Alzheimer Disease: Trabucchi M

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.

This publication has no abstract.

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.

Trabucchi M. · Alzheimer's Unit, S. Cuore FBF Hospital, Brescia, Italy. · J Geriatr Psychiatry Neurol. · Pubmed #10447152 No free full text.

Abstract: The rapid growth of the world's Alzheimer's disease (AD) population has resulted in a tremendous financial burden on society, a situation exacerbated by the fact that the funding of health and social services faces increasing restrictions in the coming years. As a consequence, several cost-of-illness studies, aimed at assessing the total costs associated with the care of an AD patient or with individual components thereof, have been conducted, with a view to identifying areas in which costs might be reduced. For example, the Costs of Dementia (CoDem) study, described here, aims to give a profile of the total economic costs of AD in Italy. While this study found the number of Instrumental Activities of Daily Living lost to be the principal predictor of the weekly costs for home care, other studies have reported a correlation between total cost and Mini-Mental State Examination (MMSE) score. The basis for a correlation between cost and disease severity is discussed. Pharmacoeconomics aims to assess the cost effectiveness of interventions that may form part of an overall management strategy in AD. As institutionalization is the largest cost element in the care of any AD patient, efforts at cost containment have focused on maintaining patients at home for as long as possible. The results of studies on a number of interventions, namely, screening, reality orientation therapy, special care units, family interventions, and drug treatment, are discussed, although the costs and, indeed, the long-term benefits associated with many of these remain unknown. Although information concerning costs is essential in health resource allocation, it is also vital that meaningful ways in which to assess quality-of-life issues be developed as the basis for genuine cost-benefit judgments.

Solerte SB, Fioravanti M, Racchi M, Trabucchi M, Zanetti O, Govoni S. · Department of Internal Medicine, University of Pavia, Italy. · Maturitas. · Pubmed #10227001 No free full text.

Abstract: The positive efficacy of estrogen replacement therapy (ERT) in the treatment of neurodegenerative disorders such as Alzheimer's disease (AD) is a matter of intense debate among clinicians and neuroscientists. The experimental and preliminary clinical evidence supporting the use of ERT are based on epidemiological data and on the study of the effect of estrogens on several aspects of brain homeostasis, including the modulation of neurotransmitters and vascular changes. In spite of numerous data available the mechanisms underlying the putative estrogen effects in neurodegenerative diseases are largely unknown. The aim of this paper is to discuss and elaborate on some of the hypotheses and controversial findings currently present in this field.

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.

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.

Geroldi C, Akkawi NM, Galluzzi S, Ubezio M, Binetti G, Zanetti O, 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 #10896691 links to  free full text

Abstract: OBJECTIVE: To test the hypothesis that delusions are associated with asymmetric involvement of the temporal lobe regions in Alzheimer's disease. METHODS: Temporal lobe atrophy was assessed with a linear measure of width of the temporal horn (WTH) taken from CT films. Temporal asymmetry was computed as the right/left (R/L) ratio of the WTH in 22 non-delusional and 19 delusional patients with Alzheimer's disease. Delusional patients had paranoid delusions (of theft, jealousy, persecution). None of the patients had misidentifications or other delusions of non-paranoid content. RESULTS: The R/L ratio indicated symmetric temporal horn size in the non-delusional (mean 1. 05 (SD 0.20), and right greater than left temporal horn in the delusional patients (mean 1.30, (SD 0.46); t=2.27, df=39, p=0.03). When patients were stratified into three groups according to the R/L ratio, 47% of the delusional (9/19) and 14% of the non-delusional patients (3/21; chi(2)=5.6, df=1, p=0.02) showed right markedly greater than left WTH. CONCLUSIONS: Predominantly right involvement of the medial temporal lobe might be a determinant of paranoid delusions in the mild stages of Alzheimer's disease.

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

This publication has no abstract.

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.

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.

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.

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.

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.

Rozzini L, Chilovi BV, Conti M, Bertoletti E, Delrio I, Trabucchi M, Padovani A. · Department of Neurology, University of Brescia, Italy. · Int J Geriatr Psychiatry. · Pubmed #17562522 No free full text.

