Change Memory Research Articles

Interpersonal, Community, and Societal Stressors Mediate Black-White Memory Disparities.

Structural racism creates contextual stressors that disproportionately affect Black, relative to White, older adults in the United States and may contribute to worse cognitive health. We examined the extent to which interpersonal, community, and societal stressors uniquely explain Black-White disparities in initial memory and memory change. The sample included 14,199 non-Latino Black and White older adults (Mage = 68.32, 19.8% Black) from the U.S. Health and Retirement Study who completed psychosocial questionnaires at baseline and a word list memory task every 2 years over an 8-year period. Interpersonal, community, and societal stressors were operationalized as self-reported everyday discrimination, neighborhood physical disorder, and subjective societal status, respectively. Latent growth curves modeled longitudinal memory performance. Stressors were modeled simultaneously and allowed to correlate. Covariates included age, sex, education, wealth, parental education, and Southern residence. Compared to White participants, Black participants experienced more discrimination (β = -0.004, standard error [SE] = 0.001, p < .001), more neighborhood physical disorder (β = -0.009, SE = 0.002, p < .001), and lower perceived societal status (β = -0.002, SE = 0.001, p = .001), each of which uniquely mediated the racial disparity in initial memory. Sensitivity analyses utilizing proxy-imputed memory scores revealed an additional racial disparity in memory change, wherein Black participants evidenced a faster decline than White participants. This disparity in memory change was only uniquely mediated by more everyday discrimination among Black participants. Elements of structural racism may contribute to cognitive disparities via disproportionate stress experiences at multiple contextual levels among Black older adults. Future research should consider multilevel protective factors that buffer against negative impacts of racism on health.

Cognitive Performance is Associated With 1-Year Participation and Life Satisfaction Outcomes: A Traumatic Brain Injury Model Systems Study.

To determine, in persons with traumatic brain injury (TBI), the association between cognitive change after inpatient rehabilitation discharge and 1-year participation and life satisfaction outcomes. Secondary analysis of prospectively collected TBI Model Systems (TBIMS) data. Inpatient rehabilitation and community. 499 individuals with TBI requiring inpatient rehabilitation who completed the Brief Test of Adult Cognition by Telephone (BTACT) at inpatient rehabilitation discharge (ie, baseline) and 1-year postinjury. Participation Assessment with Recombined Tools-Objective (PART-O) and Satisfaction with Life Scale (SWLS). Of 2,840 TBIMS participants with baseline BTACT, 499met inclusion criteria (mean [standard deviation] age=45 [19] years; 72% male). Change in BTACT executive function (EF) was not associated with 1-year participation (PART-O; β=0.087, 95% CI [-0.004, 0.178], P =.061) when it was the sole model predictor. Change in BTACT episodic memory (EM) was associated with 1-year participation (β=0.096, [0.007, 0.184], P =.035), but not after adjusting for demographic, clinical, and functional status covariates (β=0.067, 95% CI [-0.010, 0.145], P =.089). Change in BTACT EF was not associated with life satisfaction total scores (SWLS) when it was the sole model predictor (β=0.091, 95% CI [-0.001, 0.182], P =.0503). Change in BTACT EM was associated with 1-year life satisfaction before (β=0.114, 95% CI [0.025, 0.202], P =.012) and after adjusting for covariates (β=0.103, [0.014, 0.191], P =.023). In secondary analyses, change in BTACT EF was associated with PART-O Social Relations and Out and About subdomains before (Social Relations: β=0.127, 95% CI [0.036, 0.217], P =.006; Out and About: β=0.141, 95% CI [0.051, 0.232], P =.002) and after (Social Relations: β=0.168, 95% CI [0.072, 0.265], P <.002; Out and About: β=0.156, 95% CI [0.061, 0.252], P <.002) adjusting for functional status and further adjusting for covariates (Social Relations: β=0.127, 95% CI [0.040, 0.214], P =.004; Out and About: β=0.136, 95% CI [0.043, 0.229], P =.004). However, only the models adjusting for functional status remained significant after multiple comparison correction (ie, Bonferroni-adjusted alpha level=0.002). EF gains during the first year after TBI were related to 1-year social and community participation. Gains in EM were associated with 1-year life satisfaction. These results highlight the potential benefit of cognitive rehabilitation after inpatient rehabilitation discharge and the need for interventions targeting specific cognitive functions that may contribute to participation and life satisfaction after TBI.

