Dementia in the Ancient Greco-Roman World Was Minimally Mentioned.

Background: The possibility that Alzheimer's disease and related dementias (ADRD) is a modern disease arises from the minimal mention of advanced cognitive decline by ancient Greeks and Romans, who were mainly concerned with the physical frailties of older ages. Objective: Because standard medical histories of elderly health lacked mention of cognitive decline, we examined texts by Greek and Roman authors that mentioned memory loss and dementia. Methods: Primary texts of Greco-Roman authors, 8th century BCE into the 3rd century CE, that mentioned cognitive decline were identified and critically evaluated. Secondary sources were excluded. Results: No ancient account of cognitive loss is equivalent to modern clinical data. The term dementia was occasionally used in antiquity, but not invariably linked to old age. Ancient Greeks and Romans expected intellectual competence beyond age 60. While some memory loss was acknowledged, we found only four accounts of severe cognitive loss that might represent ADRD. The possibility of modest ADRD prevalence in ancient Greece and Rome is consistent with its low prevalence in the Tsimane of Bolivia. These contemporary Amerindians live under conditions of high mortality from frequent infections and minimal cardiovascular disease with physically demanding lives. Tsimane after age 60 had increased mild cognitive impairment; the few cases of dementia were not clinically consistent with AD. Conclusions: The modern 'epidemic level' of advanced dementias was not described among ancient Greco-Roman elderly. The possible emergence of advanced ADRD in the Roman era may be associated with environmental factors of air pollution and increased exposure to lead. Further historical analysis may formulate critical hypotheses about the modernity of high ADRD prevalence.

[Prevalence of subjective memory complaints: Population study in Spain]. / Prevalencia de quejas subjetivas de memoria: estudio poblacional en España.

INTRODUCTION: Subjective memory complaints (SMC) might be an early sign of further deterioration in cognitive functions. However, no population studies have been published covering all Spain to determine the SMC prevalence. The objective of the present study was to determine the SMC prevalence in the general population residing in Spain >50 years of age and also which related actions were done. MATERIALS AND METHODS: Interviews were conducted with a nationally representative sample >50 years of age using an online/computer assisted web interview (CAWI) questionnaire. The survey consisted of 34 items divided into two blocks. Presence of SMC was considered when in question 1 the subject answered that "Yes" he had some memory problem. RESULTS: Two thousand three hundred people (53.7% women; 23.9% ≥75 years old) were interviewed. 31% answered that they considered they had a memory problem (no differences between sexes, mean time with memory problems of 3.0 years). A higher prevalence of SMC was observed in ≥75 years old (44%). 90% did not include any specific foods in their diet for their memory problems, neither were taking any pharmaceuticals, diet supplements or nutritional supplements (92%). 78% of those interviewed with SMC have not consulted health professionals for their memory problems. CONCLUSIONS: SMC are considerably prevalent in our environment affecting almost a third of people ≥50 years of age. Most of the interviewees with SMC did not go to health professionals to manage their SMC.

Individual differences in frequency and impact of daily memory lapses: results from a national lifespan sample.

BACKGROUND: Everyday memory problems are believed to increase with age, leading many researchers to focus on older ages when examining reports of memory lapses. However, real world memory lapses are ubiquitous across the adult lifespan, though less is known about the types of problems and their impacts at younger ages. The current study examined occurrence and impacts of memory lapses using daily diaries in a broad age range and whether characteristics of lapses varied across age, gender, or education level. METHODS: Using an 8-day daily diary protocol, 2,018 individuals (ages 25-91) provided reports of their experiences of two types of daily memory lapses (retrospective and prospective) as well as the impact those lapses had on their emotional and functional well-being that day. Using multilevel modeling, we examined the likelihood of reporting memory lapses and their impacts on daily life and whether these depended on age, gender, or education level. RESULTS: Participants reported lapses on approximately 40% of days; retrospective memory lapses were significantly more likely than prospective lapses. Older ages and higher education level were related to greater likelihood of reporting retrospective lapses. Women (compared to men) were more likely to report prospective memory lapses. Women also tended to report greater impacts of their memory lapses. Lower education levels were related to greater impacts of memory lapses compared to higher education levels. Interestingly, age was not related to impacts of lapses. DISCUSSION: Our results indicate that memory lapses are common across the lifespan and that those individuals more likely to report lapses are not necessarily those that experience the greatest impacts of those lapses on daily life. Additional work is needed to understand the daily experience of memory lapses and how they differentially affect individuals regardless of age, gender, and education. CONCLUSIONS: Memory lapses are an important aspect of daily life across the lifespan and require measurement in an individual's real-world environments. Better measurement of these experiences will allow the development of more sensitive measures of changes in cognitive functioning that may impact an individual's ability to live independently.

