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We present the case of a patient with an atypical course of frontotemporal lobar degeneration (FTLD) complicated by the use of an anticholinergic drug. A 70-year-old patient, followed by psychiatrists for depression and behavioral disorders, received a diagnosis of dementia with Lewy bodies (DLB) at another Center due to auditory hallucinations, gait impairment, and tendency to fall. He was then admitted to our Memory Clinic Unit for behavioral disturbances, such as delusional thinking, auditory hallucinations, and memory complaints. At that time, the patient's therapy included Lorazepam, Quetiapine, Promazine, and Biperiden. The latter was immediately suspended for the absence of extrapyramidal signs and to avoid the anticholinergic cognitive side effects. A 18F-FDG PET showed a derangement of cortical metabolism with diffusely reduced activity, and limited areas of hyperactivity involving lateral frontal and lateral temporal inferior regions bilaterally. The patient underwent a series of exams, including neuropsychological tests, 123I-MIBG scintigraphy, cerebrospinal fluid examination, and genetic analysis. A second 18F-FDG PET showed an extensive remodulation of metabolic activity: relative higher concentration of the tracer in the prefrontal and inferior temporal cortex was no more detectable. Similarly, the diffuse reduced metabolic activity could not be traced anymore. Nonetheless, the metabolic activity still appeared reduced in the frontal lobe, in the anterior cingulate bilaterally, and in the anterior part of the hemispheric fissure. Taken together, clinical and neuroimaging features would point to a FTLD-like form. Furthermore, the diagnostic work-up was likely confounded by the anticholinergic drug on 18F-FDG PET, highlighting the importance of carefully checking the patient's pharmacology during the diagnostic process.

We report the case of a woman firstly referred to our Memory Clinic at the age of 61, following the development of cognitive complaints and difficulties in sustained attention. The investigation that was performed showed: predominant executive dysfunctions at the neuropsychological evaluation, with mild, partial and stable involvement of the memory domain; cortical and subcortical atrophy with well-preserved hippocampal structures at MRI; marked fronto-temporal and moderate parietal hypometabolism from 18F-FDG PET study with a sparing of the posterior cingulate and precuneus; positivity of amyloid-β at 18F-Flutemetamol PET; an hexanucleotide intermediate repeats expansion of C9ORF72 gene (12//38 repeats) and ApoE genotype ɛ4/ɛ4. The patient was diagnosed with probable early onset frontal variant of Alzheimer's disease (AD), presenting with a major executive function impairment. The lack of specific areas of brain atrophy, as well as the failure to meet the clinical criteria for any frontotemporal dementia, drove us to perform the aforementioned investigations, which yielded our final diagnosis. The present case highlights the need to take into consideration a diagnosis of frontal variant of AD when the metabolic and the clinical picture are somehow dissonant.

A new institutional clinical trial assessed the improvement of sleep disorders in 40 children with autism treated by immediate-release melatonin formulation in different regimens (0.5 mg, 2 mg, and 6 mg daily) for one month. The objectives of present study were to (i) prepare low-dose melatonin hard capsules for pediatric use controlled by two complementary methods and (ii) carry out a stability study in order to determine a use-by-date. Validation of preparation process was claimed as ascertained by mass uniformity of hard capsules. Multicomponent analysis by attenuated total reflectance Fourier transformed infrared (ATR-FTIR) of melatonin/microcrystalline cellulose mixture allowed to identify and quantify relative content of active pharmaceutical ingredients and excipients. Absolute melatonin content analysis by high performance liquid chromatography in 0.5 mg and 6 mg melatonin capsules was 93.6%±4.1% and 98.7%±6.9% of theoretical value, respectively. Forced degradation study showed a good separation of melatonin and its degradation products. The capability of the method was 15, confirming a risk of false negative <0.01%. Stability test and dissolution test were compliant over 18 months of storage with European Pharmacopoeia. Preparation of melatonin hard capsules was completed manually and melatonin in hard capsules was stable for 18 months, in spite of low doses of active ingredient. ATR-FTIR offers a real alternative to HPLC for quality control of high-dose melatonin hard capsules before the release of clinical batches.

Dementia is one of the most disabling health conditions in older people. Increasing attention is paid to the preclinical phase of dementia and to the prevention programs to reduce the number of patients in the future. Aims of the current study are: a) to present Mild Cognitive Impairment (MCI) as a heterogeneous risk factor and to expose the relationship between cognitive impairment and lifestyles such as physical activity, Mediterranean diet, reading and socialization; b) to present a model, called "Camminando e leggendo… ricordo" (CLR), as a practical experience of secondary prevention aimed at MCI older people. The CLR model is composed of a program of physical and reading activities in group to promote healthy lifestyles. Here we present a protocol to evaluate the effectiveness of our intervention model. A multidimensional geriatric assessment will be carried out. A questionnaire for the detection of frailty, disability and for the adherence to the Mediterranean diet will be administered. The Psychological General Well-Being Index (PGWBI) will be used to assess the quality of life. CLR is an intervention model for secondary prevention in MCI subjects. It is the description of a practical proposal aimed at improving lifestyles and reducing the risk of dementia.

