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Background: Few studies have examined the associations between personality facets and dementia risk and rarely included individuals from rural settings or with low education., Objective: To examine the association between personality and the risk of cognitive impairment., Methods: Participants (N = 1,668; age 50 to 94 at baseline; 56.4% women; 86.5% less than high school diploma) were from a rural region of Sardinia (Italy) who completed the Revised NEO Personality Inventory (NEO-PI-R) during the first wave (2001-2004) and the Mini-Mental State Examination (MMSE) at waves two to five (2005-2021). Cox regression was used to test personality and covariates as predictors of cognitive impairment based on MMSE education-adjusted cutoffs., Results: During the up to 18-year follow-up (M = 10.38; SD = 4.76), 187 individuals (11.2%) scored as cognitively impaired. Participants with higher neuroticism (particularly the depression facet [HR = 1.22, 95% CI = 1.06-1.40]), and lower agreeableness (particularly the modesty facet [HR = 0.83, 95% CI = 0.71-0.97]) and lower conscientiousness (particularly the dutifulness facet [HR = 0.78, 95% CI = 0.67-0.92]) were at higher risk of cognitive impairment. Lower warmth ([HR = 0.75, 95% CI = 0.65-0.87], facet of extraversion) and ideas ([HR = 0.76, 95% CI = 0.65-0.89], facet of openness) were also associated with increased risk of impairment. These associations were virtually unchanged in models that accounted for other risk factors, including smoking, depression, obesity, hypertension, diabetes, and apolipoprotein E (APOE) ɛ4 carrier status. Across the five domains, sex and the APOE variant did not moderate the associations., Conclusion: In a sample with demographic characteristics underrepresented in dementia research, this study identifies personality domains and facets most relevant to the risk of cognitive impairment.

Objectives: This case control study sought to assess the presence and characteristics of cardiac abnormalities in patients with Alzheimer disease (AD)., Background: Protein misfolding is involved in the pathophysiology of neurodegenerative disorders such as AD. Recently, amyloid-beta (Aβ) aggregates were identified within the cardiomyocytes and interstitium of patients with AD, suggesting that Aβ oligomers may reach and damage the heart., Methods: The authors studied 32 patients with AD and 34 controls matched by age and sex, all of whom were free from cardiac or systemic diseases. A clinical evaluation, an electrocardiogram, and an echocardiogram were performed in all subjects. Furthermore, patients with AD underwent genetic analyses (of the PSEN1, PSEN2, APP, and APOE genes)., Results: Compared to the control group, patients with AD had a higher prevalence of low-voltage electrocardiographic QRS complexes (28% vs. 3%, respectively; p = 0.004), a lower voltage/mass ratio (p = 0.05), a greater echocardiographic interventricular septum (10.1 ± 1.3 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.01), a greater maximum wall thickness (10.8 ± 1.7 mm vs. 9.3 ± 1.1 mm, respectively; p = 0.0001), and a 2-fold higher prevalence of diastolic dysfunction (70% vs. 35%, respectively; p = 0.007). Symptoms and signs of heart failure were absent in all patients with AD., Conclusions: This study shows that electrocardiographic and echocardiographic abnormalities, including diastolic dysfunction, are present in patients with AD and that these studies reproduce the pattern of cardiac amyloidosis. These findings suggest that, in AD, there may be subclinical cardiac involvement likely associated with Aβ amyloid deposition. The clinical relevance of these cardiac abnormalities should be evaluated in larger prospective studies., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Prophylaxis of hepatitis B after liver transplantation with antiviral(s) and immunoglobulins efficiently protect the majority of recipients; however recent experiences suggest a decline of HBsAg-positive candidates and the use of hepatitis B Immunoglobulin-free schedules., Methods: This national survey evaluated the epidemiology and clinical results of hepatitis B prophylaxis among 10,365 liver transplants performed in 25 years in 13 Italian centers., Results: With a percentage of 22, 2260 procedures were performed in HBsAg-positive recipients and 714 out of 1080 anti-HBc-positive grafts were used in HBsAg-negative recipients; a total of 2974 patients (29%) were considered at risk of hepatitis B after liver transplantation. Similar rates (18% of HBsAg-positive candidates and 15% of anti-HBc-positive grafts) were registered in the last collected year. Combined prophylaxis with Hepatitis B Immunoglobulins remained prevalent among centers and was effective in 96% of HBsAg-positive recipients and in 94% of HBsAg-negative recipients of anti-HBc-positive grafts., Conclusions: Data from this survey confirm: the excellent results of combined prophylaxis; the past and persistent use of Hepatitis B Immunoglobulin-on and only rare -off prophylactic regimens, in contrast with the newest reports; the increasing use of anti-HBc-positive grafts; the past and present high prevalence of HBsAg-positive recipients, due to an increase in candidates with either hepatocellular carcinoma and Hepatitis Delta Virus coinfection in the last years.

