Alzheimer Disease: Padovani 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.

Frisoni GB, Padovani A, Wahlund LO. · No affiliation provided · Alzheimer Dis Assoc Disord. · Pubmed #15249846 No free full text.

This publication has no abstract.

Borroni B, Premi E, Di Luca M, Padovani A. · Department of Neurology, and Centre for Ageing Brain and Neurodegenerative Disorders, University of Brescia, Italy. · Curr Med Chem. · Pubmed #17504137 No free full text.

Abstract: Few public health problems have captured the attention of the biomedical and lay communities alike as has Alzheimer Disease (AD). Several questions remain still open in disease management, as the necessity to delineate disease process from "normal ageing". In the last few years, Mild Cognitive Impairment (MCI) has received significant attention, thus it represents the major risk factor for AD. Not all people diagnosed as having MCI, however, will develop AD, hence there is a need to reliably predict progression. To this aim, different biomarkers have been proposed with the attempt to identify MCI people who already have pre-clinical AD. Neuropsychological assessment, peripheral and CSF biomarkers as well as neuroimaging findings (both structural and functional) have reported variable accuracy values, but better results have been obtained by combined biomarker approach. In this review, we summarise the most recent findings on combined biomarkers and their usefulness in clinical practice for the early and preclinical diagnosis of AD.

Borroni B, Di Luca M, Padovani A. · Department of Medical Sciences, University of Brescia, Italy. · Eur J Pharmacol. · Pubmed #16831417 No free full text.

Abstract: A correct clinical diagnosis in the early stage of Alzheimer disease is not only of importance given the current available treatment with acetylcholine esterase inhibitors, but would be the basis for disease-modifying therapy slowing down or arresting the degenerative process. Moreover, in the last years, several efforts have been made to determine if a patient with mild cognitive impairment has incipient Alzheimer disease, i.e. will progress to Alzheimer disease with dementia, or have a benign form of mild cognitive impairment. In this review, the recent published reports regarding progress in early and preclinical Alzheimer disease diagnosis are discussed and the role of peripheral and cerebrospinal fluid biomarkers highlighted. Approaches combining panels of different biomarkers show promise for discovering profiles that are characteristic of Alzheimer disease, even in the pre-symptomatic stage. More work is needed but available novel perspectives offered by recent introduced technologies shed some lights in identifying incipient Alzheimer disease in mild cognitive impairment subjects.

Padovani A, Borroni B, Di Luca M. · Department of Neurological Sciences, University of Brescia, 25100 Brescia, Italy. · Adv Clin Chem. · Pubmed #16013669 No free full text.

This publication has no abstract.

Borroni B, Akkawi N, Martini G, Colciaghi F, Prometti P, Rozzini L, Di Luca M, Lenzi GL, Romanelli G, Caimi L, Padovani A. · Clinica Neurologica, Spedali Civili di Brescia, Università degli Studi di Brescia, Piazza Ospedale 1, Brescia 25125, Italy. · J Neurol Sci. · Pubmed #12417382 No free full text.

Abstract: Accumulating evidence from epidemiological and clinical studies suggests that vascular risk factors may be involved in Alzheimer disease (AD). Although the precise contribution of vascular disturbances to the pathogenesis of AD is still unclear, various biochemical and neuropathological data strengthen the view that cerebrovascular deficiencies such as reduced blood supply to the brain and disrupted microvascular integrity in brain parenchyma play a direct or intermediate role in the chain of events ending with a dementia syndrome. The present review focuses on platelet abnormalities and hemostatic alterations in AD. In particular, data from our group, along with current literature, are discussed with regard to the evidence of platelets amyloid precursor protein (APP) processing disturbances in early AD as well as to the recent observations of increased serum levels of thrombomodulin and sE-selectin, which are sensitive markers of endothelial dysfunction. These findings strongly indicate that platelet dysfunction and microvasculature deficiencies occur rather early during the course of AD, thus suggesting a further link between AD-related processes and vascular disorders.

Padovani A, Borroni B, Colciaghi F, Pastorino L, Archetti S, Cottini E, Caimi L, Cattabeni F, Di Luca M. · Dipartimento Scienze Mediche e Chirurgiche, Clinica Neurologica-Università degli Studi di Brescia, Piazza Ospedale 1, 25125, Brescia, Italy. · Mech Ageing Dev. · Pubmed #11589917 No free full text.