Focused Ultrasound Combined With Microbubbles Attenuate Symptoms in Heroin-Addicted Mice

ObjectiveTo explore the efficacy and mechanisms of stimulating the nucleus accumbens (NAc) in heroin-addicted mice using focused ultrasound and microbubbles (MBs). MethodsThe conditioned place preference (CPP) method was employed to establish a heroin-addicted mice model. Mice were randomized into control (C), heroin (H), heroin + ultrasound (H + U) and H + U + MBs. Ultrasound (2 MHz fundamental frequency, 1.34 MPa peak-negative pressure, 1 MHz pulse repetition frequency, 5% duty cycle, 15 min/d, over 2 d) was applied to stimulate the NAc in the latter 2 groups. Whereas H + U + MBs received an injection of sulfur hexafluoride MBs during the stimulation. Subsequently, CPP scores, open-field test (OFT), and elevated plus-maze test (EPMT) were conducted to assess behavioral changes in addiction memory, anxiety and exercise status. HE staining was performed to detect pathological structures. Neurotransmitters such as dopamine (DA), serotonin (5-HT) and glutamate (Glu) were detected using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Transmission electron microscopy (TEM) was used to observe ultrastructural changes of synapses in NAc. Immunohistochemistry (IHC) was utilized to detect Cleaved Caspase-3 in the NAc region. Western blotting (WB) was used to detect the protein expression of Cleaved Caspase-3, Bax and Bcl-2 in NAc. ResultsHE staining showed small patches of erythrocyte exudation were observed in the NAc and adjacent areas in H + U + MBs. The CPP scores of H + U + MBs were lower (p < 0.05) than H. After ultrasound treatment, all indices of the OFT and EPMT in H + U + MBs were significantly higher than H (p < 0.05). UPLC-MS/MS revealed that the levels of DA, 5-HT and Glu in H + U + MBs were lower than H (p < 0.01). TEM showed decrease the number of synapses (p < 0.05), and noticeable swelling of mitochondria, membrane damage, as well as damage to the cristae. Further detection by IHC and WB showed that the pro-apoptotic proteins Cleaved Caspase-3 and Bax increased and Bcl-2 decreased as anti-apoptotic proteins after ultrasound combined with MBs (p < 0.05). ConclusionFocused ultrasound combined with MBs stimulate the NAc can weaken the addictive memory and improve anxiety of heroin-related mice. The mechanical effect of ultrasound combined with the cavitation effect may be a potential treatment for addiction.

Changes in memory and cognition during the SARS-CoV-2 human challenge study

Patient-reported outcomes and cross-sectional evidence show an association between COVID-19 and persistent cognitive problems. The causal basis, longevity and domain specificity of this association is unclear due to population variability in baseline cognitive abilities, vulnerabilities, virus variants, vaccination status and treatment. Thirty-four young, healthy, seronegative volunteers were inoculated with Wildtype SARS-CoV-2 under prospectively controlled conditions. Volunteers completed daily physiological measurements and computerised cognitive tasks during quarantine and follow-up at 30, 90, 180, 270, and 360 days. Linear modelling examined differences between 'infected' and 'inoculated but uninfected' individuals. The main cognitive endpoint was the baseline corrected global cognitive composite score across the battery of tasks administered to the volunteers. Exploratory cognitive endpoints included baseline corrected scores from individual tasks. The study was registered on ClinicalTrials.gov with the identifier NCT04865237 and took place between March 2021 and July2022. Eighteen volunteers developed infection by qPCR criteria of sustained viral load, one without symptoms and the remainder with mild illness. Infected volunteers showed statistically lower baseline-corrected global composite cognitive scores than uninfected volunteers, both acutely and during follow up (mean difference over all time points=-0.8631, 95% CI=-1.3613,-0.3766) with significant main effect of group in repeated measures ANOVA (F (1,34)=7.58, p=0.009). Sensitivity analysis replicated this cross-group difference after controlling for community upper respiratory tract infection, task-learning, remdesivir treatment, baseline reference and model structure. Memory and executive function tasks showed the largest between-group differences. No volunteers reported persistent subjective cognitive symptoms. These results support larger cross sectional findings indicating that mild Wildtype SARS-CoV-2 infection can be followed by small changes in cognition and memory that persist for at least a year. The mechanistic basis and clinical implications of these small changes remain unclear. This study was funded through the UK Vaccine Taskforce of the Department for Business, Energy and Industrial Strategy (BEIS) of Her Majesty's Government. WT was funded by the EPSRC through the CDT for Neurotechnology Imperial College London.