We evaluated the clinical usefulness of the combined use of I-ioflupane brain single photon emission computed tomography (SPECT) and I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy in discriminating uncertain parkinsonism with vascular lesions in striatal nuclei at magnetic resonance imaging (MRI). Forty-three consecutive patients with uncertain parkinsonism and vascular lesions at MRI in striatal nuclei were retrospectively evaluated; the uncertain differential diagnosis was between Parkinson's disease and vascular parkinsonism (PD/VP) in 22 patients, between PD and other neurodegenerative parkinsonism (PD/PS) in 11 patients and between Lewy body dementia and Alzheimer disease (LBD/AD) in the remaining 10 cases. All patients underwent I-ioflupane SPECT with striatal dopaminergic activity determination as binding potentials (BP; cut-off: 3.3). I-MIBG cardiac planar scintigraphy was performed 2 weeks later, in early (15 minutes) and delayed (240 minutes) phases also calculating heart to mediastinum (H/M) ratio (cut-off: 1.56). I-Ioflupane uptake was normal in 9 patients with BP values >3.3, while it was reduced in 34/43 cases with BP values <3.3 at least in one of the striatal nuclei. I-MIBG uptake was normal in 21/43 patients (5 of whom with normal and 16 with I-ioflupane striatal defects) showing the H/M ratio >1.56 in all cases; the uptake was reduced in 22/43 cases, (4 of whom were normal and 18 were with I-ioflupane striatal defects) with the H/M ratio <1.56 in all cases. No statistical differences were found when early and delayed H/M ratios were mutually compared. Combining the 2 radioisotopic procedures, a more reliable diagnosis was achieved in 39/43 cases properly classifying 13 PD, 10 VP, 7 PS, 5 LBD, and 4 AD. However, the diagnosis remained uncertain in four patients with normal I-ioflupane and reduced I-MIBG uptake. The results of the present study confirmed that in uncertain parkinsonian syndromes associated with vascular lesions in striatal nuclei, brain I-ioflupane SPECT alone did not prove able to discriminate between the different forms of disease. Only the association with I-MIBG cardiac scintigraphy, also with the early acquisition alone, allowed the most appropriate diagnosis in 90.7% of our cases. However, patients with normal I-ioflupane and reduced I-I-MIBG uptakes need a close clinical and instrumental follow-up as sympathetic damage could precede striatal disorders in the early stage of PD and LBD.

