Alzheimer Disease: Bianchetti A

Caltagirone C, Bianchetti A, Di Luca M, Mecocci P, Padovani A, Pirfo E, Scapicchio P, Senin U, Trabucchi M, Musicco M, Anonymous00252. · Fondazione IRCCS, Santa Lucia, Università Tor Vergata, Rome, Italy. · Drugs Aging. · Pubmed #16506439 No free full text.

Abstract: A committee of experts from the Italian Association of Psychogeriatrics compiled the following report, which was then approved by a Steering Committee (comprising 20 specialists in neurology, psychiatry or geriatrics) from the Association and by two Alzheimer associations representing patients and families: the Italian Association for Alzheimer's Disease and the Italian Federation for Alzheimer's Disease. The report is based on a comprehensive review of the scientific literature on the treatment of Alzheimer's disease, discusses methodological aspects of dementia management, and details the limitations of current therapies. These guidelines are, in general, consistent with the principles of evidence-based medicine; however, for some controversial or poorly investigated issues, the guidelines integrate scientific evidence with experience and opinions from experts working in the clinical setting. In particular, the clinical experience of experts has been used to define recommendations for starting and interrupting pharmacotherapy, and to critically review evidence about the efficacy of non-pharmacological interventions. The principal pharmacotherapeutic interventions covered in the guidelines are acetylcholinesterase inhibitors (donepezil, galantamine, rivastigmine, and tacrine) and memantine. The main non-pharmacological interventions reviewed are memory training, reality orientation therapy, and combined non-pharmacological interventions. Other issues covered are opportunities for Alzheimer's disease prevention, various modalities of care, and the treatment of comorbidities.

Trabucchi M, Bianchetti A. · No affiliation provided · Recenti Prog Med. · Pubmed #11021167 No free full text.

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Bianchetti A, Ranieri P, Margiotta A, Trabucchi M. · Department of Medicine, S. Anna Hospital, Brescia, Italy. · Aging Clin Exp Res. · Pubmed #16702787 No free full text.

Abstract: BACKGROUND AND AIMS: The treatment of Alzheimer's disease (AD) is a challenge for physician, families, and patients. An individualized, multimodal treatment plan addressing the treatment of cognitive, behavioural and functional decline is essential. Aim of the paper is to describe the principal components of the treatment plan of AD patients. METHODS: A review of the recent literature was performed. RESULTS: Acetylcholinesterase inhibitors (AChEIs) play an important role in the improvement of cognitive decline in mild to moderate AD, even if the improvement is not permanent. Data obtained from the CRONOS project (involving about 500 Alzheimer Evaluation Units) replicate in the real world those obtained in controlled trials, confirming that AD patients may benefit from AChEI treatment. Treatment of behavioral and psychological symptoms of dementia (BPSD) requires education of caregivers, non pharmacological interventions, identification and treatment of medical illnesses or environmental precipitating conditions, specific pharmacological treatment. Traditional neuroleptics are widely used for BPSD treatment, but limited data support their use, and side-effects are frequent and severe. Atypical antipsychotics are effective in treating BPSD, and safer than traditional neuroleptics. However, the increased risk of cerebrovascular accident in patients taking risperidone or olanzapine limited currently their use in demented subjects. The use of antidepressant drugs, as well as behavioral approach, may improve depressive symptoms frequently accompanying AD. CONCLUSIONS: Although at present there is no cure for AD, several drug treatments and care strategies may improve or stabilize cognitive and behavioral symptoms, and improve the quality of life of patients and families.

Bianchetti A, Trabucch M. · Geriatric Research Group, Brescia, Italy. · Aging (Milano). · Pubmed #11442304 No free full text.

