Decline In Memory Function Research Articles

Effect of negative emotional stimuli on working memory: Impact of voluntary and automatic attention.

Emotions are known to influence cognitive performance, particularly working memory (WM) in both its aspects, processing, and maintenance. One explanatory mechanism might be that negative stimuli capture attentional resources, leaving fewer resources for attentional maintenance and processing of information in WM. However, this attentional capture was only investigated using WM tasks in which participants were explicitly asked to process negative items. The aim of this paper was to determine whether explicit processing of emotional stimuli is necessary to impair WM performance, or if their mere presence is enough to capture attention. For this purpose, participants performed a complex span task in which they alternated between memorizing a series of neutral words and processing either emotional images or neutral ones. In Experiment 1, participants were instructed to explicitly process emotional images, whereas in Experiment 2, emotional images were presented without any processing being required. In both experiments, we observed a decrease in memory performance when the images were negative compared to neutral. Whether or not voluntary processing is involved, emotional images seem to capture attentional resources, which in turn leads to a decline in memory performance. These results were discussed in relation to attentional theories and the influence of emotion on the specific mechanisms of WM.

Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model.

The American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-β deposition, glycogen synthase kinase 3 beta (GSK3β), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3β/TTBK1 pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200μg/kg/day sc) or liraglutide (0.6mg/kg/day sc) for 6weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3β/TTBK1 expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.

Executive Functions, Processing Speed, and Memory Performance: Untangling the Age-related Effects

Abstract Context: Age-related decline in memory function is a universal phenomenon. However, several factors are known to affect memory decline associated with aging. Aim: The present research aimed to study the differences between young adults and older adults in neurocognitive functions. It also aimed to examine the relative contribution of aging and executive functions to memory performance. Subjects and Methods: The sample consisted of two groups: 43 young adults and 40 older adults. Participants were selected from the community using purposive sampling. Each participant underwent screening using the Edinburgh Handedness Inventory, Modified Mini Screen, and Global Cognitive Screen. A detailed neuropsychological assessment was individually conducted using standardized measures of executive functions, processing speed, episodic memory, and semantic memory. We examined group differences between younger and older participants using the Mann Whitney U test. Additionally, we investigated the contributions of age, processing speed, and executive function to memory through stepwise multiple regression analysis. Results: Analysis of the results suggests significantly worse performance by older participants compared to younger participants on learning and memory (p<.001), semantic memory (p<.001), processing speed (p<.001), and executive functions (p<.001). Our results further indicate that age, processing speed, and executive functions were associated with better performance in learning and memory. However, age emerged as the strongest predictor, followed by processing speed and working memory. Conclusion: Our study demonstrates that aging plays the most significant role in predicting the decline of learning and memory, as well as semantic memory. However, executive functions and processing speed can differentially influence age-associated memory decline. Future studies are warranted on larger populations and more diverse age groups to better comprehend the differential roles of speed, executive functions, and aging on memory performance. We recommend developing age- and education-based normative data for neuropsychological tools specifically tailored to the Indian population.

Aripiprazole Attenuates Cognitive Impairments Induced by Lipopolysaccharide in Rats through the Regulation of Neuronal Inflammation, Oxidative Stress, and Apoptosis.

