1.
The Gut Microbiome in Early Life Stress: A Systematic Review.
Agusti, A, Lamers, F, Tamayo, M, Benito-Amat, C, Molina-Mendoza, GV, Penninx, BWJH, Sanz, Y
Nutrients. 2023;15(11)
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Children exposed to early life stress (ELS) show alterations in brain development and are at increased risk of developing mental illness. This study aims to clarify whether ELS influences the gut microbiome and whether this can be a predictor for the development of mental disorders. 13 articles were included in this systemic review. 4 looked at pre-natal stress and 9 at post-natal stress. Prenatal stress (via maternal stress) may be associated with an increase in Proteobacteria phylum and with a lower abundance of Bifidobacterium and lactic acid bacteria. In the postnatal group, greater microbiome diversity was related to lower depression and anxiety. In boys scores for adaptive skills were higher in those with good levels of Bifidobacterium. A positive association was found between EA (early adversity) experiences and gastrointestinal symptoms and anxiety. This review demonstrates links between ELS and gut microbiome changes. Further research will be necessary to draw more robust conclusions.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This systematic review consolidated and discussed existing evidence on the link between early life stress (ELS) and changes to the human microbiome
- Exposure to ELS, prenatal or postnatal during childhood and adolescence, may impact mental and physical health.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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X
B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
A systematic review was conducted to consolidate clinical evidence examining the impact of early life stress (ELS) on the human intestinal microbiome.
Method
Thirteen observational studies were included in the review, sourced from Pubmed, Scopus, Web of Science, and EMBASE. Methodological quality was assessed using the Newcastle-Ottawa Assessment Scale (NOS), with most studies scoring seven or eight out of nine stars.
Study designs varied, including prospective prenatal studies, postnatal longitudinal studies, case-control studies, and cross-sectional studies. Four prenatal studies were prospective in design. The other nine postnatal studies included one longitudinal study, five case-control studies, and three cross-sectional studies. All 13 studies were published between 2015 and 2022. Because study designs and outcome assessments varied, the results were presented in a narrative form. Data was extracted by 2 independent authors.
Results
The primary findings from the review were as follows:
- Four longitudinal stress studies indicated that pregnant mothers experiencing psychological stress, increased cortisol levels, HIV, and lack of social support exhibited a lower abundance of beneficial Bifidobacterium and an increased abundance of Enterobacter genus.
- One postnatal stress longitudinal study (n=260) demonstrated lower depression and anxiety and improved internalising behaviour in patients with high microbiome diversity.
- . One postnatal stress case-control study (n=344) showed changes in the microbiome and an abundance of several bacterial taxa in stressed groups, including genera Prevotella, Bacteroides (Bacteroidetes), Coprococcus, Streptococcus, and Escherichia.
- One cross-sectional study of 128 adults without psychiatric conditions revealed that higher stress correlated with increased levels of Bacteroides, Parabacteroides, Rhodococcus, Methanobrevibacter, and Roseburia at the genus level, as well as lower Phascolarcto bacterium and Firmicutes at the phylum level.
- One large prospective study (n=446) found infants exposed to higher cumulative stress exhibited an increased relative abundance of Proteobacteria groups and lower Bifidobacterium.
Conclusion:
Due to the inconsistency of study designs and their results this review failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both.
Clinical practice applications:
- Early life stress, and alterations in the gut microbiome, have been linked to mental health conditions
- Maternal prenatal stress may be linked to emotional, behavioural, and cognitive outcomes in infants.
Considerations for future research:
- Future research should standardise questionnaires, to ensure consistency and comparability across studies
- Additionally, future studies should consider using standard procedures and specific species and strain resolution shotgun metagenomics sequencing
- Consideration should be given to the influence of environmental variables (diet, physical activity, etc.) and sex in gut microbiome analysis.
Abstract
Exposure to early life stress (ELS), prenatal or postnatal during childhood and adolescence, can significantly impact mental and physical health. The role of the intestinal microbiome in human health, and particularly mental health, is becoming increasingly evident. This systematic review aims to summarize the clinical data evaluating the effect of ELS on the human intestinal microbiome. The systematic review (CRD42022351092) was performed following PRISMA guidelines, with ELS considered as exposure to psychological stressors prenatally and during early life (childhood and adolescence). Thirteen articles met all inclusion criteria, and all studies reviewed found a link between ELS and the gut microbiome in both prenatal and postnatal periods. However, we failed to find consensus microbiome signatures associated with pre- or postnatal stress, or both. The inconsistency of results is likely attributed to various factors such as different experimental designs, ages examined, questionnaires, timing of sample collection and analysis methods, small population sizes, and the type of stressors. Additional studies using similar stressors and validated stress measures, as well as higher-resolution microbiome analytical approaches, are needed to draw definitive conclusions about the links between stress and the human gut microbiome.
