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Umberto Senin

Publications and source records attributed to Umberto Senin.

32 records · Page 2Linked to original sources

Axonal injury within language network in primary progressive aphasia.

Primary progressive aphasia (PPA) is characterized by an isolated progressive impairment of word use and comprehension reflecting the distribution of pathological processes within the left hemisphere. We used proton magnetic resonance spectroscopy (1H-MRS) to study in vivo the integrity of axonal fibers connecting perisylvian language areas in 11 patients with PPA, 11 subjects with Alzheimer's disease, and 22 controls. Brain metabolites (N-acetylaspartate, myoinositol, choline, creatine) were measured bilaterally within a volume of interest located in the central portion of the superior longitudinal fasciculus, a long associative bundle connecting Broca's area with Wernicke's area, and other language regions of the temporal lobe. In the PPA group, there was an asymmetrical N-acetylaspartate to creatine ratio reduction compared with Alzheimer's disease and controls, with greater changes on the left side. The myoinositol to creatine ratio was increased in the PPA group bilaterally compared with controls. The choline to creatine ratio did not differ among the three groups. These results indicate an asymmetrical focal axonal injury within the language network in PPA. The marked difference in the distribution of N-acetylaspartate to creatine between PPA and Alzheimer's disease suggests that proton magnetic resonance spectroscopy may help to differentiate between these two conditions.

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Validation of the five-item geriatric depression scale in elderly subjects in three different settings.

OBJECTIVES: To test the effectiveness of a five-item version of the Geriatric Depression Scale (GDS) for the screening of depression in community-dwelling older subjects, hospitalized older patients, and nursing home residents. DESIGN: A cross-sectional study. SETTING: A geriatric acute care ward, a geriatric outpatient clinic, and a nursing home. PARTICIPANTS: One hundred eighty-one cognitively intact older subjects. MEASUREMENT: All the participants had a comprehensive geriatric assessment including a neuropsychological evaluation by a geriatrician experienced in the management of depression. The five-item GDS was compared with the 15-item version of the GDS using the clinical diagnosis according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria as the criterion standard. The sensitivity, the specificity, the overall accuracy, positive and negative predictive values, and positive and negative likelihood ratios were calculated. The agreement between each of two different versions of the GDS and the clinical diagnosis and the test-retest and the interrater reliability of the five-item scale were also evaluated. RESULTS: In the whole sample, 48.1% of the subjects were depressed. The five-item GDS had a sensitivity of 0.94 (0.91-0.98), a specificity of 0.81 (0.75-0.87), a positive predictive value of 0.81 (0.75-0.87), a negative predictive value of 0.94 (0.90-0.97), a positive likelihood ratio of 4.92 (4.39-5.5), and a negative likelihood ratio of 0.07 (0.06-0.08). The five-item GDS and the 15-item GDS showed a significant agreement with the clinical diagnosis of depression (kappa = 0.74 for both scales). The five-item GDS had good interrater reliability (kappa = 0.88) and test-retest reliability (kappa = 0.84). Similar values were obtained in each setting and in both sexes. CONCLUSION: The five-item GDS is as effective as the 15-item GDS for the screening of depression in cognitively intact older subjects.

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Cathepsin D polymorphism in Italian elderly subjects with sporadic late-onset Alzheimer's disease.

Alzheimer's disease (AD) is the most frequent cause of dementia in elderly people. Different pathological pathways have been involved in the development of late-onset AD. Among them, numerous genes have been proposed as pathogenetic factors acting independently or interactively. It has been suggested that the cathepsin D gene (CTSD) is associated with late-onset AD. We analyzed an exonic polymorphism of the CTSD gene [C-->T (Ala-->Val) transition at position 224] in 142 AD patients and 120 controls. Our data indicate no significant association between this polymorphism and the risk of AD. Likewise there was no association between CTSD polymorphism and the apolipoprotein E genotype in the risk of developing AD.

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Marked decrease in plasma antioxidants in aged osteoporotic women: results of a cross-sectional study.