Abstract: Alzheimer Disease (AD) is characterized by the progressive deposition of beta-amyloid in the parenchyma and cerebral microvasculature. The beta-amyloid peptide derives from the metabolism of a larger precursor, Amyloid Precursor Protein (APP). This protein is present in central nervous system, but it is also expressed in peripheral tissues such as circulating cells. An alteration of the APP forms pattern in platelets has been recently reported in AD patients when compared to platelets both of control subjects or non AD patients (NADD). The accuracy of the assay to identify AD is high and decreased levels are found throughout the course of AD with a significant association with severity of symptoms. Moreover, a recent study has demonstrated that AD patients on donepezil (5 mg daily) for 4 weeks displayed two-fold increase in their APPr baseline levels up to normal range. Thus, platelet APP ratio (APPr) holds the potential to be a clinical marker, which might be of helpful and adjunctive value in the diagnosis of AD and in tracking the course of illness, also in the early stages when pharmacological treatment has the greatest potential of being effective.

Di Luca M, Colciaghi F, Pastorino L, Borroni B, Padovani A, Cattabeni F. · Institute of Pharmacological Sciences, University of Milano, via Balzaretti, 9-20133, Milan, Italy. · Eur J Pharmacol. · Pubmed #11033334 No free full text.

Abstract: Alzheimer disease is a progressive neurodegenerative disease, characterised by a progressive cognitive and memory decline. From a neuropathological point of view, Alzheimer disease is defined by the presence of characteristic lesions, i.e. mature senile plaques, neurofibrillary tangles (NFTs) and amyloid angiopathy. In particular, accumulation of the amyloid beta-peptide in the brain parenchyma and vasculature is an invariant event in the pathogenesis of both sporadic and familial Alzheimer cases. Amyloid beta-peptide originates from a larger precursor, the amyloid precursor protein (APP) ubiquitously expressed. Among the different peripheral cells expressing APP forms, platelets are particularly interesting since they show concentrations of its isoforms equivalent to those found in brain. Moreover, a number of laboratories independently described alterations in APP metabolism/concentration in platelets of Alzheimer patients when compared to control subjects matched for demographic characteristics. These observations defined the frame of our work aimed to investigate if a correlation between levels of platelet APP forms and Alzheimer disease could be detected. We have reported that patients affected by Alzheimer disease show a differential level of platelet APP forms. This observation has several implications: APP processing abnormalities, believed to be a very early change in Alzheimer disease in neuronal compartment, do occur in extraneuronal tissues, such as platelets, thus, suggesting that Alzheimer disease is a systemic disorder; further, our data strongly indicate that a differential level of platelet APP isoforms can be considered a potential peripheral marker of Alzheimer disease allowing for discrimination between Alzheimer and other types of dementia.

Rozzini L, Chilovi BV, Bertoletti E, Ghianda D, Conti M, Trabucchi M, Padovani A. · Department of Neurology, University of Brescia, Brescia, Italy. · Aging Clin Exp Res. · Pubmed #19179833 No free full text.

Abstract: BACKGROUND AND AIMS: The most successful therapeutic approaches to Alzheimer's disease (AD) have involved acetylcholinesterase inhibitors (ChEIs). In view of the different response rates to ChEIs therapy, it is important to identify the pharmacokinetic and pharmacodynamic mechanisms which may interfere with this effect. The aim of the study is to evaluate the efficacy on cognition of donepezil, a cholinesterase inhibitor, in a sample of mild to moderate AD patients with various serum albumin levels, a condition modifying drug distribution. METHODS: Ninety-eight Alzheimer patients treated with donepezil were analyzed in an outpatient clinic between January 2003 and January 2005. At study entry, participants underwent multidimensional assessment evaluating cognitive, functional and psychobehavioral domains. All concomitant illnesses and treatments were recorded. Patients were grouped in three categories (with low, medium and high albumin levels). RESULTS: The total sample of patients showed cognitive improvement from baseline of the ADAS Cog score at three months (ADAS Cog mean change -1.4+5.4; p=0.01), cognitive stabilization at nine (ADAS Cog mean change 0.03+6.7; p=ns), and not statistically significant worsening at fifteen months (ADAS Cog mean change 0.9+7.3; p=ns). The low serum albumin level group was associated with a greater response to donepezil. In fact, cognition, evaluated by the ADAS Cog mean change from baseline, improved during the first 15 months of treatment in the low serum albumin level group, but worsened in the two higher groups. CONCLUSION: Our preliminary data suggest that serum albumin level should be monitored to evaluate the clinical efficacy of ChEIs therapy.

