Explore the vast range of titles available.

Depressive symptoms may increase the risk of progressing from mild cognitive impairment (MCI) to dementia. Consumption of n-3 PUFA may alleviate both cognitive decline and depression. The aim of the present study was to investigate the benefits of supplementing a diet with n-3 PUFA, DHA and EPA, for depressive symptoms, quality of life (QOL) and cognition in elderly people with MCI. We conducted a 6-month double-blind, randomised controlled trial. A total of fifty people aged >65 years with MCI were allocated to receive a supplement rich in EPA (1·67 g EPA+0·16 g DHA/d; n 17), DHA (1·55 g DHA+0·40 g EPA/d; n 18) or the n-6 PUFA linoleic acid (LA; 2·2 g/d; n 15). Treatment allocation was by minimisation based on age, sex and depressive symptoms (Geriatric Depression Scale, GDS). Physiological and cognitive assessments, questionnaires and fatty acid composition of erythrocytes were obtained at baseline and 6 months (completers: n 40; EPA n 13, DHA n 16, LA n 11). Compared with the LA group, GDS scores improved in the EPA (P = 0·04) and DHA (P = 0·01) groups and verbal fluency (Initial Letter Fluency) in the DHA group (P = 0·04). Improved GDS scores were correlated with increased DHA plus EPA (r 0·39, P = 0·02). Improved self-reported physical health was associated with increased DHA. There were no treatment effects on other cognitive or QOL parameters. Increased intakes of DHA and EPA benefited mental health in older people with MCI. Increasing n-3 PUFA intakes may reduce depressive symptoms and the risk of progressing to dementia. This needs to be investigated in larger, depressed samples with MCI.

There is increasing clinical and molecular evidence for the role of hormones and specifically estrogen and its receptor in schizophrenia. A selective estrogen receptor modulator, raloxifene, stimulates estrogen-like activity in brain and can improve cognition in older adults. The present study tested the extent to which adjunctive raloxifene treatment improved cognition and reduced symptoms in young to middle-age men and women with schizophrenia. Ninety-eight patients with a diagnosis of schizophrenia or schizoaffective disorder were recruited into a dual-site, thirteen-week, randomized, double-blind, placebo-controlled, crossover trial of adjunctive raloxifene treatment in addition to their usual antipsychotic medications. Symptom severity and cognition in the domains of working memory, attention/processing speed, language and verbal memory were assessed at baseline, 6 and 13 weeks. Analyses of the initial 6-week phase of the study using a parallel groups design (with 39 patients receiving placebo and 40 receiving raloxifene) revealed that participants receiving adjunctive raloxifene treatment showed significant improvement relative to placebo in memory and attention/processing speed. There was no reduction in symptom severity with treatment compared with placebo. There were significant carryover effects, suggesting some cognitive benefits are sustained even after raloxifene withdrawal. Analysis of the 13-week crossover data revealed significant improvement with raloxifene only in attention/processing speed. This is the first study to show that daily, oral adjunctive raloxifene treatment at 120 mg per day has beneficial effects on attention/processing speed and memory for both men and women with schizophrenia. Thus, raloxifene may be useful as an adjunctive treatment for cognitive deficits associated with schizophrenia.