Abstract: Alzheimer's disease (AD) is the most common of the dementing disorders. AD begins insidiously and progresses gradually; it is characterized clinically not only by an impairment in cognition, but also by a decline in global function, a deterioration in the ability to perform activities of daily living, and the appearance of behavioral disturbances. No definitive tests for the diagnosis are available, and AD is a diagnosis of inclusion based on patient history, physical examination, neuropsychological testing, and laboratory studies. Disease progression is highly variable, and median survival after the onset of dementia ranges from 5 to 9.3 years. Early recognition of AD allows time to plan for the future, and to treat patients before marked deterioration occurs.

Bianchetti A, Rozzini R, Trabucchi M. · Geriatric Research Group, Brescia, Italy. · Curr Med Res Opin. · Pubmed #12841930 No free full text.

Abstract: Acetyl-L-carnitine (ALC) is a compound acting as an intracellular carrier of acetyl groups across inner mitochondrial membranes. It also appears to have neuroprotective properties and it has recently been shown to reduce attention deficits in patients with Alzheimer's disease (AD) after long-term treatment. We performed an open study to evaluate the effect of ALC (2 g/day orally for 3 months) in association with donepezil or rivastigmine in 23 patients with mild AD who had not responded to treatment with acetylcholinesterase inhibitors (AChE-I). Clinical effects were evaluated by assessing cognitive functions, functional status and behavioural symptoms. The response rate, which was 38% after AChE-I treatment, increased to 50% after the addition of ALC, indicating that the combination of these two drugs may be a useful therapeutic option in AD patients. These data do not permit a conclusion as to the possible mechanism of action of the association of the two treatments.

Laakso MP, Frisoni GB, Könönen M, Mikkonen M, Beltramello A, Geroldi C, Bianchetti A, Trabucchi M, Soininen H, Aronen HJ. · Department of Neurology, Kuopio University Hospital, Finland. · Biol Psychiatry. · Pubmed #10862805 No free full text.

Abstract: BACKGROUND: Magnetic resonance imaging (MRI) of hippocampal atrophy is a sensitive but not specific method to support the clinical diagnosis of early Alzheimer's disease (AD). We recently described our findings that atrophy of the entorhinal cortex (ERC) in frontotemporal dementia (FTD) is equal to that found in AD but that hippocampal atrophy in FTD is less than that found in AD. The MRI volumes of these structures provide a topographic representation of the region of interest. We hypothesized that two different dementias with distinct histopathologic and clinical features might, in addition to quantitative patterns, display topographically different patterns of atrophy. METHODS: We adopted a morphometric approach to monitor the pattern of atrophy of the hippocampus and the ERC by computing two-dimensional profiles from MRI volumes of the structures in control subjects and patients with FTD and AD. RESULTS: Compared with control subjects, atrophy of the hippocampus in patients with AD was diffuse. In patients with FTD, atrophy of the hippocampus was localized predominantly in the anterior hippocampus, suggesting a different pattern of hippocampal atrophy in FTD compared with AD. The amount and pattern of atrophy of the entorhinal cortex was virtually equal in both demented groups. CONCLUSIONS: This study provides novel data on the nature of medial temporal lobe atrophy in FTD. Morphometric MRI may be a useful technique for characterizing different patterns of atrophy in primary degenerative dementias in vivo.

Frisoni GB, Bianchetti A, Pignatti F, Gozzetti A, Trabucchi M. · No affiliation provided · Am J Psychiatry. · Pubmed #10588430 links to  free full text

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Frisoni GB, Rozzini L, Gozzetti A, Binetti G, Zanetti O, Bianchetti A, Trabucchi M, Cummings JL. · Alzheimer's Unit, IRCCS S. Giovanni di Dio, 'Fatebenefratelli', Geriatric Research Group, Brescia, Italy. · Dement Geriatr Cogn Disord. · Pubmed #10026387 No free full text.

