Antonio Leo

Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression

To date there are no biomarkers with proven reliability as a measure of disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to assess the neurofilament light chain (NFL) in cerebrospinal fluid (CSF) samples as a measure of disease activity and progression in ALS.

Cerebrospinal fluid neurofilament light chain levels: marker of progression to generalized amyotrophic lateral sclerosis

To evaluate whether cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels could predict the time to generalization (TTG) in amyotrophic lateral sclerosis (ALS).

The prevalence of peripheral and central hearing impairment and its relation to cognition in older adults.

Age-related hearing loss (ARHL) and dementia are two highly prevalent conditions in the adult population. Recent studies have suggested that hearing loss is independently associated with poorer cognitive functioning. The aim of this study was to evaluate the prevalence of ARHL and cognitive impairment in a large sample of subjects older than 65 years and to correlate hearing function with cognitive function. A total of 488 subjects older than 65 years (mean age 72.8 years) participating in the Great Age Study underwent a complete audiological, neurological and neuropsychological evaluation as part of a multidisciplinary assessment. The prevalence of a hearing loss greater than 25 dB HL was 64.1%, of Central Auditory Processing Disorder (CAPD) was 14.3 and 25.3% of the subjects reported a hearing handicap as reported on the Hearing Handicap Inventory for the Elderly Screening Version questionnaire. Multiple logistic regression analysis corrected for gender, age and education duration showed that mild cognitive impairment (MCI) was significantly associated with hearing impairment (CAPD and hearing threshold; odds ratio 1.6, p = 0.05) and that Alzheimers disease (AD) was significantly associated with CAPD (odds ratio 4.2, p = 0.05). Given that up to 80% of patients affected by MCI convert to AD, adding auditory tests to a screening cognitive battery might have value in the early diagnosis of cognitive decline.

Emerging drugs to reduce abnormal β-amyloid protein in Alzheimer’s disease patients

ABSTRACT Introduction: Currently available drugs against Alzheimer’s disease (AD) target cholinergic and glutamatergic neurotransmissions without affecting the underlying disease process. Putative disease-modifying drugs are in development and target β-amyloid (Aβ) peptide and tau protein, the principal neurophatological hallmarks of the disease. Areas covered: Phase III clinical studies of emerging anti-Aβ drugs for the treatment of AD were searched in US and EU clinical trial registries and in the medical literature until May 2016. Expert opinion: Drugs in Phase III clinical development for AD include one inhibitor of the β-secretase cleaving enzyme (BACE) (verubecestat), three anti-Aβ monoclonal antibodies (solanezumab, gantenerumab, and aducanumab), an inhibitor of receptor for advanced glycation end products (RAGE) (azeliragon) and the combination of cromolyn sodium and ibuprofen (ALZT-OP1). These drugs are mainly being tested in subjects during early phases of AD or in subjects at preclinical stage of familial AD or even in asymptomatic subjects at high risk of developing AD. The hope is to intervene in the disease process when it is not too late. However, previous clinical failures with anti-Aβ drugs and the lack of fully understanding of the pathophysiological role of Aβ in the development of AD, put the new drugs at substantial risk of failure.

Serum N-acetylaspartate Level in Amyotrophic Lateral Sclerosis

BACKGROUND N -acetylaspartate (NAA) level is a biomarker of functional integrity and vitality in neurons. In vivo multisection proton ((1)H)-magnetic resonance spectroscopy studies indicate that NAA level decreases in specific cortical brain areas of patients with amyotrophic lateral sclerosis (ALS). OBJECTIVE To study NAA level in serum samples as a possible biomarker of ALS. DESIGN Serum NAA assay by liquid chromatography-mass spectrometry in a case-control series. SETTING Department of Neurological and Psychiatric Sciences, Policlinico, University of Bari, Bari, Italy. PATIENTS One hundred twelve consecutive patients with ALS and 51 age- and sex-matched healthy control subjects. MAIN OUTCOME MEASURES General estimating equations tested associations between serum NAA level and clinical variables in patients with ALS. RESULTS Serum NAA level was significantly higher in ALS cases than in controls. Multivariate logistic regression analysis showed a direct association between serum NAA level and the presence of ALS. After stratifying serum NAA level based on the median value (0.171 mmol/L), the age- and sex-adjusted odds ratio for ALS was 19.97 (95% confidence interval, 7.18-55.55) (P < .001). N -acetylaspartate level did not differ across ALS clinical phenotypes. Riluzole treatment did not affect NAA level. A significant correlation was found between serum NAA level and ALS progression rate. CONCLUSIONS High serum NAA level was found in patients with ALS, which may relate to greater excretion of NAA into the blood circulation following increased release of this metabolite from damaged neurons. The correlation between serum NAA level and disease progression rate suggests that it may be a useful biomarker of ALS.

Qualitative analysis of the capacity to consent to treatment in patients with a chronic neurodegenerative disease: Alzheimer’s disease / Analisi qualitativa sulla capacità a prestare consenso al trattamento in pazienti con malattie cronico degenerative neuropsicoorganiche: Demenza di Alzheimer:

Objective: Informed consent is an essential element in doctor–patient relationship. In particular, obtaining valid informed consent from patients with neurocognitive diseases is a critical issue at present. For this reason, we decided to conduct research on elderly patients with Alzheimer’s disease (Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) to assess their capacity to make treatment decisions. Methods: The experimental group comprised 70 Alzheimer patients who were admitted to the Neurodegenerative Disease Unit of the University of Bari. The control group consisted of 83 elderly patients without neurocognitive disorders who were hospitalized in the Geriatric Unit at the same university. After providing written consent to participate in the research, each subject underwent the following assessments: (a) assessment of comprehension sheet, (b) Neuropsychiatric Inventory (NPI) and Global Functioning Evaluation (GFE), (c) neurological evaluation, (d) neuropsychological assessment with a full battery of tests, (d) The MacArthur Treatment Competence Study (MacArthur Competence Assessment Tool for Treatment (MacCAT-T); understanding, appreciating, reasoning and expressing a choice) and (e) a semi-structured interview administered by the patient’s caregiver. Results/conclusion: The present survey was designed to analyze possible qualitative and quantitative correlations between cognitive functioning and capacity to consent in relation to different degrees of severity of the neurodegenerative disorder. A large portion of the patients in our experimental sample did not appear to have the capacity to provide a valid consent. The authors present initial results of this study and discuss their possible implications.

Approach to the patient hospitalized during the Muslim Ramadan: bioethical and clinical considerations

Multi-ethnicity has been persuading the healthcare professionals to increasingly learn new tools in terms of cultural and social skills, in order to cope with a diversified variety of patients. The coexistence of different cultures in Italy can be found in the migration flows over the last few decades. The cohabitations between individuals with different ethnicity in our territory has led the health professionals to address some anthropological, moral, religious and political issues implied in populations and cultures different from ours. Clinical literature has made us aware of the importance of correct communication between doctor and patient in order to determine the diagnostic-therapeutic plan, especially in the patients with a foreign origin due to the linguistic and intercultural differences implicated. In an emergency condition, it may occur to cure the patients neglecting their cultural identity and, in so doing, to create misunderstandings that, in turn, can lead to a lack of human relationship and frustrate the therapeutic project. An example is the treatment of Muslim people. The authors, through the description of a case observed during Ramadan, analyze the variables applying to the therapeutic decision making process.