Abstract: BACKGROUND: Mild Cognitive Impairment defines a transitional stage between normal ageing and dementia, and reflects the clinical situation where a person has memory complaints and objective evidence of cognitive impairment but no evidence of dementia. To plan the care of patients with MCI, it is important to predict as accurately as possible potential risk factors modulating the conversion to AD. AIM: To investigate the risk factors associated of conversion to dementia of Alzheimer type (AD) for subjects with amnestic Mild Cognitive Impairment (aMCI). METHODS AND MATERIALS: One hundred nineteen subjects consecutively recruited who met the operational criteria for aMCI (with or without deficits in other cognitive domains). They underwent multidimensional assessment and a neuropsychological battery at baseline and at follow-up, after 1 year. Diagnosis for dementia was based on a deficit in two or more cognitive domains severe enough to affect the participant functional abilities. Subjects converted to AD over time were classified as Demented; subjects that remained unchanged, or became cognitively normal during follow-up, were defined as Stable. RESULTS: Demented MCI (N = 40; 33.6%) were older (mean age 73.5 +/- 8.5 vs. 69.2 +/- 7.0; p = 0.006) when compared to Stable (N = 79; 66.4) and their global cognitive performances, at baseline, were more compromised when assessed by ADAS-Cog (mean score 10.7 +/- 3.9 vs 6.7 +/- 3.4; p = .000) and by MMSE (mean score 26.1 +/- 1.9 vs. 27.3 +/- 1.8; p = 0.002). Demented were similarly compromised in basic activities of daily living (BADL mean 0.2 +/- 0.4 vs 0.1 +/- 0.3 functions lost; p = NS) but more compromised on instrumental daily functions (IADL mean 0.7 +/- 0.8 vs. 0.1 +/- 0.5 functions lost; p = 0.001). The presence of white matter lesions (WML) on CT or MRI was more pronounced in Demented group (p = 0.02). After 1 year; Demented worsened on phonemic verbal fluency (PFL) (p = 0.009), Raven's coloured matrices (p = 0.003), Trail Making test A and B (p = 0.008 and p = 0.007 respectively) and in Instrumental Activities of Daily Living (IADL) (p =0 .000) respect to Stable. Logistic regression analysis revealed that ADAS-Cog basal score, Trail Making B, IADL but not memory deterioration were significantly associated to the conversion to AD. CONCLUSIONS: In subjects with aMCI poor global cognitive performance at baseline, the worsening on executive functions and on functional status but not the worsening on memory functions are independently associated with the conversion to dementia of Alzheimer type at 1 year, follow-up.

Rozzini L, Chilovi BV, Bertoletti E, Conti M, Delrio I, Trabucchi M, Padovani A. · Department of Neurology, University of Brescia, Italy. · Am J Alzheimers Dis Other Demen. · Pubmed #17534001 No free full text.

Abstract: Cholinesterase inhibitors (ChEIs) are effective in improving cognition and behavior in patients affected by Alzheimer's disease (AD) as well as by Lewy bodies dementia (DLB). The authors compared the effect of rivastigmine in the treatment of cognitive impairment and behavioral and psychological symptoms of dementia (BPSD) in 30 AD and in 30 DLB patients. At baseline, DLB compared to AD patients showed a greater number of extrapyramidal symptoms (P < .005) and were similar regarding cognitive symptoms and BPSD. After treatment, both groups showed a comparable cognitive and psycho-behavioral improvement. A significant difference between AD and DLB patients was found for hallucinations (P < .002). Rivastigmine produces comparable cognitive benefits in patients with DLB and AD and also a significant improvement of behavioral disorders. These findings support the view that ChEIs should be considered a first-line treatment of the cognitive and psycho-behavioral symptoms of both AD and DLB.

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.

Lucchi E, Minicuci N, Magnifico F, Mondini S, Calza A, Avanzi S, Villani D, Bellelli G, Trabucchi M. · Alzheimer's Evaluation Unit, Ancelle della Caritá Hospital, I-26100 Cremona, Italy. · Arch Gerontol Geriatr Suppl. · Pubmed #15207422 No free full text.

Abstract: The improvement in cognitive performances due to cholinesterase inhibitors (ChEls) is not homogeneous among Alzheimer's disease (AD) subjects. Aim of this study is to evaluate whether a specific pattern of change in mini mental state examination (MMSE) could be observed in AD subjects after 9-month treatment with ChEls. From September 2000 to September 2002, 99 subjects enrolled in the CRONOS project. They have never been previously treated with ChEls. All of them completed both the 3- and the 9-month follow-up. The multidimensional assessment included MMSE, activity of daily living (ADL), instrumental activity of daily living (IADL), somatic health status, according to design of the CRONOSproject. The MMSE was analyzed both as a total score and disaggregated in 11 items. All subjects were divided in 2 groups according to the degree of change in MMSE total score from baseline to the 9th month. Subjects with a change </= -1 were defined as non-responders(NR), whereas those with a change >0 as responders (R). At start, no statistically significant differences were found between the 2 groups. MMSE score was significantly higher in the R group both at 3 (p < 0.0001) and 9 months (p < 0.0001), while functional status (ADL and IADL) was significantly lower in NR group at 9 months (p = 0.025; p =0.018, respectively). In MMSE qualitative analysis of 3-month, NR significantly worsened in temporal (p </= 0.05) and spatial orientation (p </= 0.001), and in delayed recall items (p </= 0.0005) in comparison to their counterpart. At 9-month the differences between the 2 groups were observed also for registration (p < 0.001), attention (p </= 0.0005), obeying oral commands (p < 0.0005), reading and obeying commands (p </= 0.0005), writing a sentence (p </= 0.0005) and copying a design (p </= 0.05). In a multivariate regression model, after adjustment for demographic (age, education, gender) and clinical factors (duration of disease), only the change at 3 months in 5 MMSE items (temporal and spatial orientation,delayed recall, obeying an oral command and reading and obeying command) is associated with global cognitive change observed at 9 months. Data suggest that the change in cognitive performances of AD subjects treated with ChEls involves few and specific MMSE items at 3-month, while it tend to generalize to almost all the others at 9-month treatment.