A qualitative exploration of older people's lived experiences of homelessness and memory problems - stakeholder perspectives.

BACKGROUND: The numbers of older people experiencing both homelessness and memory problems are growing, yet their complex health, housing and care needs remain undelineated and unmet. There is a critical gap in understanding what can improve the care, support and experiences of this group. In this qualitative study we explore how stakeholders understand memory problems among older people in the context of homelessness and consider what they judge gets in the way of achieving positive outcomes. METHOD: We conducted reflexive thematic analysis of qualitative interviews (n = 49) using a semi-structured topic guide, with 17 older people (aged ≥ 50 years) experiencing memory problems and homelessness, 15 hostel staff and managers, and 17 health, housing and social care practitioners. We recruited participants from six homelessness hostels, one specialist care home and National Health and Local Authority Services in England. RESULTS: We identified four overarching themes. The population is not taken seriously; multiple causes are hard to disentangle; risk of exploitation and vulnerability; and (dis)connection and social isolation. The transience and lack of stability associated with homelessness intensified the disorienting nature of memory and cognitive impairment, and those providing direct and indirect support required flexibility and persistence, with staff moving beyond traditional roles to advocate, provide care and safeguard individuals. Memory problems were perceived by frontline staff and older people to be overlooked, misinterpreted, and misattributed as being caused by alcohol use, resulting in pervasive barriers to achieving positive and desired outcomes. CONCLUSIONS: Efforts to meet the needs of older people living with memory problems and experiencing homelessness and future interventions must reflect the complexity of their lives, often in the context of long-term alcohol use and current service provision and we make suggestions as to what could be done to improve the situation.

Association of perceived stress with memory decline in older Chinese: The Guangzhou Biobank Cohort Study.

BACKGROUND: Previous studies on associations of perceived stress with poor memory performance in older adults showed inconsistent results. We examined the prospective associations of perceived stress with memory decline using data from Guangzhou Biobank Cohort Study (GBCS). METHODS: Perceived stress was measured by the Perceived Stress Scale (PSS) at baseline (2003-2006), with greater scores indicating greater stress. Memory function was measured by delayed 10-word recall test (DWRT) and immediate 10-word recall test (IWRT), with greater scores indicating better performance, at baseline and follow-up (2008-2012) examinations, analyzed as mean annual change in scores. RESULTS: 9656 participants (72 % women) with mean age 61.6 (standard deviation = 6.4) years were included. During an average of 4.4 years of follow-up, after adjusting for confounders, each one-point greater PSS score was associated with mean annual decline in DWRT scores (ß (95 % CI) = -0.005 (-0.008 to -0.002)). Greater Perceived Helplessness (PH) scores, but not Perceived Self-efficacy scores, was associated with greater mean annual decline in DWRT and IWRT scores (ß (95 % CI) = -0.005 (-0.009 to -0.001) and - 0.012 (-0.018 to -0.005), respectively), and similar patterns were observed in five out of seven PH items (ßs from -0.02 to -0.07). Interaction analysis showed that the association of greater PSS with greater decline in DWRT scores was observed only in those with low family income (ß (95 % CI) = -0.08 (-0.13 to -0.04), P for interaction = 0.03). CONCLUSIONS: Greater perceived stress was associated with a greater decline in delayed recall memory, especially in those with low family income.

Heterogeneity in Measures and Rates of Reported Dementia and Subjective Memory Complaints Across U.S. National Surveys.

