Margherita Alberoni

A PET Follow-up Study of Recovery after Stroke in Acute Aphasics ☆

The neural correlates of recovery from aphasia are largely unknown. Several different sources of evidence, from clinical studies to neurophysiological investigations, have suggested a contribution of the contralateral, undamaged hemisphere in recovery from aphasia. Eight patients with unilateral left hemispheric stroke were submitted to a standard language examination and to a [18F]FDG PET study in the recent phase after stroke (within 2 weeks) and 6 months later. All patients had a substantial recovery of specific aspects of language functions at the follow-up. Analysis of regional glucose metabolism showed hypometabolism in structurally unaffected regions both in the left and in the right hemisphere (diaschisis), in the acute stage. Glucose metabolism increased significantly on both sides in all patients at the second PET study. Regional analysis showed significant positive correlations between changes in metabolic values in several cortical and subcortical regions in the right hemisphere and changes in language performance at follow-up. The present findings show that an extensive, bihemispheric depression of metabolism is found in the acute stage after stroke in aphasic patients. Language recovery in the first months after aphasia onset is associated with regression of functional depression (diaschisis) in structurally unaffected regions, in particular in the right hemisphere.

Brain MRI correlates of cognitive impairment in primary and secondary progressive multiple sclerosis.

Brain magnetic resonance imaging (MRI) and an extensive battery of neuropsychological tests exploring frontal functions, short and long-term memory, visuo-spatial skills, attention and language were applied to 14 patients with primary progressive multiple sclerosis (PPMS) and 17 patients with secondary progressive MS (SPMS). Patients with PPMS and SPMS did not differ in degree of physical disability, but cognitive deficits were found in 9/17 (53%) patients with SPMS and in only 1/14 (7%) of those with PPMS (p = 0.01). Patients with SPMS had higher total (p = 0.004), periventricular (p = 0.008) and non-periventricular (p = 0.04) MRI lesion loads than patients with PPMS. In detail, patients with SPMS had greater involvement of frontal (p = 0.05) and occipital (p = 0.02) horns, trigones (p = 0.04), third ventricle (p = 0.03), basal ganglia (p = 0.02), parietal (p = 0.02), temporal (p = 0.004) and occipital (p = 0.03) lobes. Patients with SPMS and neuropsychological deficits had higher non-periventricular lesion loads than patients with SPMS who did not have such deficits (p = 0.005). Our results indicate that both neuropsychological and brain MRI abnormalities are more extensive in patients with SPMS. Since physical disability was similar for both groups, disability in PPMS may be predominantly due to spinal cord involvement.

Metabolic Impairment in Human Amnesia: A PET Study of Memory Networks

Human amnesia is a clinical syndrome exhibiting the failure to recall past events and to learn new information. Its “pure” form, characterized by a selective impairment of long-term memory without any disorder of general intelligence or other cognitive functions, has been associated with lesions localized within Papezs circuit and some connected areas. Thus, amnesia could be due to a functional disconnection between components of this or other neural structures involved in long-term learning and retention. To test this hypothesis, we measured regional cerebral metabolism with 2-[18F]fluoro-2-deoxy-d-glucose ([18F]FDG) and positron emission tomography (PET) in 11 patients with “pure” amnesia. A significant bilateral reduction in metabolism in a number of interconnected cerebral regions (hippocampal formation, thalamus, cingulate gyrus, and frontal basal cortex) was found in the amnesic patients in comparison with normal controls. The metabolic impairment did not correspond to alterations in structural anatomy as assessed by magnetic resonance imaging (MRI). These results are the first in vivo evidence for the role of a functional network as a basis of human memory.

Influence of Clinical Variables on Neuropsychological Performance in Multiple Sclerosis

The effects of age, educational level, duration and course of the disease, physical disability and mood status on several cognitive functions (short- and long-term memory, frontal functions, attention, language and visuospatial skills) have been evaluated in 42 multiple sclerosis (MS) patients. The Hamilton Depression Rating Scale (HDRS) scores and a secondary progressive disease course significantly influenced neuropsychological performance. Factorial analysis revealed that indexes of (1) frontal function impairment, (2) long-term verbal memory and language function impairment, and (3) visuospatial short- and long-term memory and visuoperceptive function impairment accounted for 85% of the variance in neuropsychological performance. Only the first factor was significantly related to the presence of depressive symptomatology, as assessed by the HDRS. These results indicate that both the course of the disease and the presence of affective disorders must be taken into account when evaluating the natural history of cognitive impairment in MS and suggest that depressive symptomatology and cognitive dysfunction in MS are related to the involvement of at least partially overlapping anatomofunctional circuits.