Cognitive dysfunction in patients with chronic hepatitis C virus (HCV) infection is a distinct form of minimal hepatic encephalopathy (MHE). In fact, the majority of HCV-positive patients, irrespective of the grading of liver fibrosis, display alterations of verbal learning, attention, executive function, and memory when they are evaluated by suitable neuropsychological tests. Similarities between the cognitive dysfunction of HCV patients and MHE of patients with different etiologies are unclear. It is also unknown how the metabolic alterations of advanced liver diseases interact with the HCV-induced cognitive dysfunction, and whether these alterations are reversed by antiviral therapies. HCV replication in the brain may play a role in the pathogenesis of neuroinflammation. HCV-related brain dysfunction may be associated with white matter neuronal loss, alterations of association tracts and perfusion. It is unclear to what extent, in patients with cirrhosis, HCV triggers an irreversible neurodegenerative brain damage. New insights on this issue will be provided by longitudinal studies using the protocols established by the diagnostic and statistical manual of mental disorders fifth edition for cognitive disorders. The domains to be evaluated are complex attention; executive functions; learning and memory; perceptual motor functions; social cognition. These evaluations should be associated with fluorodeoxyglucose positron emission tomography and magnetic resonance imaging (MRI) protocols for major cognitive disorders including magnetic resonance spectroscopy, diffusion tensor imaging, magnetic resonance perfusion, and functional MRI. Also, the characteristics of portal hypertension, including the extent of liver blood flow and the type of portal shunts, should be evaluated.

Background: Rapid and early virological responses to peginterferon-alpha and ribavirin are predictive of sustained virological response (SVR) in hepatitis C virus (HCV) infection. We aimed at finding a simple rule to determine the shortest duration of dual therapy for all HCV genotypes, obtained by multiplying time to Initial Viral Response, IVR (first undetectable HCV-RNA) by 4 (Tailored Therapy-4, or TT4)., Method: 267 naïve HCV-infected patients with compensated liver disease were randomized (2:1) to the TT4 (n=180) or current standard-of-care (SoC, n=87) and received peginterferon-alpha plus ribavirin. Patients with HCV-RNA decrease ≤2log10 at week 12 or detectable HCV-RNA at week 24 discontinued treatment., Results: Both groups had comparable baseline characteristics, SVR rates were similar in the whole population (60.6% vs. 60.9%) and within each genotype subgroup (G1: 46.6% vs. 55.6%; G2: 90.2% vs. 94.4%; G3: 74.1% vs. 58.3%; G4: 45.8% vs. 33.3%). Relapse rate was higher in G1-TT4 than G1-SoC. Treatment duration in SVR patients was shorter in TT4 compared to SoC, both overall [25±15 vs. 36±12.1 weeks], and for subgroups: G1 [35.3±16.7 vs. 47.3±2.6 weeks], G2 [18.3±7.5 vs. 24±2.8 weeks], G3 [15.2±8.7 vs. 22.8±3 weeks] and G4 [26.9±13 vs. 48 weeks]., Conclusions: In HCV-naive patients, TT4-rule treatment yields similar SVR rates compared to SoC but with shorter treatment duration and remarkable cost reduction., (Published by Elsevier Ltd.)

Background: Pegylated interferon (PEG-IFN)-alpha monotherapy is the current standard of care for short-term antiviral treatment of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). We aimed to assess the safety and efficacy of PEG-IFN-alpha plus adefovir dipivoxil (ADV) versus PEG-IFN-alpha monotherapy for compensated HBeAg-negative CHB., Methods: A multicentre randomized controlled trial was performed in eight outpatient hepatology/infectious disease clinics in central Italy. A total of 60 patients (67% male and median age 48 years) with biopsy-proven HBeAg-negative compensated CHB (mean alanine aminotranferase [ALT] levels 3.3 +/-3x the upper normal limit and serum hepatitis B virus [HBV] DNA 5.8 +/-0.9 log(10) IU/ml) were randomized at baseline to receive PEG-IFN-alpha2a 180 microg/week plus ADV 10 mg/day or PEG-IFN-alpha2a monotherapy for 48 weeks. Post-treatment follow-up was for 24 additional weeks. The primary end point was sustained HBV DNA suppression defined as serum HBV DNA<2,000 IU/ml after 24 weeks of post-treatment follow-up. The secondary end point was ALT normalization at the end of follow-up., Results: At week 48, HBV DNA was undetectable in 20/30 (67%) in the combination group versus 11/30 (37%) patients in the monotherapy group (P=0.02). ALT normalization was achieved in 17/30 (57%) versus 10/30 (30%) patients, respectively (P=0.03). At week 72, sustained virological response was achieved in 7/30 (23.3%) in the combination group versus 6/30 (20%) patients in the monotherapy group (P=0.75); 5 (16%) patients in each group dropped out because of adverse events or non-compliance., Conclusions: In HBeAg-negative CHB, combination PEG-IFN-alpha2a plus ADV for 48 weeks is safe and resulted in greater on-treatment efficacy than PEG-IFN-alpha2a monotherapy. No difference in sustained virological and biochemical response rates were observed between the two treatment regimens.

