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Fulltext Development of clinical pathway for Mild Cognitive Impairment and Dementia to quantify cost of age-related cognitive disorders in Malaysia

Syed Mohamed Aljunid, Namaitijiang Maimaiti, Zafar Ahmed, Amrizal Muhammad Nur, Norashidah Mohamed Nor, Normazwana Ismail, et al.

Malaysian Journal of Public Health Medicine, 2014;14(3):0-0.
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As the Malaysian population ages, the burden of age-related cognitive disorders such as dementia and Alzheimer’s disease will increase concomitantly. This is one of the sub-study under a research project titled by quantify the cost of age-related cognitive impairment in Malaysia, which was undertaken to develop a clinical pathway for Mild Cognitive Impairment (MCI) and Dementia. The clinical pathway (CP) will be used to support the costing studies of MCI and Dementia. An expert group discussion (EGD) was conducted among selected experts from six (6) government hospitals from different states of Malaysia, Ministry of Health, and United Nations University, International Institute for Global Health, UKM and UPM. The expert group includes psychiatrist specialists and public health medicine specialists. A total of 15 participants took part in the EGD. The group was presented with the different approach in managing MCI and Dementia. Finally, the group came to the consensus agreement on the most appropriate and efficient ways of managing the two conditions. In the EGD, an operational definition for MCI and Dementia was agreed upon and a pathway was developed for the usual practice in the Malaysian health system. A typical case used, as a reference is a 60-year-old patient referred to a memory clinic with complaint of “forgetfulness”. After three outpatient visits in the clinic, the diagnosis of MCI and Dementia could be clinically established. The clinical pathways covered all active clinical and non-clinical management of the patient over a period of one year. The experts identified the additional resources required to manage these patients for the whole spectrum of lifetime based on the expected life expectancy. The Clinical pathway (CP) for MCI and Dementia was successfully developed in EGD with strong support from practitioners in the health system. The findings will help the researchers to identify all-important clinical activities and interventions that will be included in the costing study.

Matched MeSH terms: Memory Disorders
Fulltext Working Memory From the Psychological and Neurosciences Perspectives: A Review

Chai WJ, Abd Hamid AI, Abdullah JM

Front Psychol, 2018;9:401.
PMID: 29636715 DOI: 10.3389/fpsyg.2018.00401

Since the concept of working memory was introduced over 50 years ago, different schools of thought have offered different definitions for working memory based on the various cognitive domains that it encompasses. The general consensus regarding working memory supports the idea that working memory is extensively involved in goal-directed behaviors in which information must be retained and manipulated to ensure successful task execution. Before the emergence of other competing models, the concept of working memory was described by the multicomponent working memory model proposed by Baddeley and Hitch. In the present article, the authors provide an overview of several working memory-relevant studies in order to harmonize the findings of working memory from the neurosciences and psychological standpoints, especially after citing evidence from past studies of healthy, aging, diseased, and/or lesioned brains. In particular, the theoretical framework behind working memory, in which the related domains that are considered to play a part in different frameworks (such as memory's capacity limit and temporary storage) are presented and discussed. From the neuroscience perspective, it has been established that working memory activates the fronto-parietal brain regions, including the prefrontal, cingulate, and parietal cortices. Recent studies have subsequently implicated the roles of subcortical regions (such as the midbrain and cerebellum) in working memory. Aging also appears to have modulatory effects on working memory; age interactions with emotion, caffeine and hormones appear to affect working memory performances at the neurobiological level. Moreover, working memory deficits are apparent in older individuals, who are susceptible to cognitive deterioration. Another younger population with working memory impairment consists of those with mental, developmental, and/or neurological disorders such as major depressive disorder and others. A less coherent and organized neural pattern has been consistently reported in these disadvantaged groups. Working memory of patients with traumatic brain injury was similarly affected and shown to have unusual neural activity (hyper- or hypoactivation) as a general observation. Decoding the underlying neural mechanisms of working memory helps support the current theoretical understandings concerning working memory, and at the same time provides insights into rehabilitation programs that target working memory impairments from neurophysiological or psychological aspects.

Matched MeSH terms: Memory Disorders
Fulltext Ethanolic Extract of Orthosiphon stamineus Improves Memory in Scopolamine-Induced Amnesia Model