Rozzini L, Vicini Chilovi B, Bellelli G, Bertoletti E, Trabucchi M, Padovani A. · Department of Neurology and University of Brescia, Italy. · Int J Geriatr Psychiatry. · Pubmed #15920713 No free full text.

Abstract: INTRODUCTION: There is increasing evidence that hypertension may contribute to development of dementia. Studies show that blood pressure lowering therapy might protect against cognitive deterioration and that antihypertensive treatment reduce the incidence of dementia. AIM: We hypothesize that administration of cholinesterase inhibitors (AChEis) to patients with Alzheimer's Disease (AD) receiving antihypertensive medications therapy would result in clinical benefits for a period of 40 weeks in routine clinical practice. METHODS AND MATERIALS: Patients with possible or probable AD were enrolled from 16 Alzheimer evaluation units (UVA) of Brescia and Cremona (Northern Italy). Patients treated with donepezil, rivastigmine and galantamine for 40 weeks independently of dosages were selected. Patients were evaluated at baseline (T0), 4 weeks (T1), 16 weeks (T2) and 40 weeks (T3). RESULTS: 416 patients completed the study at 40 weeks; of these 255 were 'non users' while 161 utilized antihypertensive drugs ('users'). The mean change in MMSE score from baseline to week 40 demonstrate that antihypertensive-treated patients improved by 0.7 points while patients receiving only AChEis remain stables. Analyzing separately patients (n = 183) that ameliorate (responders) on cognition at T3 ( >/= 1 point MMSE score increase) a significant differences in favor of 'users' antihypertensive drugs over 'non users' on cognition at weeks 16 and 40 has been demonstrated. In particular, at T2 the mean change of MMSE from baseline in 'users' was 3.2 +/- 2.6 vs 'non users' 2.2 +/- 2.3 ( p = 0.016) and at T3 was 3.5 +/- 2.5 vs 'non users' 2.0.2.7+/-1.6 ( p = 0.018). Antihypertensive drugs were independently associated with cognitive improvement in responder patients treated with AChEis (95% CI: 0.41-1.79; p = 0.002). CONCLUSION: Antihypertensive medications in AD patients treated with AChEis are associated with an independent improvement on cognition after 40 weeks of treatment.

Borroni B, Pettenati C, Bordonali T, Akkawi N, Di Luca M, Padovani A. · Department of Medical Sciences, Neurological Clinic, University of Brescia, P.za Spedali Civili, 1, 25100 Brescia, Italy. · Neurosci Lett. · Pubmed #12770699 No free full text.

Abstract: The clinical, genetic or biological variables which regulate long-term efficacy of cholinesterase inhibitors (ChEIs) in Alzheimer disease (AD) are still unknown and it is not possible to predict who will benefit from the treatment. In this study we showed that high cholesterol levels correlated with faster decline at 1-year follow-up in AD patients on ChEIs. These findings suggest that serum cholesterol is a modulating factor of treatment response and additional therapies aimed at reducing treatable high cholesterol levels may represent an alternative strategy to improve ChEIs efficacy and slow down disease progression over time.

Borroni B, Colciaghi F, Pastorino L, Pettenati C, Cottini E, Rozzini L, Monastero R, Lenzi GL, Cattabeni F, Di Luca M, Padovani A. · Department of Neurology, University of Brescia, Italy. · Arch Neurol. · Pubmed #11255448 links to  free full text

