Memory Performance Research Articles

Treating Cognition in Schizophrenia: A Whole Lifespan Perspective

Background/Objectives: Cognitive impairment is a core feature of schizophrenia, affecting attention, memory, and executive function and contributing significantly to the burden of the disorder. These deficits often begin before the onset of psychotic symptoms and persist throughout life, making their treatment essential for improving outcomes and functionality. This work aims to explore the impact of these impairments at different life stages and the interventions that have been developed to mitigate their effects. Methods: This narrative review examined literature searching for different approaches to treat cognitive impairments in schizophrenia across the lifespan. Results: Cognitive alterations appear before psychosis onset, suggesting a window for primary prevention. Then, a period of relative stability with a slight decline gives the period to secondary and eventually tertiary prevention for more than two decades. Finally, another window for tertiary prevention occurs from the third decade of illness until the later stages of the illness, when a progression in cognitive decline could be accelerated in some cases. Cognitive remediation and physical exercise are evidence-based interventions that should be provided to all patients with disabilities. Conclusions: Treating cognition throughout the whole lifespan is crucial for improving functional outcomes. It is necessary to consider the need for personalized, stage-specific strategies to enhance cognitive function and functioning in patients.

Plasma neurofilament light chain in fibromyalgia: A case control study exploring correlation with clinical and cognitive features.

Plasma neurofilament light chain (NFL) has been measured as a biomarker of neuronal damage in various neurological disorders. Elevated tau and β-amyloid levels have been found in patients with fibromyalgia (FM). The aim of the present study was to compare plasma neurofilament levels in fibromyalgia patients with normal controls and to investigate the correlation with clinical features and cognitive tests. Plasma NFL levels were assessed in 33 FM patients and compared with 22 age-matched controls. All patients were also assessed with clinical scales examining fibromyalgia disability, sleep quality and duration, fatigue, anxiety, and depression, and a neuropsychological battery examining executive function, verbal short-term memory, and working memory, as well as attentional executive function and selective attention, interference sensitivity, and inhibition of automatic responses. NFL levels were higher in FM patients (controls 6.19± 1.92; FM 17.28± 15.94 pg/mL ANOVA p 0.002). Working memory was the most impaired cognitive function significantly correlated with high NFL scores (Pearson p 0.034). Short sleep times also correlated with higher NFL scores (Pearson p 0.02) and poorer working memory performance (Pearson p 0.02). No correlation was found with indices of disease severity and duration. Plasma NFL levels are elevated in fibromyalgia patients, suggesting neuronal damage and correlating with a slight decrease in working memory and short sleep duration. Plasma neurofilament levels are elevated in patients with fibromyalgia, regardless of disease severity and duration. Neurofilament levels are higher in patients with mild working memory impairment and sleep disorders. Subgroups of patients with primary neuronal damage phenomena could be individualized for prospective evaluation with regard to the possible development of cognitive decline and sleep disturbances, which would justify a tailored therapeutic approach.

Difficulty in artificial word learning impacts targeted memory reactivation and its underlying neural signatures.

Sleep associated memory consolidation and reactivation play an important role in language acquisition and learning of new words. However, it is unclear to what extent properties of word learning difficulty impact sleep associated memory reactivation. To address this gap, we investigated in 22 young healthy adults the effectiveness of auditory targeted memory reactivation (TMR) during non-rapid eye movement sleep of artificial words with easy and difficult to learn phonotactical properties. Here, we found that TMR of the easy words improved their overnight memory performance, whereas TMR of the difficult words had no effect. By comparing EEG activities after TMR presentations, we found an increase in slow wave density independent of word difficulty, whereas the spindle-band power nested during the slow wave up-states - as an assumed underlying activity of memory reactivation - was significantly higher in the easy/effective compared to the difficult/ineffective condition. Our findings indicate that word learning difficulty by phonotactics impacts the effectiveness of TMR and further emphasize the critical role of prior encoding depth in sleep associated memory reactivation.