OBJECTIVES: Several U.S. health surveillance surveys contain items related to self- and proxy reports of dementia and subjective memory complaints (SMC). Despite their similar content, these items differ in terminology, item specificity, and time frame. The goal of this study was to analyze whether item features might influence endorsement rates for dementia and SMC. METHODS: We calculated design-appropriate estimates for the endorsement of dementia and SMC across U.S.-based national surveys and employed pairwise comparisons to evaluate endorsement rates across surveys. We also examined item characteristics to explore possible effects on endorsement rates. RESULTS: Endorsement rates were wide-ranging for dementia (ranging from 2.7% to 9.9%) and SMC (5.6% to 46.6%). Pairwise comparisons revealed statistically significant differences on most dementia-related items (76%), and all SMC comparisons (100%). Items varied substantially in the terminology used to assess dementia and SMC (e.g., "dementia" vs "Alzheimer's disease") and used different time frames (e.g., "past month" vs "5 years"). DISCUSSION: National survey data on reported dementia and SMC can have important research, training, and policy implications, yet endorsement rates vary widely across surveys. That variability could emerge from subtle but influential item characteristics, and our findings highlight the need for item harmonization, in even their most basic characteristics. Standardizing items across national surveillance surveys facilitates comparison across surveys so that we can better understand the true burden of these conditions to inform public health initiatives.

Association Between Socioeconomic Factors, Race, and Use of a Specialty Memory Clinic.

BACKGROUND AND OBJECTIVES: The capacity of specialty memory clinics in the United States is very limited. If lower socioeconomic status or minoritized racial group is associated with reduced use of memory clinics, this could exacerbate health care disparities, especially if more effective treatments of Alzheimer disease become available. We aimed to understand how use of a memory clinic is associated with neighborhood-level measures of socioeconomic factors and the intersectionality of race. METHODS: We conducted an observational cross-sectional study using electronic health record data to compare the neighborhood advantage of patients seen at the Washington University Memory Diagnostic Center with the catchment area using a geographical information system. Furthermore, we compared the severity of dementia at the initial visit between patients who self-identified as Black or White. We used a multinomial logistic regression model to assess the Clinical Dementia Rating at the initial visit and t tests to compare neighborhood characteristics, including Area Deprivation Index, with those of the catchment area. RESULTS: A total of 4,824 patients seen at the memory clinic between 2008 and 2018 were included in this study (mean age 72.7 [SD 11.0] years, 2,712 [56%] female, 543 [11%] Black). Most of the memory clinic patients lived in more advantaged neighborhoods within the overall catchment area. The percentage of patients self-identifying as Black (11%) was lower than the average percentage of Black individuals by census tract in the catchment area (16%) (p < 0.001). Black patients lived in less advantaged neighborhoods, and Black patients were more likely than White patients to have moderate or severe dementia at their initial visit (odds ratio 1.59, 95% CI 1.11-2.25). DISCUSSION: This study demonstrates that patients living in less affluent neighborhoods were less likely to be seen in one large memory clinic. Black patients were under-represented in the clinic, and Black patients had more severe dementia at their initial visit. These findings suggest that patients with a lower socioeconomic status and who identify as Black are less likely to be seen in memory clinics, which are likely to be a major point of access for any new Alzheimer disease treatments that may become available.

Heterogeneity of short-term memory deficits in children with dyslexia.

Many studies have highlighted short-term memory (STM) impairment in dyslexic individuals. Several studies showed deficits for both item and serial order aspects of verbal STM in dyslexic individuals. These group-based studies, however, do not inform us about the prevalence of these deficits and, importantly, their potential heterogeneity at the individual level. The present study examined both group-level and individual STM profiles in dyslexic and age-matched non-dyslexic children. While confirming previous group-based results of both item and serial order STM deficits, individual analyses indicated two distinct profiles: one profile was associated with verbal item STM and phonological impairment while another profile showed selective serial STM deficits in both verbal and visual domains. Our results highlight the need for practitioners to consider the heterogeneous nature of STM impairment in dyslexia and to adapt STM and reading treatment strategies accordingly.

Depressive Symptoms Longitudinally Mediate the Effect of Hyperglycemia on Memory Decline in Type 2 Diabetes.

