Impaired Memory Consolidation Research Articles

A Strategy for Allowing Earlier Diagnosis and Rigorous Evaluation of BACE1 Inhibitors in Preclinical Alzheimer's Disease.

Given continued failure of BACE1 inhibitor programs at symptomatic and prodromal stages of Alzheimer's disease (AD), clinical trials need to target the earlier preclinical stage. However, trial design is complex in this population with negative diagnosis of classical hippocampal amnesia on standard memory tests. Besides recent advances in brain imaging, electroencephalogram, and fluid-based biomarkers, new cognitive markers should be established for earlier diagnosis that can optimize recruitment to BACE1 inhibitor trials in presymptomatic AD. Notably, accelerated long-term forgetting (ALF) is emerging as a sensitive cognitive measure that can discriminate between asymptomatic individuals with high risks for developing AD and healthy controls. ALF is a form of declarative memory impairment characterized by increased forgetting rates over longer delays (days to months) despite normal storage within the standard delays of testing (20-60 min). Therefore, ALF may represent a harbinger of preclinical dementia and the impairment of systems memory consolidation, during which memory traces temporarily stored in the hippocampus become gradually integrated into cortical networks. This review provides an overview of the utility of ALF in a rational design of next-generation BACE1 inhibitor trials in preclinical AD. I explore potential mechanisms underlying ALF and relevant early-stage biomarkers useful for BACE1 inhibitor evaluation, including synaptic protein alterations, astrocytic dysregulation and neuron hyperactivity in the hippocampal-cortical network. Furthermore, given the physiological role of the isoform BACE2 as an AD-suppressor gene, I also discuss the possible association between the poor selectivity of BACE1 inhibitors and their side effects (e.g., cognitive worsening) in prior clinical trials.

Age-Related Changes in Sleep and Its Implications for Cognitive Decline in Aging Persons With Schizophrenia: A Critical Review.

Cognitive impairment is a core feature of schizophrenia that worsens with aging and interferes with quality of life. Recent work identifies sleep as an actionable target to alleviate cognitive deficits. Cardinal non-rapid eye movement (NREM) sleep oscillations such as sleep spindles and slow oscillations are critical for cognition. People living with schizophrenia (PLWS) and their first-degree relatives have a specific reduction in sleep spindles and an abnormality in their temporal coordination with slow oscillations that predict impaired memory consolidation. While NREM oscillatory activity is reduced in typical aging, it is not known how further disruption in these oscillations contributes to cognitive decline in older PLWS. Another understudied risk factor for cognitive deficits among older PLWS is obstructive sleep apnea (OSA) which may contribute to cognitive decline. We conducted a narrative review to examine the published literature on aging, OSA, and NREM sleep oscillations in PLWS. Spindles are propagated via thalamocortical feedback loops, and this circuitry shows abnormal hyperconnectivity in schizophrenia as revealed by structural and functional MRI studies. While the risk and severity of OSA increase with age, older PLWS are particularly vulnerable to OSA-related cognitive deficits because OSA is often underdiagnosed and undertreated, and OSA adds further damage to the circuitry that generates NREM sleep oscillations. We highlight the critical need to study NREM sleep in older PWLS and propose that identifying and treating OSA in older PLWS will provide an avenue to potentially mitigate and prevent cognitive decline.

Nigrostriatal Inflammation Is Associated with Nonmotor Symptoms in an Experimental Model of Prodromal Parkinson’s Disease