Effects of home-based exercise alone or combined with cognitive training on cognition in community-dwelling older adults: A randomized clinical trial

BackgroundStructured and supervised physical exercise and cognitive training are two efficient ways to enhance cognition in older adults. Performing both within a combined intervention could maximize their effect on cognition due to their potential synergy on brain functions. During the COVID-19 pandemic, these interventions were particularly relevant due to the collateral impact of social restrictions regarding physical activity and the level of cognitive stimulation. However, the benefits of remotely monitored intervention combining physical exercise and cognitive training for older adult cognition remain to be demonstrated. Methods127 older adults (age: 65.20 ± 7.95) were randomized in two arms, encouraging self-engagement in six months of home-based physical exercise alone or combined with cognitive training, monitored by phone once a week. Neuropsychological assessment was performed under videoconference supervision at baseline and after three and six months. Composite Z-scores were calculated for processing speed, executive functioning, working, and episodic memory to assess changes after three and six months of training. The weekly metabolic expenditure of self-reported activities was estimated using the compendium of physical activity to distinguish participants performing higher and lower doses of exercise (median split). Results106 participants (83.46 %) completed the 6-month training. Results showed a greater Z-score change in executive functioning for participants in the combined arm than those who only exercised (F = 4.127, p = 0.046, ηp2 = 0.050). Group x Exercise dose interaction was observed for episodic memory Z-score change (F = 6.736, p = 0.011, ηp2 = 0.070), with a greater improvement for participants performing higher doses of exercise compared to those who performed a lower dose, only in exercise alone arm. Performing a higher dose of exercise increased the working memory Z-score change in both intervention arms compared to a lower dose (F = 7.391, p = 0.008, η p2 = 0.076). ConclusionRemote combined training may lead to larger improvement in executive functioning than exercise alone. Physical exercise showed a dose-related improvement in working and episodic memory performances. The combination of cognitive interventions mitigated the effects of exercise on episodic memory. These results suggest that home-based exercise and cognitive training may help improve older adults' cognition. Trial registrationCOVEPIC was retrospectively registered on December 03, 2020. Clinical trials Identifier: NCT04635462 - https://clinicaltrials.gov/ct2/show/record/NCT04635462?term=NCT04635462&draw=2&rank=1

Difficulty in artificial word learning impacts targeted memory reactivation and its underlying neural signatures

Sleep associated memory consolidation and reactivation play an important role in language acquisition and learning of new words. However, it is unclear to what extent properties of word learning difficulty impact sleep associated memory reactivation. To address this gap, we investigated in 22 young healthy adults the effectiveness of auditory targeted memory reactivation (TMR) during non-rapid eye movement sleep of artificial words with easy and difficult to learn phonotactical properties. Here, we found that TMR of the easy words improved their overnight memory performance, whereas TMR of the difficult words had no effect. By comparing EEG activities after TMR presentations, we found an increase in slow wave density independent of word difficulty, whereas the spindle-band power nested during the slow wave up-states – as an assumed underlying activity of memory reactivation – was significantly higher in the easy/effective compared to the difficult/ineffective condition. Our findings indicate that word learning difficulty by phonotactics impacts the effectiveness of TMR and further emphasize the critical role of prior encoding depth in sleep associated memory reactivation.

Protective Effects of Lemna minor Linn. On Hepatic and Cognitive Impairments in Acetaminophen Induced Hepatic Encephalopathy in Rats