A - 108 Changes in Memory and Attention Function Post-COVID-19 Infection in Older Adults with MCI

Abstract Objective Persons with mild cognitive impairment (MCI) are more likely to develop dementia due to pre-existing cognitive impairment. COVID-19 is associated with an increased risk of developing dementia one-year post-infection. The purpose of this study is to explore the impact of COVID-19 infection on memory and attention in an amnestic sample. It was hypothesized that older adults with MCI would have significantly worse cognitive function post-COVID-19 infection. Method The current sample was drawn from a larger study of late life brain health. Our sample consisted of 9 older adults (mean age = 77.89 ± 9.89) with MCI. Participants were predominately White (77.78%) and male (100%). Participants completed the Rey Auditory Verbal Learning Test (RAVLT) at baseline (T1) and 6 months (T2). All participants received the COVID-19 vaccine prior to T1 and contracted COVID-19 between T1 and T2. Paired sample t-tests evaluated cognitive change over time. Results Participants experienced non-significant change on the RAVLT Trial 6 (t = 0.00, p = 0.91), RAVLT Delayed Recall (t = 1.00, p = 0.35), RAVLT Sum Trials 1–5 (t = −1.49, p = 0.18), and RAVLT Trial 1 (t = −0.12, p = 0.91). Conclusions In our sample of older adults with MCI, contracting COVID-19 was not associated with significant worsening of learning, memory, or attention over a 6-month period. These findings suggest that the 6–12-month period post-COVID-19 infection may be a critical window for significant worsening of cognitive function. Future research should directly assess cognitive function in older at-risk groups 6–12 months post-COVID-19 infection.

Improving Memory Through Better Sleep in Community-Dwelling Older Adults: A Tai Chi Intervention Study.

The relationship between sleep and memory has been well documented. However, it remains unclear whether a mind-body exercise, that is, Tai Chi exercise, can improve memory performance in older adults by improving their subjective and objective sleep. A randomized controlled trial was conducted with participants (M = 67.36, 56-79 years) randomly assigned to Tai Chi and control groups. The primary outcomes were sleep, both subjectively reported and objectively assessed by actigraphy, and memory performance, as well as the mediating role of sleep in memory improvement with Tai Chi practice. Tai Chi exercise led to improvements in subjective sleep, as indicated by Insomnia Severity Index (ISI) (p < .001, Cohen's d = 0.62) and daytime dysfunction of the Pittsburgh sleep quality index (PSQI) (p = .02, Cohen's d = 0.80), and in actigraphy-assessed sleep onset latency (p < .01, Cohen's d = 0.61), as well as improved memory performance on digit span forward (p < .001, Cohen's d = 1.20) and visual spatial memory tasks (p < .01, Cohen's d = 0.83) compared to the control group. Importantly, Tai Chi practice improved digit span forward memory performance through parallel mediation of both subjective sleep (i.e., daytime dysfunction of the PSQI) and objective sleep (i.e., sleep onset latency; b = 0.29, p < .01). Our findings uncovered the potential benefits of Tai Chi exercise in relation to both subjective and objective sleep in older adults, in turn, how sleep changes played a role in the link between Tai Chi exercise and memory changes in older adults.

The Relationship Between 10-Year Changes in Cognitive Control Beliefs and Cognitive Performance in Middle and Later Adulthood.

