Mid-Life Household Food Insecurity and Subsequent Memory Function and Rate of Decline in Rural South Africa, 2004-2022.

INTRODUCTION: We aimed to investigate mid-life food insecurity over time in relation to subsequent memory function and rate of decline in Agincourt, rural South Africa. METHODS: Data from the longitudinal Agincourt Health and Socio-Demographic Surveillance System (Agincourt HDSS) were linked to the population-representative Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI). Food insecurity (yes vs. no) and food insecurity intensity (never/rarely/sometimes vs. often/very often) in the past month were assessed every 3 years from 2004 to 2013 in Agincourt HDSS. Cumulative exposure to each food insecurity measure was operationalized as 0, 1, and ≥2 time points. Episodic memory was assessed from 2014/15 to 2021/22 in HAALSI. Mixed-effects linear regression models were fitted to investigate the associations of each food insecurity measure with memory function and rate of decline over time. RESULTS: A total of 3,186 participants (mean age [SD] in 2004: 53 [12.87]; range: 30-96) were included and 1,173 (36%) participants experienced food insecurity in 2004, while this figure decreased to 490 (15%) in 2007, 489 (15%) in 2010, and 150 (5%) in 2013. Experiencing food insecurity at one time point (vs. never) from 2004 to 2013 was associated with lower baseline memory function (ß = -0.095; 95% CI: -0.159 to -0.032) in 2014/15 but not rate of memory decline. Higher intensity of food insecurity at ≥2 time points (vs. never) was associated with lower baseline memory function (ß = -0.154, 95% CI: -0.338 to 0.028), although the estimate was imprecise. Other frequencies of food insecurity and food insecurity intensity were not associated with memory function or decline in the fully adjusted models. CONCLUSION: In this setting, mid-life food insecurity may be a risk factor for lower later-life memory function, but not decline.

Severe memory decline along with unaffected executive functions under 400 mg/day of cenobamate leading to a collapse in school performance.

Cenobamate (CNB) is one of the newer antiseizure medications for the treatment of focal-onset seizures. The cognitive profile of CNB is not yet known in detail. Here we present the case of an 18-year-old male high school student with epilepsy who received adjunctive CNB. Under 400 mg/d of CNB in combination with lamotrigine, a neuropsychological reassessment revealed a severe deterioration of the formerly normal episodic memory functions, while executive functions remained unaffected. The de novo memory deficit had already led to a collapse in school performance and he unexpectedly failed to obtain the general qualification for university entrance. Given the beneficial effect of CNB on seizure control, a dose reduction of CNB to 200 mg/d and introduction of valproic acid was performed. This led to a full recovery of objective memory performance. To our knowledge this is the very first report of a dose-dependent, selective and severe decline in episodic memory performance under CNB, potentially impeding academic achievement. The findings call for a cognitive monitoring of CNB which also addresses episodic memory in addition to executive functions. Systematic studies on episodic memory upon CNB treatment would help to appreciate the scope of this apparently reversible adverse effect.

The altered hippocampal functional connectivity and serum brain-derived neurotrophic factor level predict cognitive decline in patients with knee osteoarthritis.

Patients with knee osteoarthritis (KOA) often suffer from cognitive decline and increased dementia risk, but the neurobiological mechanisms remain unclear. In this study, we evaluated cognitive performance and collected brain magnetic resonance imaging (MRI) data and blood samples from cognitively normal KOA patients at baseline sessions and reevaluated their cognition after 5 years. We also collected MRI data from matched healthy controls. Results showed that KOA patients exhibited dysregulated functional connectivities between the hippocampus and thalamus/superior frontal gyrus compared with healthy controls. The altered hippocampal functional connectivities were associated with serum brain-derived neurotrophic factor (BDNF) levels and spatial expression of genes enriched in synaptic plasticity. The hippocampus-thalamus functional connectivity was significantly correlated with patients' memory scores. Moreover, the baseline hippocampus-thalamus functional connectivity and BDNF levels significantly predicted the development of cognitive decline in KOA patients in the follow-up session. Our findings provide insight into the neurobiological underpinnings of KOA and cognitive decline.