In the 24-month MS-STAT phase 2 trial, we showed that high-dose simvastatin significantly reduced the annualised rate of whole brain atrophy in patients with secondary progressive multiple sclerosis (SPMS). We now describe the results of the MS-STAT cognitive substudy, in which we investigated the treatment effect on cognitive, neuropsychiatric, and health-related quality-of-life (HRQoL) outcome measures. We did a secondary analysis of MS-STAT, a 24-month, double-blind, controlled trial of patients with SPMS done at three neuroscience centres in the UK between Jan 28, 2008, and Nov 4, 2011. Patients were randomly assigned (1:1) to either 80 mg simvastatin (n=70) or placebo (n=70). The cognitive assessments done were the National Adult Reading Test, Wechsler Abbreviated Scale of Intelligence, Graded Naming Test, Birt Memory and Information Processing Battery (BMIPB), Visual Object and Space Perception battery (cube analysis), Frontal Assessment Battery (FAB), and Paced Auditory Serial Addition Test. Neuropsychiatric status was assessed using the Hamilton Depression Rating Scale and the Neuropsychiatric Inventory Questionnaire. HRQoL was assessed using the self-reported 36-Item Short Form Survey (SF-36) version 2. Assessments were done at study entry, 12 months, and 24 months. Patients, treating physicians, and outcome assessors were masked to treatment allocation. Analyses were by intention to treat. MS-STAT is registered with ClinicalTrials.gov, number NCT00647348. Baseline assessment revealed impairments in 60 (45%) of 133 patients on the test of frontal lobe function (FAB), and in between 13 (10%) and 43 (33%) of 130 patients in tests of non-verbal and verbal memory (BMIPB). Over the entire trial, we noted significant worsening on tests of verbal memory (T score decline of 5·7 points, 95% CI 3·6–7·8; p<0·0001) and non-verbal memory (decline of 6·8 points, 4·8–8·7; p<0·0001). At 24 months, the FAB score was 1·2 points higher in the simvastatin-treated group than in the placebo group (95% CI 0·2–2·3). The simvastatin group also had a 2·5 points better mean physical component score of the SF-36 (95% CI 0·3–4·8; p=0·028). A treatment effect was not noted for any other outcomes. To our knowledge, this SPMS cohort is the largest studied to date with comprehensive longitudinal cognitive, neuropsychiatric, and HRQoL assessments. We found evidence of a positive effect of simvastatin on frontal lobe function and a physical quality-of-life measure. Although we found no effect of simvastatin on the other outcome measures, these potential effects warrant confirmation and underline the importance of fully assessing cognition and quality of life in progressive multiple sclerosis treatment trials. The Moulton Foundation, the Berkeley Foundation, the Multiple Sclerosis Trials Collaboration, the Rosetrees Trust, a personal contribution from A W Pidgley CBE, and the National Institute for Health Research University College London Hospitals Biomedical Research Centre and University College London.

Background Iron deficiency (ID) limits the neurodevelopmental potential of more than 200 million children each year. Iron therapy started when IDA is first diagnosed—typically by screening for anemia or detection of clinical symptoms of IDA at 12 months of age—does not fully correct earlier ID-mediated brain dysfunction, underscoring the need for low-cost, easily implementable adjunct therapies to iron to treat or prevent this dysfunction in high-risk populations. Supplementation with the essential nutrient choline lessens damage done to the developing hippocampus when given with iron in pre-clinical rodent models, and choline supplementation improves hippocampus-mediated memory and learning in 2–3-year-old children with Fetal Alcohol Spectrum Disorders, a condition associated with hippocampal damage and one for which ID is a component of the neuropathology. Choline has not been tested in children with IDA. Our overall aim is to conduct a randomized, placebo-controlled clinical trial to test whether nine months of daily choline supplementation along with standard iron therapy improves hippocampus-dependent neurobehavioral outcomes in Ugandan infants with IDA. Methods Three hundred 6-month-old infants with IDA who present to immunization clinics at Mulago and Kawempe National Referral Hospitals in Kampala, Uganda, will be randomized to iron plus choline or iron plus placebo. Iron (oral ferrous sulfate 2 mg/kg/day) will be given for the first 3 months of follow-up, and a dispersible tablet of choline (200 mg as choline bitartrate) or identical placebo will be given daily for all 9 months of follow-up. We will conduct neurobehavioral tests assessing hippocampus-specific memory and attention and global cognition at enrollment (when each infant is 6 months of age) and after 9 months of follow-up (when each infant is 15 months of age). Discussion If we find a neurobehavioral benefit when choline is given along with iron, choline could be added immediately to standard of care treatment for IDA. This low-cost intervention could safely mitigate the brain dysfunction of early-life ID that is often not diagnosed until the hippocampal critical window is closing, providing life-long benefit for both the individual and the economic and social prosperity of entire regions. Trial registration Clinical trials.gov NCT06527391. Registered on 24 July 2024.