Background and Objectives: Aripiprazole (APZ), an atypical antipsychotic, is mainly prescribed for conditions such as schizophrenia and bipolar disorder, while ongoing research indicates promising neuroprotective qualities. APZ's mechanism of action, involving the regulation of neurotransmitter levels, appears to contribute to its potential to shield neural tissues from specific forms of harm and degeneration. Materials and Methods: To investigate its neuroprotective mechanisms, groups of rats were orally administered APZ at 1 or 2 mg/kg once daily for a 30-day period. In addition, neuronal toxicity was induced through intraperitoneal injection of four doses of lipopolysaccharide (LPS) at a concentration of 1 mg/kg. To evaluate cognitive function, particularly, short-term recognition memory, the procedure implemented the novel object recognition (NOR) task. Subsequently, brain tissues were gathered to examine markers linked with neuroinflammation, oxidative stress, and apoptosis. Results: The administration of LPS led to a decline in memory performance during the NOR tasks. Simultaneously, this LPS treatment raised inflammatory markers like cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, and nuclear factor kappa B (NF-κB), increased oxidative markers such as malondialdehyde (MDA), and triggered apoptosis markers like Caspase-3 and Bcl2 associated X protein (Bax) within the brain. Furthermore, it decreased levels of antioxidants like reduced glutathione (GSH) and catalase, as well as the anti-apoptotic marker B-cell lymphoma (Bcl)-2 in brain tissue. The use of APZ resulted in enhanced recognition memory performance, as indicated by improved exploration and discrimination abilities of the objects in the NOR task. Moreover, APZ lowered the markers associated with neuronal vulnerability, such as COX-2, NF-κB, MDA, Caspase-3, and Bax. Additionally, it increased the levels of protective markers, including GSH, catalase, and Bcl-2 in LPS-challenged brains. Conclusions: In summary, the findings suggest that APZ exhibits protective properties against neuronal inflammation, oxidative stress, and apoptosis markers in the context of inflammatory-related neurodegeneration. Additional in-depth investigations are needed to further explore potential applications.

10 Semantic Memory as a Predictor of Future Memory Decline

Objective:To determine if the degree of split between phonemic verbal fluency and semantic verbal fluency at initial visit is predictive of decline in memory performance between initial evaluation and follow-up.Participants and Methods:Data from a retrospective multidisciplinary memory clinic database at Spectrum Health was utilized. We examined data from 90 participants who had both an initial and follow-up evaluation completed (initial age = 77.1±4.7 years, follow-up age = 78.4±4.7 years, education = 13.9±3.1 years, race = 91% White, 7% Black, & 2% Hispanic, sex = 61% female, time between evaluations = 15.2±9.9 months). Patients who returned for follow-up did not meet criteria for dementia at time one. Split between phonemic and semantic fluency, termed the semantic-phonological delta (SPD) was measured at the initial evaluation by subtracting the Controlled Oral Word Association Test (COWAT; FAS) T-score from the Animal Naming Test (ANT) T-score. Change in memory score was defined in two ways: 1) subtracting the follow-up evaluation Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) List Recognition Score (RBANS percentiles were converted to a scaled score) from the initial evaluation List Recognition Score (List Recognition Delta), and 2) computing the difference in the RBANS Delayed Memory Index Standard Score between the initial evaluation and the follow-up evaluation (RBANS Memory Delta).Results:Average semantic fluency T scores were (M = 40.3, SD = 12.3) and phonemic fluency T scores were (M = 42.7, SD = 10.3) at initial evaluation. Bivariate correlations were used to determine the relationship between the clinical variables. SPD was significantly correlated with List Recognition Delta, r(88) = .23, p = .026, with greater discrepancies in verbal fluency scores associated with higher level of decline in List Recognition at follow-up. By comparison, Semantic Fluency performance itself at initial evaluation was not significantly correlated with List Recognition Delta, r(88) = .17, p = .097. The correlation between SPD and the RBANS Memory Delta was also not significant, r(88) = .14, p = .166. At follow-up evaluation, 39% of the sample received a diagnosis of Alzheimer’s disease. Of those diagnosed with Alzheimer’s disease, 66% had a negative SPD split at time one, performing worse on semantic fluency compared to phonemic fluency.Conclusions:SPD is a better predictor of decline in RBANS List Recognition performance between evaluations than semantic fluency alone, with a larger negative SPD score (worse semantic fluency performance compared to phonemic fluency) at initial evaluation predicting decline in List Recognition performance at follow-up evaluation. SPD at initial evaluation was not significantly correlated with change in RBANS Delayed Memory Index score between evaluations. This may be because there are some patients who are similarly impaired in both semantic and phonemic verbal fluency at initial evaluation who later demonstrate progressive decline in memory retrieval due to hippocampal-sparing etiologies (e.g., vascular dementia). Overall, these findings are consistent with previous work suggesting that declines in the semantic memory system precede declines in episodic memory retention in conditions such as Alzheimer’s disease.