Abstract: INTRODUCTION: Behavioral disturbances in patients with Alzheimer's disease (AD) are ill-defined conditions. We hypothesize that the many behavioral disturbances hitherto described and studied might be grouped into few syndromes with separate determinants and correlates. PATIENTS AND METHODS: 162 consecutive patients with probable AD admitted to a dementia unit were assessed by the UCLA Neuropsychiatric Inventory (NPI). RESULTS: Factor analysis was carried out on NPI subscales, leading to three syndromes: 'mood', 'psychotic' and 'frontal'. Patients with the 'psychotic' syndrome were older, had older age at dementia onset, had poorer cognition, were more often males, and had faster rate of dementia progression. Patients with the 'frontal' syndrome had higher education, longer disease duration, and slower rate of progression. DISCUSSION: Some combinations of behavioral disturbances occur more frequently together and might represent separate behavioral syndromes. Different clinical correlates of the syndromes suggest separate etiologies.

Talassi E, Cipriani G, Bianchetti A, Trabucchi M. · Department of Medicine, Istituto Clinico S. Anna, Hospital, Brescia, Italy. · Aging Ment Health. · Pubmed #17882590 No free full text.

Abstract: BACKGROUND: Assessment of personality changes in patients with dementia has received little systematic investigation, although caregivers report personality modifications in every phase of dementia. METHODS: A group of 52 patients with probable Alzheimer's disease (AD) vs. a group of fifteen control subjects were selected for these personality tests before and after the manifestation of dementia using an Italian version of Brooks and McKinaly's Personality Inventory (PI). RESULTS: After the onset of AD, a significant shift from positive to negative characteristics in PI was observed in 12 of 18 bipolar pairs of adjectives constituting the instrument and the total mean PI score decreased significantly (p < 0.001), indicating a substantial worsening of personality profile. In the control group however, evaluated before and after retirement, personality traits and total mean PI score did not show a significant change. The association of personality traits and total PI score with demographic, cognitive and functional characteristics of AD patients was calculated. CONCLUSION: Personality changes have been depicted to be influenced by severity of cognitive, functional and behavioural complaints rather than age, sex, education and disease duration. These first applications of the Italian version of PI confirmed that personality modifications make a consistent aspect of the phenomenology of AD although in the negative direction. Further studies are needed to understand the nature of personality changes in dementia and the utility of PI to investigate these changes.

Talassi E, Guerreschi M, Feriani M, Fedi V, Bianchetti A, Trabucchi M. · Istituto Clinico S. Anna Hospital, Brescia, Italy. · Arch Gerontol Geriatr. · Pubmed #17317481 No free full text.

Abstract: Data support the evidence that neuropsychological rehabilitation is effective in Alzheimer disease (AD), to strengthen the pharmacological treatment to delay the progression of dementia. At moment, a few studies have examined the efficacy of non-pharmacological treatment in MCI. This is a controlled study that assesses the effectiveness of neuropsychological rehabilitation on cognitive and behavioral symptoms and functional status in a group of community-dwelling subjects with MCI and MD. Our results demonstrate that a systematic rehabilitation, that provides a computerized cognitive program training, produces an improvement in cognitive and affective status of patients with MCI and MD, while a rehabilitation program not providing a punctual stimulation of cognitive functions, does not have significant effects.

Cipriani G, Bianchetti A, Trabucchi M. · Department of Medicine, S. Anna Hospital, Via del Franzone, 31, I-25127 Brescia, Italy. · Arch Gerontol Geriatr. · Pubmed #16451811 No free full text.