The present study used a cross-lagged panel design with longitudinal data to test if there is a reciprocal relationship between cognitive control beliefs and cognition (e.g., executive functioning and episodic memory) over 10 years, whether frequency of engaging in stimulating cognitive activities mediated this relationship, and if these relationships varied by age. Data were collected as part of the second (M2, 2004-2005) and third (M3, 2013-2014) waves of the Midlife in the United States Study. The analysis sample included 2,532 participants with all variables at M2 and M3. Participants' ages ranged from 33 to 83 (M = 54.92, standard deviation = 11.13) at M2. There was a reciprocal relationship between cognitive control beliefs and executive functioning. Higher executive functioning was related to greater maintenance of cognitive control beliefs for older, not younger, adults. Higher cognitive control beliefs were related to less decline in executive functioning. Though cognitive control beliefs predicted 10-year changes in episodic memory, the inverse relationship was not supported. Frequency of engaging in stimulating cognitive activities mediated the relationship between executive functioning and 10-year changes in cognitive control beliefs, but not cognitive control beliefs and 10-year changes in cognition. Cognitive control beliefs are a promising mechanism to help protect against age-related declines in both executive functioning and episodic memory. Moreover, executive functioning also affects cognitive control beliefs. Specifically, those with higher executive functioning engage more frequently in stimulating cognitive activities, which helps maintain higher cognitive control beliefs.

The brain and systemic oxidative stress and memory changes induced by inhaled paraquat in rat improved by Crocus sativus

The present study aimed to investigate the effect of Crocus sativus (Cs) on paraquat (PQ)-induced learning and memory deficits as well as brain and lung oxidative stress and systemic inflammation, and oxidative stress in rats.Rats were exposed to saline (Ctrl) or PQ (PQ groups) aerosols. PQ groups were treated with 0.03 mg/kg/day dexamethasone (Dexa), 20 and 80 mg/kg/day Cs-L and Cs-H, 5 mg/kg/day pioglitazone (Pio), and Cs-L+Pio for 16 days during PQ exposure period. Learning and memory abilities were assessed by Morris water maze (MWM) and passive avoidance tests.PQ group showed increased numbers of total and differential WBCs in blood, and increased malondialdehyde (MDA), in the serum, brain, and lung but reduced thiol, catalase (CAT), and superoxide dismutase (SOD) levels compared to the control group (for all, p < 0.001). The escape latency and traveled distance were increased in the PQ group. However, the time spent in the target quadrant in the MWM test and the latency to enter the dark room were reduced after receiving an electrical shock (p < 0.05 to P<0.001). In all treated groups, measured values were improved compared to PQ group (p < 0.05 to p < 0.001). The combination of Cs-L+Pio showed more pronounced effects compared to either treatment alone (p < 0.05 to p < 0.001).These findings suggest that Cs has neuroprotective properties and may be beneficial in the treatment of neurodegenerative diseases induced by noxious agents such as PQ.

Abstract P160: Sex Differences in Age-Dependent Hypertension and Cognitive Impairment in Sprague-Dawley Rats

Objective: We previously found that male (M), but not female (F), Sprague-Dawley (SD) rats develop age-dependent hypertension (HTN) that is associated with cognitive impairment. We hypothesized that ovariectomy (OVRX) at midlife, to model human menopause, would induce hypertension and cognitive impairment with age. Methods: In M and F SD rats at 3-, 8-, and 16-months-old (MO), blood pressure (MAP; mmHg) and sympathetic tone to the vasculature (iv hexamethonium, PeakΔMAP; mmHg) was measured via femoral artery cannulation. Recognition memory was assessed using the novel object recognition task. Blood brain barrier (BBB) integrity in the PVN was assessed as FITC extravasation following carotid artery cannulation. In a separate group of female rats at 8 MO, sham procedure, OVRX, or OVRX with estradiol replacement for 8-months (s.c. estradiol valerate, 1.5 mg extended-release pellet) was performed and rats were aged to 16MO. At 16MO, the previously described procedures were carried out. Results: M, but not F, SD rats develop age-dependent HTN and increased sympathoexcitation that is associated with recognition memory deficits and BBB disruption. Following OVRX, female rats develop age-dependent HTN that is associated with recognition memory deficits and BBB disruption. Replacement of estrogen with 17β-estradiol prevented the development of HTN, cognitive impairment, and BBB disruption. Conclusions: In males, HTN induces BBB disruption and is associated with cognitive impairment. Our studies suggest midlife loss of estrogen likely contributes to the development of age-dependent HTN and cognitive impairment in females. We speculate estrogen supplementation may mitigate HTN-related changes in memory with age.