Recent evidence has supported a pathogenic role for neuroinflammation in Parkinson’s disease (PD). Inflammatory response has been associated with symptoms and subtypes of PD. However, it is unclear whether immune changes are involved in the initial pathogenesis of PD, leading to the non-motor symptoms (NMS) observed in its prodromal stage. The current study aimed to characterize the behavioral and cognitive changes in a toxin-induced model of prodromal PD-like syndrome. We also sought to investigate the role of neuroinflammation in prodromal PD-related NMS. Male mice were subjected to bilateral intranasal infusion with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or saline (control group), followed by comprehensive behavioral, pathological and neurochemical analysis. Intranasal MPTP infusion was able to cause the loss of dopaminergic neurons in the substantia nigra (SN). In parallel, it induced impairment in olfactory discrimination and social memory consolidation, compulsive and anxiety-like behaviors, but did not influence motor performance. Iba-1 and GFAP expressions were increased in the SN, suggesting an activated state of microglia and astrocytes. Consistent with this, MPTP mice had increased levels of IL-10 and IL-17A, and decreased levels of BDNF and TrkA mRNA in the SN. The striatum showed increased IL-17A, BDNF, and NFG levels compared to control mice. In conclusion, neuroinflammation may play an important role in the early stage of experimental PD-like syndrome, leading to cognitive and behavioral changes. Our results also indicate that intranasal administration of MPTP may represent a valuable mouse model for prodromal PD.

Infralimbic activity during REM sleep facilitates fear extinction memory

Rapid eye movement (REM) sleep is known to facilitate fear extinction and play a protective role against fearful memories.1,2 Consequently, disruption of REM sleep after a traumatic event may increase the risk for developing PTSD.3,4 However, the underlying mechanisms by which REM sleep promotes extinction of aversive memories remain largely unknown. The infralimbic cortex (IL) is a key brain structure for the consolidation of extinction memory.5 Using calcium imaging, we found in mice that most IL pyramidal neurons are intensively activated during REM sleep. Optogenetically suppressing the IL specifically during REM sleep within a 4-h window after auditory-cued fear conditioning impaired extinction memory consolidation. In contrast, REM-specific IL inhibition after extinction learning did not affect the extinction memory. Whole-cell patch-clamp recordings demonstrated that inactivating IL neurons during REM sleep depresses their excitability. Together, our findings suggest that REM sleep after fear conditioning facilitates fear extinction by enhancing IL excitability and highlight the importance of REM sleep in the aftermath of traumatic events for protecting against traumatic memories.

The alpha1A antagonist tamsulosin impairs memory acquisition, consolidation and retrieval in a novel object recognition task in mice

Tamsulosin is an α1-adrenoceptor antagonist used to treat benign prostatic hyperplasia. This drug exhibits high affinity for α1A- and α1D-adrenoceptor subtypes, which are also expressed in the brain. While dementia symptoms have been reported after administration of tamsulosin in humans, studies on its effects on the rodent brain are still rare. The present study investigated the effects of tamsulosin (and biperiden, an amnesic drug) on cognitive performance in the object recognition task (ORT). Tamsulosin (0.001–0.01 mg/kg) was orally administrated in mice at three distinct time points: pre-training, post-training and pre-test session. Tamsulosin 0.01 mg/kg impaired object recognition regardless of when it was injected, whereas at lower doses did not affect mouse performance in the ORT. Biperiden also impaired acquisition and consolidation of object recognition in mice. Furthermore, the effects of tamsulosin on locomotion, motivation and anxiety were excluded as potential confounding factors. At all doses tested, tamsulosin did not alter distance moved, time spent exploring objects in the ORT, and anxiety-related behaviors in the elevated plus-maze test. By contrast, diazepam evoked a significant reduction of anxiety-like behaviours. In conclusion, tamsulosin impaired memory acquisition, consolidation and retrieval in an object recognition task in mice, thus affecting memory performance in a non-specific phase manner. These findings contribute to our understanding of the potential adverse effects of tamsulosin, and shed light on the role played by α1-adrenoceptors, particularly α1A- subtype, in cognitive processes.

Acute physical exercise prevents memory amnesia caused by protein synthesis inhibition in rats' hippocampus

