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Objective\ud To investigate the potential therapeutic benefits and tolerability of inhibitory transcranial direct current stimulation (tDCS) on the remediation of visual hallucinations in Charles Bonnet Syndrome (CBS).\ud \ud Design\ud Randomized, double-masked(blind), placebo-controlled crossover trial.\ud \ud Participants\ud Sixteen individuals diagnosed with CBS secondary to visual impairment caused by eye disease experiencing recurrent visual hallucinations.\ud \ud Intervention\ud All participants received four consecutive days of active and placebo cathodal stimulation (current density: 0.29mA/cm2) to the visual cortex (Oz) over two defined treatment weeks, separated by a four-week wash-out period.\ud \ud Main Outcome Measures\ud Ratings of visual hallucination frequency and duration following active and placebo stimulation, accounting for treatment order, using a 2x2 repeated measures model. Secondary outcomes included impact ratings of visual hallucinations and electrophysiological measures.\ud \ud Results\ud When compared to placebo treatment, active inhibitory stimulation of visual cortex resulted in a significant reduction in the frequency of visual hallucinations measured by the North East Visual Hallucinations Interview, with a moderate-to-large effect size. Impact measures of visual hallucinations improved in both placebo and active conditions suggesting support and education for CBS may have therapeutic benefits. Participants who demonstrated greater occipital excitability on electroencephalography assessment at the start of treatment were more likely to report a positive treatment response. Stimulation was found to be tolerable in all participants with no significant adverse effects reported, including no deterioration in pre-existing visual impairment.\ud \ud Conclusions\ud Findings indicate that inhibitory tDCS of visual cortex may reduce the frequency of visual hallucinations in people with CBS, particularly individuals who demonstrate greater occipital excitability prior to stimulation. tDCS may offer a feasible, novel intervention option for CBS with no significant side effects, warranting larger scale clinical trials to further characterize its efficacy.

Background Identifying predictors of incident cognitive impairment (CI), one of the most problematic long‐term outcomes, in Parkinson's disease (PD) is highly relevant for personalized medicine and prognostic counseling. The Nonmotor Symptoms Scale (NMSS) provides a global clinical assessment of a range of NMS, reflecting NMS burden (NMSB), and thus may assist in the identification of an “at‐risk” CI group based on overall NMSB cutoff scores. Methods To investigate whether specific patterns of PD NMS profiles predict incident CI, we performed a retrospective longitudinal study on a convenience sample of 541 nondemented PD patients taking part in the Nonmotor Longitudinal International Study (NILS) cohort, with Mini‐Mental State Examination (MMSE), NMSS, and Scales for Outcomes in PD Motor Scale (SCOPA Motor) scores at baseline and last follow‐up (mean 3.2 years) being available. Results PD patients with incident CI (i.e., MMSE score ≤ 25) at last follow‐up (n = 107) had severe overall NMSB level, significantly worse NMSS hallucinations/perceptual problems and higher NMSS attention/memory scores at baseline. Patients with CI also were older and with more advanced disease, but with no differences in disease duration, dopamine replacement therapy, sex, and comorbid depression, anxiety, and sleep disorders. Conclusions Our findings suggest that a comprehensive baseline measure of NMS and in particular hallucinations and perceptual problems assessed with a validated single instrument can be used to predict incident CI in PD. This approach provides a simple, holistic strategy to predict future CI in this population., A comprehensive baseline measure of NMS and in particular hallucinations and perceptual problems assessed with a validated single instrument can be used to predict incident cognitive impairment in PD. This approach provides a simple, holistic strategy to predict future cognitive impairment in this population.

BACKGROUND: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). OBJECTIVE: We sought to characterize the relationship between Aβ and tau ligands as well as with other measures of pathology. METHODS: We conducted a multi-center observational study in early AD (MMSE >20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of Aβ and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline. RESULTS: 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aβ associated with entorhinal cortex tau while CSF tau/Aβ ratio correlated strongly with cortical tau but not Aβ. CONCLUSION: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker- the CSF total tau/Aβ ratio.

Self-monitoring, defined as the ability to distinguish between self-generated stimuli from other-generated ones, is known to be impaired in schizophrenia. This impairment has been theorised as the basis for many of the core psychotic symptoms, in particular, poor clinical insight. This study aimed to investigate verbal self-monitoring related neural substrates of preserved and poor clinical insight in schizophrenia. It involved 40 stable schizophrenia outpatients, 20 with preserved and 20 with poor insight, and 20 healthy participants. All participants underwent functional magnetic resonance imaging with brain coverage covering key areas in the self-monitoring network during a verbal self-monitoring task. Healthy participants showed higher performance accuracy and greater thalamic activity than both preserved and poor insight patient groups. Preserved insight patients showed higher activity in the putamen extending into the caudate, insula and inferior frontal gyrus, compared to poor insight patients, and in the anterior cingulate and medial frontal gyrus, compared to healthy participants. Poor insight patients did not show greater activity in any brain area compared to preserved insight patients or healthy participants. Future studies may pursue therapeutic avenues, such as meta-cognitive therapies to promote self-monitoring or targeted stimulation of relevant brain areas, as means of enhancing insight in schizophrenia., Highlights • We investigate neural substrates of both preserved and poor clinical insight in schizophrenia. • We report an association between neural networks involved in verbal self-monitoring and clinical insight. • We present evidence of functional deficits in the putamen and inferior frontal gyrus associated with poor insight.

