The Latest Articles on Aging, Diet, and Cognitive Health
Our staff editors continue to share exciting, interesting, and thought-provoking reading material in the recommended articles series.
This week, we would like to share several latest articles on Aging, Diet, and Cognitive Health.
Title: Existing and future strategies to manipulate the gut microbiota with diet as a potential adjuvant treatment for psychiatric disorders.
Authors: Fiona Catherine Ross, Dylan E. Mayer, Arpana Gupta, Chris Ian Richard Gill, Daniele Del Rio, John Francis Cryan, Aonghus Lavelle, Reynolds Paul Ross, Catherine Stanton, Emeran Anton Mayer
Type: Review
Abstract:
Nutrition and diet quality play key roles in preventing and slowing cognitive decline and have been linked to multiple brain disorders. This review compiles available evidence from preclinical studies and clinical trials on the impact of nutrition and interventions regarding major psychiatric conditions and some neurological disorders. We emphasize the potential role of diet-related microbiome alterations in these effects and highlight commonalities between various brain disorders related to the microbiome. Despite numerous studies shedding light on these findings, there are still gaps in our understanding due to the limited availability of definitive human trial data firmly establishing a causal link between a specific diet and microbially mediated brain functions and symptoms. The positive impact of certain diets on the microbiome and cognitive function is frequently ascribed with the anti-inflammatory effects of certain microbial metabolites or a reduction of proinflammatory microbial products. We also critically review recent research on pro- and prebiotics and non-dietary interventions, particularly fecal microbial transplants. The recent focus on diet in relation to brain disorders could lead to improved treatment outcomes with combined dietary, pharmacological, and behavioral interventions.
Access this article: https://doi.org/10.1016/j.biopsych.2023.10.018
Title: Ketogenic therapies in Parkinson's disease, Alzheimer's disease, and mild cognitive impairment: An integrative review
Authors: Susan Price MSN, RN, FNP-BC, Todd M. Ruppar PhD, RN, FAAN
Type: Research Article
Abstract:
Background
Ketogenic therapies have shown benefit for seizure reduction in epilepsy but their impact on other neurologic conditions is less known. In this literature review, the efficacy of ketogenic therapies were assessed in Parkinson's disease (PD), Alzheimer's disease (AD), and mild cognitive impairment (MCI).
Methods
A literature search was conducted using PubMed, Scopus, and Google Scholar focusing on ketogenic therapies in PD, AD, and MCI.
Results
A total of 2565 records were identified with a total of 15 studies (3 for PD and 12 for MCI/AD) meeting criteria for analysis. The ketogenic diet was used in all the PD studies and did show significant improvement in motor function either through vocal quality, gait, freezing, tremor, and/or balance. A variety of ketogenic therapies were utilized in the MCI and AD groups including a ketogenic diet, low-carbohydrate diet, modified Adkins diet, Mediterranean diet with coconut oil supplementation, a ketogenic diet with a ketogenic medium chain triglyceride (kMCT) supplement, as well as ketogenic supplements including a ketogenic drink with kMCT, oral ketogenic compounds (Axona and AC-1202), and MCT oil or emulsion. The ketogenic diet independently showed a non-significant trend towards improvement in cognition. The Mediterranean diet, modified Adkins diet, and low-carbohydrate diet showed statistically significant improvements in some, although not all, of their cognitive measures. Use of ketogenic supplements, drinks, or compounds showed variable results in the AD and MCI groups. The Axona and AC-1202 compounds showed no significant improvement in cognition at the end of their respective 90-day trials. Most MCT supplements did show cognitive improvements, although only after 6 months of adherence. Adherence to the intervention was problematic in most of the diet studies.
Conclusion
Ketogenic therapies have promise in PD, AD, and MCI for symptom improvement although larger studies are needed to support their implementation in clinical practice.
Access this article: https://doi.org/10.1016/j.apnr.2023.151745
Title: High-fat diet induces cognitive impairment through repression of SIRT1/AMPK-mediated autophagy
Authors: Wenmin Yi, Fei Chen, Minghao Yuan, Chuanling Wang, Shengyuan Wang, Jie Wen, Qian Zou, Yinshuang Pu, Zhiyou Cai
Type: Research Article
Abstract:
Aims: Recent evidence suggests an association between a high-fat diet (HFD) and cognitive decline. HFD may reduce synaptic plasticity and cause tau hyperphosphorylation, but the mechanisms involved remain unclear. The purpose of this study was to explore whether Sirtuin1 (SIRT1)/AMP-activated protein kinase (AMPK) pathway was involved in this pathogenic effect in the HFD exposed mice.