К оценке риска негативного воздействия электромагнитных полей сотовой связи на центральную нервную систему детей и подростков (Обзор). Часть 2. Параметры когнитивных процессов

This paper continues the authors’ review that dwells on modeling radiofrequency electromagnetic fields (RF EMF) and results obtained by measuring electroencephalography indicators, sensorimotor reactions, fatigue, work capacity, duration of an individual minute and the reproduction of a given rhythm in children and adolescents. Health risk assessment is always based on data obtained by either laboratory tests or epidemiological studies. This paper analyses publications that describe effects of RF EMF exposure, including Wi-Fi, on cognitive processes in children and adolescents as well as methodical approaches to investigating this exposure. However, there are few such studies; in particular, effects produced by Wi-Fi exposure on cognitive indicators of adolescents aged 14–17 years, were found only in two publications. Literature analysis has established that research findings do not always give an unambiguous estimation of RF EMF effects. The review covers the reasons for ambiguous interpretation of research results: a variable range of test-systems used for investigating indicators of cognitive processes; simultaneous analysis of single exposures including descriptions of ‘effect of improvement’ in indicators; changes in cognitive indicators registered for a group of children and adolescents in a wide age range. Nevertheless, most results give evidence of negative changes in attention and memory of children and adolescents. Given that, longitudinal studies are becoming especially relevant since they estimate changes in various indicators in dynamics, including those induced by changes in mobile phone use. The review highlights the relevance of comprehensive investigations with their focus on health outcomes of RF EMF exposure intrinsic to 5G technologies considering their global implementation.

Assessing the risk of negative effects produced by electromagnetic fields of cellular communication on the central nervous system of children and adolescents (Review). Part 2. Indicators of cognitive processes

This paper continues the authors’ review that dwells on modeling radiofrequency electromagnetic fields (RF EMF) and results obtained by measuring electroencephalography indicators, sensorimotor reactions, fatigue, work capacity, duration of an individual minute and the reproduction of a given rhythm in children and adolescents. Health risk assessment is always based on data obtained by either laboratory tests or epidemiological studies. This paper analyses publications that describe effects of RF EMF exposure, including Wi-Fi, on cognitive processes in children and adolescents as well as methodical approaches to investigating this exposure. However, there are few such studies; in particular, effects produced by Wi-Fi exposure on cognitive indicators of adolescents aged 14–17 years, were found only in two publications. Literature analysis has established that research findings do not always give an unambiguous estimation of RF EMF effects. The review covers the reasons for ambiguous interpretation of research results: a variable range of test-systems used for investigating indicators of cognitive processes; simultaneous analysis of single exposures including descriptions of ‘effect of improvement’ in indicators; changes in cognitive indicators registered for a group of children and adolescents in a wide age range. Nevertheless, most results give evidence of negative changes in attention and memory of children and adolescents. Given that, longitudinal studies are becoming especially relevant since they estimate changes in various indicators in dynamics, including those induced by changes in mobile phone use. The review highlights the relevance of comprehensive investigations with their focus on health outcomes of RF EMF exposure intrinsic to 5G technologies considering their global implementation.

Update: the role of epigenetics in the metabolic memory of diabetic complications.