Although recent epidemiological studies found a positive correlation between dietary vitamin C intake and bone mineral density, data on plasma levels of vitamin C or other antioxidants in osteoporotic subjects are scanty. The aim of this study was to evaluate whether antioxidant defenses are decreased in elderly osteoporotic women and, if this is the case, to understand whether osteoporosis is a condition characterized by increased oxidative stress. To answer these questions, plasma vitamins C, E, and A; uric acid; and the enzymatic activities of superoxide dismutase in plasma and erythrocytes and of glutathione peroxidase in plasma were measured in 75 subjects with osteoporosis and 75 controls. Dietary and endogenous antioxidants were consistently lower in osteoporotic than in control subjects. On the other hand, plasma levels of malondialdehyde, a byproduct of lipid peroxidation, did not differ between groups. Our results reveal that antioxidant defenses are markedly decreased in osteoporotic women. The mechanisms underlying antioxidant depletion and its relevance to the pathogenesis of osteoporosis deserve further investigation.

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Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.

Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene were measured in 30 patients with class II and III congestive heart failure (CHF) according to the New York Heart Association (NYHA) classification and in 55 controls. Ejection fraction was evaluated by echocardiography in all patients as a measure of the emptying capacity of the heart. Plasma levels of all measured compounds were significantly lower and MDA significantly higher in patients compared to controls (p <.001). Class II NYHA patients showed significantly lower MDA levels and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene than class III patients. Ejection fraction was inversely correlated with MDA levels and directly correlated with vitamin A, vitamin E, lutein, and lycopene levels in patients. The present study supports the concept that an increased consumption of vitamin-rich fruits and vegetables might help in achieving cardiovascular health.

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Lymphocyte oxidative DNA damage and plasma antioxidants in Alzheimer disease.

CONTEXT: A large body of experimental evidence suggests that in Alzheimer disease (AD) pathogenesis an important role is played by oxidative stress, but there is still a lack of data on in vivo markers of free radical-induced damage. OBJECTIVES: To evaluate levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative damage to DNA, in peripheral lymphocytes; to measure plasma concentrations of several nonenzymatic antioxidants; and to assess the relationships between any observed changes in lymphocyte DNA 8-OHdG content and plasma antioxidant levels in patients with AD and healthy aged control subjects. SUBJECTS: Forty elderly outpatients with AD and 39 healthy age- and sex-matched controls were studied. MAIN OUTCOME MEASURES: The level of 8-OHdG was determined in DNA extracted from lymphocytes and plasma levels of vitamin C, vitamin A, vitamin E, and carotenoids (zeaxanthin, beta-cryptoxanthin, lycopene, lutein, and alpha- and beta-carotene) were measured by high-performance liquid chromatography. RESULTS: Lymphocyte DNA 8-OHdG content was significantly higher and plasma levels of antioxidants (with the exception of lutein) were significantly lower in patients with AD compared with controls. In patients with AD, a significant inverse relationship between lymphocyte DNA 8-OHdG content and plasma levels of lycopene, lutein, alpha-carotene, and beta-carotene, respectively, was observed. CONCLUSIONS: Markers of oxidative damage are increased in AD and correlate with decreased levels of plasma antioxidants. These findings suggest that lymphocyte DNA 8-OHdG content in patients with AD reflects a condition of increased oxidative stress related to a poor antioxidant status.

8-Hydroxy-2'-Deoxyguanosine↗

Proton magnetic resonance spectroscopy reveals similar white matter biochemical changes in patients with chronic hypertension and early Alzheimer's disease.

OBJECTIVES: Hypertension is a risk factor for dementia and is associated with some of the brain changes that are found in Alzheimer's disease and other neurodegenerative diseases, such as atrophy and neurofibrillary tangles. We evaluated the cerebral white matter biochemical pattern in healthy older subjects, older patients with chronic hypertension, and patients with Alzheimer's disease (AD) using proton magnetic resonance spectroscopy (1H-MRS). DESIGN: Cross-sectional study. SETTING: University-affiliated outpatient clinic. PARTICIPANTS: Ten healthy older subjects, 10 cognitively intact older patients with chronic hypertension, and 10 older patients with early AD. MEASUREMENTS: All subjects underwent clinical examination, neuropsychological assessment, and 1H-MRS to measure N-acetylaspartate (NAA), myoinositol, choline, and creatine resonance signals in an 8-cm3 voxel located in the paratrigonal white matter region bilaterally. NAA/creatine, myoinositol/creatine, and choline/creatine ratios were measured, and the mean values were compared using one-way analysis of variance with Tukey test for post hoc analysis. RESULTS: A significantly higher mean myoinositol/creatine (ratio +/- standard deviation) was found in hypertensive patients (0.67 +/- 0.05) and in AD patients (0.68 +/- 0.08) than in controls (0.56 +/- 0.04) (P <.001). Conversely neither NAA/creatine ratio nor choline/creatine ratio differed among the three groups. CONCLUSIONS: In this study, cognitively intact chronic hypertensive older patients had a higher white matter myoinositol/creatine ratio compared with healthy older subjects, suggesting that myoinositol may be a sensitive marker of the effects of chronic hypertension on the brain. Moreover, the similar increase of myoinositol/creatine ratio in patients with hypertension and in those with early AD provides further evidence of common brain changes with these conditions.