Stress is assumed to cause a shift from flexible 'cognitive' memory to more rigid 'habit' memory. In the spatial memory domain, stress impairs place learning depending on the hippocampus whereas stimulus-response learning based on the striatum appears to be improved. While the neural basis of this shift is still unclear, previous evidence in rodents points towards cortisol interacting with the mineralocorticoid receptor (MR) to affect amygdala functioning. The amygdala is in turn assumed to orchestrate the stress-induced shift in memory processing. However, an integrative study testing these mechanisms in humans is lacking. Therefore, we combined functional neuroimaging of a spatial memory task, stress-induction, and administration of an MR-antagonist in a full-factorial, randomized, placebo-controlled between-subjects design in 101 healthy males. We demonstrate that stress-induced increases in cortisol lead to enhanced stimulus-response learning, accompanied by increased amygdala activity and connectivity to the striatum. Importantly, this shift was prevented by an acute administration of the MR-antagonist spironolactone. Our findings support a model in which the MR and the amygdala play an important role in the stress-induced shift towards habit memory systems, revealing a fundamental mechanism of adaptively allocating neural resources that may have implications for stress-related mental disorders.

Dysfunction of neuroplasticity due to N-methyl-d-aspartate (NMDA) receptor hypofunction may be a causal factor for memory and executive dysfunctioning in schizophrenia. Deregulation of NMDA transmission in the prefrontal cortex may also explain negative and positive symptoms. Clozapine augmentation with memantine targets altered NMDA receptor-mediated neurotransmission in schizophrenia and showed substantial beneficial effects on several symptom domains in a small proof-of-concept study. We evaluate effects of memantine add-on treatment to clozapine for memory and executive function, and negative and positive symptoms in schizophrenia. Clozapine-treated patients with refractory schizophrenia were randomly assigned to 12 weeks of double-blind adjunctive treatment with memantine (n = 26) or placebo (n = 26). Crossover occurred after a 2-week placebo wash-out period. Primary endpoints were change from baseline to 12 weeks treatment and 14 weeks to 26 weeks treatment on memory and executive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB), Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impression Severity Scale (CGI-S). Side effects were assessed using the Liverpool University Neuroleptic Side-Effect Rating Scale. When compared with placebo, memantine improved a composite memory score comprising verbal recognition memory and paired associates learning task scores on the CANTAB (effect size = 0.30) and PANSS negative subscale score (effect size = 0.29). Side effects were mild and transient. In patients with clozapine-treated refractory schizophrenia, memantine addition significantly improved verbal and visual memory and negative symptoms without serious adverse effects. These results justify further investigations on long-term memantine augmentation to clozapine in treatment-resistant schizophrenia.

The neurosteroid pregnenolone and its sulfated derivative enhance learning and memory in rodents. Pregnenolone sulfate also positively modulates NMDA receptors and could thus ameliorate hypothesized NMDA receptor hypofunction in schizophrenia. Furthermore, clozapine increases pregnenolone in rodent hippocampus, possibly contributing to its superior efficacy. We therefore investigated adjunctive pregnenolone for cognitive and negative symptoms in patients with schizophrenia or schizoaffective disorder receiving stable doses of second-generation antipsychotics in a pilot randomized, placebo-controlled, double-blind trial. Following a 2-week single-blind placebo lead-in, patients were randomized to pregnenolone (fixed escalating doses to 500 mg/day) or placebo, for 8 weeks. Primary end points were changes in BACS and MCCB composite and total SANS scores. Of 21 patients randomized, 18 completed at least 4 weeks of treatment ( n =9/group). Pregnenolone was well tolerated. Patients receiving pregnenolone demonstrated significantly greater improvements in SANS scores (mean change=10.38) compared with patients receiving placebo (mean change=2.33), p =0.048. Mean composite changes in BACS and MCCB scores were not significantly different in patients randomized to pregnenolone compared with placebo. However, serum pregnenolone increases predicted BACS composite scores at 8 weeks in the pregnenolone group ( r s =0.81, p =0.022). Increases in allopregnanolone, a GABAergic pregnenolone metabolite, also predicted BACS composite scores ( r s =0.74, p =0.046). In addition, baseline pregnenolone ( r s =−0.76, p =0.037), pregnenolone sulfate ( r s =−0.83, p =0.015), and allopregnanolone levels ( r s =−0.83, p =0.015) were inversely correlated with improvements in MCCB composite scores, further supporting a possible role for neurosteroids in cognition. Mean BACS and MCCB composite scores were correlated ( r s =0.74, p <0.0001). Pregnenolone may be a promising therapeutic agent for negative symptoms and merits further investigation for cognitive symptoms in schizophrenia.

