Biomedical subjects

Patrizia Mecocci

Publications and source records attributed to Patrizia Mecocci.

At least 37 records · Page 2Linked to original sources

PubMed2004

Oxidative stress in mild cognitive impairment and Alzheimer disease: a continuum.

Although several studies show the importance of oxidative stress in the pathogenesis of Alzheimer's disease (AD), there are few evidences on the role of free radicals in Mild Cognitive Impairment (MCI). Our results showing a marked decrease of the main components of the antioxidant defense system of the organism support the hypothesis that in MCI there is a condition of oxidative stress. This work also gives an overview on the existing evidence of the early occurrence of oxidative processes in the development of dementing disorders of the Alzheimer type. Since MCI represents a condition of increased risk for AD, use of antioxidants in MCI could be of importance for prevention.

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PubMed2003

Rapidly progressive aphasic dementia with motor neuron disease: a distinctive clinical entity.

The association of motor neuron disease (MND) with rapidly progressive aphasic dementia has been recognized as a distinct clinical syndrome within the group of frontotemporal dementias (FTDs). Although the clinical and neuropsychological features of this syndrome have been defined, a small number of post-mortem studies have been published with heterogeneous neuropathological findings. We performed cognitive, neuro-imaging and neuropathological studies on a 71-year-old male with rapidly progressive aphasic dementia and MND. We initially found a selective non-fluent aphasia associated with hypoperfusion of the left frontotemporal cortex. Proton magnetic resonance spectroscopy revealed an asymmetric change of brain metabolites, with greater changes in the left temporal lobe. The bulbar manifestations of MND occurred over the following 6 months, and the patient died of bronchopneumonia. The neuropathological examination revealed loss of neurons in the hypoglossal nucleus and anterior horns of the cervical spinal cord with microvacuolation and dot-like ubiquitin-positive deposits in the frontoparietotemporal cortex, but no changes suggestive of Alzheimer's, Pick's or Lewy body disease. These findings support the conclusion that MND with rapidly progressive aphasic dementia is a distinctive clinical entity within the group of FTD-MND.

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PubMed2003

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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PubMed2003

Cognitive impairment: a key feature of congestive heart failure in the elderly.

Congestive heart failure (CHF) has been proposed as a possible cause of cognitive dysfunction but only a few studies have directly assessed cognitive performance in CHF. The aim of the present study was to compare the cognitive patterns of patients with CHF and patients having cardiovascular diseases uncomplicated by CHF (no-CHF group). In a multicenter observational case-control study, we studied 149 hospitalized elderly CHF patients in the New York Heart Association (NYHA) class II (CHFm, m: moderate), 159 CHF patients in NYHA class III-IV (CHFs, s: severe), and 207 no-CHF patients. Patients underwent a multidimensional assessment and neuropsychological tests for the following cognitive domains: attention, visual-spatial intelligence, verbal attainment, verbal and visuo-spatial memory. Neuropsychological performances of groups were compared by multivariate analysis. Correlates of an abnormal performance on at least three neuropsychological tests were assessed by logistic regression analysis. CHFs performed worse than no-CHF patients on 4 of the 7 neuropsychological measures, the largest difference being in tests of attention and verbal learning (p < 0.001). Prevalence of abnormal performance on at least 3 tests was 57.9 % in CHFs, 43% in CHFm and 34.3 % in no-CHF groups (chi square = 17.3, p < 0.0001). The following qualified as independent correlates of the outcome at logistic regression analysis: CHFs group membership (Odds Ratio-OR = 2.56, 95% Confidence Interval-CI = 1.49-4.40), depression (OR = 2.37, 95% CI = 1.54-3.66), hypertension (OR = 1.88, 95% CI = 1.18-2.99). Our results demonstrate that cognitive impairment is common among CHF patients and seems to be causally related to CHF severity, depression and hypertension. The cognitive dysfunction also characterizes a relevant fraction of patients with cardiovascular diseases uncomplicated by CHF.

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PubMed2003

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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PubMed2003

Cigarette smoking cessation increases plasma levels of several antioxidant micronutrients and improves resistance towards oxidative challenge.