Abstract: BACKGROUND: Amyloid precursor protein (APP) forms with apparent molecular weights of 130, 110, and 106 kd are present in human platelets. It has been demonstrated that Alzheimer disease (AD) is specifically associated with a decreased APP forms ratio in platelets. OBJECTIVE: To investigate whether acetylcholinesterase (AChE) inhibitor treatment modifies the ratio of platelet APP forms in patients with AD. PATIENTS AND METHODS: From a large sample of patients with probable AD, 30 with mild to moderate AD were selected. Each patient underwent a clinical evaluation including the Mini-Mental State Examination (MMSE) and platelet APP forms analysis at baseline and after 30 days. During this interval, 20 of 30 patients with AD were treated with donepezil hydrochloride (5 mg/d), a piperidine phosphate-based cholinesterase inhibitor. Platelets were subjected to Western blot analysis using monoclonal antibody (22C11). The ratio between the immunoreactivity of the higher-molecular-weight APP form (130 kd) and the lower forms (106 and 110 kd) was measured. RESULTS: All patients taking donepezil completed the 30 days of treatment without adverse effects. The platelet APP forms ratio at baseline did not differ between the 2 AD groups (mean +/- SD optical density ratio: untreated AD, 0.47 +/- 0.12; treated AD, 0.38 +/- 0.18), whereas a significant difference was found at follow-up (mean +/- SD optical density ratio: untreated AD, 0.45 +/- 0.17; treated AD, 0.77 +/- 0.29; P<.001). A significant improvement in MMSE scores in treated AD patients was observed from baseline (16.9 +/- 3.8) to 30 days (18.9 +/- 4.42) (P<.009, 30 days vs baseline), but no significant correlation was found in treated AD patients between MMSE score improvement and APP forms/ratio increase (P =.09). CONCLUSIONS: Administration of AChE inhibitors increases the ratio of APP forms in platelets of patients with AD, suggesting a potential effect of AChE inhibitors on APP trafficking or processing in a peripheral cell.

Borroni B, Agosti C, Bellelli G, Padovani A. · Department of Neurology, University of Brescia, Center for Aging Brain and Dementia, Brescia, Italy. · Eur J Neurol. · Pubmed #19049564 No free full text.

Abstract: BACKGROUND AND PURPOSE: Frontotemporal dementia (FTD) is the second most common neurodegenerative dementia in the young age after Alzheimer disease. Recent improvement in diagnostic assessment suggests that it is more common than previously, although with a great heterogeneity in clinical presentation. The different clinical patterns related to age of disease onset in behavioural variant FTD (bvFTD) have been fairly studied. Aim of the study was to evaluate whether age at disease onset modulate the heterogeneity of either cognitive impairment or behavioural disturbances in patients affected by bvFTD. METHODS: One hundred and thirty-four patients with bvFTD entered the study. Age at onset and demographic characteristics were carefully recorded. Each patient underwent a wide neuropsychological and behavioural standardized assessment, as well as a brain SPECT perfusion imaging study. RESULTS: Behavioural variant FTD were subdivided into four groups according to the age at onset. The four quartile groups did not differ for demographic characteristics and family history for dementia. Global cognitive impairment as well as analysis of the different cognitive domains and behavioural patterns were comparable. CONCLUSIONS: These findings provide evidence that the clinical heterogeneity of bvFTD is not explained by age at disease onset. Further studies are needed.

Rozzini L, Vicini Chilovi B, Bertoletti E, Conti M, Delrio I, Trabucchi M, Padovani A. · Department of Neurology, Geriatric Research Group, University of Brescia, via Romanino 1, Brescia, Italy. · J Geriatr Psychiatry Neurol. · Pubmed #19017783 No free full text.

Abstract: The aim of this study was to verify the usefulness of Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog), in screening participants at risk of developing Alzheimer disease (AD) among populations with amnestic mild cognitive impairment(aMCI). 98 outpatients with aMCI were recruited. Participants were revaluated after 1 year: 44 (44.9%) were progressed to AD (progressors), while 54 (55.1%) did not convert (nonprogressors MCI). At baseline, cognitive performances were more impaired in progressors assessed by MMSE and by a neuropsychological battery. When tested with the ADAS-Cog subscale, the 2 groups of participants at baseline, progressors, and nonprogressors MCI, were significantly different regarding total score, memory, and nonmemory subitems. Considering a cutoff of 9.5 total score, adjusted for education, ADAS-Cog subscale showed a good performance (area under the curve = 0.67; sensitivity = 0.62%; specificity = 0.73%) in predicting conversion from aMCI to AD. Progressors aMCI were characterized at baseline by a greater cognitive impairment. ADAS-Cog subscale is a useful and brief cognitive assessment tool to screen aMCI participants converting to AD within 1 year.