Aim: Lemna minor Linn., an aquatic plant, is a promising novel therapeutic agent that has been traditionally used in ethnobotanical practices as an ecofriendly supplement for the management of various ailments. This study involves the evaluation of ethanolic extract of Lemna minor Linn. against Paracetamol-induced Hepatic Encephalopathy using in vitro and in vivo Models. Methods: The acute oral toxicity study of the ethanolic extract of Lemna minor (EELM) was conducted following the OECD-425 guidelines over a 14-day period. A total of nine animals were used for this toxicity assessment. The EELM was tested in Paracetamol(PCM)-induced bioactivation animal model at two different dosages 200 and in comparison with silymarin as a standard compound. The In vivo experimental study was conducted using Sprague Dawley rats which was divided into 5 groups each group containing 6 animals so the total no of animals used in the study was 30 animals. The treatment groups included: normal control ( ), 100mg/kg silymarin (standard) and the EELM of two different doses of 200 and , p.o were administered to rats 10 hr before paracetamol ( ) treatment. Rats were orally administered their respective doses every day for total 30days. Paracetamol-induced oxidative liver damage disrupted normal levels of liver enzymes, total protein, and bilirubin, while also depleting antioxidant reserves. This oxidative stress was strongly associated with paracetamol toxicity, leading to a marked depletion of glutathione (GSH) and impairing both memory and cognitive function in the animals. Behavioral parameters are performed to evaluate the effect of drugs on cognitive behaviour of animals. Morris water maze test was performed to study how animals learn and remembers the spatial information relying on distal cues to locate the hidden platform in an opaque water. Additionally, elevated plus maze was performed to measures the anxious behaviour of rats, the criterion was tested based on the conflict between rats innate instincts to explore new environment and avoid open, well-lit areas. The potential protective effects of EELM was evaluated by measuring serum enzyme levels and antioxidants status in the liver and brain, further histopathological analysis was performed respectively. Results: The acute toxicity study did not report any mortality or toxicity signs in animals. PCM toxicity led to a statistically increase in the liver and body weight, along with brain water content. The PCM-intoxicated group exhibited a marked reduction in the level of superoxide dismutase (SOD) and glutathione (GSH) in the brain and liver, as well as an increase in lipid peroxidation and serum biomarkers (AST, ALT, ALP, and total bilirubin). EELM significantly ( ) reduced liver injury by inhibiting ALT, AST and ALP levels in serum. SOD, GSH and MDA liver content were significantly ( ) elevated by EELM, compared to PCM treated rats. Comparing the treatment and induced group, the treated group successfully recovered the activity of antioxidant levels and also been acknowledged for restored liver functioning by alleviating oxidative stress and also GSH level in brain was significantly increased by EELM and preserved the histology of brain, which was chronically produced over a period of 30 days. Conclusion: The findings of this investigation indicate the traditional use of Lemna minor in hepatoprotection and neuroprotection by regulating oxidative stress and mitigating reactive oxygen species (ROS). The insights gained from this research contribute to the development of novel therapeutic agents and paves the way for further studies on Lemna minor to enhance health outcomes, particularly in the management of neurodegenerative diseases.

Is KIBRA polymorphism associated with memory performance and cognitive impairment in Alzheimer's disease?

Genetic variations in a common single nucleotide polymorphism in the ninth intron of the KIBRA gene have been linked to memory performance and risk of Alzheimer's disease (AD). We examined the risk of AD related to presence of KIBRA T allele (versus CC homozygote) and to memory performance. The role of established genetic risk factors APOE ε4 and BDNF Met was also considered. Participants were cognitively healthy individuals (n = 19), participants with amnestic mild cognitive impairment (aMCI) due to AD (n = 99) and AD dementia (n = 37) from the Czech Brain Aging Study. Binary and multinomial logistic regressions compared odds of belonging to a certain diagnostic category and multivariate linear regressions assessed associations with memory. KIBRA T allele was associated with increased AD dementia risk (odds ratio [OR] = 5.98, p = 0.012) compared to KIBRA CC genotype. In APOE ε4 negative individuals, KIBRA T allele was associated with a greater risk of both aMCI due to AD (OR = 6.68, p = 0.038) and AD dementia (OR = 15.75, p = 0.009). In BDNF Met positive individuals, the KIBRA T allele was associated with a greater risk of AD dementia (OR = 10.98, p = 0.050). In AD dementia, the association between KIBRA T allele and better memory performance approached significance (β = 0.42; p = 0.062). The link between possessing the KIBRA T allele and better memory reached statistical significance only among BDNF Met carriers (β = 1.21, p = 0.027). Findings suggest that KIBRA T allele may not fully protect against AD dementia but could potentially delay progression of post-diagnosis cognitive deficits.

