Antonios Politis

Pregabalin augmentation of antidepressants in older patients with comorbid depression and generalized anxiety disorder-an open-label study.

The objective of this 12‐week open‐label study was to evaluate the efficacy, safety, and tolerability of pregabalin as an adjunctive treatment to antidepressants in older patients suffering from depression and comorbid generalized anxiety disorder (GAD).

Cardiac rhythm management devices and electroconvulsive therapy: a critical review apropos of a depressed patient with a pacemaker.

Electroconvulsive therapy (ECT) is an effective treatment and, with the proper risk-minimizing strategies, is relatively safe even in depressed patients with cardiovascular diseases. Specifically, patients with cardiac rhythm management devices (CRMDs) require particular attention because no controlled trials exist to support current empirical recommendations. We present a depressed patient with a pacemaker successfully treated with ECT, and we critically review the relevant literature. Pooled results from 63 patients and 821 ECT sessions showed that 90% of ECT sessions have been performed on depressed patients with their pacemakers in sensing mode and rate adaptation, where available, activated as well. Only 4% of sessions were performed with those functions disabled, whereas no data was available for 6% of ECT sessions. Pooled results from case series and reports highlight a discrepancy between current clinical practice and many guidelines. Electroconvulsive therapy is probably safe in depressed patients with asynchronous fixed-rate pacemakers, although there is a risk of ventricular tachycardia and fibrillation. A larger body of case series and reports suggests that there might be no need to convert synchronous demand pacemakers to asynchronous fixed-rate pacing. Regarding patients with implantable cardioverter defibrillators, antitachycardia treatment was deactivated during most ECT sessions. In depressed patients with CRMDs anticholinergics might be best avoided. In all cases, proper ECT procedures, namely, patient and pacemaker electrical isolation, strict grounding and adequate muscle relaxation along with interrogation and monitoring of CRMDs before and after each session should ensure uncomplicated electroconvulsive treatments.

Pharmacological and Nonpharmacological Treatment for Apathy in Alzheimer Disease.

Objective: Apathy is one of the most frequent neuropsychiatric symptoms encountered in Alzheimer disease (AD). Early diagnosis and timely treatment of apathy in AD seem to be of great importance, since apathy has been associated with poor disease outcome, reduced daily functioning, and caregiver distress. Design: Within this context, we conducted an extensive electronic search from the databases included in the National Library of Medicine as well as PsychInfo and Google Scholar for studies that have investigated the effect of pharmacological and nonpharmacological treatments of apathy in AD. Results: Acetylcholinesterase inhibitors, gingko biloba, methylphenidate, and a variety of nonpharmacological interventions were found to be successful in reducing apathy in patients with AD. Methodological heterogeneity of the studies and the small amount of studies where apathy was a primary outcome measure are limiting factors to evaluate for group effects. Conclusion: Treatment of apathy in AD is a complicated and an underexplored field. Standardized and systematic efforts primarily focused on the study of apathy in AD may establish a benefit from individualized treatment for specific disease groups that would stem from a combination of both pharmacological and nonpharmacological interventions.

Two Versus One High-Frequency Repetitive Transcranial Magnetic Stimulation Session per Day for Treatment-Resistant Depression: A Randomized Sham-Controlled Trial.

Objectives High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has proven antidepressant effects, but the optimal frequency of sessions remains unclear. Methods We conducted a 3-week, sham-controlled trial to assess the antidepressant efficacy of 1 active HF-rTMS session per day (A1 group) compared with 2 per day (A2 group) and equivalent sham sessions (once a day, S1 group; twice a day, S2 group) in patients with treatment-resistant major depression with a subsequent 2-week follow-up period. One hundred seventy-seven patients were screened, of whom 105 met eligibility criteria and 98 consented and were randomized. The HF-rTMS (20 Hz) was targeted to the left prefrontal cortex in sessions of approximately 40 trains (2 seconds each) at 100% resting motor threshold with an intertrain interval of 1 minute. Treatment response was defined as a 50% or greater decrease in the Hamilton Depression Rating Scale (HDRS) score and/or Clinician Global Impressions-Severity of Illness (CGI-S) score of 3 or less. Remission was defined as HDRS score less than 8 and/or CGI-S score of 2 or less. Results Practically none of the subjects in either sham groups achieved remission. Increased odds of remission were present for CGI-S by stimulating twice rather than once per day (odds ratio [OR] = 1.5, P = 0.018), whereas there was a marginal result for HDRS (OR = 3.9, P = 0.066). Patients who had lower baseline HDRS (OR = 0.75, P = 0.014) and CGI-S scores (OR = 0.18, P = 0.001) were more likely to achieve remission. Conclusions Twice per day active HF-rTMS might be more effective than once per day active HF-rTMS or sham stimulation.