Background: Mutations of presenilin 2 gene are a rare cause of familial Alzheimer disease (AD). We describe an Italian family with hereditary dementia associated with a novel mutation in the presenilin 2 gene., Methods: Clinical investigations of the diseased subjects; interviews with relatives; studies of medical records; pedigree analysis; and neuroradiologic, neuropathologic, and molecular genetic studies were carried out in the pedigree., Results: Genetic analysis showed a novel PSEN2 A85V mutation present in the proband and in all analyzed affected members, in a subject presenting with an amnesic mild cognitive impairment, and in a young, still asymptomatic subject. The proband showed a clinical phenotype indicative of Lewy body dementia and the neuropathologic examination demonstrated the presence of unusually abundant and widespread cortical Lewy bodies in addition to the hallmark lesions of AD. Other affected members exhibited a clinical phenotype typical of AD., Conclusions: Our findings add complexity to the spectrum of atypical phenotypes associated with presenilin mutations and should then be taken into account when considering the nosography of neurodegenerative diseases. They also support previous data that specific mutations of genes associated with familial Alzheimer disease may influence the presence and extent of Lewy bodies.

Presenilin-1 (PSEN-1) is a component of the gamma-secretase complex involved in beta-amyloid precursor protein (betaAPP) processing. To date about 140 pathogenic mutations in the PSEN-1 gene have been identified and their main biochemical effect is to increase the production of the fibrillogenic peptide Abeta(1-42). An exception is the PSEN-1 [E318G] mutation that does not alter Abeta(1-42) generation and is generally considered a non-pathogenic polymorphism. Nevertheless, this mutation was reported to be a genetic risk factor for familial Alzheimer's disease (FAD) in the Australian population. To independently confirm this indication, we performed a case-control association study in the Italian population. We found a significant association (p<0.05, Fisher's exact test) between the presence of PSEN-1 [E318G] and FAD. In addition, on measuring the Abeta(1-42) and Abeta(1-40) concentrations in fibroblast-conditioned media cultured from PSEN-1 [E318G] carriers and PSEN-1 [wild type] controls we noted a significant decrease (p<0.05, Mann-Whitney test) in the Abeta(1-42)/Abeta(1-40) ratio in PSEN-1 [E318G] carriers, suggesting a peculiar biochemical effect of this mutation.

Cognitive impairment in multiple sclerosis (MS) has received considerable interest over the last decades. Heterogeneous patterns of cognitive dysfunction have been reported in literature in relation to the subtype of the disease and the severity of specific cognitive domains affected. Event related potentials (ERPs), especially P300, have been employed to evaluate the cognitive decline in MS and neurophysiological findings agree with data obtained by neuropsychological testing. The objectivity, the reliability and the easy administration are the main features of ERP technique but more specific attention and memory tasks are needed to enhance the clinical value of the methodology. Moreover, ERP recording has the advantage of being feasible even in severe disabled patients. Finally, longitudinal ERP studies are required to investigate the natural course of cognitive dysfunction in MS, to estimate the prognostic value of subclinical defects in different clinical form of the disease and to evaluate clinical benefits of therapeutic and rehabilitative interventions.