OBJECTIVE: We sought to examine the mediating role of changes in depressive symptoms in the association between chronic hyperglycemia and longitudinal cognition in a sample of older adults with type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: We conducted a longitudinal mediation analysis using structural equation modeling of observational data collected over 6 years from 2,155 participants with T2D (aged ≥51 years) in the U.S.-wide Health and Retirement Study. T2D was defined using self-reported diagnosis, and HbA1c was assessed at study baseline. Self-reported depressive symptoms were assessed at two time points 4 years apart. Episodic memory was measured using a list-learning test administered at three time points over 6 years. We adjusted for sociodemographics, chronic health comorbidities, medication adherence, study enrollment year, and prior years' depressive symptoms and memory scores. RESULTS: At baseline, participants' mean age was 69.4 (SD = 9.1), mean HbA1c was 7.2% (SD = 1.4%), 55.0% were women, 19.3% were non-Latinx Black, and 14.0% were Latinx. Higher baseline levels of HbA1c were associated with increases in depressive symptoms over 4 years, which, in turn, were associated with poorer memory 2 years later. Depressive symptoms accounted for 19% of the longitudinal effect of HbA1c on memory over the 6-year period. Sensitivity analyses ruled out alternative directions of associations. CONCLUSIONS: Incident elevations in depressive symptoms mediated the longitudinal association between hyperglycemia and 6-year episodic memory scores. For older adults with T2D, interventions to prevent HbA1c-related incident depressive symptoms may be beneficial in reducing the neurotoxic effects of chronic hyperglycemia on cognition.

Education, incident cancer, and rate of memory decline in a national sample of US adults in mid-to-later-life.

INTRODUCTION: Middle-aged and older adults who develop cancer experience memory loss following diagnosis, but memory decline in the years before and after cancer diagnosis is slower compared to their cancer-free counterparts. Educational attainment strongly predicts memory function during aging, but it is unclear whether education protects against memory loss related to cancer incidence or modifies long-term memory trajectories in middle-aged and older cancer survivors. MATERIALS AND METHODS: Data were from 14,449 adults (3,248 with incident cancer, excluding non-melanoma skin cancer) aged 50+ in the population-based US Health and Retirement Study from 1998 to 2016. Memory was assessed every two years as a composite of immediate and delayed word recall tests and proxy assessments for impaired individuals. Memory scores all time points were standardized at to the baseline distribution. Using multivariate-adjusted linear mixed-effects models, we estimated rates of memory decline in the years before cancer diagnosis, shortly after diagnosis, and in the years after diagnosis. We compared rates of memory decline between incident cancer cases and age-matched cancer-free adults, overall and according to level of education (<12 years, "low"; 12 to <16 years, "intermediate"; ≥16 years, "high"). RESULTS: Incident cancer diagnoses were followed by short-term declines in memory averaging 0.06 standard deviation (SD) units (95% confidence interval [CI]: -0.084, -0.036). Those with low education experienced the strongest magnitude of short-term decline in memory after diagnosis (-0.10 SD units, 95% CI: -0.15, -0.05), but this estimate was not statistically significantly different from the short-term decline in memory experienced by those with high education (-0.04 SD units, 95% CI: -0.08, 0.01; p-value for education as an effect modifier = 0.15). In the years prior to and following an incident cancer diagnosis, higher educational attainment was associated with better memory, but it did not modify the difference in rate of long-term memory decline between cancer survivors and those who remained cancer-free. DISCUSSION: Education was associated with better memory function over time among both cancer survivors and cancer-free adults aged 50 and over. Low education may be associated with a stronger short-term decline in memory after a cancer diagnosis.

Steeper memory decline after COVID-19 lockdown measures.

BACKGROUND: During COVID-19 lockdown measures, memory clinic patients reported worries for faster cognitive decline, due to loss of structure and feelings of loneliness and depression. We aimed to investigate the impact of the COVID-19 lockdown on rate of cognitive decline in a mixed memory clinic population, compared to matched historical controls. METHODS: We included patients who visited Alzheimer Center Amsterdam 6 months to 1 week before the first Dutch COVID-19 lockdown, and had a second visit 1 year later, after this lockdown period (n = 113; 66 ± 7 years old; 30% female; n = 55 dementia, n = 31 mild cognitive impairment (MCI), n = 18 subjective cognitive decline (SCD), n = 9 postponed diagnosis). Historical controls (visit in 2016/2017 and second visit 1 year later (n = 640)) were matched 1:1 to lockdown patients by optimal Mahalanobis distance matching (both groups n = 113). Groups were well matched. Differences between lockdown patients and historical controls over time in Mini-Mental State Examination, Trail Making Test part A and B, Rey-Auditory Verbal Learning Test (RAVLT) immediate and delayed recall, and category fluency scores were analyzed using linear mixed effect models with random intercepts. We examined differences in rate of cognitive decline between whole groups, and after stratification in SCD, MCI, and dementia separately. RESULTS: Lockdown patients had a faster rate of memory decline compared to controls on both RAVLT immediate [B(SE) = - 2.62 (1.07), p = 0.015] and delayed recall [B(SE) = - 1.07 (0.34), p = 0.002]. Stratification by syndrome diagnosis showed that this effect was largely attributable to non-demented participants, as we observed faster memory decline during lockdown in SCD and MCI (RAVLT immediate [SCD: B(SE) = - 6.85 (2.97), p = 0.027; MCI: B(SE) = - 6.14 (1.78), p = 0.001] and delayed recall [SCD: B(SE) = - 2.45 (1.11), p = 0.035; MCI: B(SE) = - 1.50 (0.51), p = 0.005]), but not in dementia. CONCLUSION: Memory clinic patients, specifically in pre-dementia stages, showed faster memory decline during COVID-19 lockdown, providing evidence that lockdown regulations had a deleterious effect on brain health. In individuals that may have been able to deal with accumulating, subclinical neuropathology under normal and structured circumstances, the additional stress of lockdown regulations may have acted as a "second hit," resulting in less beneficial disease trajectory.