The benefits of physical exercise (PE) on memory consolidation have been well-documented in both healthy and memory-impaired animals. However, the underlying mechanisms through which PE exerts these effects are still unclear. In this study, we aimed to investigate the role of hippocampal protein synthesis in memory modulation by acute PE in rats. After novel object recognition (NOR) training, rats were subjected to a 30-min moderate-intensity acute PE on the treadmill, while control animals did not undergo any procedures. Using anisomycin (ANI) and rapamycin (RAPA), compounds that inhibit protein synthesis through different mechanisms, we manipulated protein synthesis in the CA1 region of the hippocampus to examine its contribution to memory consolidation. Memory was assessed on days 1, 7, and 14 post-training. Our results showed that inhibiting protein synthesis by ANI or RAPA impaired NOR memory consolidation in control animals. However, acute PE prevented this impairment without affecting memory persistence. We also evaluated brain-derived neurotrophic factor (BDNF) levels after acute PE at 0.5h, 2h, and 12h afterward and found no differences in levels compared to animals that did not engage in acute PE or were only habituated to the treadmill. Therefore, our findings suggest that acute PE could serve as a non-pharmacological intervention to enhance memory consolidation and prevent memory loss in conditions associated with hippocampal protein synthesis inhibition. This mechanism appears not to depend on BDNF synthesis in the early hours after exercise.

Berberine and hesperidin prevent the memory consolidation impairment induced by pentylenetetrazole in zebrafish

This study verified the effects of the natural compounds berberine and hesperidin on seizure development and cognitive impairment triggered by pentylenetetrazole (PTZ) in zebrafish. Adult animals were submitted to a training session in the inhibitory avoidance test and, after 10 minutes, they received an intraperitoneal injection of 25, 50, or 100 mg/kg berberine or 100 or 200 mg/kg hesperidin. After 30 minutes, the animals were exposed to 7.5 mM PTZ for 10 minutes. Animals were submitted to the test session 24 h after the training session to verify their cognitive performance. Zebrafish larvae were exposed to 100 µM or 500 µM berberine or 10 µM or 50 µM hesperidin for 30 minutes. After, larvae were exposed to PTZ and had the seizure development evaluated by latency to reach the seizure stages I, II, and III. Adult zebrafish pretreated with 50 mg/kg berberine showed a longer latency to reach stage III. Zebrafish larvae pretreated with 500 µM berberine showed a longer latency to reach stages II and III. Hesperidin did not show any effect on seizure development both in larvae and adult zebrafish. Berberine and hesperidin pretreatments prevented the memory consolidation impairment provoked by PTZ-induced seizures. There were no changes in the distance traveled in adult zebrafish pretreated with berberine or hesperidin. In larval stage, berberine caused no changes in the distance traveled; however, hesperidin increased the locomotion. Our results reinforce the need for investigating new therapeutic alternatives for epilepsy and its comorbidities.

No impairment of contextual fear memory consolidation by oxytocin receptor antagonism in male rats

Oxytocin is a peptide released into brain regions associated with the processing of aversive memory and threat responses. Given the expression of oxytocin receptors across this vigilance surveillance system of the brain, we investigated whether pharmacological antagonism of the receptor would impact contextual aversive conditioning and memory. Adult male rats were conditioned to form an aversive contextual memory. The effects of peripheral administration of either the competitive antagonist Atosiban or noncompetitive antagonist L-368,899 were compared to saline controls. Oxytocin receptor antagonism treatment did not significantly impact the consolidation of aversive contextual memory in any of the groups. We conclude that peripheral antagonism of oxytocin signalling did not impact the formation of aversive memory.

Effects of an Angiotensin IV Analog on 3-Nitropropionic Acid-Induced Huntington's Disease-Like Symptoms in Rats.

Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, cognitive, and psychiatric dysfunction caused by a mutant huntingtin protein. Compromised metabolic activity resulting from systemic administration of the mitochondrial toxin, 3-nitropropionic acid (3-NP), is known to mimic the pathology of HD and induce HD-like symptoms in rats. N-hexanoic-Tyr-Ile-(6)-amino hexanoic amide (PNB-0408), also known as Dihexa, has been shown to have neuroprotective and procognitive properties in animal models of Alzheimer's and Parkinson's diseases. Given the mechanism of action and success in other neurodegenerative diseases, we felt it an appropriate compound to investigate further for HD. The present study was designed to test if PNB-0408, an angiotensin IV analog, could attenuate 3-NP-induced HD-like symptoms in rats and serve as a potential therapeutic agent. Forty male Wistar rats were randomized into three groups consisting of a "vehicle" group, a "3-NP" group, and a "3-NP + PNB-0408" group. PNB-0408 was administered along with chronic exposure to 3-NP. Animal body weight, motor function, and cognitive abilities were measured for five weeks, before euthanasia and histopathological analysis. Exposure to 3-NP decreased the amount of weight rats gained, impaired spatial learning and memory consolidation, and led to marked motor dysfunction. From our observations and analysis, PNB-0408 did not protect rats from the deficits induced by 3-NP neurotoxicity. Our findings suggest that PNB-0408 may not be an efficacious treatment strategy for preventing 3-NP-induced HD-like symptoms in a preclinical model. These data highlight the need for further research of this compound in alternate models and/or alternative approaches to managing this disorder.

