-
Physiological Research Sep 2017Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as... (Review)
Review
Alzheimer's disease (AD) is a primary cause of dementia in the middle-aged and elderly worldwide. Animal models for AD are widely used to study the disease mechanisms as well as to test potential therapeutic agents for disease modification. Among the non-genetically manipulated neuroinflammation models for AD, lipopolysaccharide (LPS)-induced animal model is commonly used. This review paper aims to discuss the possible factors that influence rats' response following LPS injection. Factors such as dose of LPS, route of administration, nature and duration of exposure as well as age and gender of animal used should be taken into account when designing a study using LPS-induced memory impairment as model for AD.
Topics: Alzheimer Disease; Animals; Disease Models, Animal; Humans; Inflammation Mediators; Lipopolysaccharides; Memory Disorders; Rats
PubMed: 28406691
DOI: 10.33549/physiolres.933480 -
Cell Metabolism Aug 2022Alzheimer's disease (AD) is one of the foremost neurodegenerative diseases, characterized by beta-amyloid (Aβ) plaques and significant progressive memory loss. In AD,...
Alzheimer's disease (AD) is one of the foremost neurodegenerative diseases, characterized by beta-amyloid (Aβ) plaques and significant progressive memory loss. In AD, astrocytes are proposed to take up and clear Aβ plaques. However, how Aβ induces pathogenesis and memory impairment in AD remains elusive. We report that normal astrocytes show non-cyclic urea metabolism, whereas Aβ-treated astrocytes show switched-on urea cycle with upregulated enzymes and accumulated entering-metabolite aspartate, starting-substrate ammonia, end-product urea, and side-product putrescine. Gene silencing of astrocytic ornithine decarboxylase-1 (ODC1), facilitating ornithine-to-putrescine conversion, boosts urea cycle and eliminates aberrant putrescine and its toxic byproducts ammonia and HO and its end product GABA to recover from reactive astrogliosis and memory impairment in AD. Our findings implicate that astrocytic urea cycle exerts opposing roles of beneficial Aβ detoxification and detrimental memory impairment in AD. We propose ODC1 inhibition as a promising therapeutic strategy for AD to facilitate removal of toxic molecules and prevent memory loss.
Topics: Alzheimer Disease; Ammonia; Amyloid beta-Peptides; Astrocytes; Humans; Hydrogen Peroxide; Memory Disorders; Plaque, Amyloid; Putrescine; Urea
PubMed: 35738259
DOI: 10.1016/j.cmet.2022.05.011 -
Journal of Internal Medicine Mar 2014The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the...
The construct of mild cognitive impairment (MCI) has evolved over the past 10 years since the publication of the new MCI definition at the Key Symposium in 2003, but the core criteria have remained unchanged. The construct has been extensively used worldwide, both in clinical and in research settings, to define the grey area between intact cognitive functioning and clinical dementia. A rich set of data regarding occurrence, risk factors and progression of MCI has been generated. Discrepancies between studies can be mostly explained by differences in the operationalization of the criteria, differences in the setting where the criteria have been applied, selection of subjects and length of follow-up in longitudinal studies. Major controversial issues that remain to be further explored are algorithmic versus clinical classification, reliability of clinical judgment, temporal changes in cognitive performances and predictivity of putative biomarkers. Some suggestions to further develop the MCI construct include the tailoring of the clinical criteria to specific populations and to specific contexts. The addition of biomarkers to the clinical phenotypes is promising but requires deeper investigation. Translation of findings from the specialty clinic to the population setting, although challenging, will enhance uniformity of outcomes. More longitudinal population-based studies on cognitive ageing and MCI need to be performed to clarify all these issues.
Topics: Aged; Aging; Alzheimer Disease; Biomarkers; Cognitive Dysfunction; Critical Pathways; Disease Progression; Follow-Up Studies; Humans; Memory Disorders; Mental Competency; Neuropsychological Tests; Reproducibility of Results; Risk Factors
PubMed: 24605806
DOI: 10.1111/joim.12190 -
European Review For Medical and... Jul 2021Metformin is the most commonly prescribed drug for the treatment of type 2 diabetes mellitus. In addition to its ability to lower glucose levels, it has recently been... (Review)
Review
Metformin is the most commonly prescribed drug for the treatment of type 2 diabetes mellitus. In addition to its ability to lower glucose levels, it has recently been reported to be potentially useful for the treatment of other conditions because of its anticancer activity, cardiovascular protective effect, neuroprotective effect, and efficacy in the treatment of polycystic ovary syndrome. However, long-term use of metformin may lead to side-effects such as memory impairment. Here, we critically review the effect of metformin on memory impairment and the potential molecular mechanisms of memory dysfunction to provide a reference for researchers and a better understanding of the side-effects of metformin.
Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Memory Disorders; Metformin
PubMed: 34337723
DOI: 10.26355/eurrev_202107_26387 -
JAMA Network Open Oct 2023Perioperative neurocognitive disorder, particularly postoperative cognitive impairment, is common and associated with multiple medical and social adversities, although...
IMPORTANCE
Perioperative neurocognitive disorder, particularly postoperative cognitive impairment, is common and associated with multiple medical and social adversities, although data from China are lacking.
OBJECTIVE
To examine the incidence, trajectory, and risk factors for subjective cognitive and short-term memory impairment after surgery in the Chinese population.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study used data from the China Surgery and Anesthesia Cohort to assess surgical patients aged 40 to 65 years from 2 medical centers between July 15, 2020, and March 31, 2023, with active follow-up within 1 year after the surgery. Of 11 158 patients who were successfully recruited (response rate, 94.4%), 10 149 participants were eligible and available for analysis. From this population, separate cohorts were constructed for analyzing subjective cognitive impairment (8105 noncardiac and 678 cardiac surgery patients) and short-term memory impairment (5246 noncardiac and 454 cardiac surgery patients).
EXPOSURES
Twenty-four potential risk factors regarding comorbidities, preoperative psychological conditions, anesthesia- or surgery-related factors, and postsurgical events were included.
MAIN OUTCOMES AND MEASURES
Outcomes included subjective cognitive function measured by the 8-Item Informant Interview to Differentiate Aging and Dementia (AD8; scores range from 0 to 8, with higher scores indicating more severe cognitive impairment) and short-term memory measured by the 3-Word Recall Test (TRT; scores range from 0 to 3, with lower scores indicating more severe short-term memory impairment) at 1, 3, 6, and 12 months after noncardiac and cardiac surgery. Generalized linear mixed models were used to identify risk factors associated with the presence of AD8 (score ≥2) or TRT (score <3) abnormality as well as the aggressively deteriorative trajectories of those cognitive measurements.
RESULTS
For noncardiac surgery patients, the AD8 analysis included 8105 patients (mean [SD] age, 52.3 [7.1] years; 3378 [41.7%] male), and the TRT analysis included 5246 patients (mean [SD] age, 51.4 [7.0] years; 1969 [37.5%] male). The AD8 abnormality incidence rates after noncardiac surgery increased from 2.2% (175 of 8105) at 7 days to 17.1% (1059 of 6191) at 6 months after surgery, before appearing to decrease. In contrast, the TRT abnormality incidence rates followed a U-shaped pattern, with the most pronounced incidence rates seen at 7 days (38.9% [2040 of 5246]) and 12 months (49.0% [1394 of 2845]). Similar patterns were seen among cardiac surgery patients for the AD8 analysis (678 patients; mean [SD] age, 53.2 [6.3] years; 393 [58.0%] male) and TRT analysis (454 patients; mean [SD] age, 52.4 [6.4] years; 248 [54.6%] male). Among noncardiac surgery patients, the top risk factors for aggressively deteriorative AD8 trajectory and for AD8 abnormality, respectively, after surgery were preoperative sleep disturbances (Pittsburgh Sleep Quality Index ≥16 vs 0-5: odds ratios [ORs], 4.04 [95% CI, 2.20-7.40] and 4.54 [95% CI, 2.40-8.59]), intensive care unit stay of 2 days or longer (ORs, 2.43 [95% CI, 1.26-4.67] and 3.07 [95% CI, 1.67-5.65]), and preoperative depressive symptoms (ORs, 1.76 [95% CI, 1.38-2.24] and 2.23 [95% CI, 1.79-2.77]). Analyses for TRT abnormality and trajectory, as well as the analyses conducted among cardiac surgery patients, found fewer associated factors.
CONCLUSIONS AND RELEVANCE
This cohort study of middle-aged Chinese surgery patients found subjective cognitive and short-term memory impairment within 12 months after both cardiac and noncardiac surgery, with multiple identified risk factors, underscoring the potential of preoperative psychological interventions and optimized perioperative management for postoperative cognitive impairment prevention.
Topics: Female; Humans; Male; Middle Aged; Cognition; Cognitive Dysfunction; Cohort Studies; Delirium; East Asian People; Memory, Short-Term; Adult; Aged; Postoperative Cognitive Complications; Memory Disorders; Surgical Procedures, Operative
PubMed: 37815831
DOI: 10.1001/jamanetworkopen.2023.36985 -
Aging & Mental Health May 2022To examine relationships between subjective memory impairment (SMI) and parental dementia among in older adults while considering the interactive influence of depressive...