2.
Mediterranean diet and structural neuroimaging biomarkers of Alzheimer's and cerebrovascular disease: A systematic review.
Gregory, S, Pullen, H, Ritchie, CW, Shannon, OM, Stevenson, EJ, Muniz-Terrera, G
Experimental gerontology. 2023;172:112065
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Nearly a million people in the UK have Alzheimer's disease, the most common type of dementia. Mediterranean diet (MedDiet) adherence is associated with healthy brain ageing, a reduced stroke risk, and a lower incidence of dementia. Seven studies were included in this review to evaluate the effects of MedDiet on hippocampal volume and white matter hyperintensity volume, predictors of stroke and dementia. This systematic review did not reveal any associations between MedDiet adherence and hippocampal volume. However, there was a significant negative relationship between MedDiet adherence and white matter hyperintensity volume in two of the studies included. It is necessary to conduct more robust studies to investigate the associations between MedDiet adherence and structural brain imaging findings and understand the mechanisms behind dementia and other cerebrovascular diseases. This study could provide healthcare professionals with valuable information about the effects of increased MedDiet adherence on brain health, including its potential to delay neurodegenerative disease progression.
Expert Review
Conflicts of interest:
None
Take Home Message:
Due to inconclusive results on the associations between MedDiet adherence and AD and cerebrovascular related structural neuroimaging findings, specific recommendations for the MedDiet cannot be made on the basis of this study until further research has been completed.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Background:
Changes in hippocampal volume (HV) and white matter intensity volume (WMIV) have been identified as structural neuroimaging biomarkers of neurodegenerative disease such as Alzheimer’s Disease (AD) and Cerebrovascular disease (CVD) respectively. Evidence has shown adherence to the Mediterranean Diet (MedDiet) has been associated with reduced risk for strokes. This review evaluated the MedDiet in relation to HV and WMIV.
Methods:
The review followed PRISMA guidelines and was registered on PROSPERO. Literature searching resulted in seven studies published between 2012 and 2022, which met the inclusion criteria. Six studies analysed cross-sectional data and one analysed longitudinal data. The NIH Quality Assessment Tool for Observational and Cross-Sectional Studies was used to assess risk of bias.
Overall, the studies were rated as low-risk of bias with details of the research question, participant group exposure and outcome variables included. Due to moderate to high heterogeneity in some studies, a meta-analysis was deemed unsuitable and narrative synthesis was conducted to present the results.
Results:
Mean participant age ranged from 53.19 to 80.3 years and volunteers were healthy or had subjective cognitive decline and a few participants had dementia (n=46).
Hippocampal Volume:
Four studies included 20,077 participants and found no significant associations between MedDiet adherence and hippocampal volume. All four studies were cross-sectional from larger cohort studies. To establish causative relationships longitudinal and RCT trials are required.
White Matter Hyperintensity Volumes:
Four studies included 1938 participants. Two studies found a significant negative association between MedDiet and WMHV, demonstrating higher Mediterranean Scores were associated with lower level of WHMV. The other two studies found no significant associations.
Although the review methodology with a piloted search strategy was considered a key strength, the lack of meta-analysis as planned in the a priori protocol, due to minimal eligible studies and high heterogeneity was a limitation as well as the restriction of brain imaging outcomes.
Conclusion:
Overall, these results are inconclusive on the associations between the MedDiet and HV and WMHV, and identify a gap in the knowledge, therefore further research such as RCT’s remains a priority to further understand the impact diet may have on neuroimaging markers of AD and CVD.
Clinical practice applications:
There were no significant associations between MedDiet adherence and HV, which was surprising given the evidence stating adherence to the MedDiet is associated with a lower incidence of dementia and stroke. However all four studies were cross-sectional studies and in order to detect causal associations, longitudinal and RCT’s are needed. Two studies did show a significant association between higher MedDiet adherence and lower WMHV, whereas two studies reported no significant associations.
Caution needs to be taken when recommending the MedDiet specifically for a reduction in HV and WMHV until further research has been undertaken.
Considerations for future research:
Future research should consider:
- larger cohorts and participants from the Mediterranean region where lifelong adherence to the MedDiet is more likely.
- looking at other risk factors to include obesity, lack of activity, poor sleep quality and stress.
- evaluating different socio-economic status, which has been shown to impact dietary behaviour.
- alternative imaging outcomes such as cortical thinning, PET amyloid and tau.
- . gold standard for methodology in particular dietary analysis and scanning and outcome derivation.