From gains to gaps? How Selective Androgen Receptor Modulator (SARM) YK11 impact hippocampal function: In silico, in vivo, and ex vivo perspectives

Selective Androgen Receptor Modulators (SARMs), particularly (17α,20E)-17,20-[(1-methoxyethylidene)bis(oxy)]-3-oxo-19-norpregna-4,20-diene-21-carboxylic-acid-methyl-ester (YK11), are increasingly popular among athletes seeking enhanced performance. Serving as an Androgen Receptor (AR) agonist, YK11 stimulates muscle growth while inhibiting myostatin. Our study delved into the impact of YK11 on the rat hippocampus, analyzing potential alterations in neurochemical mechanisms and investigating its synergistic effects with exercise (EXE), based on the strong relationship between SARM users and regular exercise. Utilizing Physiologically Based Pharmacokinetic (PBPK) modeling, we demonstrated YK11 remarkable brain permeability, with molecular docking analysis revealing YK11 inhibitory effects on 5-alpha-reductase type II (5αR2), suggesting high cell bioavailability. Throughout a 5-week experiment, we divided the animals into the following groups: Control, YK11 (0.35 g/kg), EXE (swimming exercise), and EXE + YK11. Our findings showed that YK11 displayed a high binding affinity with AR in the hippocampus, influencing neurochemical function and modulating aversive memory consolidation, including the downregulation of the BDNF/TrkB/CREB signaling, irrespective of EXE combination. In the hippocampus, YK11 increased pro-inflammatory IL-1β and IL-6 cytokines, while reducing anti-inflammatory IL-10 levels. However, the EXE + YK11 group counteracted IL-6 effects and elevated IL-10. Analysis of apoptotic proteins revealed heightened p38 MAPK activity in response to YK11-induced inflammation, initiating the apoptotic cascade involving Bax/Bcl-2/cleaved caspase-3. Notably, the EXE + YK11 group mitigated alterations in Bcl-2 and cleaved caspase-3 proteins. In conclusion, our findings suggest that YK11, at anabolic doses, significantly alters hippocampal neurochemistry, leading to impairments in memory consolidation. This underscore concerns about the misuse risks of SARMs among athletes and challenges common perceptions of their minimal side effects.

Astrocytic phagocytosis in the medial prefrontal cortex jeopardises postoperative memory consolidation in mice.

Memory impairment is one of the main characteristics of postoperative cognitive dysfunction. It remains elusive how postoperative pathological changes of the brain link to the memory impairment. The clinical setting of perioperation was mimicked via partial hepatectomy under sevoflurane anaesthesia together with preoperative restraint stress (Hep-Sev-stress) in mice. Memory changes were assessed with fear conditioning. The medial prefrontal cortex (mPFC)-dorsal hippocampus connectivity was evaluated with injecting neurotracer 28 days before surgery. Astrocytic activation was limited via injecting AAV-GFAP-hM4Di-eGFP into the mPFC. Astrocytic and microglial phagocytosis of synapses were visualised with co-labelling hippocampal neuronal axon terminals with PSD-95 and S100β or Iba1. Neuroinflammation and oxidative stress status were also detected. Hep-Sev-stress impaired the memory consolidation (mean [standard error], 49.91 [2.55]% vs. 35.40 [3.97]% in the contextual memory, p = 0.007; 40.72 [2.78]% vs. 27.77 [2.22]% in cued memory, p = 0.002) and the cued memory retrieval (39.00 [3.08]% vs. 24.11 [2.06]%, p = 0.001) in mice when compared with these in the naïve controls. Hep-Sev-stress damaged the connectivity from the dorsal hippocampus to mPFC but not from the mPFC to the dorsal hippocampus and increased the astrocytic but not microglial phagocytosis of hippocampal neuronal axon terminals in the mPFC. The intervention also induced neuroinflammation and oxidative stress in the dorsal hippocampus and the mPFC in a regional-dependent manner. Limiting astrocyte activation in the mPFC alleviated memory consolidation impairment induced by Hep-Sev-stress. Postoperative memory consolidation was impaired due to astrocytic phagocytosis-induced connectivity injury from the dorsal hippocampus to the medial prefrontal cortex.