Methods: C57BL/6 mice at 12 months of age were fed a standard (9% kcal fat) or high-fat (60% kcal fat) diet for 22 weeks, and Neuro-2a (N2a) cells were treated with normal culture medium or a palmitic acid (PA) medium (100uM) for 40 h. After that, cognitive function was tested by Morris water maze (MWM). The levels of proteins involved in SIRT1/AMPK pathway and autophagy were measured using western blotting and immunofluorescence. We also assessed the phosphorylation of tau protein and synapse.
Results: The mice presented impaired learning and memory abilities. We further found decreased levels of synaptophysin (Syn) and brain-derived neurotrophic factor (BDNF), increased tau46 and phosphorylated tau protein, and damaged neurons in mice after HFD or in N2a cells treated with PA medium. Moreover, HFD can also reduce the expression of SIRT1, inhibit AMPK phosphorylation, and block autophagic flow in both mice and cells. After treating the cells with the SIRT1 agonist SRT1720, SIRT1/AMPK pathway and autophagy-related proteins were partially reversed and the number of PA-induced positive cells was alleviated in senescence-associated β-galactosidase (SA-β-gal) staining.
Conclusions: HFD may inhibit the expression of SIRT1/AMPK pathway and disrupt autophagy flux, and result in tau hyperphosphorylation and synaptic dysfunction during aging, which ultimately lead to cognitive decline.
Access this article: https://doi.org/10.1016/j.expneurol.2023.114591
Title: Time-restricted feeding and Alzheimer’s disease: you are when you eat
Authors: Melvin W. King, Yining Chen, Erik S. Musiek
Type: Mini review
Abstract:
Time-restricted feeding (TRF) has emerged as a means of synchronizing circadian rhythms, which are commonly disrupted in Alzheimer’s disease (AD). Whittaker et al. demonstrate that TRF exerts protective effects in two mouse models of AD. We discuss the effects of TRF on brain health and mechanisms linking TRF to neurodegeneration.
Access this article: https://doi.org/10.1016/j.molmed.2023.10.004
Title: Taste receptor type 1 member 3 mediates diet-induced cognitive impairment in mice
Authors: Keon-Hee Lee, Jae Won Song, Chong-Su Kim, Hobin Seong, Dong-Mi Shin, Woo-Jeong Shon
Type: Research Article
Abstract:
Aims
Long-term consumption of a western diet (WD), which is characterized by high intake of saturated fats and sugary drinks, causes cognitive impairment. However, the molecular mechanism by which WD induces cognitive impairment remains unclear. Taste receptor type 1 member 3 (TAS1R3), activated by ligands of WD, is expressed in extra-oral tissues, including the brain, and particularly in the hippocampus. This study investigated whether TAS1R3 regulates WD-induced cognitive impairment in mice.
Main methods
Male C57BL/6J wild-type (WT) and Tas1r3 knock-out (KO) mice were fed either a normal diet (ND) or WD for 18 weeks. Cognitive functions were assessed using novel object recognition and Barnes maze tests. The mechanisms underlying WD-induced cognitive impairment were assessed using RNA-sequencing and bioinformatics analysis.
Key findings
Cognitive impairment was observed in WT mice fed WD (WT–WD) compared with WT–ND mice. Conversely, mice lacking TAS1R3 were not cognitively impaired even under long-term WD feeding. Hippocampal transcriptome analysis revealed upregulated AMP-activated protein kinase (AMPK) signaling and increased AMPK-targeted sirtuin 3 expression in KO–WD mice. Pathway enrichment analysis showed that response to oxidative stress was downregulated, whereas neurogenesis was upregulated in dentate gyrus of KO–WD mice. In vitro studies validated the findings, indicating that Tas1r3 knockdown directly upregulated decreased sirtuin 3 expression, its downstream genes-related to oxidative stress, and apoptosis induced by WD condition in hippocampal neuron cells.
Significance
TAS1R3 acts as a critical mediator of WD-induced cognitive impairment in mice, thereby offering potential as a novel therapeutic target to prevent WD-induced cognitive impairment.
Access this article: https://doi.org/10.1016/j.lfs.2023.122194
