Overtreating Alzheimer's Disease.

The management of frailty in older persons is not easy, implying interventions beyond the simple prescription of medications. Biological complexity, multimorbidity, polypharmacy, and social issues often hamper the possibility to directly translate the evidence coming from research into clinical practice. Frailty indeed represents the most relevant cause of the "evidence-based medicine issue" influencing clinical decisions in geriatric care. Today, patients with Alzheimer's disease (AD) are much older and frailer than some decades ago. They also tend to have more drugs prescribed. In parallel, research on AD has evolved over the years, hypothesizing that anticipating the interventions to the earliest stages of the disease may provide beneficial effects (to date, still lacking). In this article, we argue that, by focusing exclusively on "the disease" and pushing to anticipate its detection (sometimes even before the appareance of its clinical manifestations) may overshadow the person's values and priorities. Research should be developed for better integrating the concept of aging and frailty in the design of clinical trials in order to provide results that can be implemented in real life. On the other hand, clinicians should be less prone to the easy (but unsupported by evidence) pharmacological prescription.

Vascular risk factors and white matter hyperintensities in patients with amnestic mild cognitive impairment.

BACKGROUND: Subjects affected by aMCI are considered at high risk for AD. Nevertheless, the role of both vascular risk factors and WMH is matter of debate. PATIENTS AND METHODS: We enrolled consecutively 21 aMCI subjects according to Petersen Criteria; the study included routine screening for dementia, neuropsychological evaluation and brain MRI. Six vascular risk factors were assessed and WMH was quantified by means of a semiautomatic lesion-detection program. RESULTS: Conversion to AD, according to NINCDS-ADRDA criteria, was 47.6%. Converters tended to be more affected by the most of vascular risk factors while no difference was noted in WMH. The best predictors of conversion to AD were scores obtained at several neuropsychological examination. CONCLUSION: Our results show that criteria for aMCI identify subjects with a high risk to develop AD. WMH doesn't seem to have a role in progression from aMCI to AD, while some vascular risk factors seem to promote it.

Evaluación no invasiva del status volémico. Confrontación entre indicadores radiográficos y volumétricos / Not invasive evaluation of the status volémico. Confrontation between warning radiográficos and volumetric

La finalidad de nuestro estudio ha sido la de evaluar la existencia de posibles correlaciones entre los principales indicadores volumétricos de carga previa y de función cardiaca, obtenida mediante el sistema PiCCO® (Pulsion Medical Systems, Munich, Alemania), con todos los datos derivados del análisis sistemático de la radiografía de tórax en proyección antero posterior, así como el pedúnculo vascular (VPW) y el índice cardiotorácico (RCT). Materiales y Métodos: Hemos incluido 15 pacientes y analizado conjuntamente 79 radiografías de pacientes electivos. Todos fueron sometidos a monitorización hemodinámica mediante PiCCO y al estudio de los parámetros radiográficos obtenidos (VPW, RCT). El análisis: cálculo de la media y desviación estándar; un análisis de la correlación para las siguientes parejas de parámetros: volumen de sangre intratorácica (ITBVI)-RCT, ITBVI-VPW, agua extravascular (EVLWI )-RCT, EVLWI-VPW . Resultados. Las parejas de los valores estudiados han evidenciado una correlación linear con R igual a 0.54 entre EVLWI-RCT. Discusión. Aunque es un estudio preliminar, los hallazgos más significativos se ven en las variaciones de RCT, que presentan una correspondencia con el edema intersticial antes de que aparezca un incremento crítico de la rata de líquido alveolar. En nuestra experiencia no hemos evidenciado una fuerte correlación entre VPW y los normales indicadores volumétricos de precarga. De acuerdo con los datos en literatura y también en la experiencia pediátrica, estos instrumentos presentan límites que aún no consienten sustituir completamente a la correcta cuantificación de la rata de agua extravascular, en respuesta al incremento volémico. Palabras Claves: Monitorización Hemodinámica, Monitor de PiCCO, Volemia, pedúnculo vascular, índice cardiotorácico, Volumen de sangre intratorácica, Volumen de agua extravascular intrapulmonar, Índice de función cardiaca...