Puerarin Attenuates Cycloheximide-Induced Oxidative Damage and Memory-Consolidation Impairment in Rats.

Cycloheximide (CXM), an antifungal antibiotic, causes impaired memory consolidation as a side effect partially by disturbing the activities of the central catecholaminergic and cholinergic system. Some reports indicated that puerarin prevented memory impairment in various models in rodents. However, the protective effects of puerarin on the side effects of cycloheximide for memory consolidation impairment have not yet been investigated. The protective effects of puerarin on CXM-induced memory-consolidation impairment, and memory impairment produced by central administration of AF64A neurotoxin, were investigated using a passive avoidance task in rats. A combination of transmitter receptor agonists and antagonists was used to explore the effects of puerarin on nervous system function. The activity of antioxidant defense systems and neurotransmitter systems in the prefrontal cortex and hippocampus were assayed. Systemic (25 and 50 mg/kg, i.p.) or central (5 and 10 µg/brain, i.c.v.) administration of puerarin attenuated CXM-induced memory-consolidation impairment produced by 1.5 mg/kg CXM (s.c.) in rats. The improvements produced by 50 mg/kg puerarin were blocked by cholinergic antagonists, a 5-HT2 receptor agonist, and an adrenergic receptor antagonist. Puerarin (only at 50 mg/kg, i.p.) reversed the CXM-induced alterations of the levels of norepinephrine in the prefrontal cortex and the levels of monoamines in the hippocampus. Puerarin also increased antioxidant-defense-system activities in the prefrontal cortex and hippocampus, which had been decreased by CXM. We suggested that the attenuating effects of puerarin on CXM-induced memory-consolidation impairment may be due to decrease oxidative damage and the normalition of the neurotransmitter function in the prefrontal cortex and hippocampus.

The role of glutamate NMDA receptors of the mediodorsal thalamus in scopolamine-induced amnesia in rats

The current study was designed to examine the role of glutamate NMDA receptors of the mediodorsal thalamus (MD) in scopolamine-induced memory impairment. Adult male rats were bilaterally cannulated into the MD. According to the results, intraperitoneal (i.p.) administration of scopolamine (1.5 mg/kg) immediately after the training phase (post-training) impaired memory consolidation. Bilateral microinjection of the glutamate NMDA receptors agonist, N-Methyl-D-aspartic acid (NMDA; 0.05 µg/rat), into the MD significantly improved scopolamine-induced memory consolidation impairment. Co-administration of D-AP5, a glutamate NMDA receptor antagonist (0.001–0.005 µg/rat, intra-MD) potentiated the response of an ineffective dose of scopolamine (0.5 mg/kg, i.p.) to impair memory consolidation, mimicking the response of a higher dose of scopolamine. Noteworthy, post-training intra-MD microinjections of the same doses of NMDA or D-AP5 alone had no effect on memory consolidation. Moreover, the blockade of the glutamate NMDA receptors by 0.003 ng/rat of D-AP5 prevented the improving effect of NMDA on scopolamine-induced amnesia. Thus, it can be concluded that the MD glutamatergic system may be involved in scopolamine-induced memory impairment via the NMDA receptor signaling pathway.

