Paolo Caffarra

Rey-Osterrieth complex figure: normative values in an Italian population sample

The Rey-Osterrieth complex figure test (ROCF) is a neuropsychological test extensively used in clinical practice to investigate visuospatial constructional functions, visuographic memory and some aspects of planning and executive function. The aim of the present study was to collect normative values in an Italian normal population sample (n=280) for the direct copying and delayed (10 min) reproduction of the ROCF. Multiple regression analysis revealed significant effects of age and education on performance of both copying tasks, whereas sex appeared to affect only performance on the delayed copying task. Inferential cut-offs have been determined and equivalent scores computed. The availability of equivalent scores for the ROCF will prove useful in clinical assessment since it allows the comparison of a subjects performance on the ROCF with that on other neuropsychological tests for which normative values collected with similar methods are already available for the Italian population.

Neural Basis of Endogenous and Exogenous Spatial Orienting: A Functional MRI Study

Whole-brain functional magnetic resonance imaging (MRI) was used to examine the neural substrates of internally (endogenous) and externally (exogenous) induced covert shifts of attention. Thirteen normal subjects performed three orienting conditions: endogenous (location of peripheral target predicted by a central arrow 80 of the time), exogenous (peripheral target preceded by a noninformative peripheral cue), and control (peripheral target preceded by noninformative central cue). Behavioral results indicated faster reaction times (RTs) for valid than for invalid trials for the endogenous condition but slower RTs for valid than for invalid trials for the exogenous condition (inhibition of return). The spatial extent and intensity of activation was greatest for the endogenous condition, consistent with the hypothesis that endogenous orienting is more effortful (less automatic) than exogenous orienting. Overall, we did not observe distinctly separable neural systems associated with the endogenous and exogenous orienting conditions. Both exogenous and endogenous orienting, but not the control condition, activated bilateral parietal and dorsal premotor regions, including the frontal eye fields. These results suggest a specific role for these regions in preparatory responding to peripheral stimuli. The right dorsolateral prefrontal cortex (BA 46) was activated selectively by the endogenous condition. This finding suggests that voluntary, but not reflexive, shifts of attention engage working memory systems.

Prevalence of Sleep Disturbances in Mild Cognitive Impairment and Dementing Disorders: A Multicenter Italian Clinical Cross-Sectional Study on 431 Patients

Background/Aims: Sleep disturbances are common in the elderly and in persons with cognitive decline. The aim of this study was to describe frequency and characteristics of insomnia, excessive daytime sleepiness, sleep-disordered breathing, REM behavior disorder and restless legs syndrome in a large cohort of persons with mild cognitive impairment or dementia. Methods: 431 consecutive patients were enrolled in 10 Italian neurological centers: 204 had Alzheimer’s disease, 138 mild cognitive impairment, 43 vascular dementia, 25 frontotemporal dementia and 21 Lewy body dementia or Parkinson’s disease dementia. Sleep disorders were investigated with a battery of standardized questions and questionnaires. Results: Over 60% of persons had one or more sleep disturbances almost invariably associated one to another without any evident and specific pattern of co-occurrence. Persons with Alzheimer’s disease and those with mild cognitive impairment had the same frequency of any sleep disorder. Sleep-disordered breathing was more frequent in vascular dementia. REM behavior disorder was more represented in Lewy body or Parkinson’s disease dementia. Conclusion: A careful clinical evaluation of sleep disorders should be performed routinely in the clinical setting of persons with cognitive decline. Instrumental supports should be used only in selected patients.

Modified Card Sorting Test: normative data.

The Modified Card Sorting Test (MCST), a shortened version of the Wisconsin Card Sorting Test, proposed by Nelson in 1976 is a neuropsychological test that is widely used in clinical settings for the evaluation of executive functions in patients with focal, traumatic and degenerative brain diseases. Despite its frequent use, normative data for the MCST are scant. The aim of this study was to collect normative data for the MCST on a sample including 248 healthy individuals ranging from 20 to 90 years of age and equally distributed for education level and sex (124 males and 124 females). Performance on the MCST was scored by computing the number of categories achieved by a participant, and the number of perseverative errors. Multiple regression analyses revealed a significant effect of age and education on the number of categories and perseverative errors but no effect of sex. Cut-off scores were then determined and equivalent scores computed for both the number of categories and the perseverative errors. The availability of normative data for the MCST will be very valuable in clinical settings for testing patients with focal, traumatic and degenerative brain diseases. The use of reference norms will permit a better characterisation of a patient’s impaired and spared abilities.