Epidemiological evidence on multiple system atrophy.

Multiple system atrophy (MSA), is a sporadic neurodegenerative disorder characterized clinically by any combination of parkinsonian, autonomic, cerebellar or pyramidal symptoms and signs. The frequence of disease is estimated for the incidence rate to 0.6 cases per 100.000 person-years, while the prevalence rate is included between 1.86 and 4.9 cases per 100.000 pop. A risk factor seems to be the occupational history of farming also if the occupational exposure to pesticides is not associated with MSA. Smoking is probably a protective factor in MSA as Parkinson's disease. MSA seems a sporadic disease also if recently a German family with two MSA cases has been reported. The polymorphism association studies support a role for inflammation-related genes in risk for MSA. The current epidemiological and clinical evidence suggests that likely the etiopathogenesis of MSA is complex, and that many genetic as well as environmental factors are involved. Unfortunately, the most of studies in MSA are lacking in a sample size estimate to test the hypothesis, then the scientific evidence is poor. Then, much larger numbers of cases and controls are necessary for these studies to reach sufficient power, but collecting such large numbers is feasible only in the framework of multicentric consortia.

Observations on EEG patterns in neurally-mediated syncope: an inspective and quantitative study.

We performed an observational EEG study in 43 patients with neurally-mediated syncope in basal condition and during hyperventilation (HV), and compared it with 32 healthy controls. On blind analysis at rest, EEG was classified as normal in 47% of patients (vs. 94% of controls, P < 0.001). More abundant and pronounced delta-theta activities and alpha slowing were found in patients than in control subjects on both visual inspection and quantitative spectral analysis. During prolonged HV, the EEG remained normal in 21% of patients only. Slow activities became more evident in patients than in control subjects, and intermittent rhythmic delta activity appeared in 40% of syncopal patients. These "pseudoparoxysmal" EEG changes differed from the common slowings induced by HV in adult subjects and were not observed in our control subjects. Moreover, these distinctive EEG changes, a common finding in syncopal patients, could not be confused with epileptiform activity of any kind. Further studies will clarify the pathophysiology of these EEG modifications.

DJ-1( PARK7), a novel gene for autosomal recessive, early onset parkinsonism.

Four chromosomal loci ( PARK2, PARK6, PARK7, and PARK9) associated with autosomal recessive, early onset parkinsonism are known. We mapped the PARK7 locus to chromosome 1p36 in a large family from a genetically isolated population in the Netherlands, and confirmed this linkage in an Italian family. By positional cloning within the refined PARK7 critical region we recently identified mutations in the DJ-1 gene in the two PARK7-linked families. The function of DJ-1 remains largely unknown, but evidence from genetic studies on the yeast DJ-1 homologue, and biochemical studies in murine and human cell lines, suggests a role for DJ-1 as an antioxidant and/or a molecular chaperone. Elucidating the role of DJ-1 will lead to a better understanding of the pathogenesis of DJ-1-related and common forms of Parkinson's disease.

A case-control study on Alzheimer's disease and exposure to anesthesia.

Aretrospective hospital-based case-control study was performed with the aim to evaluate the association between exposure to anesthesia and Alzheimer's disease (AD). A total of 115 AD patients, 230 Parkinson's disease (PD) patients and 230 patients with non-degenerative neurological disease were studied. Each AD case was matched for sex, age (+/-3 years) and geographic area of residence with four controls (2 PD patients and 2 with other neurological disease). Information about exposure to general anesthesia and other variables was gathered through hospital records. No associations were found between the risk of AD and the exposure to anesthesia in the 1 and 5 years preceding disease onset, nor between the risk of AD and the number of surgical operations. A significant difference was observed between the mean age of AD patients and controls undergoing surgical procedures. The present study reveals a lack of association between exposure to general anesthesia and AD. Prospective epidemiological studies are needed in order to investigate levels of exposure to anesthesia, as well as any possible relationships between anesthetic exposure and genetic factors (e. g. APOEepsilon4 genotype).