Memory profiles predict dementia over 23-28 years in normal but not successful aging.

OBJECTIVES: Prospective studies suggest that memory deficits are detectable decades before clinical symptoms of dementia emerge. However, individual differences in long-term memory trajectories prior to diagnosis need to be further elucidated. The aim of the current study was to investigate long-term dementia and mortality risk for individuals with different memory trajectory profiles in a well-characterized population-based sample. METHODS: 1062 adults (aged 45-80 years) who were non-demented at baseline were followed over 23-28 years. Dementia and mortality risk were studied for three previously classified episodic memory trajectory groups: maintained high performance (Maintainers; 26%), average decline (Averages; 64%), and accelerated decline (Decliners; 12%), using multistate modeling to characterize individuals' transitions from an initial non-demented state, possibly to a state of dementia and/or death. RESULTS: The memory groups showed considerable intergroup variability in memory profiles, starting 10-15 years prior to dementia diagnosis, and prior to death. A strong relationship between memory trajectory group and dementia risk was found. Specifically, Decliners had more than a fourfold risk of developing dementia compared to Averages. In contrast, Maintainers had a 2.6 times decreased dementia risk compared to Averages, and in addition showed no detectable memory decline prior to dementia diagnosis. A similar pattern of association was found for the memory groups and mortality risk, although only among non-demented. CONCLUSION: There was a strong relationship between accelerated memory decline and dementia, further supporting the prognostic value of memory decline. The intergroup differences, however, suggest that mechanisms involved in successful memory aging may delay symptom onset.

Cognitive training modified age-related brain changes in older adults with subjective memory decline.

OBJECTIVES: Neuroimaging findings suggest that older adults with subjective memory decline (SMD) demonstrate some neurodegenerative brain changes and have high risk of developing dementia, but relatively little is known about the effectiveness of interventions for SMD. This study aimed to examine the effects of cognitive training on resting-state brain activity in SMD. METHOD: This study employed the amplitude of low frequency fluctuations (ALFF) and resting state functional connectivity (rs-FC) analyses. After baseline evaluations, participants were randomly allocated to the intervention and control group to receive a four-week cognitive training and lectures on health and aging, respectively. All participants were scanned before and after training with an interval of about three months. RESULTS: (1) Participants in the intervention group showed significant improvements on the Associative Learning Test (ALT) and the Digit Span Forward task compared to the control group; (2) ALFF in the occipital lobe for the control group increased significantly, while that for the intervention group remained the same; ALFF changes were negatively correlated with ALT performance in the control group; (3) The mean value of rs-FC for the intervention group decreased, while that for the control group showed a trend of increase; rs-FC changes were also negatively correlated with ALT performance in the control group. CONCLUSIONS: Resting-state brain activities in occipital region increased with aging. The cognitive training could counteract this brain function changes associated with aging or even reverse the changes. These findings provide new insights into the understanding of brain plasticity in posterior areas in SMD. TRIAL REGISTRATION: ChiCTR-IOR-15006165 in the Chinese Clinical Trial Registry.

Neuropsychological decline up to 20 years before incident mild cognitive impairment.

INTRODUCTION: Some Alzheimer's disease biomarker studies found amyloid changes 20 years or more in advance of expected symptoms, while cognitive changes lagged for more than a decade, but this apparent lag might reflect the sensitivities of the biomarker and cognitive assays used. How far in advance of incident amnestic mild cognitive impairment (MCI) does cognition begin to decline? METHODS: Longitudinal neuropsychological study of an apolipoprotein E e4 enriched cohort of cognitively normal individuals at entry. Linear mixed models for MCI converters (n = 65) and nonconverters (n = 719) fitted for each neuropsychological measure; annual changes compared between groups before and after linear model intersections (inflection points). RESULTS: 34 of 35 cognitive measures and 9 of 18 behavioral measures declined faster post-inflection in the MCI converters; the earliest cognitive inflection point was nearly 20 years in advance of MCI diagnosis. DISCUSSION: The preclinical duration of cognitive and behavioral changes approaches the earliest reported biomarker changes.