Association Analysis of Common Structural Variants in the Alzheimer’s Disease Sequencing Project

AbstractBackgroundStructural variants (SV), genomic rearrangements of >50 base pairs, are an important source of genetic variation and have a great impact on gene expression and protein function. However, their contribution to the genetic architecture of Alzheimer’s Disease (AD) has not been comprehensively investigated. Identification of SVs by short‐read alignment can be inaccurate and biased. We used a novel SV calling pipeline that leverages assembly‐based methods and graph‐based representation, to identify SVs with high accuracy in the diverse sample of the Alzheimer’s Disease Sequencing Project (ADSP). We further examined the association of common SVs with AD.MethodsWe applied Biograph for SV calling on the ADSP 17K whole genome sequence data. After filtering out low‐quality SVs and performing sample‐level quality control, we identified 222,956 deletions, 177,139 insertions, and 10,558 inversions in 12,908 individuals (6,304 AD cases; 6,604 controls). We performed association analyses of common SVs (MAF > 1%) with AD using a logistic mixed‐effects model adjusting for sex, technical covariates, principal components, and relatedness. Statistical significance was evaluated using a Bonferroni‐corrected threshold (P< 9.19.x10−7).ResultsThere were 28,634 deletions, 25,522 insertions, and 198 inversions with MAF > 1%. We identified 2 intronic deletions significantly associated with AD. The first deletion is located in CCDC88B, encoding a protein that regulates T‐cell maturation and inflammation. The second deletion is located in CCDC11, predicted to be part of the spliceosomal complex. Among 11 insertions significantly associated with AD, 3 mapped to exonic sequences. A relatively common insertion located in an exon of FOXO6 showed the most significant association with AD (P = 1.41×10−12). FOXO6 is a member of Forkhead transcription factors that have been implicated in aging. Along with its high level of expression in the hippocampus, mice lacking FOXO6 had impaired memory consolidation. We identified one inversion suggestively associated with AD (P = 3.32×10−6) and located in an intron of PDE5A. PDE5A inhibitors have been reported as potential therapeutic targets for AD.ConclusionUsing novel data structures and algorithms to call SV, we discovered 14 SVs significantly associated with AD. Validation and gene prioritization of these findings are warranted.

Associations between self-reported sleep, overnight memory consolidation, and emotion perception: A large-scale online study in the general population.

Experimental studies suggest that short or disrupted sleep impairs memory consolidation, mood, and perception of emotional stimuli. However, studies have chiefly relied on laboratory-based study designs and small sample sizes. The aim of this fully online and pre-registered study was to investigate the association between sleep and overnight memory consolidation, emotion perception, and affect in a large, self-selected UK sample. A total of 1646 participants (473 completed) took part in an online study, where they completed a declarative (word-pairs) memory task, emotion perception task (valence ratings of images), and rated their affect within 2 h of bed-time. The following morning, participants reported on their state affect, sleep for the previous night, completed a cued recall task for the previously presented word-pairs, rated the valence of previously viewed images, and completed a surprise recognition task. Demographic data and habitual sleep quality and duration (sleep traits) were also recorded. Habitual sleep traits were associated with immediate recall for the word-pairs task, while self-reported sleep parameters for the specific night were not associated with overnight memory consolidation. Neither habitual sleep traits, nor nightly sleep parameters were associated with unpleasantness ratings to negative stimuli or overnight habituation. Habitual poor sleep was associated with less positive and more negative affect, and morning affect was predicted by the specific night's sleep. This study suggests that overnight emotional processing and declarative memory may not be associated with self-reported sleep across individuals. More work is needed to understand how findings from laboratory-based studies extrapolate to real-world samples and contexts.

33 Associations Between Long-Term Forgetting and Slow Wave Activity in Autosomal-Dominant Alzheimer’s Disease: Findings from the Colombia-Boston (COLBOS) Biomarker Study