Abstract: The aim of the present study is to evaluate the outcomes of a computer-based cognitive training on patients affected by Alzheimer's disease (AD) compared with the outcomes on patients affected by mild cognitive impairment (MCI), multiple system atrophy (MSA). Ten AD patients aged 74.1+/-5.6 years, with mini-mental state examination (MMSE) score at baseline of 23.9+/-2.4, and 10 MCI patients aged 70.6+/-6.0 years, with MMSE score of 28.0+/-1.4, attending our day-hospital of neurorehabilitation were selected for the study. Three MSA patients aged 69.0+/-9.5 years, MMSE scores 26.7+/-2.3 were selected from the same setting in order to have a different control group. Each patient attended two training programs and was evaluated according to cognitive and non-cognitive functions at baseline at the end of the second training program. The AD group showed a significant MMSE score improvement (p=0.010). On the contrary, MMSE scores at baseline and at follow-up remained quite stable in the other two groups. AD patients also showed significant improvement in the areas of verbal production (p=0.036) and executive functions (p=0.050). MCI patients significantly improved in behavioral memory (p=0.017; p=0.011). No significant improvement was observed in MSA group. Our data seem to indicate that the same individualized rehabilitative intervention could have different effects according to patient's diagnosis. MCI and AD patients had significant improvements in global cognitive status and/or in specific cognitive areas. On the contrary, MSA patients did not benefit at all.

Bellelli G, Lucchi E, Minicuci N, Rozzini L, Bianchetti A, Padovani A, Trabucchi M. · Rehabilitation Unit, Ancelle della Carità Hospital, 26100 Cremona, Italy. · Aging Clin Exp Res. · Pubmed #15847123 No free full text.

Abstract: BACKGROUND AND AIMS: Recently, the Italian Ministry of Health started a national project (CRONOS project), aiming at assessing how a multi-level therapeutic approach--including 2-year free-of-charge treatment with cholinesterase inhibitors (ChE-I), pharmacologic and non-pharmacologic management of behavioral disorders, periodic multi-dimensional assessment, and informal caregivers' counseling-performs in subjects with mild-to-moderate Alzheimer's disease (AD). Five hundred and three Alzheimer Evaluation Units (AEUs) were instituted for this purpose all over Italy. In this paper we present the results of this approach in a large population of AD subjects followed for 36 weeks by 14 AEUs in Eastern Lombardy, Italy. METHODS: The project lasted for two years (September 2000-September 2002). Subjects eligible for the CRONOS project had a diagnosis of probable AD, a Mini Mental State Examination (MMSE) score at baseline ranging from 10 to 26, and onset of cognitive disorders between 40 and 90 years of age. Periodic clinical and multi-dimensional assessments, including MMSE, Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) were made at 12 and 36 weeks; ChE-I doses, psychotropic and antidepressant drugs were also re-assessed at all clinical examinations. Caregivers were instructed about dementia and drug-related problems. RESULTS: Of the 808 subjects who completed the 36-week follow-up, 441 were naïves (i.e., never previously treated with ChE-I drugs) and 367 non-naïves. At 12 weeks, both naïves (mean variation from baseline = 0.8 points) and non-naïves (mean variation from baseline = 0.5 points) improved their MMSE scores, while at 36 weeks only naïves improved (mean variation from baseline = 0.1) and non-naïves decreased (mean variation from baseline = -1.2). The IADL and ADL scores progressively and mildly declined from baseline to the 36th week (ADL, mean variation from baseline = -0.5 for naïves, -0.3 for non-naïves; IADL = -0.7 for naïves, mean variation from baseline = -0.4). However, when the MMSE, ADL and IADL variations were controlled for age, sex and education, no significant time effect was found (MMSE, Wilks' lambda p = 0.34; ADL, Wilks' lambda p = 0.25; IADL, Wilks' lambda p = 0.3, respectively). These patterns were apparently unrelated to ChE-I doses. Neuroleptic use doubled in naïves and antidepressants increased in both groups. CONCLUSIONS: This multi-level therapeutic approach seems to slow down progression in cognitive and functional performance, in both naïve and non-naïve subjects. The possibility of recurrent examinations by specialized physicians, accurate, lose management of psychotropic drugs, and informal counseling to caregivers probably aid in achieving such results in a "real world" population of AD elderly subjects living at home. Future studies are needed to assess whether a multi-level therapeutic approach including higher ChE-I dose may perform better in these subjects.