Predicting verbal memory decline following temporal lobe resection for epilepsy.

OBJECTIVES: The aim of the study was to develop a prediction model for verbal memory decline after temporal lobe resection (TLR) for epilepsy. The model will be used in the preoperative counselling of patients to give individualized information about risk for verbal memory decline. MATERIALS AND METHODS: A sample of 110 consecutive patients who underwent TLR for epilepsy at Sahlgrenska University Hospital between 1987 and 2011 constituted the basis for the prediction model. They had all gone through a formal neuropsychological assessment before surgery and 2 years after. Penalized regression and 20 × 10-fold cross-validation were used in order to build a reliable model for predicting individual risks. RESULTS: The final model included four predictors: side of surgery; inclusion or not of the hippocampus in the resection; preoperative verbal memory function; and presence/absence of focal to bilateral tonic-clonic seizures (TCS) the last year prior to the presurgical investigation. The impact of a history of TCS is a new finding which we interpret as a sign of a more widespread network disease which influences neuropsychological function and the cognitive reserve. The model correctly identified 82% of patients with post-operative decline in verbal memory, and the overall accuracy was 70%-85% depending on choice of risk thresholds. CONCLUSIONS: The model makes it possible to provide patients with individualized prediction regarding the risk of verbal memory decline following TLR. This will help them make more informed decisions regarding treatment, and it will also enable the epilepsy surgery team to prepare them better for the rehabilitation process.

Longitudinal Evidence for Increased Functional Response in Frontal Cortex for Older Adults with Hippocampal Atrophy and Memory Decline.

The functional organization of the frontal cortex is dynamic. Age-related increases in frontal functional responses have been shown during various cognitive tasks, but the cross-sectional nature of most past studies makes it unclear whether these increases reflect reorganization or stable individual differences. Here, we followed 130 older individuals' cognitive trajectories over 20-25 years with repeated neuropsychological assessments every 5th year, and identified individuals with stable or declining episodic memory. Both groups displayed significant gray matter atrophy over 2 successive magnetic resonance imaging sessions 4 years apart, but the decline group also had a smaller volume of the right hippocampus. Only individuals with declining memory demonstrated increased prefrontal functional responses during memory encoding and retrieval over the 4-year interval. Regions with increased functional recruitment were located outside, or on the borders of core task-related networks, indicating an expansion of these over time. These longitudinal findings offer novel insight into the mechanisms behind age-associated memory loss, and are consistent with a theoretical model in which hippocampus atrophy, past a critical threshold, induces episodic-memory decline and altered prefrontal functional organization.

Cardiovascular risk factors and memory decline in middle-aged and older adults: the English Longitudinal Study of Ageing.

BACKGROUND: We investigated the association between trajectories of verbal episodic memory and burden of cardiovascular risk factors in middle-aged and older community-dwellers. METHODS: We analysed data from 4372 participants aged 50-64 and 3005 persons aged 65-79 years old from the English Longitudinal Study of Ageing who were repeatedly evaluated every 2 years and had six interviews of a 10-year follow-up. We measured the following baseline risk factors: diabetes, hypertension, smoking, physical inactivity and obesity to derive a cardiovascular risk factor score (CVRFs). Adjusted linear mixed effect regression models were estimated to determine the association between number of CVFRs and six repeated measurements of verbal memory scores, separately for middle-aged and older adults. RESULTS: CVRFs was not significantly associated with memory at baseline. CVFRs was significantly associated with memory decline in middle-aged (50-64y), but not in older (65-79y) participants. This association followed a dose-response pattern with increasing number of CVFRs being associated with greater cognitive decline. Comparisons between none versus some CVRFs yielded significant differences (p < 0.05). CONCLUSIONS: Our findings confirm that the effect of cumulative CVRFs on subsequent cognitive deterioration is age-dependent. CVRFs are associated with cognitive decline in people aged 50-64 years, but not in those aged ≥65 years. Although modest, the memory decline associated with accumulation of cardiovascular risk factors in midlife may increase the risk of late-life dementia.