OBJECTIVES
To examine relationships between subjective memory impairment (SMI) and parental dementia among in older adults while considering the interactive influence of depressive symptoms, ethnicity, and race.
METHOD
The sample was drawn from the Health and Retirement Study, a nationally representative longitudinal study of aging ( = 3,809; = 66.09; = 1.88; 84.20% White; 12.23% Black; 7.88% Hispanic). Biennial assessments included two measures of SMI (current memory problems and perceived memory decline), depressive symptoms, and parental dementia, over periods of up to sixteen years. Multilevel modeling analyses examined longitudinal relationships between parental dementia and SMI and whether depressive symptoms, ethnicity, and race interactively influenced this association.
RESULTS
Results showed that when older adults reported parental dementia, they were more likely to report a decline in memory in the past two years. They also reported poorer current memory problems, especially when they experienced increased depressive symptoms. Associations of parental dementia were consistent across ethnicity and race.
CONCLUSIONS
Results demonstrate the importance of considering parental dementia as a factor that may contribute to SMI in older adults.
Topics: Aged; Dementia; Humans; Longitudinal Studies; Memory Disorders; Parents; Retirement
PubMed: 33855905
DOI: 10.1080/13607863.2021.1910790 -
Nutrients May 2023Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the...
Alzheimer's disease (AD) is a neurodegenerative disorder, characterized by memory loss and cognitive decline. Among the suggested pathogenic mechanisms of AD, the cholinergic hypothesis proposes that AD symptoms are a result of reduced synthesis of acetylcholine (ACh). A non-selective antagonist of the muscarinic ACh receptor, scopolamine (SCOP) induced cognitive impairment in rodents. Umbelliferone (UMB) is a Apiaceae-family-derived 7-hydeoxycoumarin known for its antioxidant, anti-tumor, anticancer, anti-inflammatory, antibacterial, antimicrobial, and antidiabetic properties. However, the effects of UMB on the electrophysiological and ultrastructure morphological aspects of learning and memory are still not well-established. Thus, we investigated the effect of UMB treatment on cognitive behaviors and used organotypic hippocampal slice cultures for long-term potentiation (LTP) and the hippocampal synaptic ultrastructure. A hippocampal tissue analysis revealed that UMB attenuated a SCOP-induced blockade of field excitatory post-synaptic potential (fEPSP) activity and ameliorated the impairment of LTP by the NMDA and AMPA receptor antagonists. UMB also enhanced the hippocampal synaptic vesicle density on the synaptic ultrastructure. Furthermore, behavioral tests on male SD rats (7-8 weeks old) using the Y-maze test, passive avoidance test (PA), and Morris water maze test (MWM) showed that UMB recovered learning and memory deficits by SCOP. These cognitive improvements were in association with the enhanced expression of BDNF, TrkB, and the pCREB/CREB ratio and the suppression of acetylcholinesterase activity. The current findings indicate that UMB may be an effective neuroprotective reagent applicable for improving learning and memory against AD.
Topics: Rats; Male; Animals; Scopolamine; Acetylcholinesterase; Rats, Sprague-Dawley; Memory Disorders; Neuronal Plasticity; Hippocampus; Alzheimer Disease
PubMed: 37242234
DOI: 10.3390/nu15102351 -
The Journal of Physiological Sciences :... Jan 2019The objective of this paper was to systematically evaluate the potential preventive and therapeutic effects of exercise in attenuating stress-induced memory impairment.... (Review)
Review
The objective of this paper was to systematically evaluate the potential preventive and therapeutic effects of exercise in attenuating stress-induced memory impairment. A systematic review was employed, searching PubMed, PsychInfo, Sports Discus and Google Scholar databases. For eligibility, studies had to be published in English, employ an experimental design, have the acute or chronic bout of exercise occur prior to, during or after the stressor, implement a psychophysiological stressor, and have an assessment of memory function occurring after the stressor. In total, 23 studies were evaluated, all of which were conducted among animal models. All 23 studies employed a chronic exercise protocol and a chronic stress protocol. Eight studies evaluated a preventive model, three employed a concurrent model, ten studies employed a therapeutic model, and two studies evaluated both a preventive and therapeutic model within the same study. Among the eight studies employing a preventive model, all eight demonstrated that the stress regimen impaired memory function. In all eight of these studies, when exercise occurred prior to the stressor, exercise attenuated the stress-induced memory impairment effect. Among the ten studies employing a therapeutic model, one study showed that the stress protocol enhanced memory function, one showed that the stress protocol did not influence memory, and eight demonstrated that the stress regimen impaired memory function. Among the eight studies showing that the stress protocol impaired memory function, all eight studies demonstrated that exercise, after the stressor, attenuated stress-induced memory impairment. Within animal models, chronic stress is associated with memory impairment and chronic exercise has both a preventive and therapeutic effect in attenuating stress-induced memory impairment. Additional experimental work in human studies is needed. Such work should also examine acute exercise and stress protocols.