Background: Combining PET amyloid-β (Aβ) and tau imaging may be critical for tracking disease progression in Alzheimer's disease (AD). Objective:We sought to characterize the relationship betweenAβ and tau ligands as well as with other measures of pathology. Methods: We conducted a multi-center observational study in early AD (MMSE > 20) participants aged 50 to 85 y. The schedule included cognitive assessments (ADAS-Cog) and CSF measurement of A- and tau at baseline and 6 months; PET-CT imaging with Aβ ([18F]AV45) and tau ([18F]AV1451) ligands at baseline. Results: 22 participants took part in the study with 20 completing its 6-month duration and 12 having both tau and amyloid PET. The PET biomarker analysis revealed a strong negative correlation between age and tau in multiple regions. Entorhinal cortex tau and age interacted significantly in terms of cognitive change over 6 months which may have been to older participants deteriorating faster despite lower levels of cortical tau. Cortical Aβ associated with entorhinal cortex tau while CSF tau/Aβ ratio correlated strongly with cortical tau but not Aβ Conclusion: The negative relationship between age and cortical tau whereby younger patients with mild AD had relatively greater tau burden is potentially important. It suggests that younger-age onset AD may be primarily driven by tau pathology while AD developing later may depend on a multitude of pathological mechanisms. These data also suggest that PET-tau performs better than PET-amyloid in predicting the best validated AD diagnostic marker'the CSF total tau/Aβ ratio.

Rationale An acute challenge with delta-9-tetrahydrocannabinol (THC) can induce psychotic symptoms including delusions. High electroencephalography (EEG) frequencies, above 20 Hz, have previously been implicated in psychosis and schizophrenia. Objectives The objective of this study is to determine the effect of intravenous THC compared to placebo on high-frequency EEG. Methods A double-blind cross-over study design was used. In the resting state, the high-beta to low-gamma magnitude (21–45 Hz) was investigated (n = 13 pairs + 4 THC only). Also, the event-related synchronisation (ERS) of motor-associated high gamma was studied using a self-paced button press task (n = 15). Results In the resting state, there was a significant condition × frequency interaction (p = 0.00017), consisting of a shift towards higher frequencies under THC conditions (reduced high beta [21–27 Hz] and increased low gamma [27–45 Hz]). There was also a condition × frequency × location interaction (p = 0.006), such that the reduction in 21–27-Hz magnitude tended to be more prominent in anterior regions, whilst posterior areas tended to show greater 27–45-Hz increases. This effect was correlated with positive symptoms, as assessed on the Positive and Negative Syndrome Scale (PANSS) (r = 0.429, p = 0.042). In the motor task, there was a main effect of THC to increase 65–130-Hz ERS (p = 0.035) over contra-lateral sensorimotor areas, which was driven by increased magnitude in the higher, 85–130-Hz band (p = 0.02) and not the 65–85-Hz band. Conclusions The THC-induced shift to faster gamma oscillations may represent an over-activation of the cortex, possibly related to saliency misattribution in the delusional state. Electronic supplementary material The online version of this article (doi:10.1007/s00213-014-3684-1) contains supplementary material, which is available to authorized users.

Objectives: The idea that delirium is a risk factor for dementia, broadly defined, is derived from heterogeneous patient samples. We reviewed available evidence as to whether stroke survivors who developed delirium during the acute phase of treatment are at a higher prospective risk of incident post-stroke cognitive impairment or dementia. Design: We searched 8721 records in the Cochrane database for reviews or protocols dealing with the study objective, Medline, EMBASE, PsycInfo and CINAHL for observational studies in the general adult population and PubMed for in-process articles. Additional searches of the reference lists of retrieved articles were also undertaken. Qualitative syntheses and meta-analysis were conducted according to conventional guidelines. Results: Twelve relevant articles were fully appraised. Four out of these studies, comprising 743 stroke survivors, including 199 with delirium, met criteria for qualitative syntheses. Overall, the studies presented low to moderate level evidence suggesting an association between post-stroke delirium and dementia. Conclusions: There is a need for further studies to investigate the association of post-stroke delirium and dementia using well-defined cohorts of patients and controlling for factors such as pre-stroke cognition, stroke severity and location and the presence of persistent delirium. Such studies will help understand the place of delirium identification and prevention in reducing the risk of dementia after stroke.

Background: Establishing the cognitive phenotype of psychotic symptoms in Alzheimer's disease (AD) could localise discrete pathology and target symptomatic treatment. This study aimed to establish whether psychotic symptoms would be associated with poorer performance on neuropsychological tests known to correlate with striatal dopaminergic function and to investigate whether these differences would be attributed to the paranoid (persecutory delusions) or misidentification (misidentification phenomena +/− hallucinations) subtype. Methods: Seventy patients with probable AD (34 psychotic and 36 nonpsychotic) were recruited to the study. Analysis of covariance was used to compare motor speed and the rapid visual processing test of sustained visual attention, after adjusting for potential confounding factors. Multivariate analyses were used to compare performance across other cognitive domains. Significant findings were explored by separating patients on the basis of subtype. Results: Rapid visual processing performance accuracy was reduced in patients with psychotic symptoms (F1,58 = 5.94, p = 0.02) and differed significantly across subtypes (F2,51 = 3.94, p = 0.03), largely because of poorer performance in the misidentification compared with nonpsychotic group. Multivariate analyses (corrected for multiple comparisons) showed poorer performance on the incomplete letters task in psychotic patients (F1,63 = 8.77, p = 0.004) and across subtypes (F2,55 = 10.90, p