Classification of Single Normal and Alzheimer's Disease Individuals from Cortical Sources of Resting State EEG Rhythms.

Previous studies have shown abnormal power and functional connectivity of resting state electroencephalographic (EEG) rhythms in groups of Alzheimer's disease (AD) compared to healthy elderly (Nold) subjects. Here we tested the best classification rate of 120 AD patients and 100 matched Nold subjects using EEG markers based on cortical sources of power and functional connectivity of these rhythms. EEG data were recorded during resting state eyes-closed condition. Exact low-resolution brain electromagnetic tomography (eLORETA) estimated the power and functional connectivity of cortical sources in frontal, central, parietal, occipital, temporal, and limbic regions. Delta (2-4 Hz), theta (4-8 Hz), alpha 1 (8-10.5 Hz), alpha 2 (10.5-13 Hz), beta 1 (13-20 Hz), beta 2 (20-30 Hz), and gamma (30-40 Hz) were the frequency bands of interest. The classification rates of interest were those with an area under the receiver operating characteristic curve (AUROC) higher than 0.7 as a threshold for a moderate classification rate (i.e., 70%). Results showed that the following EEG markers overcame this threshold: (i) central, parietal, occipital, temporal, and limbic delta/alpha 1 current density; (ii) central, parietal, occipital temporal, and limbic delta/alpha 2 current density; (iii) frontal theta/alpha 1 current density; (iv) occipital delta/alpha 1 inter-hemispherical connectivity; (v) occipital-temporal theta/alpha 1 right and left intra-hemispherical connectivity; and (vi) parietal-limbic alpha 1 right intra-hemispherical connectivity. Occipital delta/alpha 1 current density showed the best classification rate (sensitivity of 73.3%, specificity of 78%, accuracy of 75.5%, and AUROC of 82%). These results suggest that EEG source markers can classify Nold and AD individuals with a moderate classification rate higher than 80%.

Examination of level of knowledge in Italian general practitioners attending an education session on diagnosis and management of the early stage of Alzheimer's disease: pass or fail?

BACKGROUND: We detected the general level of knowledge about the early diagnosis of Alzheimer's disease (AD) and subsequent care in general practitioners (GPs) from Southern Italy. We explored also the GP perception about their knowledge and training on diagnosis and management of AD. METHODS: On a sample of 131 GPs, we administered two questionnaires: the GP-Knowledge, evaluating GPs' expertise about AD epidemiology, differential diagnosis, and available treatments, and the GP-QUestionnaire on Awareness of Dementia (GP-QUAD), assessing the GPs' attitudes, awareness, and practice regarding early diagnosis of dementia. RESULTS: Specific screening tests or protocols to diagnose and manage dementia were not used by 53% of our GPs. The training on the recognition of early AD signs and symptoms was considered inadequate by 55% of the participants. Females were more likely to consider their training insufficient (58%) compared to males (53%). Female GPs were less likely to prescribe antipsychotic drugs to control neuropsychiatric symptoms (NPS) and suggest specialist advice in late stage of cognitive impairment. Multiple Correspondence Analysis (MCA) performed only on GP-QUAD suggested two dimensions explaining 26.1% ("GP attitude") and 20.1% ("GP knowledge") of the inertia for a total of 46.2%, CONCLUSION: In our survey on GP clinical practice, several problems in properly recognizing early AD symptoms and subsequently screening patients to be referred to secondary/tertiary care centers for diagnosis confirmation have emerged. In the future, specific training programs and educational projects for GPs should be implemented also in Italy to improve detection rates and management of dementia in primary care.

Classification of Healthy Subjects and Alzheimer's Disease Patients with Dementia from Cortical Sources of Resting State EEG Rhythms: A Study Using Artificial Neural Networks.

Previous evidence showed a 75.5% best accuracy in the classification of 120 Alzheimer's disease (AD) patients with dementia and 100 matched normal elderly (Nold) subjects based on cortical source current density and linear lagged connectivity estimated by eLORETA freeware from resting state eyes-closed electroencephalographic (rsEEG) rhythms (Babiloni et al., 2016a). Specifically, that accuracy was reached using the ratio between occipital delta and alpha1 current density for a linear univariate classifier (receiver operating characteristic curves). Here we tested an innovative approach based on an artificial neural network (ANN) classifier from the same database of rsEEG markers. Frequency bands of interest were delta (2-4 Hz), theta (4-8 Hz Hz), alpha1 (8-10.5 Hz), and alpha2 (10.5-13 Hz). ANN classification showed an accuracy of 77% using the most 4 discriminative rsEEG markers of source current density (parietal theta/alpha 1, temporal theta/alpha 1, occipital theta/alpha 1, and occipital delta/alpha 1). It also showed an accuracy of 72% using the most 4 discriminative rsEEG markers of source lagged linear connectivity (inter-hemispherical occipital delta/alpha 2, intra-hemispherical right parietal-limbic alpha 1, intra-hemispherical left occipital-temporal theta/alpha 1, intra-hemispherical right occipital-temporal theta/alpha 1). With these 8 markers combined, an accuracy of at least 76% was reached. Interestingly, this accuracy based on 8 (linear) rsEEG markers as inputs to ANN was similar to that obtained with a single rsEEG marker (Babiloni et al., 2016a), thus unveiling their information redundancy for classification purposes. In future AD studies, inputs to ANNs should include other classes of independent linear (i.e., directed transfer function) and non-linear (i.e., entropy) rsEEG markers to improve the classification.

Subjective hypnotic efficacy of Trazodone and Mirtazapine in patients with chronic insomnia: a retrospective, comparative study.