Frisoni GB, Geroldi C, Beltramello A, Bianchetti A, Binetti G, Bordiga G, DeCarli C, Laakso MP, Soininen H, Testa C, Zanetti O, Trabucchi M. · Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio-FBF, via Pilastroni 4, I-25123 Brescia, Italy. · AJNR Am J Neuroradiol. · Pubmed #11827874 links to  free full text

Abstract: BACKGROUND AND PURPOSE: Atrophy in the medial temporal lobe (MTL) structures depicted with brain imaging is one of the most accurate markers of Alzheimer disease (AD), but practical considerations have thus far limited their routine clinical use. The aim of this study was to explore the validity of a CT- and MR-based measure of MTL atrophy that would be feasible for routine clinical use. METHODS: We acquired brain CT scans in the temporal lobe plane with thin sections in 42 patients with AD and in 29 control patients without dementia. We also acquired MR images (according to a 3D magnetization-prepared rapid gradient-echo protocol) in 28 patients with AD and in 28 control subjects without dementia. The radial width of the temporal horn (rWTH) of the lateral ventricle was measured with a precision caliper at the tip of the horn on CT scans or high-quality MR images. The validity of the rWTH variable was assessed by test-retest and interrater reliability, convergent and discriminant validity compared with progressively distant brain regions, and known-group validity (accuracy of the separation of patients with AD from control subjects). Convergent and discriminant validity compared with volumetric measures was tested in the patients who underwent MR imaging. RESULTS: Intraclass correlation coefficients for inter- and intrarater reliability were between 0.94 and 0.98. On CT scans, Pearson's correlation of the rWTH with the transverse width of the temporal horn was between 0.60 and 0.79; with Jobst's minimum thickness of the MTL, between 0.63 and 0.78 (interuncal distance approximately 0.50); and with an index of frontal atrophy, between 0.35 and 0.42. On MR images, the correlation with volumetric MR measures was 0.80 in the temporal horn, 0.74 in the hippocampus, 0.68 in the temporal lobe, 0.58 in the entorhinal cortex, and 0.49 in the frontal lobe. On CT scans (cutoff value for AD, >5.3 mm; age range of subjects, 50-90 y), the rWTH measure was a sensitive marker for AD in 39 of 42 patients with AD (sensitivity, 93%) and was a specific marker in 28 of the 29 control patients (specificity, 97%). On MR images (cutoff 3.6-6.7 mm; age range of subject, 50-90 y), the rWTH was a sensitive marker for AD in 21 of 28 patients with AD (sensitivity, 75%) and was a specific marker in 26 of 28 control subjects (specificity, 93%). The accuracy of other linear CT-based measures of MTL atrophy and linear and volumetric MR-based measures was lower. With specificity set to 95%, sensitivity ranged from 57% to 74% for CT-based measures and from 52% to 74% for MR-based measures. CONCLUSION: The rWTH is an accurate marker of AD that could be used in routine clinical settings.

Geroldi C, Laakso MP, DeCarli C, Beltramello A, Bianchetti A, Soininen H, Trabucchi M, Frisoni GB. · Laboratory of Epidemiology and Neuroimaging, IRCCS San Giovanni di Dio - FBF, via Pilastroni 4, 25125 Brescia, Italy. · J Neurol Neurosurg Psychiatry. · Pubmed #10601411 links to  free full text