Biofilm Growth in Porous Media Well Approximated by Fractal Multirate Mass Transfer With Advective‐Diffusive Solute Exchange

AbstractBiofilm growth in porous media changes not only the hydrodynamic properties of the medium (reduction in porosity and permeability, and increase in dispersivity), but also the transport itself (breakthrough curves display increasingly fast first arrivals and long tails). These features are well reproduced by multicontinuum models (Multi‐Rate Mass Transfer, MRMT) which can be used to describe reactive transport in heterogeneous porous media and facilitate the simulation of reactions that are localized within biofilms. Here, we present a conceptual and numerical model of biochemical reactive transport with dynamic biofilm growth based on MRMT formulations. Mass exchange between mobile water and immobile biofilm aggregates is represented by a memory function, which simplifies definition of MRMT parameters. We successfully tested this model on two sets of laboratory data and found that (a) a basic model based on the growth of uniformly sized biofilm aggregates fails to reproduce laboratory tracer tests and rate of biofilm growth, while a fractal growth model, which we obtain by integrating the memory functions of biofilm aggregates with a power law distribution, does; (b) the biofilm memory function evolves as the biofilm grows; and (c) the early time portion of eluted volume tracer breakthrough curves are independent of flow rate, whereas the tail becomes heavier when the flow rate is decreased, which implies that both advection controlled and diffusion controlled mass exchange coexist in biofilms. These findings imply that porous media biofilms are essentially different from those developing in human tissues or open spaces.

Encoding colors and tones into working memory concurrently: A developmental investigation.

Working memory serves as a means to accumulate information and reorganize it. Researchers have long assumed that the natural organization of information is one stream at a time. This logic leads to the expectation that, when two different series of stimuli are to be remembered, performance should be superior if the series are presented one before the other in succession, rather than concurrently. Moreover, different accounts of attentional limits lead to different expectations for the change in the ability to encode two sets across age groups in childhood. Testing children from first grade (6-7years) to adulthood, we presented sequences of colored objects and tones in succession or concurrently (with one color accompanying an unrelated tone) and found that performance was equally good no matter which presentation method was used. The results for both presentation methods closely matched the intricate pattern of development observed by Cowan etal. (2018), who used successive presentation only. We found marked developmental improvement in the ability to retain materials in each modality without an increasing cost of attention-sharing between modalities. Humans at least from the elementary school years through young adulthood thus display an ability to accommodate and organize two concurrent streams of information. RESEARCH HIGHLIGHTS: Memory for stimuli from multiple modalities is relevant to school performance and learning; here we investigate how attention is shared between remembering colors and tones. Participants received four colors and/or four tones for subsequent recognition on a trial, with dual modalities presented successively (0.5s per stimulus) or concurrently (0.5s per pair). Successive versus concurrent presentation had little effect on recognition, and the marked increase in memory performance with age did not come from dividing attention during encoding or maintenance. Children as young as first grade thus can encode and organize for later recognition colors and concurrently-presented, but unrelated, tones.

Theta Transcranial Alternating Current Stimulation Is Not Effective in Improving Working Memory Performance.

There is an extensive body of research showing a significant relationship between frontal midline theta activity in the 4- to 8-Hz range and working memory (WM) performance. Transcranial alternating current stimulation (tACS) is recognized for inducing lasting changes in brain oscillatory activity. Across two experiments, we tested whether WM could be improved through tACS of dorsomedial pFC and ACC, by affecting executive control networks associated with frontal midline theta. In Experiment 1, after either a 20-min verum or sham stimulation applied to Fpz-CPz at 1 mA and 6 Hz, 31 participants performed WM tasks, while EEG was recorded. The tasks required participants to either mentally manipulate memory items or retain them in memory as they were originally presented. No significant effects were observed in behavioral performance, and we found no change in theta activity during rest and task after stimulation. However, alpha activity during retention or manipulation of information in WM was less strongly enhanced during the delay period after verum stimulation as compared with sham. In Experiment 2 (n = 25), tACS was administered during the task in two separate sessions. Here, we changed the order of the stimulation blocks: A 25-min task block was either accompanied first by sham stimulation and then by verum stimulation, or vice versa. Again, we found no improvements in WM through either tACS after-effects or online stimulation. Taken together, our results demonstrate that theta frequency tACS applied at the midline is not an effective method for enhancing WM.