Abstract
Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hyperintensity volume (WMHV). We searched systematically for studies reporting on MedDiet and hippocampal volume or WMHV in MedLine, EMBASE, CINAHL and PsycInfo. Searches were initially carried out on 21st July 2021 with final searches run on 23rd November 2022. Risk of bias was assessed using the NIH Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Of an initial 112 papers identified, seven papers were eligible for inclusion in the review reporting on 21,933 participants. Four studies reported on hippocampal volume, with inconclusive or no associations seen with MedDiet adherence. Two studies found a significant association between higher MedDiet adherence and lower WMHV, while two other studies found no significant associations. Overall these results highlight a gap in our knowledge about the associations between the MedDiet and AD and cerebrovascular related structural neuroimaging findings.
3.
The effects of time-restricted eating on sleep, cognitive decline, and Alzheimer's disease.
Ezzati, A, Pak, VM
Experimental gerontology. 2023;171:112033
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The ageing population is expected to double, with one in four people being over 65 years in Western countries by 2050. As a consequence, the presentation of age-related disorders like Alzheimer's disease (AD) and mild cognitive impairment (MCI) is likely to increase. MCI, a pre-stage of dementia, is considered reversible. However, there are no known cures for AD so far. Hence interventions such as lifestyle modifications that can delay the onset and progression of the disease are of great interest. Previous research demonstrated that calorie restriction (CR) and time-restricted eating (TRE) have beneficial effects on brain function. The authors of this article sought to summarize the current evidence of such eating patterns, as well as their underlying mechanisms and potential benefits concerning MCI and AD. The review also looked at sleep - as sleep disturbances are a risk factor and are associated with both conditions - and the effects of sleep on cognitive decline and neuroinflammatory markers. TRE presents itself as a promising intervention as it can restore the integrity of the blood-brain barrier and support healthy brain function whilst reducing oxidative stress and inflammation. Furthermore, it can be leveraged for weight and glucose management. Preliminary results also indicate a positive impact on sleep, with adequate sleep benefiting cognitive health. As this is a relatively new field, there is still much more to be understood about the underlying mechanisms, with the optimal time window for fasting needing to be determined. The authors advocate for more research on how TRE and sleep relates to neurodegenerative disease.
Expert Review
Conflicts of interest:
None
Take Home Message:
- To highlight the potential benefits of time-restricted eating (TRE) as a potential preventative approach to delay the onset and progression of neurodegenerative disease such as AD
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
- The authors highlight Alzheimer's disease (AD) is the most prevalent neurodegenerative disease affecting over 50 million aging people worldwide. While no cure is known for AD, this review proposes lifestyle interventions such as time-restricted eating (TRE) as a potential approach to delay the onset and progression of a neurodegenerative disease and could hint at autophagic mechanisms
- TRE involves strategically limiting the eating window to 8- to 12-h with fasting—drinking only water and calorie-free coffee/tea—for 12 to 16 h within a 24-h cycle.
Objectives
- To investigate the effects of TRE on sleep and cognitive decline in healthy individuals
Results
- Nine RCTs with varied length between one and sixteen weeks were examined
- A 5-week randomised controlled trial (RCT) showed no significant change in sleep quality between early TRE (fasting between 6 a.m.–3 p.m.), mid-day TRE (11 a.m.–8 p. m.) and control (ad lib intake) in 82 healthy subjects without obesity but the sleep quality improvement was greater in early TRE group (PSQI:Δ=−1.08±1.78vs.Δ=−0.22±2.19andΔ=−0.36±1.73, respectively).
- Sleep quality using the myCircadianClock app reported significant improvement in sleep quality (23 %) following a 12-week single arm intervention of 10-h TRE.
- Following a 16-week TRE intervention sleep duration was reported to be improved from a subjective score of 6 at base line to 8 after 36 weeks in eight overweight and obese subjects; however, the study used a subjective self-assessment survey for measuring sleep duration.
- The Pittsburgh Sleep Quality Index (PSQI) was carried out to assess sleep quality and disturbances in six trials but no trial reported significant improvement in sleep quality using the PSQI survey with TRE
Conclusion
- Authors highlight TRE as promising for its potential to reduce the markers of aging and neurodegenerative disease.
Clinical practice applications:
- To inform practitioners of the potential benefits of TRE that involves limiting the eating window to 8- to 12-h with fasting—drinking only water and calorie-free coffee/tea—for 12 to 16 h within a 24-h cycle.
- TRE may improve regulation of circadian rhythm and autophagy through aligning food intake with circadian rhythm, which coordinates metabolism and physiological functions including glucose, insulin sensitivity, lipid levels, energy expenditure, inflammation, sleep and cognitive function.
- TRE activates a metabolic switch which occurs 12–36 h after fasting is initiated and free fatty acids are released into the blood.
- TRE improved sleep quality and sleep duration, where a longer fasting period in TRE approach (≥12 h fasting) was associated with significantly higher sleep duration.
Considerations for future research:
- The potential benefits of TRE in neurodegenerative diseases such as AD should be further investigated clinically.
- The optimal time to initiate fasting needs to be identified in future trials.