Long-Term Moderate Exercise Rescues Age-Related Decline in Hippocampal Neuronal Complexity and Memory.

BACKGROUND: Aging impairs hippocampal neuroplasticity and hippocampus-related learning and memory. In contrast, exercise training is known to improve hippocampal neuronal function. However, whether exercise is capable of restoring memory function in old animals is less clear. OBJECTIVE: Here, we investigated the effects of exercise on the hippocampal neuroplasticity and memory functions during aging. METHODS: Young (3 months), middle-aged (9-12 months), and old (18 months) mice underwent moderate-intensity treadmill running training for 6 weeks, and their hippocampus-related learning and memory, and the plasticity of their CA1 neurons was evaluated. RESULTS: The memory performance (Morris water maze and novel object recognition tests), and dendritic complexity (branch and length) and spine density of their hippocampal CA1 neurons decreased as their age increased. The induction and maintenance of high-frequency stimulation-induced long-term potentiation in the CA1 area and the expressions of neuroplasticity-related proteins were not affected by age. Treadmill running increased CA1 neuron long-term potentiation and dendritic complexity in all three age groups, and it restored the learning and memory ability in middle-aged and old mice. Furthermore, treadmill running upregulated the hippocampal expressions of brain-derived neurotrophic factor and monocarboxylate transporter-4 in middle-aged mice, glutamine synthetase in old mice, and full-length TrkB in middle-aged and old mice. CONCLUSION: The hippocampus-related memory function declines from middle age, but long-term moderate-intensity running effectively increased hippocampal neuroplasticity and memory in mice of different ages, even when the memory impairment had progressed to an advanced stage. Thus, long-term, moderate intensity exercise training might be a way of delaying and treating aging-related memory decline.

Contribution of Socioeconomic Status at 3 Life-Course Periods to Late-Life Memory Function and Decline: Early and Late Predictors of Dementia Risk.

Both early life and adult socioeconomic status (SES) predict late-life level of memory; however, evidence is mixed on the relationship between SES and rate of memory decline. Further, the relative importance of different life-course periods for rate of late-life memory decline has not been evaluated. We examined associations between life-course SES and late-life memory function and decline. Health and Retirement Study participants (n = 10,781) were interviewed biennially from 1998-2012 (United States). SES measurements for childhood (composite score including parents' educational attainment), early adulthood (high-school or college completion), and older adulthood (income, mean age 66 years) were all dichotomized. Word-list memory was modeled via inverse-probability weighted longitudinal models accounting for differential attrition, survival, and time-varying confounding, with nonrespondents retained via proxy assessments. Compared to low SES at all 3 points (referent), stable, high SES predicted the best memory function and slowest decline. High-school completion had the largest estimated effect on memory (ß = 0.19; 95% confidence interval: 0.15, 0.22), but high late-life income had the largest estimated benefit for slowing declines (for 10-year memory change, ß = 0.35; 95% confidence interval: 0.24, 0.46). Both early and late-life interventions are potentially relevant for reducing dementia risk by improving memory function or slowing decline.

A reverse factual analysis of the association between smoking and memory decline in China.

BACKGROUND: Whether smoking accelerates memory recession has been a topic of significant research. However, randomised controlled trials are not easy to carry out, and does not comply with the ethics of research. And observation method which based on the most readily observed data is easy to draw the wrong conclusions without adjustment. The memory difference between smokers and non-smokers may not really represent the real differences between their memories. METHODS: In response to these limitations, we adopt propensity score method to match the samples and solve the estimated selection bias and confounding bias on elderlies aged 60 years and over based on Chinese Longitudinal Healthy Longevity Survey (2011) data. The respondents are divided into non-smokers, people who used to smoke but not now, and people who used to smoke and still now. To balance the similarity between different groups on their propensity score weighted distributions of pretreatment covariates, we use generalized boosted models to estimate the multiply treatment propensity scores. RESULTS: The results show that compared with non-smokers, people who used to smoke and still now respectively have a decrease 0.0283, 0.0735, 0.0091 on self-evaluation memory, daily living activities, and cognitive function. People who used to smoke but not now have a decrease 0.0224 on daily living activities, while have an increase 0.0054 and 0.0104 on self-evaluation memory, and cognitive function. CONCLUSION: The PSM has considerable utility to control pre-treatment imbalances on observed covariates in non-randomised or observational data.