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Use of artificial networks in clinical trials: a pilot study to predict responsiveness to donepezil in Alzheimer's disease.

OBJECTIVES: To evaluate the accuracy of artificial neural networks compared with discriminant analysis in classifying positive and negative response to the cholinesterase inhibitor donepezil in a group of Alzheimer's disease (AD) patients. DESIGN: Convenience sample. SETTING: Patients with mild to moderate AD consecutively admitted to a geriatric day hospital and treated with donepezil 5 mg/day. PARTICIPANTS: Sixty-one older patients of both sexes with AD. MEASUREMENTS: Accuracy in detecting subjects sensitive (responders) or not (nonresponders) to 3-month therapy with ANNs. The criterion standard for evaluation of efficacy was the scores of Alzheimer's Disease Assessment Scale-Cognitive portion and Clinician's Interview Based Impression of Change-plus scales. RESULTS: ANNs were more effective in discriminating between responders and nonresponders than other advanced statistical methods, particularly linear discriminant analysis. The total accuracy in predicting the outcome was 92.59%. CONCLUSIONS: ANNs appear to be a useful tool in detecting patient responsiveness to pharmacological treatment in AD.

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Plasma carotenoid and malondialdehyde levels in ischemic stroke patients: relationship to early outcome.

An association between ischemic stroke and increased oxidative stress has been suggested from animal studies. However, there is a lack of evidence with respect to this association in humans. Here, the time course of plasma levels of six carotenoids, which are lipophilic micronutrients with antioxidant properties, as well as of malondialdehyde (MDA), a marker of lipid peroxidation, was followed in ischemic stroke patients. Plasma levels of lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene, as well as MDA were measured by high-performance liquid chromatography in 28 subjects (19 men and nine women aged 76.9+/-8.7 years) with an acute ischemic stroke of recent onset (<24h) on admission, after 6 and 24 h, and on days 3, 5, and 7. Carotenoid and MDA levels in patients on admission were compared with those of age- and sex-matched controls. Plasma levels of lutein, lycopene, alpha- and beta-carotene were significantly lower and levels of MDA were significantly higher in patients in comparison with controls. Significantly higher levels of MDA and lower levels of lutein were found in patients with a poor early-outcome (functional decline) after ischemic stroke as compared to patients who remained functionally stable. These findings suggest that the majority of plasma carotenoids are lowered immediately after an ischemic stroke, perhaps as a result of increased oxidative stress, as indicated by a concomitant rise in MDA concentrations. Among the carotenoids, only lutein plasma changes are associated with a poor early-outcome.

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Genetic factors associated with the absence of atherosclerosis in octogenarians.

BACKGROUND: Atherosclerosis (ATS) is a common age-related disease of large arteries. The prevalence of older subjects with vascular successful aging (VaSA), defined as the absence of clinical symptoms and instrumental signs of ATS, is low in Western countries. The possible contribution of genetics to the VaSA phenomenon is not known. METHODS: We investigated the distribution of four genetic polymorphisms (angiotensin converting enzyme [ACE], methylenetetrahydrofolate reductase [MTHFR], apolipoprotein E [apo E], and paraoxonase [PON] genes) in 30 subjects with VaSA, 30 subjects with moderate carotid atherosclerosis (ATS group), and 161 controls with a negative history for cardiovascular disease. Clinical examination; ultrasonographic examination of carotid, vertebral, abdominal aortic, iliac, and femoral arteries; and electrocardiogram were performed. RESULTS: The frequency of PON 192 B allele was lower in VaSA patients (13%) compared with ATS patients (37%) and controls (46%) ( p =.06 and.006, respectively); B/B homozygotes were 27% in the ATS group, 12% in controls, and 0% in the VaSA group. The frequency of the MTHFR thermolable + allele was higher in VaSA (0.51) compared with ATS (0.39) and controls (0.40) (VaSA vs C, p =.006). No differences in the distribution of ACE I/D and apo E alleles emerged between the three groups. CONCLUSIONS: The low prevalence of the PON 192 B allele in the VaSA subjects suggests that this polymorphism might have an important role in VaSA, probably by hydrolyzing lipid peroxides and thus preventing low-density lipoprotein from undergoing the oxidative modification. This finding further supports the oxidative hypothesis of ATS.