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.

Padovani A, Borroni B, Colciaghi F, Pettenati C, Cottini E, Agosti C, Lenzi GL, Caltagirone C, Trabucchi M, Cattabeni F, Di Luca M. · Department of Neurology, University of Brescia, Piazza Ospedale 1, 25125, Brescia, Italy. · Arch Neurol. · Pubmed #11790233 links to  free full text

Abstract: CONTEXT: Patients affected by sporadic Alzheimer disease (AD) show a significant alteration of amyloid precursor protein (APP) forms in platelets when compared with patients with dementia but without AD and age-matched controls. OBJECTIVE: To evaluate the ratio of platelet APP forms (APPr) in early-stage AD and mild cognitive impairment (MCI) and its potential as a biomarker for the early identification of AD. SETTING: Community population-based sample of patients admitted to 4 AD centers for investigation of cognitive disturbances. DESIGN AND METHODS: Thirty-five patients with mild AD (mAD), 21 patients with very mild AD (vmAD), 30 subjects with MCI, and 25 age-matched controls were included. The APPr was evaluated by Western blot analysis in platelet homogenate. RESULTS: Compared with controls (mean +/- SD, 0.93 +/- 0.3), the mean APPr was decreased in patients with mAD (0.44 +/- 0.24; P<.001) and patients with vmAD (0.49 +/- 0.3; P<.001). Regarding the MCI group, a significant decrease in APPr was found compared with controls (0.62 +/- 0.33; P<.001). Fixing a cutoff score of 0.6, sensitivity was 88.6% (31/35) for patients with mAD and 85.7% (18/21) for patients with vmAD, whereas specificity was 88% (22/25) for controls. Among patients with MCI, 18 (60%) of 30 individuals displayed APPr values below the cutoff. CONCLUSIONS: Alteration of platelet APP forms is an early event in AD, and the measurement of APPr may be useful for the identification of preclinical AD in patients with MCI.

Padovani A, Pastorino L, Borroni B, Colciaghi F, Rozzini L, Monastero R, Perez J, Pettenati C, Mussi M, Parrinello G, Cottini E, Lenzi GL, Trabucchi M, Cattabeni F, Di Luca M. · Dipt. Scienze Mediche e Chirurgiche, Unità di Neurologia, Università degli Studi di Brescia, Italy. · Neurology. · Pubmed #11756604 No free full text.

Abstract: BACKGROUND: An altered pattern of amyloid precursor protein (APP) forms consisting in a reduced ratio between the upper (130 kDa) and the lower (106 to 110 kDa) immunoreactivity bands has been described in platelets of patients with AD. OBJECTIVE: To evaluate the sensitivity and the specificity of platelet APP forms' ratio (APPr) as a marker for AD. METHODS: Eighty-five patients with probable AD and 95 control subjects (CON), including healthy individuals and neurologic patients, entered the study. Platelet APPr was evaluated by means of Western Blot analysis and immunostaining in the whole platelet homogenate, and calculated by the ratio between the optical density (OD) of the upper (130 kDa) and the lower (106 to 110 kDa) APP immunoreactive bands. RESULTS: Mean APPr levels were decreased in AD patients (mean OD +/- SD = 0.35 +/- 0.18) compared with the CON group (mean OD +/- SD = 0.92 +/- 0.38) (DF 1, 178, p < 0.0001). Accuracy levels measured by Receiver Operating Curve analysis showed that a cut-off level of 0.57 resulted in a sensitivity of 88.2% and a specificity of 89.4%, with an area under the curve of 0.945. APPr levels were significantly associated with disease severity (mild AD versus moderate AD: p < 0.0001; moderate AD versus severe AD: p < 0.05). CONCLUSION: Platelet APPr allowed to differentiate AD from normal aging and other dementing disorders with high sensitivity and specificity. These findings suggest that platelet APPr may be of help as an adjunctive diagnostic tool in clinical practice.