Time-restricted feeding prevents memory impairments induced by obesogenic diet consumption, via hippocampal thyroid hormone signaling

ObjectivesThe early consumption of calorie-rich diet disrupts circadian rhythms and has adverse effects on memory, yet the effects of time-restricted feeding (TRF) and the underlying molecular mechanisms are unknown. Here, we set out to identify the behavioral and molecular circadian rhythms disruptions generated by juvenile obesogenic diet consumption and their restoration by TRF in male mice. MethodsMetabolic rhythms were measured by indirect calorimetry and memory performances by behavioral tasks. Hippocampal translatome (pS6_TRAP), enrichment and co-regulated gene network analyses were conducted to identify the molecular pathways involved in memory impairments and their restoration by TRF. Differential exon usage analyses, mass spectrometry and pharmacological intervention were used to confirm thyroid hormone signaling involvement. ResultsWe show that four weeks of TRF restore the rhythmicity of metabolic parameters and prevents memory impairments in mice fed a high fat-high sucrose (HFS) diet since weaning, independently of body fat levels. Hippocampal translatome and differential exon usage analyses indicate that impaired memory of mice under ad libitum HFS diet is accompanied by reduced thyroid hormone signaling and altered expression of astrocytic genes regulating glutamate neurotransmission. TRF restored the diurnal expression variation of part of these genes and intra-hippocampal infusion of T3, the active form of thyroid hormone, rescues memory performances and astrocytic gene expression of ad libitum HFS diet-fed mice. ConclusionsThus, thyroid hormones contribute to the TRF positive effects on both metabolism and memory in mice fed an obesogenic diet, highlighting this nutritional approach as a powerful tool in addressing obesity brain comorbidities and paving the way for further mechanistic studies on hippocampal thyroid signaling.

CSF Parvalbumin Levels at Multiple Sclerosis Diagnosis Predict Future Worse Cognition, Physical Disability, Fatigue, and Gray Matter Damage.

Cognitive impairment (CI) in multiple sclerosis (MS) is frequent and determined by a complex interplay between inflammatory and neurodegenerative processes. We aimed to investigate whether CSF parvalbumin (PVALB), measured at the time of diagnosis, may have a prognostic role in patients with MS. In this cohort study, CSF analysis of PVALB and Nf-L levels was performed on all patients at diagnosis (T0) and combined with physical, cognitive, and MRI assessment after an average of 4 years of follow-up (T4) from diagnosis. Cognitive performance was evaluated with a comprehensive neuropsychologic battery: both global (cognitively normal, CN, mildly CI, mCI, and severely CI, sCI) and domain cognitive status (normal/impaired in memory, attention/information processing speed, and executive functions) were considered. Cortical thickness and gray matter volume data were acquired using 3T MRI scanner. A total of 72 patients with MS were included. At diagnosis, PVALB levels were higher in those patients who showed a worsening physical disability after 4 years of follow-up (p = 0.011). CSF PVALB levels were higher in sCI patients than in CN (p = 0.033). Moreover, higher PVALB levels significantly correlated with worse global cognitive (p = 0.024) and memory functioning (p = 0.044). A preliminary clinical threshold for PVALB levels at diagnosis was proposed (2.57 ng/mL), which maximizes the risk of showing CI (in particular, sCI) at follow-up, with a sensitivity of 91% (specificity 30%). No significant results were found for these associations with Nf-L. In addition, patients with higher levels of PVALB at diagnosis showed higher cognitive (p = 0.024) and global fatigue (p = 0.043) at follow-up. Finally, higher PVALB levels also correlated significantly with more pronounced CTh/volume at T4 in the inferior frontal gyrus (p = 0.044), postcentral gyrus (p = 0.025), frontal pole (p = 0.042), transverse temporal gyrus (p = 0.008), and cerebellar cortex (p = 0.041) and higher atrophy (change T0-T4) in the right thalamus (p = 0.038), pericalcarine cortex (p = 0.009), lingual gyrus (p = 0.045), and medial frontal gyrus (p = 0.028). The significant association found between parvalbumin levels in the CSF at diagnosis and cognitive, clinical, and neuroradiologic worsening after 4 years of follow-up support the idea that parvalbumin, in addition to Nf-L, might represent a new potential prognostic biomarker, reflecting MS neurodegenerative processes occurring since early disease stages.

