analysis; (iii) judgement about atrophy.

Italian epidemiologic project of Alzheimer’s disease
Progetto Italiano sull’epidemiologia della Malattia di Alzheimer

Cordinating centre: Istituto Superiore di Sanità, Roma (Emanuele Scafato)
Patner: Lab. of Epidemiology and Neuroimaging, IRCCS S.Giovanni di Dio-FBF, Brescia (Giovanni B. Frisoni)

The aim of the general study is to develop a series of national data, using experiences made by epidemiology studies about elderly in Italy, completing information coming from a study about a national cohort, still not available. The project will allow to have information about: a) prevalence, etiology, risk factors; b) incidence, comorbility and mortality; ( c) biological markers and psychodiagnostic predictive test as regards to Alzheimer’s disease and to modifications in cognitive abilities associated to dementia; (d) evaluation of factors having an influence on transition from pre-clinic stage of MCI to an acclaimed stage of Alzheimer’s disease.

The laboratory of Epidemiology and Neuroimaging is determined to execute a standard lecture of Magnetic Resonance Images coming from 500 subjects (case and controls) deriving from the general cohort. Operative Unit will collaborate to define methodology and procedures and will transfer information to coordinative Unit of Istituto Superiore di Sanità.