Abstract: Asymmetry of brain structures is common to many species and is even present in utero. Some developmental, pathological, and dementing diseases are associated with alterations in normal anatomical asymmetries. Anatomical asymmetries, however, have been only superficially studied in Alzheimer's disease. Recent evidence indicates that the allele epsilon4 of the apolipoprotein E (ApoE), a well known risk factor for Alzheimer's disease, might play a part in determining some brain morphological changes both in normal carriers and in patients with Alzheimer's disease. This study evaluated the effect of the ApoE genotype on hippocampal asymmetry in patients with Alzheimer's disease carrying 0, 1, and 2 copies of the allele. Volumetric right-left differences of the hippocampi were computed in 28 right handed patients with Alzheimer's disease (14 -/-, 9 epsilon4/-, and 5 epsilon4/4) and 30 controls without detectable cognitive deficit. In controls, the right hippocampus was larger than the left, whereas in patients with Alzheimer's disease this asymmetry was progressively reduced with increasing gene dose of the epsilon4 allele, and the asymmetry was reversed in the epsilon4/4 Alzheimer's disease group. The mean right-left volume differences were: 1.2, 0.7, 0.2, and -1.0 in controls, -/-, epsilon4/-, and epsilon4/4 patients, respectively (sex adjusted p for trend=0.017). The data indicate a dose dependent effect of the ApoE epsilon4 allele on hippocampal volume asymmetry in Alzheimer's disease.

Geroldi C, Pihlajamäki M, Laakso MP, DeCarli C, Beltramello A, Bianchetti A, Soininen H, Trabucchi M, Frisoni GB. · IRCCS San Giovanni di Dio-FBF, Brescia, Italy. · Neurology. · Pubmed #10563634 No free full text.

Abstract: OBJECTIVE: To test the hypothesis that the e4 allele of APOE is associated with a region-specific pattern of brain atrophy in AD. METHODS: Volumes of the hippocampi, entorhinal cortices, and anterior temporal and frontal lobes were measured in 28 mild to moderate AD patients and 30 controls using MRI. Within the AD group, 14 patients were noncarriers (-/-), 9 were heterozygous (e4/-), and 5 were homozygous (e4/4) for the e4 allele. Dementia severity was similar across the three AD groups. RESULTS: Smaller volumes were found with increasing dose of the e4 allele in the hippocampus, entorhinal cortex, and anterior temporal lobes in AD patients. When compared with controls, the volume loss in the right and left temporal regions ranged from -15.3 to -22.7% in the -/- AD group, from -26.2 to -36.0% in the e4/- group, and from -24.0 to -48.0% in the e4/4 group (p < 0.0005). In contrast, larger volumes were found in the frontal lobes with increasing e4 gene dose. When compared with controls, volume differences of the right frontal lobe were -11.8% in the -/- AD group, -8.5 in the e4/- group, and -1.4% in the e4/4 group (p = 0.03). CONCLUSIONS: We found smaller volumes in the temporal lobe regions but larger volumes in the frontal lobes with increasing APOE-e4 gene dose in AD patients. These data suggest a region-specific biological effect of the e4 allele in the brains of AD patients.

Brandi ML, Becherini L, Gennari L, Racchi M, Bianchetti A, Nacmias B, Sorbi S, Mecocci P, Senin U, Govoni S. · Department of Clinical Physiopathology, University of Florence, Florence, Italy. · Biochem Biophys Res Commun. · Pubmed #10558867 No free full text.

Abstract: Alzheimer's disease (AD) is a multifactorial disorder determined by the interaction of genetic, metabolic, and environmental factors. In the common late-onset familial and sporadic forms of AD apolipoprotein E type 4 allele (APOE-epsilon4) is now widely accepted as a major risk factor. The association of estrogen treatment with a reduction in the risk of AD together with the modulation by estrogen of the secretory metabolism of the amyloid precursor protein offers new possibilities for identification of other AD susceptibility genes, as those encoding for the estrogen receptors (ERs). A total of 193 patients with sporadic late-onset AD, meeting the NINCDS-ADRDA criteria, and a total of 202 control subjects, age and education matched, were included in this study. PvuII and XbaI ERalpha and HhaI APOE gene polymorphisms were evaluated in genomic DNA by Polymerase Chain Reaction (PCR). The frequency of the various ERalpha genotypes by the combination of P, p and X, x was calculated for controls and AD patients stratified based on ApoE typing. When the two ERalpha gene polymorphisms were analyzed in combination, 7 genotypes were recognized, with a significantly increased prevalence of PPXX genotype in AD patients compared to controls (P = 0.0001). Risk of AD increased by a factor of 7.6 (CI [1.10-62.3]) in homozygous APOE-epsilon4 individuals with PPXX ERalpha genotype. These results are consistent with a segregation of PPXX ERalpha genotype with a higher risk of developing late-onset sporadic AD in the Italian population. The ERalpha gene appears to interact with the APOE-epsilon4 genotype in determining AD susceptibility.