Diabetes, a chronic disease characterized by hyperglycemia, is associated with significantly accelerated complications, including diabetic kidney disease (DKD), which increases morbidity and mortality. Hyperglycemia and other diabetes-related environmental factors such as overnutrition, sedentary lifestyles, and hyperlipidemia can induce epigenetic changes. Working alone or with genetic factors, these epigenetic changes that occur without alterations in the underlying DNA sequence, can alter the expression of pathophysiological genes and impair functions of associated target cells/organs, leading to diabetic complications like DKD. Notably, some hyperglycemia-induced epigenetic changes persist in target cells/tissues even after glucose normalization, leading to sustained complications despite glycemic control, so-called metabolic memory. Emerging evidence from in vitro and in vivo animal models and clinical trials with subjects with diabetes identified clear associations between metabolic memory and epigenetic changes including DNA methylation, histone modifications, chromatin structure, and noncoding RNAs at key loci. Targeting such persistent epigenetic changes and/or molecules regulated by them can serve as valuable opportunities to attenuate, or erase metabolic memory, which is crucial to prevent complication progression. Here, we review these cell/tissue-specific epigenetic changes identified to-date as related to diabetic complications, especially DKD, and the current status on targeting epigenetics to tackle metabolic memory. We also discuss limitations in current studies, including the need for more (epi)genome-wide studies, integrative analysis using multiple epigenetic marks and Omics datasets, and mechanistic evaluation of metabolic memory. Considering the tremendous technological advances in epigenomics, genetics, sequencing, and availability of genomic datasets from clinical cohorts, this field is likely to see considerable progress in the upcoming years.

Reducing age differences in the retrieval of verbatim and gist representations: Encoding manipulations.

Aging causes changes in episodic memory. While the ability to remember the general idea or gist of past episodes is relatively preserved from the effects of aging, the ability to remember the verbatim details of these episodes declines. The aim of the present study was to examine whether age-related differences in the quality of episodic representations could be reduced by manipulations of information encoding. Two experiments were conducted with younger adults (NExp.1 = 32, NExp.2 = 31, 18-27 years old) and older adults (NExp.1 = 31, NExp.2 = 30, 54-81 years old) in which either the retrieval of gist representations of studied items was facilitated by presenting items that could be grouped within the same category (Exp. 1) or the retrieval of verbatim details of studied items was facilitated by presenting the same items repeatedly (Exp. 2). Both manipulations proved effective in increasing retrieval of either gist or verbatim representations in a recognition task in younger and older adults. Increasing gist retrieval improved correct recognition performance for both younger and older adults but also led the latter to make more recognition errors. Increasing verbatim retrieval improved correct recognition performance for both younger and older adults, and the gain was greater for older adults. These findings support the notion that age-related changes in episodic memory can be explained by changes in the specificity of representations and suggest that simple encoding manipulations could improve episodic memory in older adults.

Long-term d-allose administration ameliorates age-related cognitive impairment and loss of bone strength in male mice

Age-related physical and cognitive decline may be ameliorated by consuming functional foods. d-Allose, reported to have multiple health benefits, may temper aging phenotypes, particularly brain function. We investigated whether d-allose supplementation improves cognitive function. A standard battery of behavioral tests was administered to 18-month-old male mice after consuming diet containing 3 % d-allose for 6 months. Following a wire-hanging test, an open-field test, Morris water maze, fear-conditioning, and an analgesia test were sequentially performed. Bone density and strength were assessed afterwards. Possible mechanism(s) under-lying memory changes in hippocampus were also examined with a DNA microarray. d-Allose failed to influence muscle strength, locomotor activity and anxiety, fear memory, or pain sensitivity. However, d-allose improved hippocampus-dependent spatial learning and memory, and it may contribute to increase bone strength. d-Allose also changed the expression of some genes in hippocampus involved in cognitive functions. Long-term d-allose supplementation appears to modestly change aging phenotypes and improve spatial memory.

Enhanced and cross-reactive in vitro memory B cell response against Epstein-Barr virus nuclear antigen 1 in multiple sclerosis.