Recommendations for the Use of Serious Games in Neurodegenerative Disorders: 2016 Delphi Panel

The use of Serious Games (SG) in the health domain is expanding. In the field of neurodegenerative disorders (ND) such as Alzheimer’s disease, SG are currently employed both to support and improve the assessment of different functional and cognitive abilities, and to provide alternative solutions for patients’ treatment, stimulation, and rehabilitation. As the field is quite young, recommendations on the use of SG in people with ND are still rare. In 2014 we proposed some initial recommendations (Robert et al., 2014). The aim of the present work was to update them, thanks to opinions gathered by experts in the field during an expert Delphi panel. Results confirmed that SG are adapted to elderly people with mild cognitive impairment (MCI) and dementia, and can be employed for several purposes, including assessment, stimulation, and improving wellbeing, with some differences depending on the population (e.g., physical stimulation may be better suited for people with MCI). SG are more adapted for use with trained caregivers (both at home and in clinical settings), with a frequency ranging from 2 to 4 times a week. Importantly, the target of SG, their frequency of use and the context in which they are played depend on the SG typology (e.g., Exergame, cognitive game), and should be personalized with the help of a clinician.

Dealing with severe dementia in clinical practice: A validity and reliability study of Severe Mini-Mental State Examination in Greek population

Considering the floor effect problems of many cognitive instruments administered in patients with dementia, we aimed to evaluate the validity and reliability of the Severe Mini‐Mental State Examination (SMMSE) for monitoring patients with moderate to severe dementia in the Greek population.

Cerebrospinal Fluid BACE1 Activity and sAβPPβ as Biomarker Candidates of Alzheimer’s Disease

Background/Aims: The utility of β-site amyloid-β precursor protein (AβPP) cleaving enzyme 1 (BACE1) activity and soluble AβPP β (sAβPPβ) levels in cerebrospinal fluid (CSF) in detecting Alzheimer’s disease (AD) is still elusive. Methods: BACE1 activity and sAβPPβ concentration were measured in patients with AD dementia (n = 56) and mild cognitive impairment (MCI) due to AD (n = 76) with abnormal routine AD CSF markers, in patients with MCI with normal CSF markers (n = 39), and in controls without preclinical AD (n = 48). In a subsample with available 18F-fluorodeoxyglucose positron emission tomography (FDG PET) data, ordinal regression models were employed to compare the contribution of BACE1 and sAβPPβ to correct diagnostic classification to that of FDG PET. Results: BACE1 activity was significantly higher in patients with MCI due to AD compared to both controls and patients with MCI with normal CSF markers. sAβPPβ did not differ between any of the studied groups. Interestingly, BACE1 activity was not found to be inferior to FDG PET as predictive covariate in differentiating between the diagnostic groups. Conclusions: Further studies using biomarker-underpinned diagnoses are warranted to shed more light on the potential diagnostic utility of BACE1 activity as AD biomarker candidate in MCI.

Alzheimer’s Disease And Neurotransmission Gene Variants

Background Alzheimer disease (AD) is a chronic neurodegenerative disorder that accounts for 60% to 70% of cases of dementia. The 49% to 79% of the disease risk has been associated with the genetic background of the individuals. Two main forms of AD have been recognized: the early-Onset AD (EOAD) and the late-onset AD (LOAD). The EOAD genetic background shows an autosomal dominant mode of inheritance and is strongly related to variations within amyloid b precursor protein, presenilin 1 and presenilin 2. However, it accounts for no more than 5% of the cases of AD. The remaining part of AD cases are categorized as LOAD, which shows a multigenic inheritance. In the last years, great importance has been attributed to the gene coding for apolipoprotein E. However, other factors must be involved in the development of AD. For this reason, in the last decades, a number of other genes have been investigated. Among them, an increasing interest is accumulating in the genes involved in the molecular mechanics of neurotransmission. The aim of the present paper is to focus on some genes involved in this process. Methods The samples were recruited in two independent centers, one in Athens (Greece) and one in Emilia Romagna (Italy), for a total of 156 AD subjects and 301 healthy controls. Two sets of genes were investigated for association with AD in two independent samples. The first set includes genes involved in key points of the neurotransmission mechanisms (COMT, PPP3CC, HTR2A), while the second set includes a group of genes associated with important processes like memory learning and synaptic plasticity (SIRT1), synapses function (SORBS3), circadian function and serotonin levels balancing (RORA) and modulation of neurotransmitters release (SIGMAR1). A total of 16 SNPs within the above genes were investigated. Exploratory analyses on psychosis and depression comorbidities were also performed, as well as on other clinical and serological parameters available in the Greek sub-sample only. Analysis of variance, of co-variance and chi-square statistical analyses were performed. The samples were tested for genotype and alleles. According to Bonferronis formula, the α value for the primary analyses was set at α=0.003. Results AD was associated with rs4680 within COMT gene in the total sample, while trends of association were found in the two sub-samples as well. No relation with psychosis was found for the SNPs investigated. On the other hand, some nominal associations were found concerning depression phenotype. In particular, rs1099781 and rs10997875 within SIRT1 were nominally associated with depression in the total sample as well as in the Greek sub-sample. Rs174696 within COMT was instead associated with depressive symptomatology in the Italian sub-sample only. Discussion Our data further support the role of COMT, and particularly rs4680, in the pathogenesis of AD, while SIRT1 seems to modulate the depressive symptomatology in this population. Clearly, further studies are required to confirm our preliminarily results.