Borroni B, Malinverno M, Gardoni F, Alberici A, Parnetti L, Premi E, Bonuccelli U, Grassi M, Perani D, Calabresi P, Di Luca M, Padovani A. · Centre for Aging Brain and Dementia, Department of Neurology, University of Brescia, Italy. · Neurology. · Pubmed #18971445 No free full text.

Abstract: OBJECTIVE: In CSF, extended (55 kDa) and truncated (33 kDa) tau forms have been previously recognized, and the tau 33 kDa/55 kDa ratio has been found significantly reduced in progressive supranuclear palsy (PSP) vs in other neurodegenerative disorders. The aim of this study was to evaluate the diagnostic value of the CSF tau form ratio as a biomarker of PSP and to correlate the structural anatomic changes as measured by means of voxel-based morphometry (VBM) to CSF tau form ratio decrease. METHODS: A total of 166 subjects were included in the study (21 PSP, 20 corticobasal degeneration syndrome, 44 frontotemporal dementia, 29 Alzheimer disease, 10 Parkinson disease, 15 dementia with Lewy bodies, and 27 individuals without any neurodegenerative disorder). Each patient underwent a standardized clinical and neuropsychological evaluation. In CSF, a semiquantitative immunoprecipitation was developed to evaluate CSF tau 33 kDa/55 kDa ratio. MRI assessment and VBM analysis was carried out. RESULTS: Tau form ratio was significantly reduced in patients with PSP (0.504 +/- 0.284) when compared to age-matched controls (0.989 +/- 0.343), and to patients with other neurodegenerative conditions (range = 0.899-1.215). The area under the curve (AUC) of the receiver operating characteristic analysis in PSP vs other subgroups ranged from 0.863 to 0.937 (PSP vs others, AUC = 0.897, p < 0.0001). VBM study showed that CSF tau form ratio decrease correlated significantly with brainstem atrophy. CONCLUSIONS: Truncated tau production, which selectively affects brainstem neuron susceptibility, can be considered a specific and reliable marker for PSP. Tau form ratio was the lowest in progressive supranuclear palsy with no overlap with any other neurodegenerative illness.

Garibotto V, Borroni B, Kalbe E, Herholz K, Salmon E, Holtoff V, Sorbi S, Cappa SF, Padovani A, Fazio F, Perani D. · Vita Salute San Raffaele University, Milan, Italy. · Neurology. · Pubmed #18936426 No free full text.

Abstract: BACKGROUND: Previous reports have shown that higher education is associated with more severe brain pathology in patients with Alzheimer disease (AD), suggesting that these individuals have a functional reserve provided by education, which masks the clinical expression of a higher degree of neurodegeneration. It is unknown if a similar reserve mechanism exists in patients with amnestic mild cognitive impairment (aMCI). The aim of this study was to assess the impact of education and occupation on brain glucose metabolism (rCMRglc) measured with FDG-PET in aMCI and in a very large sample of subjects with probable AD (pAD). METHODS: A total of 242 patients with pAD, 72 with aMCI, and 144 healthy controls participated in the study. At follow-up, 21 subjects with aMCI progressed to AD. A regression analysis was conducted (SPM2), with education and occupation as independent variables, and rCMRglc as dependent variable, adjusting for demographic data, global cognitive status, and neuropsychological scores. RESULTS: The analysis showed a significant association between higher education/occupation and lower rCMRglc in posterior temporoparietal cortex and precuneus in pAD and aMCI converters, and no correlation in aMCI nonconverters and healthy controls. This means that, when submitted to FDG-PET for diagnostic evaluation, pAD and aMCI converters with higher education/occupation had, for comparable cognitive impairment, a more severe rCMRglc reduction than the ones with lower education/occupation. CONCLUSIONS: This study suggests that education and occupation may be proxies for brain functional reserve, reducing the severity and delaying the clinical expression of Alzheimer disease (AD) pathology. The results in aMCI converters suggest that functional reserve is already at play in the predementia phase of AD.

Rozzini L, Vicini Chilovi B, Trabucchi M, Padovani A. · No affiliation provided · Arch Neurol. · Pubmed #18625880 No free full text.

This publication has no abstract.