Objectives: Cognitive Stimulation (CS) trainings are non-pharmacological treatments widely used in dementia care. 3R Mental Stimulation is a particular type of CS, which consists of sequential association of ROT, Reminiscence and Remotivation during the same session. This pilot study sought to investigate whether CS, based on 3R program, could benefit cognitive functions, autonomy and behavioral disorders., Method: 3R-CS treatment was applied to 36 patients, which are part of the "TREDEM" study sample, and their caregivers. All patients received a multidimensional assessment consisting of a socio-demographic, clinical and neuropsychological data collection., Results: After CS treatment a significant improvement was detected in cognition and autonomy in basic activities of daily living. Caregiver distress was decreased. Behavioral disturbances were reduced even when considering a potential confounding factor such as treatment with anticholinesterase or NMDA receptor antagonist drugs., Conclusion: The findings demonstrated that 3R-CS can benefit cognitive functions and level of autonomy in the basic activities of daily living and also it can reduce behavioral disorders and caregiver's distress.

Background: The Multidimensional Prognostic Index (MPI) based on a comprehensive geriatric assessment has been developed to predict mortality in hospitalized elderly patients. The Treviso Dementia (TREDEM) Study is an observational prospective cohort study of 1,364 outpatients evaluated at the Cognitive Impairment Center in Treviso, Italy from 2000 to January 2010., Objective: To use the MPI in the TREDEM outpatient setting to assess the correlation of MPI with mortality and hospitalizations for acute cases that occurred after the date of assessment., Methods: MPI was consecutively applied to the last 340 of 1,364 outpatients who were evaluated at the Center from 2008 to January 2010, after the first publication of MPI index in 2008. Participants' mortality was verified by linking the cohort with Registries of Municipalities, National Register of Revenue Authorities, and Nominal Register of Causes of Death. Data about hospitalizations for acute cases that occurred within 12 months after the date of assessment were obtained from all Italian hospitals. A Cox regression method was used to investigate the effect of MPI upon mortality and hospitalizations, also considering confounder factors such as age and gender., Results: 114 men and 226 women, aged 52.1-99 years (mean age 80.4 years), were studied and had an MPI mean of 0.41. On 15 February 2013, 100 were deceased, and average hospitalizations for acute cases were 0.3, days 3.8. For MPI scores between 0 and 1, the increase in the probability of death was more than nine times (odds: 9.53 p = 0.0002) and of hospitalization was more than six times (odds: 6.50, p = 0.0079)., Conclusion: MPI discloses the risk of death and of hospitalizations for acute cases in outpatients affected by cognitive impairment.

Background: The incidence of dementia increases exponentially with age but knowledge of real disease-modifying interventions is still limited., Objectives: To describe the study design and methods of a large prospective cohort study aimed at exploring the complex underlying relationships existing among cognition, frailty, and health-related events in older persons with cognitive impairment., Design: Prospective cohort study of a representative population of outpatients attending the Treviso Cognitive Impairment Center between 2000 and 2010., Setting: The TREVISO DEMENTIA (TREDEM) Study conducted in Treviso, Italy., Participants: 490 men and 874 women, mean age 79.1 ± 7.8 years (range 40.2-100 years)., Measurements: Physiological data, biochemical parameters, clinical conditions, neuroradiological parameters (e.g., brain atrophy and cerebral vascular lesions identified by computerized tomography scans), neuropsychological assessment, and physical function markers were measured at baseline. Patients were followed-up to 10 years., Results: The final sample included in the study was predominantly composed of women and characterized by an initial physical function impairment and increased vascular risk profile. Cognitive function of the sample population showed moderate cognitive impairment (Mini Mental State Examination 20.2 ± 6.3; Clinical Dementia Rating 1.2 ± 0.7), and a prevalence of vascular dementia of 26.9%. Cortical, subcortical and hippocampus atrophy were all significantly correlated with age and cognitive function., Conclusion: Results obtained from the preliminary analyses conducted in the TREDEM study suggest that the database will support the accomplishment of important goals in understanding the nature of cognitive frailty and neurodegenerative diseases.

Background: This study is aim to investigate concurrent long-term psychiatric, cognitive and neurophysiological measures of alpha-IFN neurotoxicity in the treatment of chronic viral hepatitis., Methods: Twenty patients with HCV hepatitis were enrolled while treated with alpha-IFN (3-6 MU t.i.w. for 6-12 months). Neurotoxicity was evaluated by psychiatric [Hamilton Depression Rating Scale (HAM-D), Hamilton Scale for Anxiety (HAM-A), Beck Depression Inventory (BDI) and State-Trait Anxiety Inventory (STAI-Y)], complete cognitive and neurophysiological assessments (EEG spectral analysis, P300). Patients were assessed at baseline (t0), 2 (t1) and 6 months (t2) since the beginning of therapy., Results: Depression scores significantly increased (HAM-D: t0=4.4+/-2.6; t1=8.9+/-3.9, p<0.001; and t2=7.7+/-3.8, p<0.001). A concurrent increase was shown also for anxiety (HAM-A: t0=6.0+/-3.2; t1=9.6+/-4.5, p<0.005; and t2=9.1+/-4.5, p<0.005). Significant neurophysiological effects were also detected: increase of alpha power (p<0.05) in frontal derivations, reduction of the mean dominant frequency (p<0.005) and increase of theta power (p<0.05) in parietal derivations. In contrast, no significant cognitive changes occurred., Limitations: The study was performed on a relative small sample of patients mainly with observational intentions. Biological data (e.g. blood cytokines samples) are not available: they could have given useful information about biological mechanisms related to the alterations observed., Conclusions: Alpha-IFN treatment caused a time-dependent induction of symptoms of mild depression, concurrent anxiety and EEG changes. These psychiatric and neurophysiological changes can better explain the pharmacological profile of alpha-IFN and could help to address research on at risk population and, particularly, during pegylated-IFN therapy.