Epidemiology of multiple system atrophy. ESGAP Consortium. European Study Group on Atypical Parkinsonisms.

Multiple system atrophy (MSA) is a form of atypical parkinsonism with unknown etiology. The epidemiological studies conducted up to now on this disease are scarce. The incidence rate is about 0.6 cases per 100,000 persons per year. The prevalence rates show 4-5 cases per 100,000 persons. In Italy, about 4,900 prevalent cases have been estimated. The mean onset age is about 54 years; the median survival is 7-9 years. Only one case-control study has been performed on this disease. This study showed an increased risk of MSA associated with occupational exposure to organic solvents, plastic monomers and additives, pesticides and metals. Smoking habits seem to be less frequent in MSA cases (as in Parkinson's disease cases) than in healthy controls. Quinn's clinical criteria and those of the Consensus Conference promoted by the American Academy of Neurology are in fair agreement. We have performed a case-control study on 73 MSA cases, 146 hospital controls and 73 population controls.

[National surveillance system for acute poisoning caused by pesticides]. / Piano di sorveglianza nazionale per la rilevazione delle intossicazioni acute da antiparassitari.

In the present paper is presented the surveillance system for pesticide-related illnesses proposed by the Istituto Superiore di Sanità, in collaboration with the Ministry of Health. Through the collaboration of local or regional poison control centres and local health departments with public hospitals and emergency departments, cases of acute pesticide-related illnesses among persons seeking health care will be registered according to standard procedures. Data collected locally will be transmitted to the Istituto Superiore di Sanità for registration and evaluation of the association between symptoms and type of exposure and for severity of illnesses related to pesticide exposure. These data will be analysed at regular intervals in order to estimate the magnitude of the problem of acute pesticide-related illnesses in Italy and to identify priority areas for implementing public health prevention and intervention programs.

Smoking habits in multiple system atrophy and progressive supranuclear palsy. European Study Group on Atypical Parkinsonisms.

OBJECTIVE: To evaluate smoking habits in patients with multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) in a multicenter case-control study to determine whether these two forms of atypical parkinsonism share the inverse association with smoking previously found in PD. BACKGROUND: No epidemiologic studies have been performed on smoking habits in MSA. A previous investigation in PSP revealed no differences in smoking habits between patients and hospital control subjects. METHODS: Seventy-six MSA patients, 55 PSP patients, 140 PD patients, and 134 healthy control subjects were enrolled consecutively at seven neurologic clinics from January 1, 1994, to July 31, 1998. Detailed information on smoking habits was obtained using a structured questionnaire. RESULTS: The comparison between frequencies of never-smokers versus ever-smokers (ex-smokers/current smokers; adjusted odds ratio [ORadj], 0.56; 95% CI, 0.29 to 1.06) and a dose-response analysis for never-smokers, moderate smokers (ORadj, 0.64; 95% CI, 0.31 to 1.32), and heavy smokers (ORadj, 0.47; 95% CI, 0.21 to 1.05) suggest that MSA patients smoke less than population control subjects. By contrast, the comparison of frequencies of never-smokers versus ever-smokers (ORadj, 0.91; 95% CI, 0.42 to 1.98) and a dose-response analysis for never-smokers, moderate smokers (ORadj, 0.68; 95% CI, 0.27 to 1.69), and heavy smokers (ORadj, 1.24; CI 95%, 0.51 to 3.06) revealed no differences in smoking habits between PSP patients and population control subjects. CONCLUSIONS: The fact that the inverse association with smoking found previously in PD is shared by multiple system atrophy but not by progressive supranuclear palsy lends epidemiologic support to the notion that different smoking habits are associated with different groups of neurodegenerative disease.

Mortality cancer risk in parkinsonian patients: a population-based study.

Cancer mortality in a population-based cohort of 10,322 parkinsonian patients (448 deaths observed during 1987 to 1994) was compared with that of the Italian province of Rome using the standardized mortality ratio (SMR). The overall cancer mortality risk was lower in this cohort than in the reference population (SMR, 56; 95% CI, 51 to 61). This reduction included most cancer sites as well as both smoking-related (SMR, 51; 95% CI, 42 to 60) and nonsmoking-related cancers (SMR, 58; 95% CI, 52 to 65). The observed reduction in cancer mortality risk in this cohort cannot be explained entirely by the hypothesis that smokers are less likely to develop PD.