OBJECTIVE: To compare the efficacy of two sedating antidepressants, trazodone and mirtazapine, for the treatment of chronic insomnia. DESIGN: Retrospective cross-sectional study. Patients received trazodone or mirtazapine for at least three months at the dosage that was effective in the titration period. MATERIAL AND METHODS: 150 patients with chronic insomnia, referred to the Sleep Disorder Center of Bari, diagnosed as chronic insomniacs according to ICSD-3 diagnostic criteria, with or without dysthymic disorder according to DSM V diagnostic criteria, and treated with trazodone or mirtazapine were retrospectively chart-reviewed. 79 patients satisfying inclusion criteria were enrolled: 33 had been treated with trazodone (12 males and 21 females aged 36 to 77 years, mean age 63.57+10.38 years; 18 with psychophysiological insomnia and 15 with insomnia associated with dysthymic disorder) and 46 with mirtazapine (26 males and 20 females aged 25 to 86 years, mean age 60.04+16.67 years; 25 with psychophysiological insomnia and 21 with insomnia comorbid with dysthymic disorder). The patients were considered responsive to the treatment when they no longer met the criteria for insomnia at the end of the maintenance period. RESULTS: Both drugs were efficacious in more than 60% without any difference in the proportion of responders between the two medication groups (87.87% in the trazodone group versus 86.95% in the mirtazapine group; p=0.26 and regardless of sex, age and possible association of insomnia with depression). The minimum dosages used for both drugs (25 mg for trazodone and 7.5 mg for mirtazapine) corresponded to the highest percentage of responders in the groups treated successfully with either trazodone (37.93%) or mirtazapine (52.5%). For each medication group, subgroup analysis revealed higher statistically significant rates of responders in patients with lower final dosage (25 to 75 mg for trazodone and 7.5 to 15 mg for mirtazapine) than in those with higher final dosage (100 to 150 mg for trazodone and 15 to 30 mg for mirtazapine) (100% versus 42.85%; p<0.001 in the trazodone group and 100% versus 53.84%; p<0.001 in mirtazapine group) Conclusion. On a long term basis trazodone administration appeared as effective and well tolerated as mirtazapine in the treatment of chronic insomnia regardless of its association with dysthymia. Both medications resulted efficacious at very low doses and had a sustained efficacy, likely without problems of tolerance.

Predictors of survival in a series of clinically diagnosed progressive supranuclear palsy patients.

BACKGROUND: Investigations into prognostic factors in progressive supranuclear palsy have shown conflicting results. We performed a retrospective study in order to identify clinical predictors of survival in clinically diagnosed progressive supranuclear palsy patients referred to our centre. METHODS: Data on medical history, survival and five clinical disability milestones (inability to walk unassisted, unintelligible speech, severe dysphagia, dementia and institutionalization) were collected from outpatients' medical records and by a telephone interview to caregivers. Patients were subdivided into Richardson's syndrome and PSP-Parkinsonism according to symptoms during the first 2 years of disease. Survival was analyzed by the Kaplan-Meier method and Cox regression analysis. RESULTS: Forty-three consecutive patients were enrolled (86% Richardson's syndrome). Motor disturbances were the most frequent symptoms of onset. During the follow-up, 60.5% of patients died after a median survival of 7.1 years (2.2-18). Older age at onset (>63) (HR 2.8; 95% CI: 1.3-5.7; p = 0.007), early dysphagia (HR 2.3; 95% CI: 1-5.3; p = 0.05) and early cognitive deficits (HR 3.6; 95% CI: 1.6-8.2; p = 0.002) were predictors of shorter survival. Compared to PSP-Parkinsonism patients, Richardson's syndrome patients had shorter survival and higher mortality risk although not statistically significant (HR 3 95% CI: 0.9-9.9; p = 0.07). Seventy-seven percent of patients developed severe disability during follow-up: shorter time to the first clinical disability milestone predicted shorter survival (HR 7.8; 95% CI: 2.3-26; p = 0.0008). CONCLUSIONS: early dysphagia, cognitive impairment, older age at onset, and time to disability were predictors of shorter survival; Richardson's syndrome had a less favorable course than PSP-Parkinsonism. Clinical milestones should be considered as possible endpoints in future clinical trials.

The comorbidity of migraine and hypertension. A study in a tertiary care headache centre.

Literature data concerning the comorbidity of migraine and hypertension are conflicting and lacking in consistency. This study was designed to evaluate the distribution of hypertension in a sample of migraineurs in comparison with a group of tension type headache (TTH) patients. Hypertension prevalence was more elevated in headache sufferers than in the general population. This finding might be due to a Berkson's bias; in fact individuals seeking medical care often show a high rate of association between two medical conditions which may be independent in the general population. The highest hypertension prevalence was found in patients with TTH, supporting the hypothesis that this type of headache might be based upon vascular mechanisms.

Tertiary treatment for psychiatric comorbidity in headache patients.

The presence of significant and confounding psychiatric comorbidity is greater in patients attending headache clinics than in headache patients from the general population. The frequent comorbidity of headache with generalized anxiety disorder can take advantage of the administration of benzodiazepines. With regard to depression-related headache, it's wellknown that the antidepressive drugs can improve migraine as well as tension-type headache. Antiepileptic drugs give one more good opportunity. The recognition of a psychiatric comorbidity is mandatory for an accurate management of the patient because prevents the clinicians from using any drug that might be dangerous for a mysdiagnosed psychiatric disturbance and often permits to administer medications that can efficaciously control both headache and psychiatric disorders.