The decline of verbal memory after stroke is associated with decreased functional connectivity of hippocampal subregions

AbstractBackgroundThe hippocampus plays an important role in learning and integrating events to form episodic memory. Many ischemic stroke survivors experience memory impairments, and some report decline in memory function. We examined changes in functional connectivity (FC) of the hippocampus and its subregions in stroke survivors over 3 years compared to age‐matched stroke‐free healthy controls (HC), and the associations between hippocampal FC and verbal memory performance.MethodParticipants from the Cognition And Neocortical Volume After Stroke Study were analysed at 3‐months, 1‐year and 3‐years post‐stroke. Verbal memory performance at each timepoint was evaluated with delayed recall of the Hopkins Verbal Learning Test‐Revised that was standardized using appropriate age stratified normative data. Evaluable resting‐state functional magnetic resonance imaging sequences were compared with age‐matched healthy controls (see Table 1 for demographics) following pre‐processing. The hippocampus was parcellated into whole hippocampus and four subregions (body, head‐medial, head‐lateral and tail) and bilateral seed‐based FC analyses were conducted for each region using CONN toolbox (V20.b). Longitudinal changes of FC between two timepoints were computed by the direct subtraction.ResultGroups were age‐ and sex‐matched but HC had significantly greater years of education (see Table 1). Greater FC change was seen in stroke survivors between 3‐months to 1‐year in left hippocampal head‐medial (right lateral occipital; p‐FDR = 0.012) with years of education adjusted. Stroke patients displayed significant decline in verbal memory between the 1‐ and 3‐year timepoints. Significantly decreased FC of left hippocampal head‐medial (precuneus; p‐FDR = 0.011) correlated with verbal memory decline between 3‐months and 3 years after adjusting years of education and gender. There was no significant decline or change of verbal memory observed in HC, and the correlated hippocampal FC changes were not present in HC group either.ConclusionChange in left hippocampal subregional FC is different in stroke survivors compared to HC. Subregional hippocampal FC changes correlate with verbal memory decline. Subfield FC analyses may shed new light into mechanisms of post‐stroke memory impairment.

Relationship between angiotensin-converting enzyme inhibitors and angiotensin receptor blockers prescribing and delirium in the ICU-A secondary analysis.

Studies suggest Angiotensin-Converting Enzyme inhibitors (ACEI) and Angiotensin Receptor Blockers (ARB) may slow the decline of memory function in individuals with mild to moderate Alzheimer's disease by regulating migroglial activation and oxidative stress within the brain's reticular activating system. Therefore, we evaluated the relationship between delirium prevalence and being prescribed ACEI and ARB in participants admitted to the intensive care units (ICU). A secondary analysis of data from two parallel pragmatic randomized controlled trials was performed. ACEI and ARB exposure was defined as being prescribed an ACEI or an ARB within six months prior to the ICU admission. The primary endpoint was the first positive delirium assessment based on Confusion Assessment Method for the ICU (CAM-ICU) for up to thirty days. A total of 4791 patients admitted to the medical, surgical, and progressive ICU and screened for eligibility for the parent studies between February 2009 and January 2015 from two level 1 trauma and one safety net hospital in a large urban academic health system were included. Delirium rates in the ICU were not significantly different among participants with no exposure to ACEI/ARB (12.6%), or exposure to ACEI (14.4%), ARB (11.8%), or ACEI and ARB in combination (15.4%) in six months prior to the ICU admission. Exposure to ACEI (OR=0.97[0.77, 1.22]), ARB (OR=0.70 [0.47, 1.05]), or both (OR=0.97 [0.33, 2.89]) in six months prior to ICU admission was not significantly associated with odds of delirium during the ICU admission after adjusting for age, gender, race, co-morbidities, and insurance status. While the impact of ACEI and ARB exposure prior to the ICU admission was not associated with the prevalence of delirium in this study, further research is needed to fully understand the impact of antihypertensive medications on delirium.