Topics: Animals; Disease Models, Animal; Maze Learning; Memory Disorders; Physical Conditioning, Animal; Stress, Psychological
PubMed: 30203315
DOI: 10.1007/s12576-018-0638-0 -
Psychiatry and Clinical Neurosciences Sep 2017Using meta-analytic methods, we sought to synthesize the research literature on memory impairment in schizophrenia. Additionally, we compared performances across memory... (Meta-Analysis)
Meta-Analysis Review
Using meta-analytic methods, we sought to synthesize the research literature on memory impairment in schizophrenia. Additionally, we compared performances across memory measures to determine if task difficulty (e.g., effortful encoding and retrieval vs non-effortful encoding and retrieval) could account for variance across studies. Our primary measures of interest included the California Verbal Learning Test, Wechsler Memory Scale, Rey Auditory Verbal Learning Test, Hopkins Verbal Learning Test, Rey-Osterrieth Complex Figure Test, and the Benton Visual Retention Test. We searched for all studies that met inclusion criteria using PubMed, PsycINFO, Scholars Portal Search, and Google Scholar. Studies were included if: (i) they were published after 1980; (ii) healthy controls were compared to patients with schizophrenia; (iii) at least one of the noted measures of interest was employed in the primary study; and (iv) the primary study included data that could be transformed to point estimate effect sizes (i.e., Cohen's d). Cohen's d was calculated between patients and healthy controls, along with overall 95% confidence intervals. A two-tailed independent samples t-test was conducted to assess if performance differed on various paired subtests of the same domain. Large effect sizes were found for all memory tests. No significant differences were found between subtests. In conclusion, patients with schizophrenia experience significant verbal and visual memory impairments, which are not explained by task difficulty. Patients were unable to learn or retrieve more reliably despite repetition and cuing strategies, suggesting that memory impairment in the illness is not a function of task difficulty.
Topics: Humans; Memory Disorders; Neuropsychological Tests; Schizophrenia
PubMed: 28294468
DOI: 10.1111/pcn.12520 -
Journal of the International... Jul 2022Story memory tasks are among the most commonly used memory tests; however, research suggests they may be less sensitive to memory decline and have a weaker association...
OBJECTIVE
Story memory tasks are among the most commonly used memory tests; however, research suggests they may be less sensitive to memory decline and have a weaker association with hippocampal volumes than list learning tasks. To examine its utility, we compared story memory to other memory tests on impairment rates and association with hippocampal volumes.
METHOD
Archival records from 1617 older adults (M = 74.41, range = 65-93) who completed the Wechsler Memory Scale - 4 edition (WMS-IV) Logical Memory (LM), Hopkins Verbal Learning Test - Revised (HVLT-R), and Brief Visuospatial Memory Test - Revised (BVMT-R) as part of a clinical neuropsychological evaluation were reviewed. Scores >1.5 below age-adjusted means were considered impaired, and frequency distributions were used to examine impairment rates. A subset of participants ( = 179) had magnetic resonance imaging (MRI) data that underwent image quality assessment. Partial correlations and linear regression analyses, accounting for age, education, and total intracranial volume (TIV), examined associations between memory raw scores and hippocampal volumes.
RESULTS
For delayed recall, nearly half of the sample was impaired on HVLT-R (48.8%) and BVMT-R (46.1%), whereas a little more than a third was impaired on LM (35.7%). Better performance on all three measures was related to larger hippocampal volumes ('s =. 26-.43, < .001). Individually adding memory scores to regression models predicting hippocampal volumes improved the model fit for all measures.
CONCLUSIONS
Despite findings suggesting that story memory is less sensitive to memory dysfunction, it was not differentially associated with hippocampal volumes compared to other memory measures. Results support assessing memory using different formats and modalities in older adults.
Topics: Aged; Hippocampus; Humans; Learning; Magnetic Resonance Imaging; Memory Disorders; Neuropsychological Tests
PubMed: 34187612
DOI: 10.1017/S1355617721000850