The hormonal pathway to cognitive impairment in older men

In older men there is a multiple hormonal dysregulation with a relative prevalence of catabolic hormones such as thyroid hormones and cortisol and a decline in anabolic hormones such as dehydroepiandrosterone sulphate, testosterone and insulin like growth factor 1 levels. Many studies suggest that this catabolic milieu is an important predictor of frailty and mortality in older persons. There is a close relationship between frailty and cognitive impairment with studies suggesting that development of frailty is consequence of cognitive impairment and others pointing out that physical frailty is a determinant of cognitive decline. Decline in cognitive function, typically memory, is a major symptom of dementia. The “preclinical phase” of cognitive impairment occurs many years before the onset of dementia. The identification of relevant modifiable factors, including the hormonal dysregulation, may lead to therapeutic strategies for preventing the cognitive dysfunction. There are several mechanisms by which anabolic hormones play a role in neuroprotection and neuromodulation. These hormones facilitate recovery after brain injury and attenuate the neuronal loss. In contrast, elevated thyroid hormones may increase oxidative stress and apoptosis, leading to neuronal damage or death. In this mini review we will address the relationship between low levels of anabolic hormones, changes in thyroid hormones and cognitive function in older men. Then, giving the contradictory data of the literature and the multi-factorial origin of dementia, we will introduce the hypothesis of multiple hormonal derangement as a better determinant of cognitive decline in older men.

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

Early structural changes in individuals at risk of familial Alzheimer’s disease: a volumetry and magnetization transfer MR imaging study

Presenilin 1 (PS1) mutation carriers provide the opportunity to asses early features of neurodegeneration in familial Alzheimer’s disease (AD). Gray matter (GM) regional volume loss and decrease of magnetization transfer ratio (MTR) consistent with microstructural changes have been reported in sporadic AD. We performed a regional volumetric and MTR analysis in carriers of PS1 mutations. Six non-demented mutated PS1 carriers (5 with memory deficits) and 14 healthy subjects were examined with high resolution T1-weighted images for volumetry and with T2* weighted images for MTR. Cortical GM volume and MTR values were derived. Compared to healthy controls, the GM volume of the left temporal and inferior parietal cortex and the MTR of the temporal cortex bilaterally were significantly decreased in PS1 gene carriers. In the latter, the temporal lobe MTR showed a trend for correlation with memory and executive function scores. Early neurodegeneration in non-demented subjects at risk for familial AD may be associated with atrophy and decreased MTR in the temporal cortex.

A normative study of a shorter version of Raven's progressive matrices 1938.

Abstract.A shorter four-set (A, B, C, D) version of Raven’s progressive matrices 1938 (PM38) has gained increasing use in neuropsychological assessment. No normative data spanning across a wide age range are, however, available. This study collected norms for the shorter version of PM38, established an inferential cut-off value and derived equivalent scores in a sample of 248 individuals from 20 to 89 years of age, evenly distributed across sex, age and education levels. Results showed significant effects of age and education but no effect of sex on performance. These normative data will complement existing norms for other tests, will increase the wealth of neuropsychological tools for which normative data are available for the Italian population, and may be useful in the early detection of individuals at risk of developing dementia.

Abnormal serotonergic control of prolactin and cortisol secretion in patients with seasonal affective disorder

The effects of the serotonergic agent d,l-fenfluramine (60 mg PO) or a placebo on serum prolactin (PRL) and cortisol levels were evaluated in seven patients (five men and two women) with seasonal affective disorders (SAD) and in eight normal controls (eight men and two women). Both groups were tested in fall/winter when patients with SAD suffered depressive symptoms and in spring/summer, when patients were euthymic. Spring/summer and fall/winter tests gave similar results. PRL and cortisol patterns were similar in all subjects after placebo, whereas both hormonal responses to d,l-fenfluramine were significantly lower in patients with SAD than in normal controls. Correlation studies between the two hormonal responses revealed that on both periods the amplitudes of PRL and cortisol increments were significantly and positively correlated in patients with SAD. These data show diminished serotonergic responsiveness in SAD regardless of the actual depressive status of the patients. They are consistent with a decrease of central serotonergic activity in SAD.

Low-dose ovine corticotropin-releasing hormone stimulation test in diabetes mellitus with or without neuropathy

The function of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated in insulin-dependent diabetics without (group I, n = 10) or with (group II, n = 10) established symptomatic neuropathy and in age- and weight-matched normal controls (n = 11). Since the corticotropin (ACTH)/cortisol response to the minimal-effective dose of corticotropin-releasing hormone ([CRH] 0.03 microgram/kg body weight) represents a useful tool for HPA axis examination, all subjects were tested with the low-dose ovine CRH stimulation test. Experiments started at 8:30 AM, when CRH was injected after two basal blood samples were withdrawn, and lasted 2 hours. Basal serum levels of ACTH were similar in the three groups. Administration of CRH induced a small but significant increase in ACTH levels in all subjects; however, the CRH-induced ACTH increase was significantly higher in normal controls than in diabetic groups I and II. Furthermore, a significantly lower ACTH response was observed in group II than in group I. In contrast, basal and CRH-induced cortisol levels were significantly higher in diabetics than in normal controls. Comparisons between diabetic groups showed that both basal and stimulated cortisol secretion was significantly higher in group II than in group I. When peak ACTH responses to CRH and basal cortisol levels were combined, a significant negative correlation was found (r = .545, P < .02). These data show that even uncomplicated diabetes mellitus is associated with adrenal hyperfunction. Such an alteration is more pronounced in the presence of neuropathy.