Lipopolysaccharide induced neuroprotective effects of bacterial protease against Alzheimer's disease in male Wistar albino rats

Alzheimer's disease (AD) is a highly severe neurodegenerative condition that affects the hippocampus and is characterized by memory loss and dementia. This investigation aims to determine the potential of a bacterial protease enzyme produced by a new mutant strain of bacteria (Bacillus cereus S6-3/UM90) to influence the rat behavioural, biochemical, histological, and immuno-histochemical functions induced by lipopolysaccharides (LPS) experimentally. The administration of LPS exhibited a decline in memory performance via Morris' Water Maze test along with an elevation of IL-6, IL-17, amino acid neurotransmitters, Adenosine monophosphate (AMP), and 8-OHdG, whereas a decrease in ATP (Adenosine Triphosphate), monoamine transmitters, AChE (acetylcholinesterase) and PC (phosphatidylcholine). Additionally, there was a notable increase in GFAP (glial fibrillary acidic protein) and p-Tau protein immuno-expression levels along with obvious histological lesions in the hippocampal CA3 region. Moreover, the administration of protease or Donepezil restored the measured parameters to nearly normal levels and improved the histological architecture of the hippocampus and ameliorated memory impairments. In conclusion, the study provides evidence that the treatment with Bacterial protease can improve the memory and learning impairments of LPS–induced AD and may be used as a promising therapeutic agent to manage AD since it has anti-inflammatory and antioxidant effects.

Transportation-Related Human Factors in High-Altitude Regions: Review, Needs, and Novelties

The low pressure at high altitudes (above 2500 m) causes hypoxia (decreased oxygen) that affects people’s physiological and psychological characteristics. Specifically, hypoxia may affect the neural function of the brain, leading to severe cognitive deficits and a significant decline in memory function and attention. This article addresses the effect of human factors on transportation design and operation at high altitudes (HA), with some details on the Tibet-China region. Specifically, the paper first reviews the basic transportation-related concepts for high altitude, including oxygen and temperature levels, driver perception-reaction time, hazard perception, vehicle speed, and walking speed. Then, the transportation users affected by high altitudes are discussed, including drivers, pedestrians, cyclists, passengers, and others. Next, the impacts of human factors on highway design and operation for HA regions are discussed along with the research needs. Finally, recent innovations to address the challenges of HA transportation are presented, along with case studies comparing some human factors of the plateau and plain areas. This article represents a valuable reference for future research in HA regions to improve transportation design and safety

THE IMPACTS OF CHANGES IN DIABETES AND ORAL HEALTH CONDITIONS ON COGNITIVE TRAJECTORIES

Abstract Despite the emerging research studying the relationship between diabetes mellitus (DM), oral health problems, and cognitive function, little is known about how changes in DM and oral health status affected the trajectories of cognitive decline. Using data of 12,802 participants aged 51+ from the 2006-2018 English Longitudinal Study of Ageing, this study examined the longitudinal relationships of cognitive functions with time-varying DM and oral health status – measured by edentulism, self-rated dental condition, and oral impact on daily performance (OIDP) scale at five time-points from 2006 to 2018. Results showed that participants had DM and edentulism throughout the study period had an accelerated decline in verbal fluency (mean=20.9; b=-0.17, 95% CI=-0.28, -0.07); and those had both DM and OIDP-problem had an accelerated decline in memory function (mean=10.4; b=-0.09, 95% CI=-0.15, -0.03). Prevention and treatment of multiple chronic conditions are essential for cognitive health in later life.

SELF-REPORTED DENTAL CONDITIONS AND MEMORY DECLINE: THE MEDIATION ROLE OF STROKE

Abstract The relationship between oral health and cognitive function has been studied extensively; however, little research has examined the underlying pathways. Using a cohort of 6,403 adults aged 51+ from the 2006-2010 English Longitudinal Study of Ageing, we analyzed the effect of changes in self-rated dental conditions on memory function (ranges 0-20) and the mediation effect of stroke using a causal mediation analysis framework. Controlling for socio-demographics, lifestyle, and health status, we found that compared with participants whose dental conditions remained the same, those who reported deterioration of dental conditions in 2006-2010 (N=1,755) experienced a steeper decline in memory function, with an average total effect of -0.22 (95% CI=-0.36, -0.07). The stroke incident had an average mediation effect of -0.007 (95% CI=-0.014, -0.001), representing 3% of the average total effect. The findings accentuate the importance of dental care access for older adults with exacerbated oral health problems.