On the probabilistic-statistical approach to the analysis of nonlocality parameters of plasma density

A sample of values of plasma density in a thermonuclear facility is studied. A methodology for processing experimental data that makes it possible to establish correspondence between this sample and a model of nonstationary noise is proposed. This model is formed as convolution of a stationary sequence and a memory function, and it makes it possible to simulate the competition between space and time nonlocalities. A physical interpretation of the nonlocality parameters is described.

Remnant cholesterol and cognitive function: Evidence from the China health and retirement longitudinal study.

Evidence on associations of remnant cholesterol (RC) and its variability with cognitive function is still lacking. To explore the association of RC and its variability with cognitive function. Participants were recruited from a population-based cohort, the China Health and Retirement Longitudinal Study (CHARLS). Cognitive function was assessed by a standardized questionnaire from CHARLS, with domains of episodic memory and mental intactness. A linear mixed effects model was used to analyze the association of RC with cognitive function, along with its variability (calculated as standard deviation [SD], coefficient of variation [CV], variability independent of the mean [VIM]), with results expressed as β (95%CI). Potential subgroup differences in the association of RC and its variability with cognitive function were also explored. 4234 participants were eventually included, with mean (SD) age of 57.4 (8.0) years. Each 10 mg/dL increase in RC was associated with 0.053 (95%CI: 0.096, 0.009) points, 0.021 (95%CI: 0.042, 0.000) points, 0.032 (95%CI: 0.064, 0.001) points decrease in global cognitive function, episodic memory, and mental intactness scores, respectively. Compared with the first tertile (T1) group of RC variability (calculated as SD, VIM), T3 showed a lower level in global cognition and episodic memory after multivariate adjustment. The potential modification effects of educational level on RC and its variability in relation to cognitive function were also identified. Among Chinese middle-aged and older adults, higher RC level were associated with worse cognitive function. Greater RC variability was also associated with worse cognitive performance, especially in memory function.

Experimental Manipulation of the Bilateral Posterior Parietal Cortex Strengthens Associative Memory in Healthy Participants: A Continuous Theta-burst Stimulation.

To test whether targeting left and right posterior parietal cortex (PPC) with continuous theta-burst stimulation (cTBS) in healthy adults would strengthen associative memory (AM) performance. This study consisted of two experiments (a behavioral experiment and a formal experiment during each of the two experimental sessions). In Experiment 1, 18 adults (one male, age = 22.83 ± 3.92 years) were included in the behavioral phase and 18 adults (seven males, age = 40.11 ± 12.27 years) in the stimulation phase. There were 120 neutral facial images paired with 120 two-character nouns and then divided into six test versions (10 male faces and 10 female faces paired with 20 different nouns were considered as one version). In the behavioral experiment, participants were tested by six-version tests to assess memory materials, and in the formal experiment, participants' face-word AM performance was measured by certified tests based on a cued recall paradigm. Furthermore, 30 adults (seven males, age = 20.97 ± 1.85 years) and 15 adults (five males, age = 22.27 ± 1.29 years) participated in Experiment 2, respectively. Stimuli and procedure were the same as in Experiment 1, but the AM test was based on a forced-choice paradigm. Experiment 1 did not yield anticipated outcomes; Experiment 2 showed that cTBS of left and right PPC strengthened the AM performance compared with the control condition. In conclusion, cTBS to left and right PPC improved AM in healthy adults, which provided further experimental evidence for strengthening AM by cTBS.

