Barbara Palumbo

Proton magnetic resonance spectroscopy can differentiate Alzheimer's disease from normal aging

In order to evaluate the pattern of proton magnetic resonance spectroscopy (1H-MRS) in the gray and white matter of patients with Alzheimers disease (AD) and healthy controls, a cross-sectional study was carried out on 13 consecutive AD patients and 7 healthy older subjects who were referred to the Day-Hospital for diagnostic assessment. All examinations were performed on a 1.5 Tesla whole-body scanner. Volumes of interest were selected in both the gray (temporal region) and the white (frontal region) matter. N-acetyl group, total creatine, total choline and myo-inositol were quantified referring the metabolite peak area to the unsuppressed water peak area acquired under the same conditions, and the ratio was expressed in arbitrary units. A significant decrease in N-acetyl-aspartate (NAA) in both gray and white matter and an increase in myo-inositol (mI) in gray matter of AD patients were observed. The gray matter NAA/mI ratio clearly separated the two groups. White matter mI was significantly associated with severity and duration of dementia. No association with age was documented. It can be concluded that in vivo 1H-MRS can contribute to the knowledge of pathophysiology of AD, giving neurochemical details of both gray and white matter. In particular, the gray matter NAA/ml ratio seems to be able to differentiate normal cerebral aging from Alzheimers disease.

1H-MRS, MRI-based hippocampal volumetry, and 99mTc-HMPAO-SPECT in normal aging, age-associated memory impairment, and probable Alzheimer's disease.

OBJECTIVE: To better understand how to differentiate the “in vivo” normal aging brain from pathological conditions, namely dementia of the Alzheimer type (DAT), by means of magnetic resonance imaging (MRI), single photon emission computerized tomography (SPECT), and proton magnetic resonance spectroscopy (1H‐MRS), to show neuroanatomical, perfusional and neurochemical details, respectively.

Quitting cigarette smoking results in a fast improvement of in vivo oxidation injury (determined via plasma, serum and urinary isoprostane).

Isoprostanes (IP) have been identified as reliable markers of in vivo oxidation injury. Recently, in vascular tissue and blood as well as urine of cigarette smokers, increased IP values have been discovered. We examined 47 adults (26 males, 21 females; aged 30-66 years), admitted to a cardiovascular unit on an outpatient basis, with various risk factors but without any sign of manifestation of atherosclerosis. Refraining from cigarette smoking for a few days resulted in a significant drop of plasma, serum, and urinary 8-epi-PGF(2alpha). Thereafter, a further continuous decrease was monitored, reaching a steady state after about 4 weeks after quitting cigarette smoking. Prevalues of 8-epi-PGF(2alpha) were higher, depending on the type and number of risk factors; the decrease after quitting, however, was comparable. These results indicate that exsmokers may rapidly recover from their enhanced in vivo oxidation.

Association between brain natriuretic peptide and extracellular water in hemodialysis patients.

Background: Brain natriuretic peptide (BNP) is a hormone released by the left ventricle (LV) as a consequence of pressure or volume load. BNP increases in left ventricle hypertrophy (LVH), LV dysfunction, and it can also predict cardiovascular mortality in the general population as well as those undergoing hemodialysis (HD). We investigated the association between BNP and volume load in HD patients. Methods: We studied 32 HD patients (60 ± 17.1 years) treated thrice-weekly for at least 6 months. Exclusion criteria were: LV dysfunction, atrial fibrillation, malnutrition. Blood chemistries and BNP were determined on mid-week HD day. Blood pressure (BP) and cardiac diameters were determined on mid-week inter-HD day by using 24-hour ambulatory blood pressure monitoring and echocardiography. Bioimpedance was performed after HD and extracellular water (ECW%), calculated as a percentage of total body water, was considered as the index of volume load. Results: Patients were divided into quartiles of 8 patients depending on the BNP value: 1st qtl BNP ≤45.5 pg/ml (28.4 ± 10.9 pg/ml), 2nd qtl BNP > 45.5 pg/ml and ≤99.1 pg/ml (60.9 ± 15.8 pg/ml), 3rd qtl BNP > 99.1 pg/ml and ≤231.8 pg/ml (160.5 ± 51.8 pg/ml), 4th qtl BNP > 231.8 pg/ml (664.8 ± 576.6 pg/ml). No inter-quartile differences were reported in age, HD age, body mass index spKt/V, or blood chemistries. As expected patients in the 4th BNP quartile showed the highest values of 24-hour pulse pressure (PP) and LV mass index (LVMi). The study of body composition revealed significant differences in ECW%, which was higher in the 4th quartile when compared to the others (4th q: 50 ± 9.6%, vs 1st q. 40.1 ± 2.4%, 2nd q. 41.9 ± 5%, 3rd q. 42.8 ± 6.9%). Using multiple stepwise linear regression where BNP was the dependent variable, and PP and ECW% the independent variables, only ECW% maintained statistical significance as a predictor of BNP levels (PP: Beta = 0.86, p = 0.58; ECW%: Beta = 0.64, p < 0.001 p < 0.001). Conclusions: Few studies have investigated the relationship between plasma BNP and volume load, and direct evidence is lacking. We used bioimpedance and the determination of ECW% to assess volume state in HD patients finding an association between BNP and ECW. The increased synthesis and release of BNP from the LV in HD patients appear to be mainly related to volume stress rather than to pressure load.