- The potential benefits of TRE in neurodegenerative diseases such as AD in the context of sleep should be further investigated.
Abstract
According to the United Nations, by 2050, one in six individuals will be over age 65 globally, and one in four people would be aged 65 and older in western countries. The unprecedented growth of the aging population is associated with increased age-related disorders like Alzheimer's disease (AD) and Mild cognitive impairment (MCI). To date, no cure is known for AD, thus lifestyle interventions including calorie restriction (CR) and time-restricted eating (TRE) are proposed as potential approach to delay the onset and progression of the disease. Sleep disturbances are common in people with MCI and AD. Moreover, accumulating data indicates that pro-inflammatory cytokines including tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, IL-8 and IL-10 increase in individuals with AD and MCI versus healthy subjects. Thus, the purpose of the present review is to describe the potential effects of TRE on sleep, cognition decline, and neuroinflammatory markers in humans. Preliminary evidence suggests that TRE may produce neuroprotective effects on cognition and reduce neuroinflammatory markers related to AD in humans. To date, no studies investigated the effects of TRE on sleep disturbances and patients with AD. Thereby, the impact of TRE on cognition in individuals with cognitive decline and AD needs to be investigated further in randomized controlled trials (RCTs).
4.
Role of Ketogenic Diets in Neurodegenerative Diseases (Alzheimer's Disease and Parkinson's Disease).
Włodarek, D
Nutrients. 2019;11(1)
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The ketogenic diet (KD) is characterised by a low-carbohydrate, high-fat content that induces a fasting-like state in the body. The KD has been used clinically for children with epilepsy and recent studies have shed light on potential neuro-protective effects. The aim of this systematic review was to evaluate the role of the KD in prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Among the existing literature, there is very limited data on long-term application of the KD in patients with neurodegenerative disease. The research using animal models or in-vitro models look very promising however the use of KD in elderly adults with neurodegenerative disease is very complex. Based on these results, the authors conclude there is a need for further research to evaluate the suitability of KD for patients with AD or PD.
Expert Review
Conflicts of interest:
None
Take Home Message:
- The studies into the effectiveness of ketogenic diets in neurodegenerative diseases tend to be too small and heterogeneous to draw firm conclusions.
- Specific elements of ketogenic diets may be useful for individual cases, however healthcare practitioners are encouraged to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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X
C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
The role of ketogenic diets for the management of a number of conditions has become a discussion subject, not only for scientists and clinicians, but also for the general public, however the evidence of their effectiveness in neurodegenerative diseases is patchy. Studies are either too small to be good enough to draw conclusions from, or the interventions are too mixed / heterogeneous to be able to attribute any potential benefit to the ketogenic dietary component alone. This highlights the need to take an individualised approach to the clinical management of neurodegenerative conditions, drawing from different approaches that suit the individual living with the disease.
Clinical practice applications:
Specific elements of ketogenic diets might be useful for individual cases. However clinicians should be encouraged to draw from a wide array of approaches and not be limited to one single method when it comes to dealing with complex conditions such as Alzheimer's and Parkinson's Disease. Patient-centred care where dietary recommendations revolve around the individual's needs - based on biochemical markers but also on subjective experience of their own quality of life / wellbeing - should be the basis upon which to tailor nutrition programmes that support those living with neurodegenerative conditions.
Considerations for future research:
Good methodological quality studies with placebo / control groups and clear outcomes are needed in order to contribute to the evidence base of the potential role of ketogenic diets in the support of patients living with neurodegenerative conditions.
Abstract
The goal of this review was to assess the effectiveness of ketogenic diets on the therapy of neurodegenerative diseases. The ketogenic diet is a low-carbohydrate and fat-rich diet. Its implementation has a fasting-like effect, which brings the body into a state of ketosis. The ketogenic diet has, for almost 100 years, been used in the therapy of drug-resistant epilepsy, but current studies indicate possible neuroprotective effects. Thus far, only a few studies have evaluated the role of the ketogenic diet in the prevention of Parkinson's disease (PD) and Alzheimer's disease (AD). Single studies with human participants have demonstrated a reduction of disease symptoms after application. The application of the ketogenic diet to elderly people, however, raises certain concerns. Persons with neurodegenerative diseases are at risk of malnutrition, while food intake reduction is associated with disease symptoms. In turn, the ketogenic diet leads to a reduced appetite; it is not attractive from an organoleptic point of view, and may be accompanied by side effects of the gastrointestinal system. All this may lead to further lowering of consumed food portions by elderly persons with neurodegenerative diseases and, in consequence, to further reduction in the supply of nutrients provided by the diet. Neither data on the long-term application of the ketogenic diet in patients with neurodegenerative disease or data on its effects on disease symptoms are available. Further research is needed to evaluate the suitability of the ketogenic diet in the therapy of AD- or PD-affected persons.