Health Behavior Patterns and Associated Risk of Memory-Related Disorders Among Middle-Aged and Older Chinese Couples.

Objectives: Studies on the interdependence of couples' health behaviors and subsequent cognitive outcomes remain limited. Methods: Longitudinal data from the China Health and Retirement Longitudinal Study (2011-2018) were used (N = 1869 heterosexual couples). Latent class analysis identified the dyadic pattern of health behaviors in 2011 (i.e., alcohol consumption, smoking, and physical inactivity). Stratified Cox models examined the association of latent classes with risk of developing memory-related disorders in 2013-2018. Results: Three classes were identified: class 1 (21.25%, only husband smoke, and both active), class 2 (47.55%, both inactive, neither drink nor smoke), and class 3 (31.20%, both drink and smoke, and both active). Couples' sedentary lifestyle was associated with an increased risk of memory-related disorders among both husbands and wives. Conclusion: Couples were moderately concordant in their physical activity but weakly in smoking and drinking. Couple-based interventions, especially promoting physical activity, may reduce cognitive aging among middle-aged and older Chinese couples.

The Association Between Social Isolation and Memory Loss Among Older Adults.

INTRODUCTION: Social isolation among older individuals is associated with poor health outcomes. However, less is known about the association between social isolation and memory loss, specifically among Medicare enrollees in large, integrated health care systems. METHODS: We conducted a cross-sectional, observational study. From a cohort of 46,240 Medicare members aged 65 years and older at Kaiser Permanente Northwest (KPNW) who completed a health questionnaire, we compared self-reported memory loss of those who reported feeling lonely or socially isolated and those who did not, adjusting for demographic factors, health conditions, and use of health services in the 12 months before the survey. RESULTS: Patients who reported sometimes experiencing social isolation were more likely than those who rarely or never experienced social isolation to report memory loss in both unadjusted (odds ratio [ORsometimes]: 2.56, 95% CI= 2.42-2.70, P = 0.0076) and adjusted (ORsometimes: 2.45, 95% CI= 2.32-2.60, P = 0.0298) logistic regression models. Similarly, those who reported social isolation often or always were more likely to report memory loss than those who reported rarely or never experiencing isolation in both unadjusted (ORoften/always: 5.50, 95% CI = 5.06-5.99, P < 0.0001) and adjusted logistic regression models (ORoften/always: 5.20, 95% CI = 4.75-5.68, P < 0.0001). CONCLUSIONS: The strong association between social isolation and memory loss suggests the need to develop interventions to reduce isolation and to evaluate their effects on potential future memory loss.

Cognitive Function Trajectories and Factors among Chinese Older Adults with Subjective Memory Decline: CHARLS Longitudinal Study Results (2011-2018).

Older adults with subjective cognitive decline are at increased risk of future pathological cognitive decline and dementia. Subjective memory decline is an early sign of cognitive decline; preventing or slowing cognitive decline in at-risk populations remains an elusive issue. This study aimed to examine the cognitive trajectories and factors in older adults with subjective memory decline. Latent growth curve models (LGCMs) were fitted to examine the cognitive function trajectories and factors among 1465 older adults (aged 60+ years) with subjective memory decline. Data were obtained from four waves from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2018), which is a large nationally representative sample of the Chinese population. The results showed that older adults with better initial cognition had a slower decline rate, which may be accelerated by advanced age, low-level education, a rapid decrease in instrumental activities of daily living (IADL) ability, and rapid increase in depression levels. This study was the first to examine the trajectories of cognitive function and its factors in a high-risk population with subjective memory decline. These findings may guide prevention approaches to tackle the issues of cognitive function decline and dementia.