We describe the genetic analysis of an Alzheimer's disease (AD) sample derived from a genetically isolated population. Genetic assessment included the analysis of genes involved in AD, such as the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2). We also assessed genes for some proteins that constitute the gamma-secretase complex: nicastrin (NCSTN), presenilin enhancer-2 (PEN2), in addition to the AD risk factor apolipoprotein E (APOE). Using polymerase chain reaction and single strand conformational polymorphism method, screens for APP, PSEN1 and PSEN2 genes revealed one mutation in PSEN1. Furthermore, we found an intronic +17G>C polymorphism in PEN2 which, in homozygous form, was greater in early onset Alzheimer's disease (EOAD) compared to controls, and one haplotype in the NCSTN gene which was linked to EOAD and familial AD (FAD). Finally, the genotyping of APOE confirmed that the varepsilon4 allele could be a risk factor for the onset of AD, in particular for FAD subjects. In conclusion, these results show the existence of Sardinian genetic peculiarities, essential in studies regarding genetically inherited and multifactorial disorders, as AD.

Long-standing overt ventriculomegaly in adults (LOVA) is a clinical entity characterized by chronic hydrocephalus with infant onset, slow evolution and clinical disturbances during adulthood. Few cases are reported in literature describing the evident contrast between the severity of hydrocephalus and the relatively spared neurological functioning and cognitive aspects. The authors describe a 59-year-old man with congenital hydrocephalus complaining of persistent gait impairment. Neurological examination showed a mild paraparesis, severe higher cortical function impairment but relatively sparing of daily living activity. Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a very remarkable ventriculomegaly compressing the brain cortex but sparing the cerebellum and the brainstem. Brain Single Photon Emission Computer Tomography (SPECT) showed a prevalent cerebellar perfusion as well. Neuropsychological testing was consistent with severe cognitive deterioration and attention disorders. Language and praxis functions seemed to be preserved. Auditory oddball ERPs (P300) showed morphological abnormalities especially of late components. This case report demonstrates in vivo the level of adaptation to which human brain can reach under chronic mechanic stress conditions. The striking poor cerebral parenchyma representation and the relatively spared language and praxic abilities account for a functional reorganization of residual structures due to the neural plasticity.

Objective: (1) To assess cognitive function and cerebral magnetic resonance imaging (MRI) involvement in relapsing-remitting multiple sclerosis; (2) to monitor disease evolution, cognitive dysfunction, and cerebral lesion burden over time (mean 8.5 year follow up period); (3) to study the relation between clinical, neuropsychological, and MRI data. On follow up assessment, visual and auditory oddball event related potentials (ERPs) were recorded as psychophysiological evaluation of cognitive status. Correlations between neuropsychological, MRI, and ERP data were also analysed., Methods: Neuropsychological study assessed verbal and non-verbal IQ, deterioration index (DI) from WAIS subtests, conceptual reasoning, attention, verbal and visuospatial short-term and long term memory. MRI assessment detected presence of demyelinating lesions by using a semiquantitative method as well as cortical and subcortical atrophy over time., Results: Attention, short-term and long term visuospatial memory were mildly impaired at baseline and remained unaltered longitudinally. At retesting a significant worsening of verbal long term memory (p=0.023), DI presence (p=0.041) and the increase of supratentorial and subtentorial MRI lesions load (p=0.001) emerged. Expanded disability status scale score correlated significantly with total lesion burden at both evaluations (p=0.043 and p=0.024 respectively). Temporal, occipital, and frontal horn lesions as well as cortical atrophy correlated significantly with attention and memory tests at baseline. Follow up assessment revealed significant correlation between cortical atrophy and attention as well as visuospatial short-term memory; spatial long term memory correlated significantly with lesions in body of lateral ventricle and frontal lobe. ERP study showed P300 latency abnormalities in 75% of patients, involving specifically more visual P300 (58.4 % of cases) than auditory wave (41.6 %). Visual P300 latency and amplitude correlated significantly with DI and auditory P300 latency with frontal horn and brain stem lesions., Conclusions: These findings revealed mild cognitive impairment in MS patients particularly consistent with slowing information processing over time. Increased MRI lesions do not correlate with the clinical course of the disease and cognitive deficit evolution. Thus, cognitive dysfunction could be related to disease peculiarity and not to the time course. Correlations between P300, neuropsychological, and MRI findings provide further information about ERP application to examine cognitive impairment in MS and probably to investigate their neural origin.