Combined treatment with memantine/es-citalopram for older depressed patients with cognitive impairment: a pilot study.

OBJECTIVE: The objective of the study is to assess combined antidepressant and memantine treatment in older patients presenting with depression and cognitive impairment. METHODS: Thirty-five depressed patients with cognitive impairment participated in this open-label pilot study. We evaluated whether, over a 48-week period, combined antidepressant (primarily es-citalopram) and memantine treatment was effective in the treatment of cognitive impairment and depression. Neuropsychological testing was performed, and antidepressant response monitored at baseline and at the 12, 24, and 48-week time points. RESULTS: Treatment with escitalopram (mean daily dose 18.62 mg, SD 5.15) and memantine (mean daily dose 13.62 mg, SD 6.67) was associated with improvement in Hamilton Depression Rating Scale scores over the 48-week study period. Patients demonstrated significant improvement in the primary outcome of cognitive performance (Selective Reminding Test total immediate recall; SRT-IR) over the 48-week treatment period (p = 0.0147). Significant improvement was also observed in measures of naming and verbal fluency but not in the other cognitive domains. One of the 35 patients (2.9%) converted to Alzheimer's disease over the 48-week treatment period. In the amnestic mild cognitive impairment subsample (n = 22), the conversion rate was 4.5%, a rate lower than in other reports of patients with DEP-CI. CONCLUSIONS: In this open-label trial, combined antidepressant and memantine treatment in patients with DEP-CI was associated with improved cognition and a low rate of conversion to dementia compared with published studies in patients with DEP-CI. Although limited by the open-label study design that incorporates practice effects that can improve cognitive test performance, the findings suggest the need for a larger randomized placebo-controlled trial.

Subjective memory decline predicts greater rates of clinical progression in preclinical Alzheimer's disease.

INTRODUCTION: The objective of this study was to determine the utility of subjective memory decline (SMD) to predict episodic memory change and rates of clinical progression in cognitively normal older adults with evidence of high ß-amyloid burden (CN Aß+). METHODS: Fifty-eight CN Aß+ participants from the Australian Imaging, Biomarkers, and Lifestyle study responded to an SMD questionnaire and underwent comprehensive neuropsychological assessments. Participant data for three follow-up assessments were analyzed. RESULTS: In CN Aß+, subjects with high SMD did not exhibit significantly greater episodic memory decline than those with low SMD. High SMD was related to greater rates of progression to mild cognitive impairment or Alzheimer's disease (AD) dementia (hazard ratio = 5.1; 95% confidence interval, 1.4-20.0, P = .02) compared with low SMD. High SMD was associated with greater depressive symptomatology and smaller left hippocampal volume. DISCUSSION: High SMD is a harbinger of greater rates of clinical progression in preclinical AD. Although SMD reflects broader diagnostic implications for CN Aß+, more sensitive measures may be required to detect early subtle cognitive change.

Social interaction rescues memory deficit in an animal model of Alzheimer's disease by increasing BDNF-dependent hippocampal neurogenesis.

