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Purpose: To assess the impact of long-term use of different drugs commonly prescribed in Alzheimer's disease (AD) on its clinical course and to identify clinical and therapeutic factors associated with a delay in AD progression. Methods: We retrospectively enrolled 50 patients visited at the Neurology Unit, Careggi University Hospital (Florence), followed for at least 24 months. AD diagnosis was made according to clinical diagnostic criteria for probable/possible AD dementia, always supported at least by one biomarker. Clinical features, MMSE scores evaluated at diagnosis and every 6 months, and AD drugs used for at least 6 months, were recorded. Cox regression analysis was performed to estimate the hazard ratio (HR) for AD progression, assuming as the "final event," the progression to a more severe disease stage, defined as the achievement of an MMSE score less than 10. Results: At baseline, the median MMSE score was 22. During follow-up (median of 41 months), 56% of patients progressed to a more severe disease stage. The use of memantine, either alone (HR 0.24; 95% CI 0.09–0.60) or combined with acetylcholinesterase inhibitors (HR 0.35; 95% CI 0.14–0.88) and a higher MMSE score at baseline (HR 0.82; 95% CI 0.70–0.96) were associated with a significantly lower risk of AD progression. Conclusion: Nowadays, effective disease-modifying therapy for AD is missing. Nevertheless, when the diagnosis is established, our results support the advantage of long-term use of available pharmacological treatments, especially in combination, in delaying AD progression to its more severe disease stage. [ABSTRACT FROM AUTHOR]

Presenilin1 (PSEN1) gene is the most common known genetic cause of early-onset familial Alzheimer's disease. We describe an Italian family with the known p.Ala260Gly mutation in PSEN1 gene. The presence of an asymptomatic 64-year-old male carrying the mutation provides evidence of a possible incomplete penetrance leading to a wider range of age at onset. In order to evaluate whether or not epigenetic modifications could contribute to the phenotypic heterogeneity, we assessed global DNA methylation levels which resulted significantly higher in the three females than in their presymptomatic brother. The study suggests that DNA methylation can contribute to slowing down or possibly protecting from the manifestation of symptoms even in monogenic diseases, emphasizing the great complexity of familial Alzheimer's disease. [ABSTRACT FROM AUTHOR]

Objective: To investigate eating habits and adherence to Mediterranean Diet (MD) in relation to the risk of depression in a cohort of nonagenarians enrolled within the Mugello Study, an epidemiological study aimed at investigating both clinically relevant geriatric items and various health issues, including those related to nutritional status.Design: Cross-sectional study.Setting: Homes and nursing homes in the Mugello area, Florence, Italy.Participants: Subjects aged 90-99 years [N=388 (271F; 117M) mean age: 92.7±3.1].Measurements: All subjects were evaluated through questionnaires and instrumental examinations. Adherence to MD was assessed through the Mediterranean Diet Score. A shorter version of the Geriatric Depression Scale (GDS) was used to detect the possible presence of depressive symptoms. In addition, cognitive and functional status was assessed using the Mini-Mental State Examination, the Clock Drawing Test, as well as the Basic and Instrumental Activities of Daily Living test.Results: Depressed subjects (DS) (GDS score≥5, 43.8%) were older, females and widows, than non-depressed subjects (NDS). DS reported a slightly but not statistically significant lower MD score than NDS (33.9±3.9 vs. 34.6±3.3, p=0.149). Subjects who reported to consume a greater amount of olive oil and fruit were associated with a lower risk of depression (OR=0.35, 95%CI=0.20-0.59, p<0.001 and OR=0.46, 95%CI=0.26-0.84, p=0.011, respectively) after adjustment for many possible confounders. Similar results were obtained for women, while no statistically significant differences emerged for men.Conclusion: Our results support the hypothesis that a diet rich in olive oil and fruit, characteristics of MD, may protect against the development of depressive symptoms in older age. [ABSTRACT FROM AUTHOR]

According to the reserve hypothesis, a high educational/occupational attainment can modulate Alzheimer's disease (AD) clinical expression. The impact of the Apolipoprotein E (ApoE) ε4 allele on the reserve mechanism in AD has not been assessed. Aim of this European multicenter study was to evaluate the metabolic correlates of reserve and ApoE genotype in early probable AD. 51 AD subjects, 27 ε4 carriers, and 24 noncarriers, underwent FDG-PET brain imaging. We used the general linear model as implemented in SPM2 to test for the linear correlation of a reserve index, accounting for both educational and occupational level, with brain glucose metabolism, controlling for demographic variables (age and gender) and for cognitive performance. We found an inverse correlation between a reserve index, accounting for educational/occupational level, and metabolism in the posterior cingulate cortex and precuneus in both ε4 carriers and noncarriers, and no significant difference between the groups. We show that education and occupation act as proxies for reserve in ε4 carriers, compensating for an unfavorable genetic background; we also show that the degree of compensation does not differ significantly by ApoE ε4 status. [ABSTRACT FROM AUTHOR]