Amyloid-β and APOE genotype predict memory decline in cognitively unimpaired older individuals independently of Alzheimer’s disease polygenic risk score

Background:What combination of risk factors for Alzheimer’s disease (AD) are most predictive of cognitive decline in cognitively unimpaired individuals remains largely unclear. We studied associations between APOE genotype, AD-Polygenic Risk Scores (AD-PRS), amyloid-β pathology and decline in cognitive functioning over time in a large sample of cognitively unimpaired older individuals.Methods:We included 276 cognitively unimpaired older individuals (75 ± 10 years, 63% female) from the EMIF-AD PreclinAD cohort. An AD-PRS was calculated including 83 genome-wide significant variants. The APOE gene was not included in the PRS and was analyzed separately. Baseline amyloid-β status was assessed by visual read of [18F]flutemetamol-PET standardized uptake value images. At baseline and follow-up (2.0 ± 0.4 years), the cognitive domains of memory, attention, executive function, and language were measured. We used generalized estimating equations corrected for age, sex and center to examine associations between APOE genotype and AD-PRS with amyloid-β status. Linear mixed models corrected for age, sex, center and education were used to examine associations between APOE genotype, AD-PRS and amyloid-β status, and their interaction on changes in cognitive functioning over time.Results:Fifty-two participants (19%) had abnormal amyloid-β, and 84 participants (31%) carried at least one APOE ε4 allele. APOE genotype and AD-PRS were both associated with abnormal amyloid-β status. Increasingly more risk-full APOE genotype, a high AD-PRS and an abnormal amyloid-β status were associated with steeper decline in memory functioning in separate models (all p ≤ 0.02). A model including 4-way interaction term (APOE×AD-PRS×amyloid-β×time) was not significant. When modelled together, both APOE genotype and AD-PRS predicted steeper decline in memory functioning (APOE β(SE)=-0.05(0.02); AD-PRS β(SE)=-0.04(0.01)). Additionally, when modelled together, both amyloid-β status and AD-PRS predicted a steeper decline in memory functioning (amyloid-β β(SE)=-0.07(0.04); AD-PRS β(SE)=-0.04(0.01)). Modelling both APOE genotype and amyloid-β status, we observed an interaction, in which APOE genotype was related to steeper decline in memory and language functioning in amyloid-β abnormal individuals only (β(SE)=-0.13(0.06); β(SE)=-0.22(0.07), respectively).Conclusion:Our results suggest that APOE genotype is related to steeper decline in memory and language functioning in individuals with abnormal amyloid-β only. Furthermore, independent of amyloid-β status other genetic risk variants contribute to memory decline in initially cognitively unimpaired older individuals.

The effect of age on mnemonic discrimination is fully mediated by posterior cerebral artery‐defined white matter hyperintensities

AbstractBackgroundPrevious work has observed a decline in memory performance with age on mnemonic discrimination tasks (MDT). Other studies have recognized the contributions of white matter hyperintensities (WMH), a marker of cerebrovascular disease, on age and Alzheimer’s disease‐related memory decline. Here, we asked whether WMH, defined within vascular territories, particularly the posterior cerebral artery (PCA) defined territory, would mediate the association between age and MDT performance.MethodA sample of 120 older adults (mean age (SD) = 76.6 (10.43) years, age range: 59‐98 years, 74 (61.7%) females) were included in these analyses. Regional WMH volumes were derived from T2‐FLAIR (Figure 1A) images using ANTs, a vascular territory atlas (Figure 1B) and manual editing. The MDT was administered to assess episodic memory and pattern separation ability within both the object (MDT‐O) and spatial (MDT‐S) domains. Adjusting for sex and education, we tested for associations among age, regional WMH volumes, MDT‐S, and MDT‐O scores, correcting for multiple comparisons. Results were then used to assess the mediating role of regional WMH on the relationship between age and MDT. Lastly, we compared the accuracy of the different vascular territory WMH volumes, along with total WMH volume, in classifying cognitive impairment (MCI, QCI, CIND) using area under the receiver operating characteristic curve (ROC).ResultAge was associated with MDT‐S (β=‐0.247, p=0.005), but not MDT‐O performance (β=‐0.130, p=0.177). Only PCA‐defined WMH volume was associated with MDT‐S (β=‐0.252, p=0.005) and MDT‐O (b=‐0.229, p=0.016). PCA‐defined WMH fully mediated the association between age and MDT‐S (indirect effect: β=‐0.001, 95% CI (‐0.003, ‐0.001); Figure 2A). Similarly, PCA‐defined WMH fully mediated the association between age and MDT‐O (β=‐0.001, 95% CI (‐0.002, ‐0.003); Figure 2B). PCA‐defined WMH volume more accurately classified cognitively impaired from non‐impaired (AUC=0.780, p<0.001; Figure 3) compared with total WMH (AUC=0.624, p=0.113), ACA‐defined WMH volume (AUC=0.618, p=.130) or MCA‐defined WMH (AUC=0.592, p=0.237).ConclusionPCA‐defined WMH mediate the relationship between age and memory performance and is a better diagnostic of cognitive impairment than whole brain or other vascular territory WMH volumes. This study demonstrates that defining WMH within vascular territories provides a useful way to characterize the impact of aging on memory impairment.