Cigarette smoking is associated epidemiologically with increased risk of cardiovascular diseases, but the pathophysiological mechanisms are still not fully understood. There is evidence that smoking is related to increased free radical production and antioxidant depletion, but the effects of smoking cessation on plasma concentrations of antioxidants and susceptibility to oxidative stress are largely unknown. Plasma levels of vitamins A, C, E, uric acid, total thiols, carotenoids (including lutein, zeaxanthin, beta-cryptoxanthin, lycopene, alpha- and beta-carotene) and malondialdehyde (MDA, a biomarker of lipid peroxidation) were measured in fifteen healthy, normolipidaemic subjects (seven males, eight females, 35.2 (sd 2.3) years) before and 4 weeks after smoking cessation. To determine plasma resistance towards oxidative challenge, plasma was incubated for up to 5 h with the peroxyl radical-generator 2,2'-azobis(2-amidinopropane) (AAPH); MDA and ascorbate levels were measured at various time points. The concentrations of all plasma antioxidants were lower before smoking cessation than afterwards; MDA levels were higher before than after termination of smoking. Upon AAPH exposure, the consumption of plasma ascorbate and the production of MDA occurred at a significantly faster rate before smoking cessation as compared with afterwards. Cigarette smoking cessation is followed by a marked increase in plasma antioxidant concentrations and substantially improves plasma resistance towards oxidative challenge. Given the importance of cigarette smoking as a risk factor for cardiovascular diseases and the pathophysiological role played by oxidative stress in these illnesses, quitting smoking represents an irreplaceable preventive strategy against tobacco-induced oxidative stress and vascular damage.

Antioxidants↗

PubMed2003

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.

Age of Onset↗

PubMed2003

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.

Activities of Daily Living↗

PubMed2003

[Abridged version of the severe impairment battery (SIB)].

Until recently, severe dementia has received little attention on the part of clinicians and researchers. Yet, it represents a major problem from the point of view of Public Health because it is always accompanied by marked functional impairment with, in addition, frequent psychiatric and behavioural problems. These deficits are associated with impairment in activities of daily living that result in marked loss of autonomy and lead inevitably to the need to seek outside assistance, at least on a part-time basis. The arrival of new drugs with a potential to palliate some of the symptoms makes the assessment of severe dementia even more important. The Severe Impairment Battery (SIB) has been proposed in 1990 in order to evaluate the cognitive abilities of patients for whom standard cognitive measures are no longer adapted. Its purpose was to analyze different cognitive domains, based on the residual capacities of these patients. It evaluates the following domains: social interaction, orientation, attention, language, memory, praxis, constructional abilities and visuo spatial functions. The original SIB consisted of 51 items with a maximum score of 152. The battery was later shortened with a score of 133 and later 100. The latter version, which included 40 items, has been validated and published in France by Boller et al. However, clinical experience suggests that even this version is too long and includes some redundancies. We have therefore prepared an abridged version, which only includes 26 items with a maximum score of 50. It can be administered in 10 to 15 minutes. The selection was based mainly on clinical experience. We wanted to keep all of the domains included in the original version. Finally the selection was justified by a factorial analysis. The present version is based on a consensus reached by an US and Italian research group, in addition to ours.

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PubMed2002

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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PubMed2002

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↗

PubMed2002

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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PubMed2002

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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PubMed2002

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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PubMed2002

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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PubMed2002

Plasma susceptibility to free radical-induced antioxidant consumption and lipid peroxidation is increased in very old subjects with Alzheimer disease.

Oxidative stress is believed to play a major role in the pathogenesis of Alzheimer disease (AD). Plasma concentrations of vitamins C, A and E, of uric acid, thiols and carotenoids were lower and of malondialdehyde (MDA) higher in 35 AD patients (85.9 +/- 5.5 y) compared to 40 controls 85.5 +/- 4.4 y). Differences were significant for vitamin C, vitamin E, lutein, lycopene, alpha-carotene and MDA (p < 0.001). Plasma exposed to peroxyl radicals showed a rate of antioxidant consumption and of MDA production higher in AD patients than in controls. AD in advanced age is accompanied by a poor plasma antioxidant status and increased plasma lipid peroxidation, as well as by a low resistance to peroxyl radical exposure.

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PubMed2001

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.

Journal Article↗

PubMed1998

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.

Journal Article↗