Objective:Sleep contributes to memory retention and recall. Alzheimer’s disease (AD) patients experience decreased slow wave activity (SWA) during sleep. This decrease in SWA is associated with impaired memory consolidation (Lee et al., 2020). Long-term forgetting (LTF) over days or weeks has been linked to memory consolidation deficits and has been suggested as an early marker of AD that could be useful for identifying at-risk individuals for preclinical AD trials (Weston et al., 2018). Here, we examined associations between LTF and SWA in a sample of Presenilin-1 (PSEN1) E280A mutation carriers with autosomal dominant Alzheimer’s disease and non-carrier family members. Carriers of this mutation usually develop dementia in their forties (Fuller et al., 2019).Participants and Methods:Fourteen cognitively unimpaired PSEN1-E280A mutation carriers and sixteen age-matched non-carriers (mean age: 34.2 years) from the Colombia-Boston (COLBOS) biomarker study were included. Participants completed an overnight polysomnogram (PSG) and memory testing (NEUROPSI Word List) at 3-time points: 1) the night before PSG: immediate recall (Day1-ImmRecall) and a 20-minute delayed recall (Day1-DelayedRecall), 2) recall the following day (Day2-recall), and 3) recall one week later (Day7-recall). SWA was measured as the ratio 0. 6-1Hz/0.6-4Hz in frontopolar and frontotemporal regions and was calculated for sleep stages N2+N3 (slow wave sleep) based on an automated staging algorithm. Each participant’s LTF was calculated as the percent retention between Day 1 immediate recall and Day 7 recall (Butler, 2009). Mann-Whitney U tests were used to compare differences in recall, SWA, and LTF between groups. Spearman’s correlation was used to examine the associations between memory recall at different time points and SWA, as well as between LTF and SWA.Results:On Day 1, carriers had lower performance in immediate recall (p=0.02), compared to non-carriers, but there were no group differences in the 20-minute delayed recall. Carriers also recalled fewer words on Day 2 (p=0.03) and Day 7 (p=0.009) and had greater LTF (p=0.03). There were no group differences in SWA. In our overall sample, worse performance on word list delayed recall on Day 1, Day 2, and Day 7 was associated with less SWA across both frontotemporal (Day1: p=0.04, Day2: p=0.02, Day7: p=0.02) and frontopolar (all Ps<0.01) regions. In carriers, only worse performance on Day 1 delayed recall was associated with lower SWA in the frontopolar region (r= 0.535; p=0.049). Memory recall on other days was not associated with SWA in any brain regions. Additionally, greater LTF was associated with less SWA across both frontopolar (r= 0.507; p=0.005) and frontotemporal regions (r= 0.463 p= 0.01).Conclusions:Preliminary findings suggest that long-term forgetting is associated with less slow- wave activity in preclinical autosomal dominant Alzheimer’s disease. These results also suggest that SWA may be related to pre-sleep learning and subsequent overnight memory consolidation processes. LTF testing may be useful in selecting individuals for preclinical AD trials. Future research on the impact of slow wave activity on LTF may be useful in identifying ways to enhance short- and long-term memory consolidation in individuals at greater risk for dementia.

Impaired declarative memory consolidation in children with REM sleep-related obstructive sleep apnea.

We explored whether declarative memory consolidation is impaired in children with rapid eye movement sleep-related obstructive sleep apnea (REM-OSA) and investigated the correlation between memory consolidation and sleep-related respiratory parameters. Participants were children with habitual snoring aged 6-14 years and control children. Participants underwent polysomnography and declarative memory testing. Participants with snoring were categorized as primary snoring (PS), non-rapid eye movement sleep-related obstructive sleep apnea (NREM-OSA), stage-independent (SI)-OSA, and REM-OSA according to obstructive apnea-hypopnea index (OAHI), OAHI in REM sleep (OAHIREM), and OAHI in NREM sleep (OAHINREM). Declarative memory consolidation level was assessed by recall and recognition rates. There were 34 controls and 228 children with sleep-disordered breathing: 73 PS, 48 NREM-OSA, 59 SI-OSA, and 48 REM-OSA. Total arousal index was lower in the REM-OSA group than in the NREM-OSA group. In all groups, retest scores were higher than immediate test scores. Recall consolidation in PS, SI-OSA, and REM-OSA groups was lower than for controls and lower in REM-OSA than in NREM-OSA. There were no correlations between recall consolidation or recognition consolidation and OAHI, OAHINREM, oxygen desaturation index in REM sleep, total arousal index, or REM sleep percent. Recognition consolidation was negatively correlated with OAHIREM. Memory consolidation is impaired in children with REM-OSA compared with NREM-OSA and controls. There was no significant correlation between memory consolidation and OAHI, and recognition consolidation was negatively correlated with OAHIREM. It is important to pay attention to the OSA subtype in children. Tang Y, Yang C, Wang C, Wu Y, Xu Z, Ni X. Impaired declarative memory consolidation in children with REM sleep-related obstructive sleep apnea. J Clin Sleep Med. 2024;20(3):417-425.