Dello Buono M, Busato R, Mazzetto M, Paccagnella B, Aleotti F, Zanetti O, Bianchetti A, Trabucchi M, De Leo D. · Unit for Epidemiology and Community Medicine, University of Padua, Italy. · Int J Geriatr Psychiatry. · Pubmed #10556862 No free full text.

Abstract: OBJECTIVE: This study measures and compares use of and satisfaction with medical and social services in addition to subjectively perceived needs of family supporters of patients with probable or possible Alzheimer's disease (AD) and family supporters of non-demented elderly people. Differences in judgement of services within the subpopulation of families of AD patients are also assessed by gender and burden level.METHODS: The main family supporters of 60 community-dwelling elderly (aged over 65) with Alzheimer's disease and of 60 age- and sex-matched controls were tested with a detailed questionnaire on use and satisfaction with services, any unmet needs and kinds of intervention perceived to be helpful.RESULTS: Supporters of elderly people with AD were significantly more involved in providing care than supporters of non-demented people. Judgement on the health, social relations and financial status of their families was significantly worse in AD supporters than in supporters of non-demented elderly people. Although the former made more use of available health and social services than the control population, they did appear to make little use of such services, not only because of lack of information but also for logistic reasons or because they would prefer a service with more specifically trained operators or more tailored intervention. AD family supporters would like to receive more information and support from their general practitioner, which confirms the importance of this figure in management of this pathology. They were less satisfied with the care provided than the control population, particularly those with a moderate-high burden. Irrespective of burden level, they also expressed a need for financial and psychological support and adequate intervention schemes, especially within the home. These should be provided by specially trained personnel and be tailored to specifically manage the individual patient's problems, especially in relation to behavioural disorders. This would help alleviate caregiver burden and allow patients to continue to be managed at home.

Gasparini L, Benussi L, Bianchetti A, Binetti G, Curti D, Govoni S, Moraschi S, Racchi M, Trabucchi M. · Neurobiology Lab, Alzheimer's Disease Unit IRCCS Centro San Giovanni di Dio-Fatebenefratelli, Brescia, Italy. · Neurosci Lett. · Pubmed #10213169 No free full text.

Abstract: The present study investigates the influence of aglycemia and sodium azide (a Cytochrome c Oxidase inhibitor) on sAPP secretion from skin fibroblasts derived from sporadic AD patients and control subjects. Aglycemia reduced sAPP release in the medium of both AD and control fibroblasts to a similar extent after 2 h incubation. Treatment for 2 h with increasing azide concentrations (1 microM-100 mM) under glucose deprivation did not significantly affect sAPP secretion from control fibroblasts, but was able to significantly inhibit sAPP secretion from AD fibroblasts (maximal inhibition 51%). The failure of antioxidants like glutathione (GSH) or N-acetylcysteine (NAC) to antagonize the azide effect on AD fibroblasts and lipoperoxidation data seemed to rule out the possibility that oxidative stress could mediate the sodium azide effect on sAPP release from AD fibroblasts.

Zanetti O, Vallotti B, Frisoni GB, Geroldi C, Bianchetti A, Pasqualetti P, Trabucchi M. · Alzheimer Disease Unit IRCCS, S. Giovanni di Dio, S. Cuore Fatebenefratelli Hospital, Brescia, Italy. · J Gerontol B Psychol Sci Soc Sci. · Pubmed #10097772 No free full text.

