The Effects of Medium Chain Triglyceride for Alzheimer's Disease Related Cognitive Impairment: A Systematic Review and Meta-Analysis.

BACKGROUND: The current lack of effective drug therapies for Alzheimer's disease (AD) has prompted researchers to seek alternative nutritional therapies, such as medium chain triglycerides (MCTs). However, results are inconclusive. OBJECTIVE: This systematic review and meta-analysis aims to summarize current evidence on the effect of MCT on cognitive function in patients with mild cognitive impairment (MCI) or AD. METHODS: A systematic search was conducted up until December 16, 2022, to identify human interventions reporting the effects of MCT on cognitive functioning of MCI or AD patients. 995 non-duplicated publications were identified, of which nine (n = 10 studies) met the inclusion criteria. RESULTS: Meta-analysis showed cognitive improvements in general (SMD = 0.64; 95% CI [0.05, 1.24]), but not in memory, language, and attention domains after oral MCT administration, compared to placebo. The effect of MCT was greater among APOEɛ4 (-) subjects than APOEɛ4 (+) subjects (SMD = 1.87; 95% CI [0.35, 3.40]). CONCLUSION: This review provides some evidence that treatment with MCT could improve general cognitive function in APOEɛ4 (-) cognitive impaired patients. Better characterized clinical studies are warranted before making a definitive conclusion on the use of MCT for MCI and AD management.

Targeting the inflammasome in Parkinson's disease.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases in which neuroinflammation plays pivotal roles. An important mechanism of neuroinflammation is the NLRP3 inflammasome activation that has been implicated in PD pathogenesis. In this perspective, we will discuss the relationship of some key PD-associated proteins including α-synuclein and Parkin and their contribution to inflammasome activation. We will also review promising inhibitors of NLRP3 inflammasome pathway that have potential as novel PD therapeutics. Finally, we will provide a summary of current and potential in vitro and in vivo models that are available for therapeutic discovery and development.

Prevalence, risk and protective factors for mild cognitive impairment in a population-based study of Singaporean elderly.

The prevalence of dementia has been widely reported, and its potential risk and protective factors are well-characterized. However, there is a scarcity of related information regarding mild cognitive impairment (MCI). Thus this population-based study aimed to determine the prevalences of MCI and its subtypes, as well as to identify the risk and protective factors for MCI in the Chinese elderly population of Singapore. Results showed that the overall prevalence of MCI was 12.5%, while the gender-adjusted prevalence of MCI was 12.3%. Gender was found to be significantly associated with the subtypes of MCI, with males more likely to have amnestic MCI and females more likely to have non-amnestic MCI. Older age, lower educational levels, lower social activity levels, depression, hypertension, hyperlipidemia, diabetes and stroke were found to be risk factors for MCI in univariate analysis. However, multivariable analysis showed that only hypertension and stroke were the significant risk factors for MCI. Higher educational levels and active social engagements were significant protective factors for MCI in multivariable analysis. Age and depression had boundary significant associations with the prevalence of MCI. After adjusting for gender, the influence of hypertension, stroke, social engagement, age and depression on MCI remained unchanged, except that education became a boundary significant lower risk factor of MCI development. In conclusion, this study presented the prevalence, risk and protective factors for MCI among Singaporean Chinese older adults, which facilitates the screening of vulnerable groups for MCI.

"Hot cross bun" is a potential imaging marker for the severity of cerebellar ataxia in MSA-C.

To evaluate the correlation between "hot cross bun" sign (HCBs) and disease severity in multiple system atrophy (MSA). We recruited patients with probable and possible MSA with parkinsonism (MSA-P) or the cerebellar ataxia (MSA-C) subtypes. Clinical and imaging characteristics were collected and comparison was performed between MSA-C and MSA-P cases. Spearman test was used to evaluate the correlation between HCBs and other variables. Curve estimate and general linear regression was performed to evaluate the relationship between HCBs and the Scale for Assessment and Rating of Ataxia (SARA). Unified Multiple System Atrophy Rating Scale (UMSARS) IV was used to assess the severity of disease. Multinomial ordered logistic regression was used to confirm the increased likelihood of disability for the disease. Eighty-one MSA with HCBs comprising of 50 MSA-C and 31 MSA-P were recruited. We demonstrated that the severity of HCBs showed a positive linear correlation with SARA scores in MSA-C. Multinomial ordered logistic regression test revealed that the increase in the HCBs grade may be associated with an increased likelihood of disability for the disease severity in MSA, especially in those with cerebellar ataxia subtype. We demonstrated that HCBs is a potential imaging marker for the severity of cerebellar ataxia. The increase in the HCBs grade may be associated with an increased likelihood of disability in MSA-C, but not MSA-P cases, suggesting that it may be a useful imaging indicator for disease progression in Chinese patients with MSA-C.