Results from a randomized controlled trial of zonisamide in the treatment of alcohol use disorder

There is preliminary evidence that the anticonvulsant medication Zonisamide (ZON) may be an effective, well-tolerated treatment for alcohol use disorder (AUD). However, further evaluation of its efficacy for treating patients with AUD is needed, and much remains unknown about ZON’s therapeutic mechanisms. The present study aimed to evaluate the efficacy and tolerability of ZON in a double-blind, placebo-controlled, randomized trial. Eighty-one adults (ages 21-65) diagnosed with AUD were randomly assigned to receive either ZON (at a target dose of 400 mg/d) or a pill placebo over 12 weeks, followed by a two-week taper. All participants also received a computerized alcohol reduction program, Take Control (TC). Primary drinking outcomes were average daily drinks, percentage drinking days, and percentage heavy drinking days. Further, we evaluated changes in AUD clinical severity and performance on neuropsychological measures. For both groups, drinking outcomes generally decreased, as did AUD clinical severity, though group differences were not statistically significant. Neuropsychological testing performance was similar for both groups at baseline; however, at post-treatment, participants in the ZON group demonstrated poorer working memory and lower performance on verbal fluency tests compared to the placebo group, and these differences were statistically significant with moderate-large effect sizes. One serious adverse event was reported among individuals receiving ZON. Study findings indicate that ZON combined with TC does not demonstrate superior effectiveness for reducing average daily drinks in this clinical sample with principal AUD compared to placebo and TC, and treatment with ZON may be associated with reduced neurocognitive performance over time.

Citrus supplementation in subjective cognitive decline: results of a 36-week, randomized, placebo-controlled trial

BackgroundDeveloping interventions for older adults with subjective cognitive decline (SCD) has the potential to prevent dementia in this at-risk group. Preclinical models indicate that Citrus-derived phytochemicals could benefit cognition and inflammatory processes, but results from clinical trials are still preliminary. The aim of this study is to determine the effects of long-term supplementation with Citrus peel extract on cognitive performance and inflammation in individuals with SCD.MethodsEighty participants were randomly assigned to active treatment (400 mg of Citrus peel extract containing 3.0 mg of naringenin and 0.1 mg of auraptene) or placebo at 1:1 ratio for 36 weeks. The primary endpoint was the change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total score across the 36-week trial period. Other cognitive outcomes included tests and scales evaluating verbal memory, attention, executive and visuospatial functions, and memory concerns. The secondary endpoint was the change of interleukin-8 (IL-8) levels over the 36-week trial period in a subsample of 60 consecutive participants. An Intention-to-treat approach with generalized linear mixed models was used for data analysis.ResultsThe RBANS total score showed significant improvement in both Citrus peel extract and placebo groups at 36 weeks (p for time < .001, d = 0.36, p time x treatment = .910). Significant time effects were also found in cognitive domains of short- and long-term verbal memory (p < .001) and scales of subjective memory (p < .01), with no significant time x treatment interaction. The largest effect sizes were observed in verbal memory in the placebo group (d = 0.69 in short-term, and d = 0.78 in long-term verbal memory). Increased IL-8 levels were found at 36-week follow-up in both Citrus peel extract and placebo groups (p for time = .010, d = 0.21, p time x treatment = .772). Adverse events were balanced between groups.ConclusionsIn this randomized clinical trial, long-term Citrus peel extract supplementation did not show cognitive benefits over placebo in participants with SCD, possibly due to high placebo response. These findings might have specific implications for designing future nutraceutical trials in individuals experiencing SCD.Trial registrationThe trial has been registered at the United States National Library of Medicine at the National Institutes of Health Registry of Clinical Trials under the code NCT04744922 on February 9th, 2021 (https://www.clinicaltrials.gov/ct2/show/NCT04744922).

A Comprehensive Analysis on Galantamine Based Hybrids for the Management of Alzheimer's Disease.

