OBJECTIVE: This systematic review aimed to assess, in middle- and older-aged people, the relationship between dietary sodium intake and cognitive outcomes including cognitive function, risk of cognitive decline, or dementia.
METHODS: Six databases (PubMed, EMBASE, CINAHL, Psych info, Web of Science, and Cochrane Library) were searched from inception to 1 March 2020. Data extraction included information on study design, population characteristics, sodium reduction strategy (trials) or assessment of dietary sodium intake (observational studies), measurement of cognitive function or dementia, and summary of main results. Risk-of-bias assessments were performed using the National Heart, Lung, and Blood Institute (NHLBI) assessment tool.
RESULTS: Fifteen studies met the inclusion criteria including one clinical trial, six cohorts, and eight cross-sectional studies. Studies reported mixed associations between sodium levels and cognition. Results from the only clinical trial showed that a lower sodium intake was associated with improved cognition over six months. In analysis restricted to only high-quality studies, three out of four studies found that higher sodium intake was associated with impaired cognitive function.
CONCLUSION: There is some evidence that high salt intake is associated with poor cognition. However, findings are mixed, likely due to poor methodological quality, and heterogeneous dietary, analytical, and cognitive assessment methods and design of the studies. Reduced sodium intake may be a potential target for intervention. High quality prospective studies and clinical trials are needed.
METHOD: A total of 36 Malaysian community-dwelling older adults with MCI (60-75-year-old) were randomized into Biokesum® (n = 18) and placebo group (n = 18). Each subject consumed one capsule of Biokesum® (250 mg/capsule) or placebo (maltodextrin, 280 mg/capsule) twice daily for 6 months. Cognitive function and mood were assessed at baseline, 3rd, and 6th-month using neuropsychological tests (MMSE, Digit Span, RAVLT, Digit Symbol, and Visual Reproduction) and Profile of Mood State (POMS) questionnaire. Blood lipid profile, fasting blood glucose, and biomarkers (MDA, LPO, COX-2, iNOS, and BDNF) were measured at baseline and 6th month. By the end of the intervention, there were 30 compliers (Biokesum®: N = 15; Placebo: N = 15) and 6 dropouts. For brain activation assessment, 15 subsamples (Biokesum®: N = 8; Placebo: N = 7) completed N-back and Stroop tasks during fMRI scanning at baseline and 6th month. The dorsolateral prefrontal cortex (Brodmann's area 9 and 46) was identified as a region of interest (ROI) for brain activation analysis using SPM software.
RESULTS: Two-way mixed ANOVA analysis showed significant improvements in Visual Reproduction II (p = 0.012, partial η2 = 0.470), tension (p = 0.042, partial η2 = 0.147), anger (p = 0.010, partial η2 = 0.207), confusion (p = 0.041, partial η2 = 0.148), total negative subscales (p = 0.043, partial η2 = 0.145), BDNF (p = 0.020, partial η2 = 0.179) and triglyceride (p = 0.029, partial η2 = 0.237) following 6 months of Biokesum® supplementation. Preliminary finding also demonstrated significant improvement at 0-back task-induced right DLPFC activation (p = 0.028, partial η2 = 0.652) among subsamples in Biokesum® group. No adverse events were reported at the end of the study.
CONCLUSION: Six months Biokesum® supplementation potentially improved visual memory, negative mood, BDNF, and triglyceride levels among older adults with MCI. Significant findings on brain activation at the right DPLFC must be considered as preliminary.
TRIAL REGISTRATION: Retrospectively registered on 30th August 2019 [ ISRC TN12417552 ].
METHODS: This study included 302 ambulating Malaysian institutionalised older adults. Frailty was identified using Fried's frailty criteria. Cognitive status was assessed using the Mini Mental State Examination and Addenbrooke's Cognitive Examination. Functional fitness was assessed using the Senior Fitness test. The association between frailty groups, cognitive status and functional fitness was analysed using binary logistic regression.
RESULTS: Prevalence of frailty, prefrailty and robustness in the older adults was 56.6%, 40.7% and 2.9%, respectively. Frailty was found to be associated with hypertension (OR 2.15, 95% CI: 1.11-4.16, p = 0.024), lower cognitive status (Addenbrooke's Cognitive Examination) (OR 0.98, 95% C.I: 0.96-0.99, p = 0.038), and lower dynamic balance and mobility (Timed Up and Go test) (OR 1.09, 95% CI: 1.01-1.16, p = 0.024).