Left and right hemisphere contribution to recovery from neglect after right hemisphere damage-an [18F]FDG PET study of two cases

A 2-[18F]-Fluoro-2-Deoxy-D-Glucose ([18F]FDG) and positron emission tomography (PET) study was performed in the acute and chronic phase of stroke in one patient with unilateral neglect due to a right hemispheric lesion. In the acute phase, severe neglect, as well as hypometabolism in both the right and in the left unaffected cerebral hemisphere, was demonstrated. At follow-up evaluation the patient showed an almost complete recovery from unilateral neglect. This was associated with a return of left hemisphere metabolism to normal values and partial metabolic recovery in the right hemisphere, where frontal and parietal areas remained functionally impaired. Another patient with an extensive right cerebral ischaemic lesion on CT and severe unilateral neglect was studied by PET in chronic phase. A severe metabolic depression in the left unaffected hemisphere and in the right cerebral areas spared by the lesion, was found. These data suggest that the remission of unilateral neglect might be associated to a functional metabolic recovery in both the undamaged left hemisphere and the unaffected regions of the right hemisphere.

Increased activity of Th-17 and Th-9 lymphocytes and a skewing of the post-thymic differentiation pathway are seen in Alzheimer’s disease

Inflammatory mediators are responsible for the neuroinflammation observed in Alzheimers disease (AD), a phenomenon that might be the culprit of disease or, possibly, a reaction to pathology. To better investigate inflammation in AD we performed an extensive immunophenotypic and functional analysis of amyloid-beta (Aβ) stimulated T lymphocytes in patients with a diagnosis of AD comparing data to those obtained in individuals with mild cognitive impairment (MCI) or aged-matched healthy individuals (HC). Results showed that IL-21- and IL-9-producing Aβ stimulated CD4(+) T cells, as well as IL-23- and IL-6-producing monocytes and CD4(+) T cells expressing the RORγ and NFATc1 transcriptional factors (TF), were significantly increased, whereas IL-10-producing monocytes were decreased in AD. Notably, GATA-3 TF-expressing CD4(+) T lymphocytes were significantly increased in MCI alone. Analysis of the post-thymic differentiation pathway indicated that Aβ specific naïve and central memory CD4(+) T lymphocytes were diminished whereas effector memory and terminally differentiated CD4(+) T lymphocytes were increased in AD and MCI compared to HC. Data herein indicate that cytokines (IL-21, IL-6, IL-23) and TF (RORγ) involved in the differentiation of Th-17 cells), as well as cytokines (IL-21, IL-22) generated by such cells, and IL-9, produced by Th-9 cells, are significantly increased in AD. This is accompanied by a shift of post-thymic differentiation pathways favoring the accumulation of differentiated, effector T lymphocytes. These data shed light on the nature of AD-associated neuroinflammation. A better understanding of the complexity of this phenomenon could facilitate the search for novel therapeutic strategies.

Correlations between cognitive impairment, middle cerebral artery flow velocity and cortical glucose metabolism in the early phase of Alzheimer's disease

In a previous transcranial Doppler (TCD) study, we demonstrated a decrease in blood flow velocity in the proximal tract of the middle cerebral artery (MCA) in patients with Alzheimers disease (AD). In these patients there was also an asymmetry in blood flow velocity which positively correlated with the cognitive asymmetry often seen in the early phase of AD. In this study we found a correlation between the absolute values and asymmetry indexes of MCA blood flow velocity with adjusted metabolic values and asymmetry indexes of the relative cortical frontotemporoparietal (FTP) areas, evaluated by FDG-PET, and with neuropsychological asymmetry indexes. Patients with prevalent visuospatial deficits (right hemisphere dysfunction) showed significant decreases in right MCA blood flow velocity and right FTP cortical glucose hypometabolism, whereas in patients with prevalent language deficits (left hemisphere dysfunction), these signs were observed on the other side. In AD patients, the decrease of blood flow velocity in MCA might be due to reduced metabolic demands in the temporoparietal cortical areas primarily affected by AD.

Efficacy of recreational and occupational activities associated to psychologic support in mild to moderate Alzheimer disease : A multicenter controlled study

We evaluated the efficacy of a stimulation program mainly based on recreational and occupational activities, associated with a brief cycle of support psychotherapy for patients and caregivers, in mild to moderate Alzheimer Disease (AD) associated or not with cerebrovascular lesions. Sixty-seven patients and 31 controls from 2 Italian towns entered the study. The control group was comprised of AD subjects who voluntarily declined to participate in the program for practical reasons. Patients were divided in groups of 4 subjects: treatment was delivered for 6 weeks. Multidimensional efficacy assessment of functional, behavioral, and neuropsychologic aspects was performed. When comparing baseline with posttraining condition, patients displayed a substantial reduction in disruptive behavior, and a tendency to a general reduction of behavioral symptoms compared with controls (Revised Memory and Behavior Problems Checklist—RMBPC—symptoms frequency-total P=0.07; frequency of disruptive behavior P=0.008). This reduction was mirrored by a significant reduction of caregiver reaction to behavioral disturbances (RMBPC caregiver reaction-total P=0.035; reaction to disruptive behavior, P=0.011). At 3 months follow-up, the reduction of caregiver reaction to behavioral symptoms results was confirmed (RMBPC caregiver reaction-total P=0.014, caregiver reaction to disruptive behavior P=0.028). No other significant difference was detected. These results partially confirm findings of previous studies, showing that AD patients treated with similar techniques demonstrated an improvement in behavioral disturbances.