Association of Low Hourly Wages in Middle Age With Faster Memory Decline in Older Age: Evidence From the Health and Retirement Study.

Little research has investigated the long-term relationship between low wages and memory decline, despite the growing share of low-wage workers in the US labor market. Here, we examined whether cumulative exposure to low wages over 12 years in midlife is associated with memory decline in later life. Using 1992-2016 data from the Health and Retirement Study, we analyzed data from 2,879 individuals born in 1936-1941 using confounder-adjusted linear mixed-effects models. Low-wage work was defined as an hourly wage lower than two-thirds of the federal median wage for the corresponding year and was categorized into "never," "intermittent," and "sustained" based on wages earned from 1992 to 2004. Memory function was measured at each study visit from 2004 to 2016 via a memory composite score. The confounder-adjusted annual rate of memory decline among "never" low-wage earners was -0.12 standard units (95% confidence interval: -0.13, -0.10). Compared with this, memory decline among workers with sustained earning of low midlife wages was significantly faster (ßtime×sustained = -0.014, 95% confidence interval: -0.02, -0.01), corresponding to an annual rate of -0.13 standard units for this group. Sustained low-wage earning in midlife was significantly associated with a downward trajectory of memory performance in older age. Enhancing social policies to protect low-wage workers may be especially beneficial for their cognitive health.

Sex Differences in Memory: Do Female Reproductive Factors Explain the Differences?

Background: The sex differences in memory impairment were inconclusive, and the effect of female reproductive factors (age at menarche, age at menopause, and reproductive period) on the differences was not clear. We aimed to examine the sex differences in objective and subjective memory impairment in postmenopausal women and age- and education-matched men and explore whether the differences were differed by female reproductive factors. Methods: Data were obtained from the China Health and Retirement Longitudinal Study. Using the case-control matching method, 3,218 paired postmenopausal women and men matched for age and education were selected. Memory was assessed using the three-word recall task and a self-rated question. Poisson regression models with a robust error variance were used. Results: The relative risk was 1.22 (95% confidence interval 1.08-1.38) for objective memory impairment in women compared with men (23.87% vs. 27.36%), and 1.51 (1.36-1.67) for subjective memory impairment (39.34% vs. 28.25%) after adjusting the confounders. The higher risk of objective memory impairment in women was different among groups of age at menarche in a linear pattern, with younger age at menarche associated with higher risks of objective memory impairment (p < 0.001 for trend). It was also different among groups of menopausal age and reproductive period in an approximate U-shaped pattern, with a similar risk of objective memory with men in women menopause at 52-53 years and having a reproductive period of 31-33 years and higher risks in women with earlier or later menopause (RRs raging form 1.17 to1.41) and a shorter or longer period of reproduction (RR, 1.23-1.29). The higher risks of subjective memory impairment in women were not different among different groups of reproductive factors. Conclusions: Postmenopausal women were at an increased risk of objective and subjective memory impairment than men. The higher risks in objective memory, but not subjective memory, were varied by age at menarche, age at menopause, and reproductive periods, which may help understand the underlying mechanisms of sex differences in cognitive ageing and guide precise intervention to preventing dementia among older women and men.

Association of Perceived Job Insecurity With Subsequent Memory Function and Decline Among Adults 55 Years or Older in England and the US, 2006 to 2016.