In the prospect of improved disease management and future clinical trials in Frontotemporal Dementia, it is desirable to share common diagnostic procedures. To this aim, the Italian FTD Network, under the aegis of the Italian Neurological Society for Dementia, has been established. Currently, 85 Italian Centers involved in dementia care are part of the network. Each Center completed a questionnaire on the local clinical procedures, focused on (1) clinical assessment, (2) use of neuroimaging and genetics; (3) support for patients and caregivers; (4) an opinion about the prevalence of FTD. The analyses of the results documented a comprehensive clinical and instrumental approach to FTD patients and their caregivers in Italy, with about 1,000 newly diagnosed cases per year and 2,500 patients currently followed by the participating Centers. In analogy to other European FTD consortia, future aims will be devoted to collect data on epidemiology of FTD and its subtypes and to provide harmonization of procedures among Centers. [ABSTRACT FROM AUTHOR]

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

This study was designed to examine the correlations between resting-state brain glucose metabolism (CMRglc), as measured with Positron Emission Tomography and performance on executive function tasks in Alzheimer's disease (AD), while taking into account the severity of cognitive deterioration. We addressed this issue in 50 AD patients, classified as very mild (n = 22) and mild (n = 28) AD on the basis of an extensive neuropsychological battery. Thirteen healthy subjects were selected as controls for the neuropsychological measures. Statistical Parametric Mapping (SPM) was used to examine voxel-wise correlations between CMRglc and scores on selected cognitive tests of executive functions: the Stroop Test, the Trail Making Test, the Dual Task and the Phonemic Fluency, while correcting for age and global CMRglc. All analyses were done separately for the two AD subgroups. The very mild AD patients showed significant associations between Stroop and Trail Making Test scores and prefrontal regions metabolism, whereas the mild AD patients exhibited more widely distributed cognitive–metabolic correlations extending to the posterior brain regions. These data suggest that a large cortical network is implicated in executive dysfunction in AD, and that the pattern of cognitive–metabolic correlations varies according to disease severity. [ABSTRACT FROM AUTHOR]

The objective of this study was to verify the adherence of Italian family physicians and neurologists to the Guidelines on Diagnosis of Dementia of the Italian Society of Neurology. A multicentre survey was carried out, in 72 neurological centres. The centres included at least 15 consecutive subjects suspected of having a dementia. The adherence of family physicians to the guidelines was poor. Neurologists performed a complete neuropsychological evaluation in a minority of the cases. Patients who had a decrease of Mini Mental Status Examination scores after six months higher than or equal to 4 were more represented among those patients for whom one or more recommendations were not respected. In Italy the adherence to the Guidelines on Diagnosis of Dementia and AlzheimerValidation studys Disease of the Italian Society of Neurology is very poor for family physicians (GPs) and satisfactory, albeit improvable, on the part of neurologists. Respect for the guidelines might improve the outcome of patients with dementia. [ABSTRACT FROM AUTHOR]

A common arginine to proline polymorphism is harboured at codon 72 of the human p53 gene. In this investigation, we found that fibroblasts and lymphocytes isolated from arginine allele homozygote centenarians and sexagenarians (Arg+) undergo an oxidative-stress-induced apoptosis at a higher extent than cells obtained from proline allele carriers (Pro+). At variance, the difference in apoptosis susceptibility between Arg+ and Pro+ is not significant when cells from 30-year-old people are studied. Further, we found that Arg+ and Pro+ cells from centenarians differ in the constitutive levels of p53 protein and p53/MDM2 complex, as well as in the levels of oxidative stress-induced p53/Bcl-xL complex and mitochondria-localised p53. Consistently, all these differences are less evident in cells from 30-year-old people. Finally, we investigated the in vivo functional relevance of the p53 codon 72 genotype in a group of old patients (66-99 years of age) affected by acute myocardial ischaemia, a clinical condition in which in vivo cell death occurs. We found that Arg+ patients show increased levels of Troponin I and CK-MB, two serum markers that correlate with the extent of the ischaemic damage in comparison to Pro+ patients. In conclusion, these data suggest that p53 codon 72 polymorphism contributes to a genetically determined variability in apoptotic susceptibility among old people, which has a potentially relevant role in the context of an age-related pathologic condition, such as myocardial ischaemia.Cell Death and Differentiation (2004) 11, 962-973. doi:10.1038/sj.cdd.4401415 Published online 7 May 2004 [ABSTRACT FROM AUTHOR]

This article focuses on Italian Neurological Society guidelines for the diagnosis of dementia. It is essential to ensure that all guidelines are verified in practical terms because the behaviours foreseen at the time they are drawn up may not be feasible in clinical practice. The aim of all guidelines is to establish a standard of reference for clinicians' behaviour assuming that this will guarantee patients the best outcome compatible with the availability of resources, individual opinions and the ethical common sense of the community.