Guidelines for the diagnosis of dementia and Alzheimer's disease

SIN DOCUMENT*The Dementia Study Group is co-ordinated by Sandro Sorbi andincludes: Margherita Alberoni, Milan; Pasquale Alfieri, SommaVesuviana (NA); Serena Amici, Perugia; Daniele Antana, Rome;Ildebrando Appollonio, Monza (MI); Stefano Avanzi,Castelgoffredo (MN); Antonella Bartoli, Pescara; BrunoBergamasco, Turin; Laura Bracco, Florence; Amalia Bruni,Lamezia Terme (CZ); Orso Bugiani, Milan; Paolo Caffarra, Parma;Carlo Caltagirone, Rome; Antonio Carolei, L’Aquila; Anna RosaCasini, Rome; Luciana Ciannella, Benevento; Antonietta Citterio,Pavia; Antonio Daniele, Rome; Graziella D’Achille, Isernia;Giuseppe Del Curatolo, Grosseto; Grazia Dell’Agnello, Pisa;Daniele Durante, Parma; Elisabetta Farina, Milan; Patrizia Ferrero,Turin; Paolo Forleo, Florence; Guido Gainotti, Rome; PaoloGabriele, Cassino (FR); Emanuela Galante, Castelgoffredo (MN);Virgilio Gallai, Perugia; Roberto Gallassi, Bologna; MaddalenaGasparini, Milan; Bernardino Ghetti, Indianapolis (USA); GiorgioGiaccone, Milan; Floriano Girotti, Milan; Luigi Grimaldi, Milanand Caltanisetta; Serenella Grioli, Catania; Bianca MariaGuarnieri, Pescara; Stefano Grottoli, Fossombrone (PS); FrancescoIemolo, Ragusa; Stefania Latorraca, Florence; Francesco Le Pira,Catania; Gian Luigi Lenzi, Rome; Sebastiano Lorusso, Rimini;Claudio Mariani, Milan; Gabriella Marcon, Udine; VincenzoMascia, Carbonia (CA); Simonetta Mearelli, L’Aquila; MariaMorante, Senigallia (AN); Michela Morbin, Milan; MassimoMusicco, Segrate (MI); Ettore Nardelli, Verona; Paolo Nichelli,Modena; Alessandro Padovani, Brescia; Marco Paganini, Florence;Roberta Pantieri, Bologna; Pietro Parisen, Vicenza; LucillaParnetti, Perugia; Bruno Passerella, Brindisi; Carla Pettenati, Rho(MI); Silvia Piacentini, Florence; Federico Piccoli, Palermo; CarloPiccolini, Perugia; Gilberto Pizzolato, Padova; LeandroProvinciali, Ancona; Nicola Pugliese, Salerno; Francesco Redi,Arezzo; Rosa Maria Ruggieri, Palermo; Umberto Ruggiero,Naples; Marco Saetta, Siracusa; Rudolf Schoenuber, Bolzano;Maria Caterina Silveri, Rome; Sandro Sorbi, Florence; GiuseppeSorrentino, Naples; Patrizia Sucapane, L’Aquila; Andrea Stracciari,Bologna; Massimo Tabaton, Genova; Fabrizio Tagliavini, Milan;Vito Toso, Vicenza; Francesco Valluzzi, Putignano Noci (BA)S. Sorbi ( )Department of Neurological and Psychiatric SciencesUniversity of FlorenceViale Morgagni 85, I-50131 Florence, Italy

Specific impairments of selective attention in mild Alzheimer's Disease

The aim of the present study was to evaluate selective visual attention in subjects affected by Alzheimer’s Disease (AD), by means of a computerized spatial exploration test that adopts a Touch Screen (TS) interface, which has already proved able to characterize alternative strategies in performing search tasks. We assessed a group of 16 patients affected by mild to moderate AD, comparing them with 16 control subjects matched for age and education. In the experimental tasks the performance of the AD patients was worse than that of the normal elderly, both quantitatively (slower speeds) and qualitatively (poorer planning and higher number of omissions and perseverations). In the visual attention tasks there appeared to be no close connection between AD patients’ performance and increased Reaction Times (RT); this evidenced a specific role of non-elementary cognitive structures enclosed in a higher attentional domain, rather than a general decrease in the speed of basic cognitive processes. Our results are in line with specific AD literature: while psychomotor speed and lower attention levels (sensorimotor) are preferentially impaired in subcortical forms of dementia, the higher levels of selective and divided attention could be the first to deteriorate and appear more markedly disrupted in the Alzheimer type of dementia. This study was supported by the research funding “Ricerca Finalizzata 2001” from the Italian Ministry of Health. The authors wish to thank Barbara Carey for the linguistic revision