Abstract: Lack of insight or impaired awareness of deficits in patients with dementia is a relatively neglected area of study. The aim of this study was to evaluate insight in a group of demented patients with two assessment scales and to assess their relationship with the cognitive level of disease severity. Sixty-nine consecutive patients affected by Alzheimer's disease (n = 37) and vascular dementia (n = 32) with a wide range of cognitive impairment (MMSE = 17.0 +/- 6.4) were recruited. Insight was evaluated with the Guidelines for the Rating of Awareness Deficits (GRAD)--specifically targeted to memory deficits--and the Clinical Insight Rating scale (CIR), evaluating a broader spectrum of insight (reason for the visit, cognitive deficits, functional deficits, and perception of the progression of the disease). In the whole sample, GRAD and CIR were significantly associated with MMSE (Spearman's coefficient = .51, p < .001; and r = -.55, p < .001) and with Clinical Dementia Rating scale (-.57, p < .001; and r = .57, p < .001) respectively. The shape of the relationship of MMSE with CIR and GRAD scales was assessed with spline smoothers suggesting that the relationship follows a trilinear pattern and is similar for both scales. Insight was uniformly high for MMSE scores > or = 24, showed a linear decrease between MMSE scores of 23 and 13, and was uniformly low for MMSE scores < or = 12. The trilinear model of the association between insight and cognitive status reflects more closely the observable decline of insight and can provide estimates of when the decline of insight begins and ends.

Frisoni GB, Laakso MP, Beltramello A, Geroldi C, Bianchetti A, Soininen H, Trabucchi M. · IRCCS San Giovanni di Dio-FBF, Brescia, Italy. · Neurology. · Pubmed #9921854 No free full text.

Abstract: OBJECTIVE: To describe atrophic changes of the hippocampus and entorhinal cortex in frontotemporal dementia (FTD) and compare them with those of AD. BACKGROUND: The medial temporal lobe shows atrophic changes early in the course of AD, but whether these changes are specific to AD or occur in other degenerative dementias, and to what extent, is unclear. METHODS: The authors measured the volumes of the left and right hippocampus and entorhinal cortex from MR images (1.5 T, 2-mm-thick slices) in 12 patients with FTD, 30 with AD, and 30 elderly control subjects. RESULTS: In FTD patients, the left and right hippocampus (16% and 21% tissue loss) and the entorhinal cortex (28% and 27% loss) were more atrophic than the control subjects. Atrophy of the hippocampus in FTD was less severe than in AD, but atrophy of the entorhinal cortex was equally severe. Greater hippocampal and entorhinal cortex atrophy was present in the most severe patients in both groups (as high as a 49% tissue loss). The sensitivity of the hippocampus and the entorhinal cortex to discriminate FTD patients from control subjects was low (49% and 52%, respectively; specificity set at 90%), whereas hippocampal volumes could better differentiate AD patients from control subjects (80% sensitivity). CONCLUSIONS: At variance with AD, detectable in vivo atrophy of the hippocampus might not be an early event in FTD. Differential patterns of atrophy might help in the diagnostic process of the degenerative dementias.

Bianchetti A, Trabucchi M, Cipriani G. · No affiliation provided · Int J Geriatr Psychiatry. · Pubmed #12833312 No free full text.

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Bianchetti A, Padovani A, Trabucchi M. · No affiliation provided · Int J Geriatr Psychiatry. · Pubmed #12497562 No free full text.

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Bianchetti A, Castelletti F, Trabucchi M. · No affiliation provided · Br J Psychiatry. · Pubmed #12456528 links to  free full text

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Bianchetti A, Trabucchi M. · No affiliation provided · J Am Geriatr Soc. · Pubmed #10404943 No free full text.

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Frisoni GB, Bianchetti A, Trabucchi M, Beltramello A. · No affiliation provided · AJNR Am J Neuroradiol. · Pubmed #10369375 links to  free full text

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