Image‐based primary age‐related tauopathy as a risk of dementia: a five‐year longitudinal study

AbstractBackgroundTo investigate cognitive and pathological (amyloid and tau) changes of image‐based primary age‐related tauopathy (PART) in a long‐term follow‐up cohort study.MethodIn this study, a total of 108 patients who were both negative in amyloid and tau PET images were enrolled. All participants completed the same two PET scans (18F‐flortaucipir for tau and 18F‐florbetaben for Aβ), and neuropsychological tests at least twice over 5 years. We defined PART+ as those who had a higher standardized uptake value ratio (SUVR) in the entorhinal cortex than the cutoff calculated by the Youden index. We investigated the cognitive and 18F‐florbetaben and 18F‐flortaucipir SUVR changes longitudinally between PART+ and PART‐ participants while adjusting for age, sex, education, and ApoE4.ResultCompared with PART‐, PART+ participants had more rapid worsening of MMSE (β=‐0.274, p<0.001), CDR‐SB (β=0.081, p<0.001), and memory function (β=‐0.140, p=0.008). No significant differences were observed in the language, visuospatial, frontal‐executive, attention domains, and total cognitive battery score. In PART+ participants, the annual Aβ accumulation rate from whole cortical SUVR was also increased (β=0.016, p=0.003), and a more rapid accumulation rate was observed in Alzheimer’s disease (AD) specific hot meta‐region‐of‐interest (meta‐ROI) SUVR, compared with PART‐ participants (β=0.019, p=0.001). The annual tau accumulation rate of PART+ was higher than PART‐ in the entorhinal cortex (β=0.010, p<0.001), however, no differences were observed in whole cortical SUVR tau.ConclusionThe PART+ participants showed a rapid cognitive decline in memory function as well as MMSE, and CDR‐SB, than those of PART‐. In addition, amyloid was accumulated at a faster rate in PART+ participants and tau was accumulated more rapidly in the medial temporal area. In conclusion, our longitudinal study suggests that image‐based entorhinal tau defined as a PART+ could be an earlier stage than the preclinical stage of AD.

New Insights into Microglial Mechanisms of Memory Impairment in Alzheimer's Disease.

Alzheimer's disease (AD) is the most common progressive and irreversible neurodegeneration characterized by the impairment of memory and cognition. Despite years of studies, no effective treatment and prevention strategies are available yet. Identifying new AD therapeutic targets is crucial for better elucidating the pathogenesis and establishing a valid treatment of AD. Growing evidence suggests that microglia play a critical role in AD. Microglia are resident macrophages in the central nervous system (CNS), and their core properties supporting main biological functions include surveillance, phagocytosis, and the release of soluble factors. Activated microglia not only directly mediate the central immune response, but also participate in the pathological changes of AD, including amyloid-beta (Aβ) aggregation, tau protein phosphorylation, synaptic dissection, neuron loss, memory function decline, etc. Based on these recent findings, we provide a new framework to summarize the role of microglia in AD memory impairment. This evidence suggests that microglia have the potential to become new targets for AD therapy.