Alzheimer's disease (AD) is a progressive chronic age-related neurodegenerative brain disorder characterized by the loss of memory and other cognitive functions. The exact etiology of AD is still under investigation, however several factors such as low level of neurotransmitter acetylcholine (ACh), aggregation of amyloid beta (Aβ) in the form of Aβ plaques, hyperphosphorylation of tau protein into neurofibrillary tangles (NFTs), oxidative stress, and metal ion imbalance are the major hallmarks of this disease. Of the multiple hypotheses for AD, the amyloid-β (Aβ) and cholinergic hypothesis are the main targeting hypotheses for AD. Some researchers hypothesized that the primary event associated with the cholinergic neurotransmitter (acetylcholine) is memory loss and cognitive impairment. Due to the disease's complicated pathogenesis, long-term therapy with a single target candidate is futile. As a result, multitargeted and multifunctional therapies have emerged. Various research teams are concentrating on addressing multiple disease factors through hybridization techniques. Consequently, this hybridization approach has been applied to all core scaffolds, including galantamine. In this article, we tried to provide a thorough overview of the most recent developments on galantamine, a prospective AChE inhibitor, and its hybrid analogs as possible therapeutic agents for treating AD. Furthermore, we also provided the design, synthesis, and SAR analysis of the galantamine-based compounds used in the last decades for the management of AD.

Effects of variation in exercise training load on cognitive performances and neurotrophic biomarkers in patients with coronary artery disease.

This study compared the effects of linear (LP) and nonlinear (NLP) training periodization on cognitive functions, neurotrophic biomarkers [plasma brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1)], and cathepsin-B in patients with coronary artery disease (CAD). Forty-four patients with CAD reported to our laboratory on two occasions to undergo testing procedures before and after training sessions, and were then blindly randomized to NLP or LP for 36 training sessions. Visit 1 included blood samples and a maximal cardiopulmonary exercise testing to get maximal oxygen uptake (V̇o2peak). Visit 2 included cognitive functions assessment. Thirty-nine patients completed the study (LP: n = 20, NLP: n = 19), with no observed changes in cognitive performances after the training intervention in either group. IGF-1 concentration decreased in both groups (time-effect: P < 0.001), whereas BDNF concentration increased (time-effect: P < 0.05) without group interaction, and cathepsin-B did not change after the intervention. Associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.18, P = 0.04), and ΔIGF-1 and Δshort-term/working memory (R2 = 0.17, P = 0.01) in the pooled sample, with ΔIGF-1 and ΔBDNF accounting for 10% of the variance in Δshort-term/working memory. In the LP group, associations were found between ΔV̇o2peak and ΔBDNF (R2 = 0.45, P = 0.02), ΔBDNF and Δshort-term/working memory (R2 = 0.62, P = 0.004), ΔIGF-1 and Δshort-term/working memory (R2 = 0.31, P = 0.01), and ΔIGF-1 and Δexecutive function (R2 = 0.22, P = 0.04). This study indicates that linear and nonlinear training periodization led to an increase in BDNF, and a decrease in IGF-1, without change in cognitive function in individuals with stable CAD.NEW & NOTEWORTHY We used a novel and supervised iso-energetic training, integrating both moderate- and high-intensity aerobic exercises. Our findings indicate that greater variation in training load did not yield cognitive enhancements, although both protocols exhibited positive effects on brain-derived neurotrophic factor (BDNF) levels. Moreover, this study establishes a clear positive association between short-term and working memory and neurotrophic biomarkers. In addition, the independent predictive value of change in insulin-like growth factor-1 (IGF-1) on improvement in short-term and working memory highlight the close relationship between neurotrophic markers and cognition. Consequently, our results advocate for exercise training interventions targeting neurotrophic biomarkers to enhance cognitive function among individuals with coronary artery disease.

Examining neuropsychological differences in adults afflicted by COVID-19 with and without anosmia

This study presents the outcomes of a research endeavor aimed at comparing the neuropsychological functioning of two distinct groups: one comprising individuals with both COVID-19 and anosmia, and the other without anosmia. A comprehensive neuropsychological assessment, involving ten tests, was administered to 60 participants, divided equally into two groups of 30. The group exhibiting anosmia displayed lower scores in lexical access, inhibitory control, strategy switching, visuoconstructive praxis, nonverbal memory, and verbal fluency functions. The effect sizes for these differences generally ranged from low to medium. Overall, the identified impairments strongly indicate deficits in executive functioning. Certain theories even propose that the frontal lobes may be the primary target of SARS-CoV-2 within the brain. To enhance our comprehension, future research could delve into the specific mechanisms through which the virus interacts with the prefrontal cortex, thereby illuminating the intricacies of COVID-19-related cognitive impairments.