Zulli R, Nicosia F, Borroni B, Agosti C, Prometti P, Donati P, De Vecchi M, Turini D, Romanelli G, Grassi V, Padovani A. · Institute of Internal Medicine, Department of Medical Sciences, University of Brescia, Brescia, Italy. · Clin Neurol Neurosurg. · Pubmed #18585852 No free full text.

Abstract: OBJECTIVE: To assess the prevalence and the characteristics of silent myocardial ischaemia (SMI) and ventricular arrhythmias (VA) in subjects with Alzheimer's disease (AD) and mild cognitive impairment (MCI) and their relationships with QT interval dispersion (QTD). METHODS: Thirty-three subjects with AD, 39 subjects with MCI, and 29 cognitive healthy control subjects matched for demographic characteristics, hypertensive condition, smoking habits, and laboratory parameters were enrolled. Each subject underwent clinical and cognitive examination, a structural brain imaging study, electrocardiogram (ECG), 24-h ECG recording, 24-h blood pressure monitoring, and echocardiogram. Detection and characterization of QT dispersion, SMI and VA were performed. RESULTS: The three groups were comparable regarding demographic and basal cardiovascular characteristics: notwithstanding this, SMI episodes were observed only in AD and MCI patients (19 and 14, respectively). A significantly greater prevalence of repetitive ventricular premature beats was observed in AD (mean 8.56+/-13.1) and in MCI (1.8+/-7.2) vs. control (0.7+/-1.7). The QTD, the ischaemic burden and the number of repetitive ventricular beats revealed to be significantly related. CONCLUSIONS: Increased prevalence of SMI and potentially ominous VA were found in AD and, to a lesser extent, in MCI. SMI and repetitive VA were significantly related with QTD. These findings could be related to an increased risk of sudden cardiac death in AD and MCI patients.

Alberici A, Bonato C, Calabria M, Agosti C, Zanetti O, Miniussi C, Padovani A, Rossini PM, Borroni B. · Department of Neurological Sciences, University of Brescia, Italy. · Acta Neurol Scand. · Pubmed #18397363 No free full text.

Abstract: OBJECTIVE: Frontotemporal lobar degeneration (FTLD) includes different heterogeneous conditions mainly characterized by personality changes and cognitive deficits in language and executive functions; movement disorders have also been associated with FTLD. The present study aimed to measure the primary motor cortex (M1) inhibitory and facilitatory functions in patients affected by FTLD. MATERIALS AND METHODS: The study included 17 FTLD patients, 8 age-matched healthy controls and 8 Alzheimer's disease (AD) patients. Transcranial magnetic stimulation (TMS) was used to study intracortical inhibition (ICI) and facilitation (ICF) by using a double-pulse paradigm. RESULTS: FTLD patients were comparable with controls and AD patients for ICI and ICF. Corticobasal degeneration (CBD) patients presented significant reduced inhibition at ISI3; moreover two out of seven CBD patients had only ipsilateral responses. DISCUSSION: The present study reveals a selective impairment of M1 ICI inhibitory response in CBD, which may help in distinguishing among the FTLD clinical spectrum.

Alberici A, Bocchio L, Geroldi C, Zanardini R, Bonomini C, Bugari G, Iacobello C, Caimi L, Gennarelli M, Zanetti O, Valerio A, Nisoli E, Borroni B, Padovani A. · Department of Neurology, Brescia University, P.zzale Spedali Civili 1, 25100 Brescia, Italy. · J Neurol Neurosurg Psychiatry. · Pubmed #18245138 No free full text.

Abstract: Frontotemporal lobar degeneration (FTLD) includes different heterogeneous conditions, mainly characterised by personality changes, along with cognitive deficits in language and executive functions. Movement disorders are variably represented. Behavioural disturbances constitute the core feature of FTLD, and eating disorders represent one of the most distinguishing symptoms between FTLD and Alzheimer's disease (AD). The biochemical correlates of such dysfunctions remain to be defined. The adipocyte derived hormone leptin is known to play a foundamental role in food intake and energy balance. To understand whether leptin could be involved in FTLD eating abnormalities, we measured serum leptin levels in 59 patients with FTLD compared with 25 with AD. Serum leptin levels in patients with FTLD were comparable with those in patients with AD. Nevertheless, females with FTLD showed significantly higher leptin levels compared with females with AD. No difference was found between FTDL and AD males or within the spectrum of patients with FTLD. Hyperphagic FTLD females showed higher circulating leptin levels in comparison with those without eating abnormalities; no differences were found between males with FTLD with respect to serum leptin and food intake disturbances. The present study showed a selective gender difference in leptin levels between females with FTLD and AD, which may suggest specific cognitive and behavioural networks need to be investigated.