Mortality in a population-based cohort of patients treated with antiparkinsonian drugs.

OBJECTIVES: A number of studies have been focused on the mortality of parkinsonian patients, as compared with the rest of the population. In these studies, a mortality greater than expected on the basis of mortality of the general population has been shown. Nevertheless, just a few of these studies have investigated in detail the specific causes of death, probably as a consequence of both small cohort sizes and a short time period of observation. The aim of this study was to estimate cause-specific mortality in a cohort of patients treated with antiparkinsonian drugs. METHODS: The study was performed on a wide population-based cohort of patients identified and followed-up through the computerized health databases of the Italian province of Rome (about 3,800,000 inhabitants). The follow-up lasted from January 1987 to December 1994. Standardized Mortality Ratios (SMR) were calculated for each specific cause of death, using the Rome province population as reference. RESULTS: A cohort of 10,322 subjects, receiving antiparkinsonian drugs, were identified. There were 4328 deaths on an average follow-up of 5.7 years. This figure was 17% higher than was expected. A gradual decrease in SMR was observed in the oldest age groups. Statistically significant (95%) excesses of death were related to the nervous system (SMR = 1037; 95% CI 964-1110), mental disorders (SMR = 182; 95% CI 129-246), and endocrine and metabolic diseases (SMR = 117; 95% CI 102-133). Lower than expected mortality was found to be caused by malignant neoplasms (SMR = 56; 95% CI 51-61). CONCLUSIONS: Apart from deaths specifically related to Parkinson's disease, the main differences between our cohort of patients and the general population were related to mortality due to malignant neoplasms and mental disorders. The gradual decrease in SMR for the oldest age groups, seems to indicate a greater reduction of life expectancy for patients with early onset of symptoms. This age-related trend could explain the relatively small excess of mortality, as in our cohort the median age of patients at entry was 74 years.

[Relationship between exposure to environmental toxins and motor neuron disease: a case report]. / Rapporto tra l'esposizione a fattori tossici ambientali e malattia del neurone di moto: osservazioni su un caso.

A case is reported of amyotrophic lateral sclerosis with occupational exposure to solvents and metals. The environmental toxin theory of motorneuron disease, including aspects of epidemiological, clinical, experimental and individual susceptibility is discussed. An overall evaluation of animal and human data was made using a methodological approach developed by the International Agency for Research on Cancer and a Scandinavian group of experts. It is concluded that there is a probable linkage between metals/solvents exposure and motorneuron disease.

Mortality of filling station attendants.

OBJECTIVES: Gasoline contains established human carcinogens, such as benzene. The health impact of exposure to this fuel, however, has not been fully elucidated. We report on the mortality of a cohort of 2665 filling station managers from the Latium region (Italy). METHODS: This is the first workplace-based cohort of gas station attendants. However, only self-employed individuals were available for study (about 50% of the whole work force). The follow-up period extended from 1981 through 1992. The mortality experience of the cohort was compared with that of the regional population. RESULTS: The overall analysis for standardized mortality ratios (SMR) showed a significantly decreased mortality from all causes, mainly due to a deficit of cardiovascular diseases and malignant neoplasms. Nonsignificantly increased risks for esophageal cancer [SMR 241, 90% confidence interval (90% CI) 82-551], brain cancer (SMR 195, 90% CI 77-401) and non-Hodgkin's lymphoma (SMR 173, 90% CI 47-448) were found for the men; mortality due to lung cancer and leukemia was lower than expected, and no kidney cancer death was recorded. Among the attendants of small stations (characterized by a small number of employees and high sales of gasoline per full-time employee), the SMR values for esophageal cancer (for men SMR 351, 90% CI 120-803) and brain cancer (for men and women SMR 266, 90% CI 105-559) showed increased values. CONCLUSIONS: Filling station attendants are exposed to gasoline vapors and seem at risk of cancer of various sites. Due to the power limitations of this study, however, a precise estimate of the risk for many causes of death was not achievable. Further cohort studies of greater size are warranted.