Early-onset Alzheimer's disease shows a distinct neuropsychological profile and more aggressive trajectories of cognitive decline than late-onset.

Early- and late-onset Alzheimer's disease (EOAD and LOAD) share the same neuropathological traits but show distinct cognitive features. We aimed to explore baseline and longitudinal outcomes of global and domain-specific cognitive function in a well characterized cohort of patients with a biomarker-based diagnosis. In this retrospective cohort study, 195 participants were included and classified according to their age, clinical status, and CSF AD biomarker profile: 89 EOAD, 37 LOAD, 46 young healthy controls (age ≤ 65 years), and 23 old healthy controls (>65 years). All subjects underwent clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture. We found distinct neuropsychological profiles between EOAD and LOAD at the time of diagnosis. Both groups showed similar performances on memory and language domains, but the EOAD patients displayed worsened deficits in visual perception, praxis, and executive tasks (p < 0.05). Longitudinally, cognitive decline in EOAD was more pronounced than LOAD in the global outcomes at the expense of these non-amnestic domains. We found that years of education significantly influenced the decline in most of the neuropsychological tests. Besides, the APOE ε4 status showed a significant effect on the decline of memory-related tasks within the EOAD cohort (p < 0.05). Age of onset is a main factor shaping the cognitive trajectories in AD patients, with younger age driving to a steeper decline of the non-memory domains. Years of education are related to a transversal decline in all cognitive domains and APOE ε4 status to a specific decline in memory performance in EOAD.

Association Between Supplemental Nutrition Assistance Program Use and Memory Decline: Findings From the Health and Retirement Study.

Studies on the effect of the Supplemental Nutrition Assistance Program (SNAP) on the cognitive health of older adults are scarce. We sought to examine the associations between SNAP use and memory decline among SNAP-eligible US older adults. Participants aged 50+ years and SNAP-eligible in 1996 from the Health and Retirement Study were included. Participants' SNAP eligibility was constructed using federal criteria. Participants also self-reported whether they used SNAP. Memory function was assessed biennially from 1996 through 2016 using a composite score. To account for preexisting differences in characteristics between SNAP users and nonusers, we modeled the probability of SNAP use using demographic and health covariates. Using linear mixed-effects models, we then modeled trajectories of memory function for SNAP users and nonusers using inverse probability (IP) weighting and propensity score (PS) matching techniques. In all models, we accounted for study attrition. Of the 3,555 SNAP-eligible participants, a total of 15.7% were SNAP users. At baseline, SNAP users had lower socioeconomic status and a greater number of chronic conditions than nonusers and were more likely to be lost to follow-up. Our multivariable IP-weighted models suggested that SNAP users had worse memory scores at baseline but slower rates of memory decline compared with nonusers (the annual decline rate is -0.038 standardized units [95% CI = -0.044 to -0.032] for users and -0.046 [95% CI = -0.049 to -0.043] for nonusers). Results were slightly stronger from the PS-matched sample (N = 1,014) (the annual decline rate was -0.046 units [95% CI = -0.050 to -0.042] for users and -0.060 units [95% CI = -0.064 to -0.056] for nonusers). Put in other words, our findings suggested that SNAP users had approximately 2 fewer years of cognitive aging over a 10-year period compared with nonusers. After accounting for preexisting differences between eligible SNAP users and nonusers as well as differential attrition, we find SNAP use to be associated with slower memory function decline.

Isoflurane has no effect on cognitive or behavioral performance in a mouse model of early-stage Alzheimer's disease.