It has been recognized that the risk of cognitive decline during aging can be reduced if one maintains strong social connections, yet the neural events underlying this beneficial effect have not been rigorously studied. Here, we show that amyloid precursor protein (APP) and presenilin 1 (PS1) double-transgenic (APP/PS1) mice demonstrate improvement in memory after they are cohoused with wild-type mice. The improvement was associated with increased protein and mRNA levels of BDNF in the hippocampus. Concomitantly, the number of BrdU(+)/NeuN(+) cells in the hippocampal dentate gyrus was significantly elevated after cohousing. Methylazoxymethanol acetate, a cell proliferation blocker, markedly reduced BrdU(+) and BrdU/NeuN(+) cells and abolished the effect of social interaction. Selective ablation of mitotic neurons using diphtheria toxin (DT) and a retrovirus vector encoding DT receptor abolished the beneficial effect of cohousing. Knockdown of BDNF by shRNA transfection blocked, whereas overexpression of BDNF mimicked the memory-improving effect. A tropomyosin-related kinase B agonist, 7,8-dihydroxyflavone, occluded the effect of social interaction. These results demonstrate that increased BDNF expression and neurogenesis in the hippocampus after cohousing underlie the reversal of memory deficit in APP/PS1 mice.

Weighing the value of memory loss in the surgical evaluation of left temporal lobe epilepsy: a decision analysis.

OBJECTIVES: Anterior temporal lobectomy is curative for many patients with disabling medically refractory temporal lobe epilepsy, but carries an inherent risk of disabling verbal memory loss. Although accurate prediction of iatrogenic memory loss is becoming increasingly possible, it remains unclear how much weight such predictions should have in surgical decision making. Here we aim to create a framework that facilitates a systematic and integrated assessment of the relative risks and benefits of surgery versus medical management for patients with left temporal lobe epilepsy. METHODS: We constructed a Markov decision model to evaluate the probabilistic outcomes and associated health utilities associated with choosing to undergo a left anterior temporal lobectomy versus continuing with medical management for patients with medically refractory left temporal lobe epilepsy. Three base-cases were considered, representing a spectrum of surgical candidates encountered in practice, with varying degrees of epilepsy-related disability and potential for decreased quality of life in response to post-surgical verbal memory deficits. RESULTS: For patients with moderately severe seizures and moderate risk of verbal memory loss, medical management was the preferred decision, with increased quality-adjusted life expectancy. However, the preferred choice was sensitive to clinically meaningful changes in several parameters, including quality of life impact of verbal memory decline, quality of life with seizures, mortality rate with medical management, probability of remission following surgery, and probability of remission with medical management. SIGNIFICANCE: Our decision model suggests that for patients with left temporal lobe epilepsy, quantitative assessment of risk and benefit should guide recommendation of therapy. In particular, risk for and potential impact of verbal memory decline should be carefully weighed against the degree of disability conferred by continued seizures on a patient-by-patient basis.

Exercise as medicine! Physical activity mitigated the impact of the COVID-19 pandemic on depressive symptoms in adults with depression.

We investigated the longitudinal association between physical activity (PA) and symptoms of depression and anxiety in people with depression during the COVID-19 pandemic. We used data from baseline (June 2020) to wave 3 (June 2021) of the PAMPA Cohort, an ambispective cohort with adults in south Brazil. The Hospital Anxiety and Depression Scale assessed depressive and anxiety symptoms in all waves. Participants reported frequency (minutes), type (aerobic, strength, combined), and place (out of home, at home) of physical activity at baseline. Generalized linear models were used to investigate the interaction between time and PA, adjusting for possible confounding variables. Subjective memory decline was assessed using multivariate Cox proportional hazard regression models to obtain adjusted hazard ratio (HR) and respective 95% confidence interval (CI). Participants (n = 424) with self-reported clinically diagnosed depression were included. We observed a non-linear increase trajectory of depression during the first year of the COVID-19 pandemic. PA was associated with a slower trajectory of depressive (slope: -1.89; 95%CI: -3.34, -0.43 points) but not anxiety (slope: -1.33; 95%CI: -2.93, 0.25 points) symptoms during the COVID-19 pandemic. Participants who continued physically active from pre-pandemic in wave 1 showed a lower risk of subjective memory decline during follow-up than those who persisted inactive in the same period (HR: 0.52; 95%CI: 0.30, 0.89). PA attenuated the impact of the COVID-19 pandemic on depressive symptoms in adults living with depression in south Brazil. Regularity of physical activity was associated with fewer depression and anxiety symptoms and a lower risk of subjective memory decline.