SERUM ANTI-GFAP AND ANTI-S100 AUTOANTIBODIES IN BRAIN AGING, ALZHEIMER'S DISEASE AND VASCULAR DEMENTIA

Autoantibodies against glial fibrillary acidic protein (GFAP) and S100 protein were measured in sera of patients suffering from vascular dementia (VD), presenile Alzheimers disease (AD), senile Alzheimers disease (SDAT) and aged healthy controls by means of ELISA test. VD and SDAT showed the highest levels of both autoantibodies, AD the lowest. From these results a relationship between autoantibody titers and aging seems possible. Dosage of anti-GFAP and anti-S100 autoantibodies does not appear useful for diagnostic purpose because of the overlap observed among groups. Rather, the presence of these antibodies seems to reflect an alteration of the blood-brain barrier that promotes the access of central nervous system antigens to immunocompetent cells.

Angiotensin converting enzyme deletion allele in different kinds of dementia disorders.

In order to verify the association of Angiotensin converting enzyme (ACE) gene with different kinds of dementia, as well as its association with APO-E (genotype), we performed ACE genotyping in subjects with late-onset probable Alzheimers disease (LOAD, n = 64), early-onset probable Alzheimers disease (EOAD, n = 32), possible Alzheimers disease (pAD, n = 44), vascular dementia (VD, n = 12), age-associated memory impairment (AAMI, n = 15) and 40 healthy age-matched controls, who were previously characterized for APO-E. After the principal component analysis ACE D and Apo-Eepsilon4 alleles disclosed the highest prevalence in the cognitively impaired groups of subjects, Apo-Eepsilon4 being more specific for LOAD and pAD. ACE D allele seems to be an unspecific susceptibility factor for mental decline.

Enhanced oxidative stress in coronary heart disease and chronic heart failure as indicated by an increased 8-epi-PGF2α

The role of oxidation injury as an important factor in the pathophysiology of cardiomyopathy (CMP) has recently gained increasing interest. Semiquantitative analysis for isoprostane, 8‐epi‐prostaglandin F2α (8‐epi‐PGF2α), and oxidised low‐density lipoprotein (ox‐LDL) of coronary vascular tissue samples derived from CMP patients revealed an increased extent and intensity of uptake as compared to the respective controls. To evaluate oxidative stress in vivo, we examined plasma, serum, salivary, and urinary 8‐epi‐PGF2α in patients with dilated CMP (n=20) and ischemic CMP (n=20) with decreased left ventricular ejection fraction (LVEF). Patients with coronary heart disease (CHD) (n=20) and 20 healthy, age‐matched, and sex‐matched controls were investigated in parallel. 8‐Epi‐PGF2α levels were correlated with the functional severity of heart failure [New York Heart Association (NYHA) classification] and LVEF. 8‐Epi‐PGF2α levels were matched according to risk factors (smoking and hypercholesterolemia) and were significantly higher in patients with CMP as compared to healthy controls and patients with CHD in all investigated compartments. A positive correlation between NYHA stages and 8‐epi‐PGF2α, as well as a negative correlation to LVEF, could be demonstrated in a subgroup analysis.