Borroni B, Alberici A, Agosti C, Premi E, Padovani A. · Department of Neurology, University of Brescia, Italy. <> · Int J Geriatr Psychiatry. · Pubmed #18172915 No free full text.

Abstract: BACKGROUND: The role of modifiable and non-modifiable variables in Frontotemporal Dementia (FTD) as compared to Alzheimer's dDisease (AD) and to Progressive Supranuclear Palsy (PSP) or Corticobasal Degeneration Syndrome (CBDS) has not been extensively evaluated. In particular, low education levels have been reported to be a risk factor for AD, but their contribution in FTD is yet not known. OBJECTIVE: To investigate the role of education, other modifiable and non-modifiable factors in FTD as compared to AD, PSP and CBDS patients. METHODS: One hundred and seventeen FTD patients, 400 AD, 55 PSP, and 55 CBDS entered the study. Demographic and clinical characteristics were carefully recorded. Age, gender, family history for dementia and Apolipoprotein E (APOE) genotype were considered as non-modifiable factors; education and comorbidities were included as modifiable variables. Regression analyses were applied in order to identify differences among groups. RESULTS: FTD differed from AD patients in terms of younger age, positive family history and gender status. In regard to APOE genotype, no differences between FTD and AD were found, but FTD showed higher prevalence of epsilon 4 allele compared to both CBDS and PSP patients (p < 0.05). When modifiable factors were considered, FTD were higher educated than AD patients (p < 0.001). Regression analysis identified younger age, positive family history, and education levels as independently associated variables to FTD diagnosis compared to AD (F = 21.27, R(2) = 24.1, p = 0.036). CONCLUSION: Our results highlight that the contribution of education and non-modifiable factors is likely different in FTD and AD. Further work is needed to completely establish the role of this modifiable variable as a potential area of intervention for dementias.

Alberici A, Bonato C, Borroni B, Cotelli M, Mattioli F, Binetti G, Gennarelli M, Luca MD, Simonati A, Perani D, Rossini P, Padovani A. · Alzheimer Unit, IRCCS-S. Giovanni di Dio-FBF, Brescia, Italy. · Eur J Neurol. · Pubmed #17718701 No free full text.

Abstract: We describe a case of a young patient suffering from a rapidly progressive cognitive decline, associated with delusions, myoclonus and seizures and with no family history for dementia. Clinical features, along with skin biopsy findings were overlapping storage disease; the genetic analysis, however, demonstrated a de novo presenilin 1 mutation. The present report suggests the usefulness of genetic determinations in early-onset cases of dementia, even without an autosomal dominant trait of inheritance; for these cases and their relatives an extensive genetic counselling should be recommended.

Borroni B, Gardoni F, Parnetti L, Magno L, Malinverno M, Saggese E, Calabresi P, Spillantini MG, Padovani A, Di Luca M. · Department of Neurology, University of Brescia, Italy. · Neurobiol Aging. · Pubmed #17709155 No free full text.