Desalted Salicornia europaea L. (SE) inhibits acetylcholine esterase, attenuates oxidative stress and inflammatory cytokines, and activates neurotrophic pathway. We performed 12-week, randomized, double-blind, placebo-controlled study to evaluate the efficacy of PhytoMeal(a desalted SE)-ethanol extract (PM-EE), in improving the cognitive performance in patients with subjective memory impairment. 63 participants complaining memory dysfunction without dementia (Korean Mini-Mental State Examination [K-MMSE] score ≥ 23) were assigned to PM-EE 600 mg/day or placebo. The cognitive domain of the Alzheimer's disease assessment scale-Korean version (ADAS-K) was set as the primary outcome. After 12 weeks, there was no differences in the changes in the primary outcome or the frequency of adverse events between the groups. In the subgroup analysis for the 30 subjects with mild cognitive impairment (MCI, baseline K-MMSE scores ≤ 28), PM-EE significantly improved the color-reading score of the Korean color-word stroop test (8.2 ± 25.0 vs. − 4.7 ± 13.2, P  = 0.018). Our findings suggest that PM-EE is safe but might not be effective in this setting of this study. However, PM-EE may improve the frontal executive function in the patients with MCI. Further large-sized studies with longer follow-up period is warranted (trial registration number KCT0003418).

In this study, we tested whether the commercial transcranial direct current stimulation (tDCS) headset foc.us improves cognitive performance, as advertised in the media. A single-blind, sham-controlled, within-subject design was used to assess the effect of online and off-line foc.us tDCS—applied over the prefrontal cortex in healthy young volunteers ( n  = 24) on working memory (WM) updating and monitoring. WM updating and monitoring, as assessed by means of the N -back task, is a cognitive-control process that has been shown to benefit from interventions with CE-certified tDCS devices. For both online and off-line stimulation protocols, results showed that active stimulation with foc.us , compared to sham stimulation, significantly decreased accuracy performance in a well-established task tapping WM updating and monitoring. These results provide evidence for the important role of the scientific community in validating and testing far-reaching claims made by the brain training industry.

Cognitive sequelae often occur after acute carbon monoxide poisoning. This double-blind, randomized trial assigned subjects either to three sessions in a hyperbaric-oxygen chamber or to one normobaric-oxygen treatment plus two sessions of exposure to normobaric room air, all administered within 24 hours after the end of exposure to carbon monoxide. Cognitive sequelae six weeks later were less frequent among persons who received hyperbaric-oxygen therapy (25.0 percent) than among those who received normobaric-oxygen treatment (46.1 percent, P=0.007). Differences were sustained 12 months after the episode of acute carbon monoxide poisoning. The results of this double-blind trial support the use of hyperbaric oxygen. Carbon monoxide poisoning is a serious health problem 1 , 2 resulting in approximately 40,000 visits to the emergency department annually in the United States. 2 , 3 Unfavorable cognitive sequelae (problems with memory, attention or concentration, and affect) can occur immediately after exposure and persist or can be delayed, but they generally occur within 20 days after carbon monoxide poisoning. 1 – 6 Cognitive sequelae lasting one month 5 , 7 – 9 or more 2 , 4 appear to occur in 25 to 50 percent of patients with loss of consciousness or with carboxyhemoglobin levels greater than 25 percent. 2 , 7 , 8 The recommended treatment for acute carbon monoxide poisoning . . .