Patients with Alzheimer's disease show a sex-dependent decline of cognitive and behavioral performance. It is controversially discussed whether general anesthesia itself can aggravate or even cause this neurocognitive decline. Therefore, we investigated the effect of general anesthesia on neurocognitive and behavioral function and amyloidopathy in a mouse model of early-stage Alzheimer's disease with respect to sex. After governmental approval 10 months old Tg2576 mice and wild type (total 85 mice) either underwent general anesthesia with 1.0 minimal alveolar concentration of isoflurane for 2 h or were not exposed to isoflurane (controls). Following cognitive and behavioral testing using the modified hole board test (mHBT), brains were investigated regarding amyloidopathy, inflammation, and apoptosis. Data were analyzed using repeated measure analysis of variance (ANOVA) and univariate analysis of variance (UNIANOVA). Tg2576 mice showed a decline in memory function (p < 0.001), less anxiety (p = 0.022 and p = 0.024), increased locomotor activity (p = 0.025), and impaired fine motor skills (p < 0.001). Amyloid precursor protein (p < 0.001), soluble amyloid-beta (p < 0.001) and insoluble amyloid deposits (p < 0.001) were increased in Tg2576 animals. Neither sex nor exposure to isoflurane had an effect on cognitive or behavioral testing or expression of amyloid-related biomarkers. We found that 10 months old Tg2576 showed typical signs of early-stage Alzheimer's disease and corresponding histopathological alterations. Relevant sex-specific differences or an effect of isoflurane anesthesia could not be detected at this early stage of the disease.

Novel benzodiazepine remimazolam tosylate delays neurodegeneration of aged mice via decreasing tau phosphorylation

Benzodiazepines like midazolam were generally considered one of the possible causes affecting postoperative cognitive recovery. As a new kind of rapid-effect benzodiazepine, remimazolam tosylate was widely used in clinical anesthesia for its pharmacological advantage, but few studies reported its effects on cognitive function in the elderly. Here, we aimed to research the effects of remimazolam tosylate on cognitive function in aged mice and its underlying biological mechanisms. We measured the memory function of aged mice immediately and one month after intraperitoneal injection of remimazolam tosylate compared to the saline control. The brain metabolism level was detected by Positron Emission Tomography/Computed tomography (PET/CT). Compared with the control, we observed a decrease in memory ability， as well as an increase in tau phosphorylation level and a decrease in phosphatase level in the short term; however, one month later, contrary to the previous results, we observed better memory and brain metabolism and lower tau phosphorylation levels in the experimental group compared to the control. Therefore, we concluded that remimazolam tosylate did not cause long-term damage to the cognitive function of aged mice and even delayed the decline of memory function in the aging process to some extent.

Sphingolipids and DHA Improve Cognitive Deficits in Aged Beagle Dogs

Canine cognitive dysfunction syndrome (CDS) is a disorder found in senior dogs that is typically defined by the development of specific behavioral signs which are attributed to pathological brain aging and no other medical causes. One way of objectively characterizing CDS is with the use of validated neuropsychological test batteries in aged Beagle dogs, which are a natural model of this condition. This study used a series of neuropsychological tests to evaluate the effectiveness of supplementation with a novel lipid extract containing porcine brain-derived sphingolipids (Biosfeen®) and docosahexaenoic acid (DHA) for attenuating cognitive deficits in aged Beagles. Two groups (n = 12), balanced for baseline cognitive test performance, received a daily oral dose of either test supplement, or placebo over a 6-month treatment phase. Cognitive function was evaluated using the following tasks: delayed non-matching to position (DNMP), selective attention, discrimination learning retention, discrimination reversal learning, and spatial discrimination acquisition and reversal learning. The effect of the supplement on brain metabolism using magnetic resonance spectroscopy (MRS) was also examined. A significant decline (p = 0.02) in DNMP performance was seen in placebo-treated dogs, but not in dogs receiving the supplement, suggesting attenuation of working memory performance decline. Compared to placebo, the supplemented group also demonstrated significantly improved (p = 0.01) performance on the most difficult pattern of the spatial discrimination task and on reversal learning of the same pattern (p = 0.01), potentially reflecting improved spatial recognition and executive function, respectively. MRS revealed a significant increase (p = 0.048) in frontal lobe glutamate and glutamine in the treatment group compared to placebo, indicating a physiological change which may be attributed to the supplement. Decreased levels of glutamate and glutamine have been correlated with cognitive decline, suggesting the observed increase in these metabolites might be linked to the positive cognitive effects found in the present study. Results of this study suggest the novel lipid extract may be beneficial for counteracting age-dependent deficits in Beagle dogs and supports further investigation into its use for treatment of CDS. Additionally, due to parallels between canine and human aging, these results might also have applicability for the use of the supplement in human cognitive health.