Antipsychotic effect of diosgenin in ketamine-induced murine model of schizophrenia: Involvement of oxidative stress and cholinergic transmission.

A decrease in the levels of antioxidant arsenals exacerbate generation of reactive oxygen/nitrogen species, leading to neurochemical dysfunction, with significant impact on the pathogenesis of psychotic disorders such as schizophrenia. This study examined the preventive and reversal effects of diosgenin, a phyto-steroidal saponin with antioxidant functions in mice treated with ketamine which closely replicates schizophrenia-like symptoms in human and laboratory animals. In the preventive phase, adult mice cohorts were clustered into 5 groups (n = 9). Groups 1 and 2 received saline (10 mL/kg, i.p.), groups 3 and 4 were pretreated with diosgenin (25 and 50 mg/kg), and group 5 received risperidone (0.5 mg/kg) orally for 14 days. Mice in groups 2-5 additionally received a daily dose of ketamine (20 mg/kg, i.p.) or saline (10 mL/kg/day, i.p.). In the reversal phase, mice received intraperitoneal injection of ketamine or saline for 14 consecutive days prior to diosgenin (25 and 50 mg/kg/p.o./day) and risperidone (0.5 mg/kg/p.o./day) treatment from days 8-14. Mice were assessed for behavioral changes. Oxidative, nitrergic markers, and cholinergic (acetylcholinesterase activity) transmission were examined in the striatum, prefrontal-cortex and hippocampus. Diosgenin prevented and reversed hyperlocomotion, cognitive and social deficits in mice treated with ketamine relative to ketamine groups. The increased acetylcholinesterase, malondialdehyde and nitrite levels produced by ketamine were reduced by diosgenin in the striatum, prefrontal-cortex and hippocampus, but did not reverse striatal nitrite level. Diosgenin increased glutathione, and catalase levels, except for hippocampal catalase activity when compared with ketamine controls. Conclusively, these biochemical changes might be related to the behavioral deficits in ketamine-treated mice, which were prevented and reversed by diosgenin.

Sex-specific blood biomarkers linked to memory changes in middle-aged adults: The Framingham Heart Study.

The relationship between sex-specific blood biomarkers and memory changes in middle-aged adults remains unclear. We aimed to investigate this relationship using the data from the Framingham Heart Study (FHS). We conducted association analysis, partial correlation analysis, and causal dose-response curves using blood biomarkers and other data from 793 middle-aged participants (≤ 60 years) from the FHS Offspring Cohort. The results revealed associations of adiponectin and fasting blood glucose with midlife memory change, along with a U-shaped relationship of high-density lipoprotein cholesterol with memory change. No significant associations were found for the other blood biomarkers (e.g., amyloid beta protein 42) with memory change. To our knowledge, this is the first sex-specific network analysis of blood biomarkers related to midlife memory change in a prospective cohort study. Our findings highlight the importance of targeting cardiometabolic risks and the need to validate midlife-specific biomarkers that can accelerate the development of primary preventive strategies.

Accelerated long-term forgetting: from subjective memory decline to a defined clinical entity.

Subjective memory decline (SMD) might represent the preclinical phase of Alzheimer's disease (AD), and has been reported in epileptic amnesia associated with accelerated long-term forgetting (ALF). We investigated ALF in SMD subjects by means of RAVLT recall and recognition and ROCF recall after 1-week retention and compared with a control group. Two-way ANOVAs for RAVLT and ROCF were conducted, and stepwise regression analysis was administered considering EMQ and DASS-21 as factors. SMD subjects performed significantly worse than controls at 1-week delay on RAVLT recall and recognition, but not on ROCF, and not associated with depression or memory complaints. SMD patients showed ALF, which is usually associated with temporomesial dysfunctions, representing a cognitive marker to assess objectively memory problems in SMD, and to undisclose initial neurodegenerative disease involving temporal structures usually compromised in AD. Therefore, SMD might no longer be "subjective," but rather a specific and defined clinical entity.