Multiple sclerosis (MS) is a prototypical autoimmune disease of the central nervous system (CNS). In addition to CD4+ T cells, memory B cells are now recognized as a critical cell type in the disease. This is underlined by the fact that the best-characterized environmental risk factor for MS is the Epstein-Barr virus (EBV), which can infect and persist in memory B cells throughout life. Several studies have identified changes in anti-EBV immunity in patients with MS. Examples include elevated titers of anti-EBV nuclear antigen 1 (EBNA1) antibodies, interactions of these with the MS-associated HLA-DR15 haplotype, and molecular mimicry with MS autoantigens like myelin basic protein (MBP), anoctamin-2 (ANO2), glial cell adhesion molecule (GlialCAM), and alpha-crystallin B (CRYAB). In this study, we employ a simple in vitro assay to examine the memory B cell antibody repertoire in MS patients and healthy controls. We replicate previous serological data from MS patients demonstrating an increased secretion of anti-EBNA1380-641 IgG in cell culture supernatants, as well as a positive correlation of these levels with autoantibodies against GlialCAM262-416 and ANO21-275. For EBNA1380-641 and ANO21-275, we provide additional evidence suggesting antibody cross-reactivity between the two targets. Further, we show that two efficacious MS treatments - natalizumab (NAT) and autologous hematopoietic stem cell transplantation (aHSCT) - are associated with distinct changes in the EBNA1-directed B cell response and that these alterations can be attributed to the unique mechanisms of action of these therapies. Using an in vitro system, our study confirms MS-associated changes in the anti-EBNA1 memory B cell response, EBNA1380-641 antibody cross-reactivity with ANO21-275, and reveals treatment-associated changes in the immunoglobulin repertoire in MS.

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.

Adolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest Δ9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence. We determined how 14 daily THC injections (5mg/kg) during adolescence persistently impacts medial prefrontal cortex (mPFC) dopamine-dependent cognition. In adult Long Evans rats treated as adolescents with THC (AdoTHC), we quantify performance on two mPFC dopamine-dependent reward-based tasks-strategy set shifting and probabilistic discounting. We also determined how acute dopamine augmentation with amphetamine (0, 0.25, 0.5mg/kg), or specific chemogenetic stimulation of ventral tegmental area (VTA) dopamine neurons and their projections to mPFC impact probabilistic discounting. AdoTHC sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probabilistic discounting in either sex. When we challenged dopamine circuits acutely with amphetamine during probabilistic discounting, we found reduced discounting of improbable reward options, with AdoTHC rats being more sensitive to these effects than controls. In contrast, neither acute chemogenetic stimulation of VTA dopamine neurons nor pathway-specific chemogenetic stimulation of their projection to mPFC impacted probabilistic discounting in control rats, although stimulation of this cortical dopamine projection slightly disrupted choices in AdoTHC rats. These studies confirm a marked specificity in the cognitive processes impacted by AdoTHC exposure. They also suggest that some persistent AdoTHC effects may alter amphetamine-induced cognitive changes in a manner independent of VTA dopamine neurons or their projections to mPFC.

Syntactic flexibility and lexical encoding in aging sentence production: an eye tracking study.

Successful sentence production requires lexical encoding and ordering them into a correct syntactic structure. It remains unclear how different processes involved in sentence production are affected by healthy aging. We investigated (a) if and how aging affects lexical encoding and syntactic formulation during sentence production, using auditory lexical priming and eye tracking-while-speaking paradigms and (b) if and how verbal working memory contributes to age-related changes in sentence production. Twenty older and 20 younger adults described transitive and dative action pictures following auditory lexical primes, by which the relative ease of encoding the agent or theme nouns (for transitive pictures) and the theme and goal nouns (for dative pictures) was manipulated. The effects of lexical priming on off-line syntactic production and real-time eye fixations to the primed character were measured. In offline production, older adults showed comparable priming effects to younger adults, using the syntactic structure that allows earlier mention of the primed lexical item in both transitive and dative sentences. However, older adults showed longer lexical priming effects on eye fixations to the primed character during the early stages of sentence planning. Preliminary analysis indicated that reduced verbal working memory may in part account for longer lexical encoding, particularly for older adults. These findings indicate that syntactic flexibility for formulating different grammatical structures remains largely robust with aging. However, lexical encoding processes are more susceptible to age-related changes, possibly due to changes in verbal working memory.

Risk factors and cognitive domain markers of progression in subjective cognitive decline.