Abstract: Cerebrospinal fluid (CSF) total Tau levels vary widely in neurodegenerative disorders, thus being not useful in their discrimination over Alzheimer disease. No CSF marker for progressive supranuclear palsy (PSP) is currently available. The aim of this study was to characterise and measure Tau forms in order to verify the differential patterns among neurodegenerative disorders. Seventy-eight patients with neurodegenerative disorders and 26 controls were included in the study. Each patient underwent a standardised clinical and neuropsychological evaluation, MRI, and CSF total-Tau and phospho-Tau dosage. In CSF and cerebral cortex, a quantitative immunoprecipitation was developed. An extended (55 kDa), and a truncated (33 kDa) forms of Tau were recognised. CSF samples were assayed, the optical density of the two Tau forms was measured, and the ratio calculated (Tau ratio, 33 kDa/55 kDa forms). Tau ratio 33 kDa/55 kDa was significantly decreased in patients with PSP (0.46+/-0.16) when compared to controls, including healthy subjects (1.16+/-0.46, P=0.002) and Alzheimer disease (1.38+/-0.68, P<0.001), and when compared to frontotemporal dementia (0.98+/-0.30, P=0.008) or corticobasal degeneration syndrome (0.98+/-0.48, P=0.02). Moreover, in PSP patients Tau form ratio was lower than in other neurodegenerative extrapyramidal disorders, such as Parkinson disease (1.16+/-0.26, P=0.002) and dementia with lewy bodies (1.44+/-0.48, P<0.001). Tau ratio 33 kDa/55 kDa did not correlate either with demographic characteristics, cognitive performances or with motor impairment severity. Truncated Tau production shows a different pattern in PSP compared to other neurodegenerative disorders, supporting the view of disease-specific pathological pathways. These findings are promising in suggesting the identification of a marker for PSP diagnosis in clinical practice.

Cotelli M, Borroni B, Manenti R, Ginex V, Calabria M, Moro A, Alberici A, Zanetti M, Zanetti O, Cappa SF, Padovani A. · IRCCS, S. Giovanni di Dio-Fatebenefratelli, Brescia, Italy. · Neuropsychologia. · Pubmed #17640688 No free full text.

Abstract: INTRODUCTION: While sentence comprehension has been reported to be defective in frontotemporal dementia (FTD), it is still unclear if this disorder reflects the presence of syntactic impairment, or may be attributed to other factors, such as executive or working memory dysfunction. In order to assess the status of syntactic knowledge in a group of patients belonging to the FTD spectrum, we investigated their ability to detect violations of Universal Grammar principles in a sentence judgement task. METHODS: The group included four semantic dementia patients (SD), nine frontal variant of FTD patients (FvFTD), 15 progressive supranuclear palsy (PSP) patients, and 11 corticobasal degeneration syndrome (CBDS) patients. Their performance was compared to a group of 10 patients with mild probable Alzheimer disease (AD) and to 10 healthy volunteers. The patients underwent a standard aphasia test and a sentence comprehension test. The experimental study included five kinds of violations: semantic coherence (SC), verb-subject agreement (VSAgr), pronominalization involving clitic movement (ClM), interrogatives (WhS) and contrastive focus constructions (CFC). RESULTS: The FTD patients performed within normal range in the aphasia test, and in the sentence comprehension test. Within the FTD subgroups, only patients with CBDS were significantly impaired in detecting three of the five kinds of violations. AD patients were also impaired in the detection of WhS and SC anomalies and in sentence comprehension. DISCUSSION: The present findings indicate that, within the FTD spectrum, an impairment of syntactic knowledge can be found only in CBDS patients, even in the absence of clinical evidence of aphasia.

Rozzini L, Vicini Chilovi B, Bertoletti E, Trabucchi M, Padovani A. · Department of Neurology, University of Brescia, Brescia, Italy. · Aging Clin Exp Res. · Pubmed #17607090 No free full text.

Abstract: BACKGROUND AND AIMS: Acetylcholinesterase inhibitor (AChEis) therapy in Alzheimer Disease (AD) has been shown to provide cognitive benefits and to slow progression of the disease. AChEis have also been demonstrated to improve behavioral symptoms, although there seem to be subtle differences in the magnitude of response. The aim of our study was to evaluate the effect of 16 weeks treatment with AChEis on depressive symptoms in a selected sample of AD patients in routine clinical practice. SUBJECTS AND METHODS: A study of 135 patients with Alzheimer's disease. All subjects were assessed at baseline (upon initiation of AChEis therapy) and re-evaluated after 16 weeks. RESULTS: At baseline, "Depressed" and "Not depressed" patients were categorized according to DSM IV criteria for depression in Alzheimer Disease. After 16 weeks of treatment with AchEis, we observed an improvement of mood in the "Depressed" patients. In this group "Mood symptoms", measured with GDS, were independently associated with GDS "Mood symptoms" at baseline, but not with improvement on cognition (mean change of MMSE), age or sex. CONCLUSIONS: In depressed AD subjects, AChEis treatment improves depressive symptoms evaluated by GDS. This improvement is independent of cognition enhancement.