Retinasamy T, Shaikh MF, Kumari Y, Othman I

Front Pharmacol, 2019;10:1216.
PMID: 31736744 DOI: 10.3389/fphar.2019.01216

Alzheimer's disease (AD) is a chronic neurodegenerative brain disease which is characterized by impairment in cognitive functioning. Orthosiphon stamineus (OS) Benth. (Lamiaceae) is a medicinal plant found around Southeast Asia that has been employed as treatments for various diseases. OS extract contains many active compounds that have been shown to possess various pharmacological properties whereby in vitro studies have demonstrated neuroprotective as well as cholinesterase inhibitory effects. This study, therefore aimed at determining whether this Malaysian plant derived flavonoid can reverse scopolamine induced learning and memory dysfunction in the novel object recognition (NOR) test and the elevated plus maze (EPM) test. In the present study, rats were treated once daily with OS 50 mg/kg, 100 mg/kg, 200 mg/kg and donepezil 1 mg/kg via oral dosing and were given intraperitoneal (ip) injection of scopolamine 1 mg/kg daily to induce cognitive deficits. Rats were subjected to behavioral analysis to assess learning and memory functions and hippocampal tissues were extracted for gene expression and immunohistochemistry studies. All the three doses demonstrated improved scopolamine-induced impairment by showing shortened transfer latency as well as the higher inflexion ratio when compared to the negative control group. OS extract also exhibited memory-enhancing activity against chronic scopolamine-induced memory deficits in the long-term memory novel object recognition performance as indicated by an increase in the recognition index. OS extract was observed to have modulated the mRNA expression of CREB1, BDNF, and TRKB genes and pretreatment with OS extract were observed to have increased the immature neurons against hippocampal neurogenesis suppressed by scopolamine, which was confirmed by the DCX-positive stained cells. These research findings suggest that the OS ethanolic extract demonstrated an improving effect on memory and hence could serve as a potential therapeutic target for the treatment of neurodegenerative diseases like AD.

Matched MeSH terms: Memory Disorders
Phyllanthus amarus protects against spatial memory impairment induced by lipopolysaccharide in mice

Alagan A, Jantan I, Kumolosasi E, Azmi N

Bioinformation, 2019;15(8):535-541.
PMID: 31719762 DOI: 10.6026/97320630015535

Phyllanthus amarus Schumach. and Thonn. is a wide spread medicinal herb with various traditional uses. It is well documented for its antioxidant, anti-inflammatory, and hepatoprotective activities. Therefore, it is of interest to evaluate the 80% ethanol extract of Phyllanthus amarus (PA) on spatial memory using the 8-radial arm maze (8-RAM) in mice after induction of neuro inflammation by lipopolysaccharide (LPS) in a 14- and 28-days treatment study. LC-MS/MS was performed to profile the chemical composition in PA extract. Mice were treated orally with 5% v/v tween 20, PA extract (100, 200 and 400 mg/kg), or ibuprofen (IBF 40 mg/kg) for 14 and 28 days. All groups were challenged with LPS (1 mg/kg) via intraperitoneal (i.p.) injection a day prior to the 8-RAM task except for the negative control group which received an i.p. injection of saline. Data obtained were analyzed with one-way ANOVA followed by post hoc Dunnett's test (comparison of all groups against vehicle control). Analysis of LC-MS/MS data revealed the presence of 16 compounds in the PA extract. Administration of PA extract at 200 and 400 mg/kg for 14 and 28 days significantly (*P<0.05) decreased the working and reference memory errors against LPS-induced spatial memory impairment. The observed protective action is possibly due to the putative antineuroinflammatory effects of PA. In conclusion, PA extract possess neuroprotective effects against spatial memory impairment mediated by LPS.

Matched MeSH terms: Memory Disorders
Fulltext Neurological effects of honey: current and future prospects

Mijanur Rahman M, Gan SH, Khalil MI

Evid Based Complement Alternat Med, 2014;2014:958721.
PMID: 24876885 DOI: 10.1155/2014/958721

Honey is the only insect-derived natural product with therapeutic, traditional, spiritual, nutritional, cosmetic, and industrial value. In addition to having excellent nutritional value, honey is a good source of physiologically active natural compounds, such as polyphenols. Unfortunately, there are very few current research projects investigating the nootropic and neuropharmacological effects of honey, and these are still in their early stages. Raw honey possesses nootropic effects, such as memory-enhancing effects, as well as neuropharmacological activities, such as anxiolytic, antinociceptive, anticonvulsant, and antidepressant activities. Research suggests that the polyphenol constituents of honey can quench biological reactive oxygen species and counter oxidative stress while restoring the cellular antioxidant defense system. Honey polyphenols are also directly involved in apoptotic activities while attenuating microglia-induced neuroinflammation. Honey polyphenols are useful in improving memory deficits and can act at the molecular level. Therefore, the ultimate biochemical impact of honey on specific neurodegenerative diseases, apoptosis, necrosis, neuroinflammation, synaptic plasticity, and behavior-modulating neural circuitry should be evaluated with appropriate mechanistic approaches using biochemical and molecular tools.

Matched MeSH terms: Memory Disorders
A standardised Andrographis paniculata Burm. Nees aqueous extract prevents Lipopolysaccharide-induced cognitive deficits through suppression of inflammatory cytokines and oxidative stress mediators

Sani D, Khatab NIO, Kirby BP, Yong A, Hasan S, Basri H, et al.