We evaluated risk factor differences and cognitive domain markers associated with progression in subjects with subjective cognitive decline (SCD) at baseline from the NYU Alzheimer Disease Research Center. We included SCD non-decliners (n = 27), who remained stable, and decliners (n = 24), who progressed to mild cognitive impairment or worse, between the second to sixth yearly follow-up visits. Adjusted mixed-effects models examined group differences and associations between demographic, APOE status, psychometric test performance and comorbidities with longitudinal-decline. Overall, mean (SD) age was 67.4 (9.2) and total follow-up time was 5.1 (1.8) years. Lower education (14.9 (3.2) vs. 17.3 (2.1)), Hispanic ethnicity (50.0% vs. 11.0%), and hypercholesterolemia (aOR: 6.67), p ≤ 0.05 for all, were risk factors for progression in SCD, whereas APOE status was not. Notably, SCD decliners were at increased risk for both amnestic and non-amnestic cognitive-decline with psychometric changes in memory, executive, and language domains (p < 0.001 for all). These findings inform further work on SCD outcomes and related biomarkers, as well as preventive studies that target modifiable risk factors for SCD progression.

Adolescent THC impacts on mPFC dopamine-mediated cognitive processes in male and female rats.

Adolescent cannabis use is linked to later-life changes in cognition, learning, and memory. Rodent experimental studies suggest Δ9-tetrahydrocannabinol (THC) influences development of circuits underlying these processes, especially in the prefrontal cortex, which matures during adolescence. We determined how 14 daily THC injections (5mg/kg) during adolescence persistently impacts medial prefrontal cortex (mPFC) dopamine-dependent cognition. In adult Long Evans rats treated as adolescents with THC (AdoTHC), we quantify performance on two mPFC dopamine-dependent reward-based tasks-strategy set shifting and probabilistic discounting. We also determined how acute dopamine augmentation with amphetamine (0, 0.25, 0.5 mg/kg), or specific chemogenetic stimulation of ventral tegmental area (VTA) dopamine neurons and their projections to mPFC impacts probabilistic discounting. AdoTHC sex-dependently impacts acquisition of cue-guided instrumental reward seeking, but has minimal effects on set-shifting or probabilistic discounting in either sex. When we challenged dopamine circuits acutely with amphetamine during probabilistic discounting, we found reduced discounting of improbable reward options, with AdoTHC rats being more sensitive to these effects than controls. In contrast, neither acute chemogenetic stimulation of VTA dopamine neurons nor pathway-specific chemogenetic stimulation of their projection to mPFC impacted probabilistic discounting in control rats, although stimulation of this cortical dopamine projection slightly disrupted choices in AdoTHC rats. These studies confirm a marked specificity in the cognitive processes impacted by AdoTHC exposure. They also suggest that some persistent AdoTHC effects may alter amphetamine-induced cognitive changes in a manner independent of VTA dopamine neurons or their projections to mPFC.

Mnemonic brain state engagement is diminished in healthy aging.

Healthy older adults typically show impaired episodic memory - memory for when and where an event oc-curred - but intact semantic memory - knowledge for general information and facts. As older adults also have difficulty inhibiting the retrieval of prior knowledge from memory, their selective decline in episodic memory may be due to a tendency to over engage the retrieval state, a brain state in which attention is focused internally in an attempt to access prior knowledge. The retrieval state trades off with the encoding state, a brain state which supports the formation of new memories. Therefore, episodic memory declines in older adults may be the result of differential engagement in mnemonic brain states. Our hypothesis is that older adults are biased toward a retrieval state. We recorded scalp electroencephalography while young, middle-aged and older adults performed a memory task in which they were explicitly directed to either encode the currently presented object stimulus or retrieve a previously presented, categorically-related object stimulus. We used multivariate pattern analysis of spectral activity to decode engagement in the retrieval vs. encoding state. We find that all three age groups can follow top-down instructions to selectively engage in encoding or retrieval and that we can decode mnemonic states for all age groups. However, we find that mnemonic brain state engagement is diminished for older adults relative to middle-aged adults. Our interpretation is that a combination of executive control deficits and a modest bias to retrieve modulates older adults' mnemonic state engagement. Together, these findings suggest that dif-ferential mnemonic state engagement may underlie age-related memory changes.