The role of age-related sleep EEG changes in memory decline: experiments and computational modeling.

The slow oscillation (SO) observed during deep sleep is known to facilitate memory consolidation. However, the impact of age-related changes in sleep electroencephalography (EEG) oscillations and memory remains unknown. In this study, we aimed to investigate the contribution of age-related changes in sleep SO and its role in memory decline by combining EEG recordings and computational modeling. Based on the detected SO events, we found that older adults exhibit lower SO density, lower SO frequency, and longer Up and Down state durations during N3 sleep compared to young and middle-aged groups. Using a biophysically detailed thalamocortical network model, we simulated the "aged" brain as a partial loss of synaptic connections between neurons in the cortex. Our simulations showed that the changes in sleep SO properties in the "aged" brain, similar to those observed in older adults, resulting in impaired memory consolidation. Overall, this study provides mechanistic insights into how age-related changes modulate sleep SOs and memory decline.Clinical Relevance- This study contributes towards finding feasible biomarkers and target mechanism for designing therapy in older adults with memory deficits, such as Alzheimer's disease patients.

Memory Deficits in Parkinson's Disease Are Associated with Impaired Attentional Filtering and Memory Consolidation Processes.

The present study examined mechanisms underlying memory deficits in Parkinson's disease (PD) and their associations with brain structural metrics. Nineteen PD patients and twenty-two matched controls underwent two memory experiments. In Experiment 1 (delayed memory task), subjects were asked to remember an array of colored rectangles with varying memory set sizes (Low-Load (2 items), Low-Load (relevant 2 items) with Distractor (irrelevant 3 items), and High-Load (5 items)). After a 7 s delay period, they reported whether the orientation of any relevant figures had changed (test period). In Experiment 2 (working memory task), memory arrays were presented in varying set sizes (2 to 6 items) without distractors, followed by a 2 s delay period and a subsequent test period. Brain MRI data were acquired to assess structural differences (volumes and cortical thickness) in areas related to attention, working memory storage capacity, and episodic memory. Multivariate analyses of covariance revealed that, compared with controls, PD patients had lower memory capacity scores in all memory load conditions for Experiment 1 (p < 0.021), whereas there were no group differences in any memory load conditions for Experiment 2 (p > 0.06). In addition, PD patients had lower cortical thickness in the left superior temporal gyrus (p = 0.02), a region related to the ventral attentional system. Moreover, regression analyses revealed that lower cortical thickness values in the left superior temporal gyrus significantly predicted lower memory scores of Low-Load and Low-Load with Distractor conditions in Experiment 1 (p < 0.044) and lower scores of memory load conditions of 4 and 5 items in Experiment 2 (p < 0.012). These findings suggest that memory deficits in PD may partly be due to impaired attentional filtering and memory consolidation processes that may be related to superior temporal neurodegeneration. Future studies are warranted to confirm the current findings to guide the development of effective treatments for memory deficits in PD.

Heat exposure following encoding can interfere with subsequent recognition memory

Correlational studies suggest that high temperatures may impair online cognitive performance and learning processes. Here, we tested the hypothesis that heat exposure blocks offline memory consolidation. We report two studies, including a pre-registered replication. First, during a study phase, participants were familiarized with neutral and negatively valenced images. One day later, half of the participants were exposed to high temperatures in a sauna session at 50 °C. Recognition memory was tested 24 h later. We found that participants exposed to high temperature showed an impairment in recognition memory performance, relative to a control group of participants that were not exposed to heat or that had a sauna at 28 °C. This occurred for both emotional and neutral items. These results indicate that heat exposure impairs memory consolidation, thereby opening the possibility of using heat exposure as an agent for the treatment of clinical mental disorders.