J Adv Res, 2019 Mar;16:87-97.
PMID: 30899592 DOI: 10.1016/j.jare.2018.11.005

Substantial evidence has shown that most cases of memory impairment are associated with increased neuroinflammation and oxidative stress. In this study, the potential of a standardised Andrographis paniculata aqueous extract (APAE) to reverse neuroinflammation and cognitive impairment induced by lipopolysaccharide (LPS) was examined in vivo. Rats were treated with APAE (50, 100, 200, and 400 mg·kg-1, p.o.) for 7 consecutive days prior to LPS (1 mg·kg-1, i.p.)-induced neuroinflammation and cognitive impairment. Spatial learning and memory were evaluated using the Morris water maze (MWM) test, while neuroinflammation and oxidative stress were assessed through the measurement of specific mediators, namely, tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), IL-1β, superoxide dismutase (SOD), catalase (CAT), antioxidant glutathione (GSH), reactive oxygen species (ROS), and thiobarbituric acid reactive substance (TBARS). Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were also evaluated. LPS caused significant memory deficits in the 2-day MWM protocol, whereas pretreatment with standardised APAE dose-dependently improved performance in the MWM test. APAE treatment also blocked the LPS-induced hippocampal increase in the concentration and expression of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) and production of ROS and TBARS and enhanced the activities of AChE and BChE. Furthermore, APAE enhanced the decrease in the levels and expression of hippocampal antioxidant enzymes (SOD and CAT) following LPS-induced neuroinflammation and cognitive deficit. The findings from these studies suggested that standardised APAE improved memory and had potent neuroprotective effects against LPS-induced neurotoxicity.

Matched MeSH terms: Memory Disorders
Beneficial effects of TQRF and TQ nano- and conventional emulsions on memory deficit, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble Aβ levels in high fat-cholesterol diet-induced rats

Ismail N, Ismail M, Azmi NH, Bakar MFA, Yida Z, Stanslas J, et al.

Chem Biol Interact, 2017 Sep 25;275:61-73.
PMID: 28734741 DOI: 10.1016/j.cbi.2017.07.014

The study determined the effect of thymoquinone rich fraction (TQRF) and thymoquinone (TQ) in the forms of nano- and conventional emulsions on learning and memory, lipid peroxidation, total antioxidant status, antioxidants genes expression and soluble β-amyloid (Aβ) levels in rats fed with a high fat-cholesterol diet (HFCD). The TQRF was extracted from Nigella sativa seeds using a supercritical fluid extraction system and prepared into nanoemulsion, which later named as TQRF nanoemulsion (TQRFNE). Meanwhile, TQ was acquired commercially and prepared into thymoquinone nanoemulsion (TQNE). The TQRF and TQ conventional emulsions (CE), named as TQRFCE and TQCE, respectively were studied for comparison. Statin (simvastatin) and non-statin (probucol) cholesterol-lowering agents, and a mild-to-severe Alzheimer's disease drug (donepezil) were served as control drugs. The Sprague Dawley rats were fed with HFCD for 6 months, and treated with the intervention groups via oral gavage daily for the last 3 months. As a result, HFCD-fed rats exhibited hypercholesterolaemia, accompanied by memory deficit, increment of lipid peroxidation and soluble Aβ levels, decrement of total antioxidant status and down-regulation of antioxidants genes expression levels. TQRFNE demonstrated comparable effects to the other intervention groups and control drugs in serum biomarkers as well as in the learning and memory test. Somehow, TQRFNE was more prominent than those intervention groups and control drugs in brain biomarkers concomitant to gene and protein expression levels. Supplementation of TQRFNE into an HFCD thus could ameliorate memory deficit, lipid peroxidation and soluble Aβ levels as well as improving the total antioxidant status and antioxidants genes expression levels.

Matched MeSH terms: Memory Disorders/drug therapy
Development of the clinical assessment scale in autoimmune encephalitis

Lim JA, Lee ST, Moon J, Jun JS, Kim TJ, Shin YW, et al.

Ann Neurol, 2019 03;85(3):352-358.
PMID: 30675918 DOI: 10.1002/ana.25421

OBJECTIVE: There is no scale for rating the severity of autoimmune encephalitis (AE). In this study, we aimed to develop a novel scale for rating severity in patients with diverse AE syndromes and to verify the reliability and validity of the developed scale.
METHODS: The key items were generated by a panel of experts and selected according to content validity ratios. The developed scale was initially applied to 50 patients with AE (development cohort) to evaluate its acceptability, reproducibility, internal consistency, and construct validity. Then, the scale was applied to another independent cohort (validation cohort, n = 38).
RESULTS: A new scale consisting of 9 items (seizure, memory dysfunction, psychiatric symptoms, consciousness, language problems, dyskinesia/dystonia, gait instability and ataxia, brainstem dysfunction, and weakness) was developed. Each item was assigned a value of up to 3 points. The total score could therefore range from 0 to 27. We named the scale the Clinical Assessment Scale in Autoimmune Encephalitis (CASE). The new scale showed excellent interobserver (intraclass correlation coefficient [ICC] = 0.97) and intraobserver (ICC = 0.96) reliability for total scores, was highly correlated with modified Rankin scale (r = 0.86, p

Matched MeSH terms: Memory Disorders/etiology; Memory Disorders/physiopathology