Importance: Intensified global economic competition and recent financial crises, including those associated with the COVID-19 pandemic, have contributed to uncertainty about job security. However, little is known about the association of perceived job insecurity with memory function and decline among older adults. Objectives: To investigate the association between perceived job insecurity and subsequent memory function and rate of memory decline among older adults in the US and England. Design, Setting, and Participants: This 10-year prospective population-based cohort study used data from the US Health and Retirement Study (HRS) and the English Longitudinal Study of Ageing (ELSA) collected from 2006 to 2016. Participants included 9538 adults 55 years or older. Data were analyzed from August 1 to 31, 2021. Exposures: Perceived job insecurity (yes vs no) at baseline. Main Outcomes and Measures: Episodic memory z scores at baseline and rate of decline during the follow-up. Results: Among the 9538 study participants, the mean (SD) age at baseline was 60.97 (6.06) years, and 4981 (52.22%) were women. A total of 2320 participants (24.32%) reported job insecurity at baseline (1088 of 3949 [27.55%] in England and 1232 of 5589 [22.04%] in the US). Perceived job insecurity after 55 years of age was associated with lower baseline memory z scores in the fully adjusted model (ß = -0.04 [95% CI, -0.08 to -0.01]) but not with rate of memory decline (ß = 0.01 [95% CI, -0.01 to 0.01]). The association appeared to be stronger in the US than in England (job insecurity × US, ß = -0.05 [95% CI, -0.11 to 0.02]), but the estimate was imprecise, potentially owing to low statistical power. Conclusions and Relevance: The findings of this cohort study suggest that exposure to job insecurity in middle to late life was associated with worse memory function among older adults in the US and England. This association may vary across socioeconomic and social welfare contexts, although future studies with large samples from diverse socioeconomic settings are warranted.

Disruption of hippocampal P2RX2/CaMKII/NF-κB signaling contributes to learning and memory impairment in C57BL/6 mice induced by surgery plus anesthesia in neonatal period.

A great number of pediatric patients undergoing varied procedures make neonatal surgery plus anesthesia become a matter of great concern owing to underlying neurotoxicity in developing brain. The authors set out to assess long-term effects of surgery plus anesthesia in mouse model. Six-day-old C57BL/6 mice were randomized to receive either anesthesia with 3% sevoflurane, abdominal surgery under the same anesthesia, or the control condition. These mice were examined of learning and memory at juvenile age in Morris water maze test. The brain tissues of mice were harvested for Western blot analysis, including purinergic receptors P2X family, CaMKII and NF-κB. Another battery of mice were administered with inhibitors of P2RX2/3 (e.g., A317491) into hippocampal dentate gyrus before behavioral testing. We found that neonatal surgery plus anesthesia, but not sevoflurane anesthesia alone, impaired the learning and memory of juvenile mice, as evidenced by delayed escape latency and reduced platform-crossing times. Immunoblotting analysis showed that behavioral abnormalities were associated with increased levels of P2RX2, phosphorylated-CaMKIIß and activated NF-κB in mouse hippocampus. Injection of A317491 ameliorated the impaired learning and memory of juvenile mice undergoing neonatal surgery plus anesthesia, and it also mitigated the neonatal surgery-induced signaling enhancement of P2RX2/CaMKII/NF-κB. Together, these results indicate that neonatal surgery plus anesthesia may cause long-term cognitive dysfunction, with potential mechanism of increasing P2RX2 and downstream signaling of phosphorylated-CaMKII and NF-κB. Our findings will promote more studies to assess detrimental effects of surgery and accompanying inflammation, diverse anesthetics and even sleeping deprivation on mouse neurodevelopment and neurobehavioral performance.

Adolescent Verbal Memory as a Psychosis Endophenotype: A Genome-Wide Association Study in an Ancestrally Diverse Sample.

Verbal memory impairment is one of the most prominent cognitive deficits in psychosis. However, few studies have investigated the genetic basis of verbal memory in a neurodevelopmental context, and most genome-wide association studies (GWASs) have been conducted in European-ancestry populations. We conducted a GWAS on verbal memory in a maximum of 11,017 participants aged 8.9 to 11.1 years in the Adolescent Brain Cognitive Development Study®, recruited from a diverse population in the United States. Verbal memory was assessed by the Rey Auditory Verbal Learning Test, which included three measures of verbal memory: immediate recall, short-delay recall, and long-delay recall. We adopted a mixed-model approach to perform a joint GWAS of all participants, adjusting for ancestral background and familial relatedness. The inclusion of participants from all ancestries increased the power of the GWAS. Two novel genome-wide significant associations were found for short-delay and long-delay recall verbal memory. In particular, one locus (rs9896243) associated with long-delay recall was mapped to the NSF (N-Ethylmaleimide Sensitive Factor, Vesicle Fusing ATPase) gene, indicating the role of membrane fusion in adolescent verbal memory. Based on the GWAS in the European subset, we estimated the SNP-heritability to be 15% to 29% for the three verbal memory traits. We found that verbal memory was genetically correlated with schizophrenia, providing further evidence supporting verbal memory as an endophenotype for psychosis.