[Exposure to benzene of service station employees and composition of benzene]. / Esposizione a benzene tra gli addetti alle stazioni di rifornimento e composizione della benzina.

The International Agency for Research on Cancer (IARC) classifies gasoline vapours and exhaust fumes from gasoline fueled automobiles as potential human carcinogens. Data on the chemical composition of gasoline marketed in Italy and especially on the concentration of benzene, are rather poor. Within the framework of an investigation aimed at assessing the mean annual level of exposure to aromatic hydrocarbons among gasoline pump attendants, made on a sample of attendants in Rome between December 1991 and November 1992, samples of gasoline were also collected so as to determine the benzene content of the gasoline over the investigation period, assess the variability of benzene concentration in the various gasolines and according to the season of the year, and take account of gasoline composition in analysing the factors determining individual exposure levels of pump attendants. Benzene exposure was measured via gas chromatography of air samples obtained with personal pumps in the breathing zone. The mean benzene exposure level (8 h TWA) of the 27 subjects under study was 1.73 mg/m3 (SD = 5.53). The benzene concentration in the samples of gasoline, which were collected on the same day as personal exposure monitoring was performed, was measured by means of high resolution gas chromatography (hr-GC). Mean benzene levels of 25.03 g/l (SD = 3.47), equivalent to 2.86% by volume, were measured in 24 samples of alkylated gasoline, and mean levels of 23.18 g/l (SD = 3.93), equivalent to 2.65% v/v, were measured in 10 samples of lead-free gasoline. Statistically significant associations were found between individual exposure to benzene and the quantity of gasoline pumped (r = 0.69) and the quantity of benzene present in the gasoline sold on the day monitoring was performed (r = 0.70). Using regression analysis, the estimated increase in the level of personal benzene exposure was 0.01 mg/m3 for every increase of 100 g in the benzene content of the total amount of gasoline sold. This estimation could be used to quantify the expected reduction in benzene exposure levels in service station attendants following a reduction in the benzene content of gasoline.

Parkinsonism after chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate).

Permanent parkinsonism was observed in a man with chronic exposure to the fungicide maneb (manganese ethylene-bis-dithiocarbamate). Symptoms developed at 37 years of age, two years after exposure had ceased. To our knowledge, this is the second report on parkinsonism associated with exposure to maneb. Manganese is a well-known parkinsonigen toxin in humans. More recently, it has been shown that dithiocarbamates can also induce extrapyramidal syndromes. The biochemical effects of manganese and dithiocarbamates are reviewed and their possible neurotoxic mechanisms are discussed. Both of these components may have played a role in this case.

Exposure assessment in a historical cohort of filling station attendants.

A historical cohort of service station attendants is underway. It is aimed at evaluating possible excess cancer risk in relation to exposure intensity. In this paper we discuss the feasibility of a retrospective exposure assessment by evaluating the association between indicators of workload and the exposure intensity to some aromatic hydrocarbons measured in a sample of current employees. Available for the analysis were 703 personal samples from 111 filling station workers. Measured concentrations of benzene, toluene and xylenes (8-hour time weighted averages) averaged 0.55 mg/m3, 0.71 mg/m3 and 0.32 mg/m3, respectively. The number of vehicles filled, the daily sales of super premium gasoline and motorbike fuel, and the winter season were all significant predictors of the log concentration of benzene in simple regression analyses. The size of the station acted as an effect modifier. While no single variable was able to predict the benzene level in large stations, for small stations an increase of 0.0579 and of 0.0418 in the log benzene concentration per unit increase in super premium gasoline (100 I) and in motorbike fuel (10 I) dispensed, was estimated. The overall variance explained by the multivariate model, however, was only 12.3%. Therefore, a clear categorization of groups with homogeneous and significantly different exposure levels is not achievable. From the point of view of exposure assessment, workers in small stations with higher sales of super premium gasoline tend to have higher exposure levels. This group should be examined in detail when the final results of the cohort study are available.