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We studied the effect of phosphatidylserine (PdtSER) on oxygen metabolite toxicity in skin fibroblast cell lines from apparently normal subjects. Fibroblast damage was produced by the generation of oxygen metabolites during the enzymatic oxidation of acetaldehyde by xanthineoxidase (Xo). In order to quantify cell damage, we measured lactate dehydrogenase (LDH) activity in culture medium and cell viability in fibroblast cultures, with and without preincubation for 4 days with PdtSER 13 μM, after Xo incubation. We found a significant increase of LDH activity in culture medium of cells without preincubation with PdtSER. No significant increase of LDH activity was observed in the same cell lines after preincubation with PdtSER. [ABSTRACT FROM AUTHOR]

Pyruvate dehydrogenase complex (PDHc), a link between carbohydrate and acetylcholine metabolism, is a regulatory enzyme for glucose and neurotransmitter metabolism in the brain and is reduced in Alzheimer-diseased brain. To study functional consequences of an inhibition of PDHc on muscarinic receptor binding, bromopyruvate, a suicide inhibitor of PDHc, was injected intracerebroventricularly (icv) in rats. Bromopyruvate caused a reduction of PDHc activity in the 3 brain regions examined, however, reaching significance only in the cerebral cortex and the hippocampus and not in the striatum, 24h after injection. 3, 6, and 12 weeks later, there was a normalization or transiently increased activity, respectively, of PDHc in these brain regions. No changes in concentrations of energy-rich phosphates could be demonstrated in the cerebral cortex 12 weeks after brompyruvate injection. The number of muscarinic receptors was significantly reduced in the cerebral cortex 12 weeks after injection. the data indicate that a transient reduction of brain PDHc activity in vivo is associated with a long-lasting reduction in muscarinic cholinergic receptors. Because comparable changes of PDHc and muscarinic receptors are found in dementia of Alzheimer type, the model of bromopyruvate inhibition of PDHc in rats is suggested to be useful for experimental dementia research. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented reporting on human herpesvirus 6-associated limbic encephalitis in adult recipients of unrelated umbilical cord blood transplantation.

Risperidone is a heterocyclic neuroleptic with prominent antiserotoninergic (5HT2) as well as antidopaminergic (D2) activity. We studied the efficacy of risperidone in the treatment of idiopathic and symptomatic dystonias in seven patients using the Fahn and Marsden rating scale for torsion dystonia before and after four weeks of treatment (2-6 mg/day). The twisting and involuntary movements with abnormal postures decreased in all the patients treated, with a statistically significant mean improvement (41%; p = 0.009, CI 95%). Our results suggest that risperidone is useful in idiopathic and symptomatic dystonia. [ABSTRACT FROM AUTHOR]

We selected 14 patients with advanced idiopathic Parkinson's disease (PD) and examined the clinical effects of STN DBS versus GPi DBS. Nine patients underwent bilateral STN DBS and five underwent bilateral GPi patients. All patients were followed for at least 12 months. The evaluation was performed on and off drug before surgery; on-drug/on-DBS and off-drug/on-DBS at 1, 3, 6 and 12 months after stereotactic surgery. At 1 and 3 months after surgery in off-drug/on-DBS condition, both groups showed an improvement in motor score (UPDRS III). Nevertheless, the results changed after long-term stimulation in the two groups. Chronic STN DBS is superior to GPi DBS in the amelioration of the clinical features and in the decrease of time spent in the off state. The efficacy in reduction of LID was comparable at 1 and 3 months after surgery, but the results were better in STN DBS after chronic stimulation. The L-dopa dose was reduced only in the STN group. [ABSTRACT FROM AUTHOR]

The article cites that beta-amyloid immunization is able to reduce cognitive impairment in animal models of Alzheimer's disease and is also able to reduce plaque formation in the brain. These experimental results allow us to hypothesize that this treatment could prevent cognitive impairment in human Alzheimer's disease. Passive immunization could be a good alternative to the vaccine. Subacute administration of antibodies against beta-amyloid induces evident memory improvement of a murine model of Alzheimer's disease.