67Ga-SPECT/CT with a hybrid system in the clinical management of lymphoma

PurposeThe purpose of this study was to investigate the added value of co-registered fusion imaging using a hybrid system in patients with lymphoma.MethodsTwenty-four lymphoma patients underwent 67Ga-SPECT/CT using a hybrid tomograph consisting of a dual-head, variable-angle gamma camera and a low-dose X-ray tube. Results were compared with those of SPECT alone.Results Forty-five lesions were identified by SPECT alone, while 49 were detected by SPECT/CT. Forty out of the 45 lesions observed on SPECT were confirmed as lymphoma, but five were due to other causes (thoracic aorta blood pool activity, sialoadenitis in the submandibular gland, bowel activity, rib fracture and bone marrow activation due to radiotherapy). SPECT/CT identified nine more neoplastic lesions compared with SPECT alone: four areas of radiopharmaceutical accumulation were observed in para-aortic lymph nodes, three in the spleen, one in the liver and one in para-iliac lymph nodes. In five cases, SPECT/CT provided additional anatomical information over SPECT alone. In four patients, four large areas of 67Ga uptake (one mediastinal, two supraclavicular and one para-aortic) were better characterised; in one subject uptake was localised in the seventh thoracic vertebra only by SPECT/CT. Hybrid imaging provided additional data in 13 patients (54.2%), thus inducing oncologists to reconsider the therapeutic approach in eight subjects (33.2%): unnecessary treatment was avoided in four (16.6%) while therapy was altered in another four (16.6%).ConclusionSPECT/CT hybrid system is able to provide information not obtained by SPECT alone. It allows the anatomical localisation of lymphoma and physiological radiopharmaceutical uptake, facilitates the diagnosis of tumours located in the abdomen (subdiaphragmatic lesions) and provides information that may cause a change in therapeutic strategy.

Isoprostanes quickly normalize after quitting cigarette smoking in healthy adults.

Background: Isoprostanes and in particular 8-epi-PGF2alpha have been claimed as a useful measure for in-vivo oxidation injury. While smokers show elevated 8-epi-PGF2alpha, the behaviour during quitting smoking is unknown. Methods and results: We determined 8-epi-PGF2alpha in 7 healthy adults ready to quit smoking in plasma, serum and urine by means of an enzyme immunoassay after extraction and purification before quitting smoking and during a follow-up period of 4 weeks. After quitting smoking, 8-epi-PGF2alpha shows a rapid decline within a few days almost completely normalizing within 4 weeks. Conclusion: The cigarette-smoking associated in-vivo oxidation injury almost completely disappears within 4 weeks of quitting smoking.BACKGROUND Isoprostanes and in particular 8-epi-PGF2 alpha have been claimed as a useful measure for invivo oxidation injury. While smokers show elevated 8-epi-PGF2 alpha the behaviour during quitting smoking is unknown. METHODS AND RESULTS We determined 8-epi-PGF2 alpha in 7 healthy adults ready to quit smoking in plasma, serum and urine by means of an enzyme immunoassay after extraction and purification before quitting smoking and during a follow-up period of 4 weeks. After quitting smoking, 8-epi-PGF2 alpha shows a rapid decline within a few days almost completely normalizing within 4 weeks. CONCLUSION The cigarette-smoking associated invivo oxidation injury almost completely disappears within 4 weeks of quitting smoking.

Cerebrospinal fluid neuron-specific enolase in Alzheimer's disease and vascular dementia

Levels of neuron-specific enolase (NSE), a glycolytic enzyme localized in neurons, were measured in serum and cerebrospinal fluid (CSF) of patients with early-onset (e-AD) and late-onset (l-AD) Alzheimers disease, vascular dementia (VD) and controls. Mean CSF NSE levels in patients with Alzheimers disease did not significantly differ from those in controls, although in the AD group a correlation was found between NSE levels and severity of cognitive deficits. In VD patients, CSF NSE was lower than in controls or in AD patients. These findings are of physiopathological interest but suggest that CSF NSE is not a useful biological marker in dementia disorders.