Multimodal analysis of gene expression from postmortem brains and blood identifies synaptic vesicle trafficking genes to be associated with Parkinson's disease.

OBJECTIVE: We aimed to identify key susceptibility gene targets in multiple datasets generated from postmortem brains and blood of Parkinson's disease (PD) patients and healthy controls (HC). METHODS: We performed a multitiered analysis to integrate the gene expression data using multiple-gene chips from 244 human postmortem tissues. We identified hub node genes in the highly PD-related consensus module by constructing protein-protein interaction (PPI) networks. Next, we validated the top four interacting genes in 238 subjects (90 sporadic PD, 125 HC and 23 Parkinson's Plus Syndrome (PPS)). Utilizing multinomial logistic regression analysis (MLRA) and receiver operating characteristic (ROC), we analyzed the risk factors and diagnostic power for discriminating PD from HC and PPS. RESULTS: We identified 1333 genes that were significantly different between PD and HCs based on seven microarray datasets. The identified MEturquoise module is related to synaptic vesicle trafficking (SVT) dysfunction in PD (P < 0.05), and PPI analysis revealed that SVT genes PPP2CA, SYNJ1, NSF and PPP3CB were the top four hub node genes in MEturquoise (P < 0.001). The levels of these four genes in PD postmortem brains were lower than those in HC brains. We found lower blood levels of PPP2CA, SYNJ1 and NSF in PD compared with HC, and lower SYNJ1 in PD compared with PPS (P < 0.05). SYNJ1, negatively correlated to PD severity, displayed an excellent power to discriminating PD from HC and PPS. CONCLUSIONS: This study highlights that SVT genes, especially SYNJ1, may be promising markers in discriminating PD from HCs and PPS.

Cohort profile: the Diet and Healthy Aging (DaHA) study in Singapore.

How diet is related with cognition and health has not been systematically examined in Asians whose eating habits are very different from their counterparts in the West and the biological mechanisms underlying such links are not well known yet. The diet and healthy aging (DaHA) study is a community-based longitudinal study conducted to examine the role of diet and nutrition in promoting cognitive, emotional, and physical health among community-living elderly Singaporeans. The first wave of DaHA, conducted from 2011 to 2017, provided detailed information on diet and baseline cognitive function and health from 1010 community-living elderly in Singapore. Biomarkers of oxidative stress, systemic inflammation, and genetic information were collected. The ongoing second wave of DaHA is conducted from 2017 to 2020, which provides follow- up assessments using established cognitive tests and clinical tools. This well-characterized cohort, with its archived biological samples and high-quality data on diet and lifestyle factors will allow researchers to explore the relationships among diet, nutrition, genes, cognition, mental and physical health in an extremely cost-effective manner. Translations of the research findings into clinical and public health practices will potentially help to promote cognitive health at the population level and reduce healthcare costs related to cognitive impairment.

New Insights into Immune-Mediated Mechanisms in Parkinson's Disease.

The immune system has been increasingly recognized as a major contributor in the pathogenesis of Parkinson's disease (PD). The double-edged nature of the immune system poses a problem in harnessing immunomodulatory therapies to prevent and slow the progression of this debilitating disease. To tackle this conundrum, understanding the mechanisms underlying immune-mediated neuronal death will aid in the identification of neuroprotective strategies to preserve dopaminergic neurons. Specific innate and adaptive immune mediators may directly or indirectly induce dopaminergic neuronal death. Genetic factors, the gut-brain axis and the recent identification of PD-specific T cells may provide novel mechanistic insights on PD pathogenesis. Future studies to address the gaps in the identification of autoantibodies, variability in immunophenotyping studies and the contribution of gut dysbiosis to PD may eventually provide new therapeutic targets for PD.

Corrigendum: Gut-Brain Axis: Potential Factors Involved in the Pathogenesis of Parkinson's Disease.

[This corrects the article DOI: 10.3389/fneur.2020.00849.].