Objectives: To investigate the relationship between amyotrophic lateral sclerosis (ALS) and cognitive function by means of oddball event-related potentials (ERPs) and to determine the usefulness of this methodology in the cognitive status assessment of physically disabled patients., Methods: Visual and auditory oddball ERPs were recorded in 16 consecutive sporadic ALS patients. A comprehensive battery of neuropsychological (NP) tests assessed intelligence, executive functions, attention, memory, word fluency, visuo-motor and visual-constructive skills., Results: All patients performed visual and auditory ERPs and 75% of cases showed abnormal N200 and/or P300 waves. Ten patients (62.5%) carried out the entire psychometric evaluation with significant impairment on tests of executive function and attention. A significant correlation between delayed visual (P<0.04) and auditory (P<0.04) P300 latency and impaired NP tests was found., Conclusions: In agreement with literature data, our findings confirm the hypothesis of cognitive impairment in ALS patients especially on attention and executive functions suggesting a more extensive degeneration beyond the motor areas. ALS causes severe physical disabilities and such a condition may interfere with NP testing. Thus, the P300 seems to be a useful tool for the assessment of cognition and attention when severe physical deficits are present.

To evaluate possible cause-effect relationships between hyperostosis frontalis interna and cognitive dysfunction, we performed a neurophysiological (event-related potentials, ERPs) and neuropsychological study in a case of Morgagni-Stewart-Morel (MSM) syndrome associated with frontal lobe compression. Neuropsychological evaluation evidenced selective impairment of executive function. Visual and auditory oddball ERPs revealed delayed P300 latency and reduced auditory P300 amplitude with multi-peaked morphology. ERP abnormalities and cognitive dysfunction could be due to the frontal bone-cortex conflict documented by neuroradiological investigations.

We report a case of a 35-year-old female who underwent total hepatectomy and liver transplantation for a diffuse clear cell variant of hepatocellular carcinoma in non-cirrhotic liver. Preoperative clinical evaluation showed no extrahepatic metastatic involvement. However, scheletal metastases of the tumour were detected five months later. Although clear cell variant is generally considered to run a relatively favorable course, this case proved rapidly progressive and seems therefore to be a debatable candidate for liver transplantation among primary hepatic cancers.

We report the case of a patient long resident in Sardinia in whom the clinical history, neurological symptoms, serological and neuroradiological investigations pointed to the diagnosis of neuroborreliosis. We emphasize the rarity of cerebellar involvement in this disease.

A woman with peripheral neuropathy and cerebral atrophy, both secondary to a selective folic acid deficiency caused by severe gastrointestinal disturbances, was given folic acid replacement therapy, which improved her clinical, blood and neurophysiological status.

From 1957 to 1980 in Sardinia, 182 cases of ALS with a mean annual incidence of 0.51 per 100,000 inhabitants and a prevalence rate of 3.65 per 100,000 inhabitants (prevalence day 21.10.1971) were observed. The disease was found to be more common in males, in subjects aged 50 to 70 years and in farmers and shepherds. Incidence in various areas of the island was found to be different. The common form was more frequent, had earlier onset and greater median survival rate.

A young woman with oral apraxia and a well-defined brain lesion on CT scan developed buccolingual dyskinesia lasting 40 days after low phenobarbital (PB) doses. Disruption of the corticostriatal glutamatergic pathway from areas 6 and 4 may have been important both in causing oral apraxia and in lowering the threshold for PB-induced buccolingual dyskinesia.

Serum gastrin concentrations under basal conditions and following stimulation were assessed in 40 patients suffering from rheumatoid arthritis (RA) and compared with healthy individuals. The RA groups showed no significant differences in comparison with the control population. These conclusions lead the authors to seek the reasons for the rare instances of confirmed hypergastrinaemia in RA.