CONCLUSION: Frailty is highly prevalent among Malaysian institutionalised older adults. Hypertension, cognitive impairment and lower dynamic balance and mobility were found to be risk factors of frailty. Screening of frailty and its associated factors should be prioritized among institutionalised older adults in view of early prevention and rehabilitation.
METHODS: Two hundred subjects (104 patients, 96 controls) underwent extensive clinical phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. Fecal metabolomics were performed using two platforms, nuclear magnetic resonance (NMR) spectroscopy and liquid chromatography-mass spectrometry.
RESULTS: Fecal microbiome and metabolome composition in PD was significantly different from controls, with the largest effect size seen in NMR-based metabolome. Microbiome and NMR-based metabolome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant fecal metabolite features and predicted functional changes in PD versus controls included bioactive molecules with putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, and salicylate) and other compounds increasingly implicated in neurodegeneration (eg, ceramides, sphingosine, and trimethylamine N-oxide). In the PD group, cognitive impairment, low body mass index (BMI), frailty, constipation, and low physical activity were associated with fecal metabolome compositional differences. Notably, low SCFAs in PD were significantly associated with poorer cognition and low BMI. Lower butyrate levels correlated with worse postural instability-gait disorder scores.
INTERPRETATION: Gut microbial function is altered in PD, characterized by differentially abundant metabolic features that provide important biological insights into gut-brain pathophysiology. Their clinical relevance further supports a role for microbial metabolites as potential targets for the development of new biomarkers and therapies in PD. ANN NEUROL 2021;89:546-559.
THE AIM OF THE STUDY: To investigate the effects of the chronic (28 days) oral administration of CT root extract on CCH-induced cognitive impairment, neuronal damage and cholinergic deficit, and its toxicity profile in the CCH rat model.
MATERIALS AND METHODS: The permanent bilateral occlusion of common carotid arteries (PBOCCA) surgery method was employed to develop a CCH model in male Sprague Dawley (SD) rats. Then, these rats were given oral administration of CT root extract at doses of 100, 200, and 300 mg/kg, respectively for 28 days and subjected to behavioural tests. At the end of the experiment, the brain was harvested for histological analysis and cholinesterase activities. Then, blood samples were collected and organs such as liver, kidney, lung, heart, and spleen were procured for toxicity assessment.
RESULTS: Chronic treatment of CT root extract at doses of 200 and 300 mg/kg, restored memory impairments induced by CCH. CT root extract was also found to diminish CCH-induced neuronal damage in the CA1 region of the hippocampus. High dose (300 mg/kg) of the CT root extract was significantly inhibited the increased acetylcholinesterase (AChE) activity in the frontal cortex and hippocampus of the PBOCCA rats. In toxicity study, repeated doses of CT root extract were found to be safe in PBOCCA rats after 28 days of treatment.
CONCLUSIONS: Our findings provided scientific evidence supporting the therapeutic potential of CT root extract in the treatment of vascular dementia (VaD)-related cholinergic abnormalities and subsequent cognitive decline.
METHOD: Electronic literature search on PubMed was conducted using the following keywords: methylphenidate, cancer, carcinoma, oncology, oncological and tumour. We identified forty two relevant studies and publications on the use of methylphenidate in cancer patients to be included in this review.
RESULTS: Methylphenidate was found to have some evidence in reducing opioid-induced sedation, improving cognitive symptoms and reduction of fatigue in cancer patients. Nevertheless, the results were inconsistent due to variations in the study populations, study design and outcome measures, among others. There was minimal evidence on its use in treating depression. Otherwise, methylphenidate was generally well-tolerated by patients.
CONCLUSION: This review potentially supports the use of methylphenidate for opioid-induced sedation, cognitive decline and fatigue in cancer patients. Further placebo-controlled trials would help in strengthening the evidence for this treatment.
PATIENTS AND METHODS: The available data related to cognitive frailty among a sub-sample of older adults aged 60 years and above (n=815) from two states in Malaysia were analysed. In the LRGS-TUA study, a comprehensive interview-based questionnaire was administered to obtain the socio-demographic information of the participants, followed by assessments to examine the cognitive function, functional status, dietary intake, lifestyle, psychosocial status and biomarkers associated with cognitive frailty. The factors associated with cognitive frailty were assessed using a bivariate logistic regression (BLR).