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Dementia, depression and parkinsonism: A frequent association in the elderly.

Depression and parkinsonism constitute two frequent findings in elderly demented patients. A large body of research, including epidemiological, retrospective, and prospective studies have contributed to the understanding of complex and common situations in the elderly, in which depression, parkinsonian signs, and cognitive impairment coexist. Many aspects regarding the "associated syndromes of dementia", however, are still object of debate as well as under current active investigation. The recent dramatic aging of the population is leading to an increasing prevalence of neuropsychiatric comorbidities. This is a problem of great clinical and socio-economical interest, because, when present in the same subject, depression, parkinsonism-related motor impairment and cognitive impairment may not only act additively or synergistically in deteriorating the functional outcome of the patient, but also lead to their institutionalization. We observed that one half of institutionalized subjects in two nursing homes of Central Italy suffer from an associated syndrome dementia / parkinsonism / depression, that these subjects are significantly more dependent than subjects hospitalized for the same reasons, and that their grade of depression or cognitive impairment is independent of which disease is diagnosed first. Depressed mood, memory impairment and motor difficulties, however, are often underestimated in the elderly, being considered as "normal" aspects of the aging process. The aim of this review is to highlight the clinical relevance of the associated syndromes of dementia, in a way that early diagnosis and treatment of these pathologies are attempted.

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The Effects of Aging and Endurance Exercise on Cardiovascular Performance in Healthy Elderly: A Review of the Literature.

CV performance declines over time in healthy elderly subjects due to aging, as well as declining physical activity. Recent studies with older, often sedentary individuals, demonstrate that aerobic endurance exercise may improve several measures of CV function. Although further research is needed to characterize the CV effects of exercise, particularly in elderly women and the oldest old population, aerobic endurance exercise should be advocated in the healthy elderly.

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Comparative effects of lercanidipine, lacidipine, and nifedipine gastrointestinal therapeutic system on blood pressure and heart rate in elderly hypertensive patients: the ELderly and LErcanidipine (ELLE) study.

This study was conducted to compare the antihypertensive efficacy and safety of lercanidipine with those of lacidipine and nifedipine gastrointestinal therapeutic systems in patients aged 65 years or above with mild-to-moderate hypertension. Patients were randomized to receive lercanidipine 5 mg, lacidipine 2 mg, or nifedipine 30 mg for 24 weeks. After 2 weeks, the dose was doubled in non-responding patients. At 24 weeks, blood pressure was significantly reduced in the three treatment groups. The decrease in systolic blood pressure was similar in all three groups. The decrease in diastolic blood pressure in the lercanidipine group (-18.3 mmHg) was comparable to that in the nifedipine group (-17.7 mmHg), but exceeded that in the lacidipine group (-16.6 mmHg). The incidence of adverse drug reactions (ADRs) was lowest in the lercanidipine group (19.4%) compared with the nifedipine group (28.4%) and the lacidipine group (27.1%). In particular, edema was least frequent in the lercanidipine group (2.8%) compared with the lacidipine group (7.5%) and the nifedipine group (10.1%). These data demonstrate that lercanidipine is effective in lowering blood pressure in older adult hypertensive patients while maintaining a superior tolerability and safety profile.

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[Impact of population aging on the social and the health care system: need for a new model of long-term care].

Population aging is characterized by a marked increase in the number of subjects aged 80 years or more (the oldest old). In this group frailty is extremely common. Frailty is a recently identified condition resulting from a severely impaired homeostatic reserve, that places the elderly at the highest risk for adverse health outcomes, including dependency, institutionalization and death, following even trivial events. Geriatric medicine proposes an original methodology for the management of frail elderly subjects, the so called "comprehensive geriatric assessment", as well as a model of long-term care. These have been shown to reduce the risk of hospitalization and nursing home admission, with a parallel decrease in expenses and an improvement in the patient's quality of life. The effectiveness of the long-term care system depends on: 1) the availability of all the services that are necessary for the frail elderly, both in the hospital and in the community; 2) the presence of a coordinating team, the comprehensive geriatric assessment team, that develops and implements the individualized treatment plans, identifies the most appropriate setting for each patient and verifies the outcomes of the interventions; 3) the use of common comprehensive geriatric assessment instruments in all the settings; 4) the gerontological and geriatric education and training of all the health care and social professionals.

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