RESULTS: The majority of the older adults were categorized as robust (68.4%), followed by cognitively pre-frail (37.4%) and cognitively frail (2.2%). The data on the cognitively frail and pre-frail groups were combined for comparison with the robust group. A hierarchical BLR indicated that advancing age (OR=1.04, 95% CI:1.01-1.08, p<0.05) and depression (OR=1.49, 95% CI:1.34-1.65, p<0.001) scored lower on the Activity of Daily Living (ADL) scale (OR=0.98, 95% CI:0.96-0.99, p<0.05), while low social support (OR=0.98, 95% CI:0.97-0.99, p<0.05) and low niacin intake (OR=0.94, 95% CI:0.89-0.99, p<0.05) were found to be significant factors for cognitive frailty. Higher oxidative stress (MDA) and lower telomerase activity were also associated with cognitive frailty (p<0.05).
CONCLUSION: Older age, a lower niacin intake, lack of social support, depression and lower functional status were identified as significant factors associated with cognitive frailty among older Malaysian adults. MDA and telomerase activity can be used as potential biomarkers for the identification of cognitive frailty.
METHODS: We propose a Bayesian joint modelling approach to determine mortality due to cognitive impairment via repeated measures of 3MS scores trajectories over a 21-year follow-up period. Data for this study are taken from the Osteoporotic Fracture longitudinal study among women aged 65+ which started in 1986-88.
RESULTS: The standard relative risk model from the analyses with a baseline 3MS score after adjusting for all the significant covariates demonstrates that, every unit decrease in a 3MS score corresponds to a non-significant 1.059 increase risk of mortality with a 95% CI of (0.981, 1.143), while the extended model results in a significant 0.09% increased risk in mortality. The joint modelling approach found a strong association between the 3MS scores and the risk of mortality, such that, every unit decrease in 3MS scores results in a 1.135 (13%) increased risk of death via cognitive impairment with a 95% CI of (1.056, 1.215).
CONCLUSION: It has been demonstrated that a decrease in 3MS results has a significant increase risk of mortality due to cognitive impairment via joint modelling, but insignificant when considered under the standard relative risk approach.
METHODS: The study included 2322 community-dwelling older adults in Malaysia who were randomly selected through a multistage proportional cluster random sampling technique. Global cognition construct was measured by the Mini-Mental State Examination and Montreal Cognitive Assessment; psychosocial stress construct was measured by perceived stress, depression, loneliness, and neuroticism; and processing speed was assessed by the Digit Symbol Substitution Test. Structural equation modelling was used to analyze the mediation and moderation tests.
RESULTS: Processing speed was found to partially mediate the relationship between psychosocial stress and global cognition (β in the direct model = -0.15, P
METHOD: Cognitive decline was determined by Montreal Cognitive Assessment (MoCA). Oxidative stress markers (malondialdehyde-MDA and superoxide dismutase-SOD) were determined and DNA damage was assayed using Alkaline Comet Assay. Toenail samples were taken and analyzed using ICP-MS to determine trace element levels.
RESULTS: A total of 62.1 % of subjects had cognitive impairment. Subjects with cognitive impairment had significantly higher levels of MDA and DNA damage as compared to the group with normal cognitive function; MDA (2.07 ± 0.05 nmol/L vs 1.85 ± 0.06 nmol/L) (p<0.05) and DNA damage (% Tail Density, 14.52 ± 0.32 vs 10.31 ± 0.42; Tail Moment, 1.79 ± 0.06 vs 1.28 ± 0.06) (p<0.05 for all parameters). However, the level of SOD among subjects with cognitive impairment (6.67 ± 0.33 u.e/min/mg protein) was lower than the level among those with normal cognitive functions (11.36 ± 0.65 u.e/min/mg protein) (p<0.05). Multiple logistic regression revealed the predictors for cognitive impairment among the subjects were DNA damage (Adjusted odd ratio [OR], 1.37; 95% confidence interval [CI], 1.18-1.59), level of trace elements in toenails namely, lead (OR, 2.471; CI, 1.535-3.980) and copper (OR, 1.275; CI, 1.047-1.552) (p<0.05).
CONCLUSION: High levels of lead and copper can lead to increase in oxidative stress levels and are associated with DNA damage that eventually could be associated with cognitive decline.