The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ...ignored to date. In this Perspective, we present a rationale for an urgent need to investigate this possible impact and therapeutic options for COVID-19 based on dietary and microbiome modifications. The mitigating role of nanotechnology with relation to the impact of SARS-CoV-2 virus is highlighted.
The atypical antipsychotic (AAP) class is often associated with metabolic disease, but the mechanistic underpinnings of this risk are not understood. Due to reports linking gut bacteria function to ...metabolic disease, we hypothesize that AAP treatment in adults results in gut dysbiosis potentiating metabolic criteria. This report describes recent findings linking AAP treatment with differences in gut microbiota communities in a human cohort with bipolar disorder (BD).
In a cross-sectional design, we obtained 16S ribosomal sequences from 117 BD patients (49 AAP treated, 68 non-AAP treated). Analysis of molecular variance (AMOVA) was used to detect significant clustering of microbial communities between groups, and the inverse Simpson Diversity Index was used to calculate alpha diversity. Detection of differentially abundant operational taxonomic units (OTUs) between groups was performed using linear discriminant analysis effect size.
The AAP-treated cohort was significantly younger and had an increased body mass index compared with non-AAP-treated patients. Groups did not differ in other psychotropic medication use with the exception of higher use of benzodiazepines in the AAP cohort. We detected significant separation between microbiota communities of AAP-treated and nontreated patients (AMOVA; p=0.04). AAP-treated females showed significant decreased species diversity when compared with non-AAP-treated females (p=0.015). Males showed no significant diversity between treatment groups (p=0.8). Differentially abundant OTUs between treatment groups were OTU1, OTU25, and OTU32 that classified to Lachnospiraceae, Akkermansia, and Sutterella, respectively.
These data suggest that AAP treatment is associated with specific representation of gut bacterial families in AAP-treated patients. In addition, AAP treatment is associated with decreased species richness in female AAP-treated patients.
Background
Poor nutritional status is a risk factor for the development of frailty. Likewise, oral health is independently associated with nutrition. The potential association between oral health and ...frailty in hospitalised elderly adults has, however, not previously been investigated.
Objective
To investigate the relationship between oral health and frailty in hospitalised elderly adults and to identify the predictors of frailty.
Method
A cross‐sectional study of 168 geriatric inpatients >65 years old was performed from August to December 2016. Patients of non‐English speaking background, with impaired cognition (MMSE <24), severe hearing or visual impairment or active delirium were excluded. Oral health, nutrition and frailty were assessed using previously validated tools, namely the Geriatric Oral Health Assessment Index (GOHAI), Mini Nutrition Assessment (MNA) and Reported Edmonton Frailty Scale (REFS). Other data collected included demographics, co‐morbidities, level of education and smoking/alcohol history.
Results
On univariate analysis, the REFS score decreased with better nutritional status/higher MNA (P < 0.001) and better self‐reported oral health/higher GOHAI (P = 0.023). Nutritional status accounted for 17% of variability in frailty assessment. On multivariate analysis, co‐morbidities (P < 0.001), MNA (P < 0.001) and living in residential care (P < 0.001) were independent predictors of frailty. After adjusting for nutrition and co‐morbidities, self‐reported oral health was found to have an independent negative association with frailty (P = 0.019).
Conclusion
Poor self‐reported oral health was found to be independently associated with frailty. Further research should be directed at whether interventions to maintain good oral health can prevent or slow the progression of frailty.
OBJECTIVETo determine the effect of low-dose aspirin vs placebo on incident all-cause dementia, incident Alzheimer disease (AD), mild cognitive impairment (MCI), and cognitive decline in older ...individuals.
METHODSAspirin in Reducing Events in the Elderly (ASPREE) was a double-blind, placebo-controlled trial of low-dose aspirin. In the United States and Australia, community-dwelling individuals aged ≥70 years (US minorities ≥65 years) and free of cardiovascular disease, physical disability, and diagnosed dementia were enrolled. Participants were randomized 1:1–100 mg daily aspirin or placebo. The Modified Mini-Mental State Examination, Hopkins Verbal Learning Test–Revised, Symbol Digit Modalities Test, and Controlled Oral Word Association Test assessed cognition at baseline and over follow-up. Additional cognitive testing was performed in participants with suspected dementia (“trigger”) based on within-study assessments or clinical history. Dementia was adjudicated according to DSM-IV criteria. National Institute on Aging–Alzheimer’s Association criteria were used for AD and MCI subclassification.
RESULTSA total of 19,114 participants were followed over a median 4.7 years and 964 triggered further dementia assessments. There were 575 adjudicated dementia cases, and 41% were classified as clinically probable AD. There was no substantial difference in the risk of all dementia triggers (hazard ratio HR, 1.03; 95% confidence interval CI, 0.91–1.17), probable AD (HR, 0.96; 95% CI, 0.74–1.24), or MCI (HR, 1.12; 95% CI, 0.92–1.37) between aspirin and placebo. Cognitive change over time was similar in the aspirin and placebo groups.
CONCLUSIONSThere was no evidence that aspirin was effective in reducing risk of dementia, MCI, or cognitive decline. Follow-up of these outcomes after initial exposure is ongoing.
CLASSIFICATION OF EVIDENCEThis study provides Class II evidence that for healthy older individuals, low-dose aspirin does not significantly reduce the incidence of dementia, probable AD, MCI, or cognitive decline.
CLINICALTRIALS.GOV IDENTIFIERNCT01038583.
Background
Dementia is a progressive syndrome characterised by deterioration in memory, thinking and behaviour, and by impaired ability to perform daily activities. Two classes of drug ‐ ...cholinesterase inhibitors (donepezil, galantamine and rivastigmine) and memantine ‐ are widely licensed for dementia due to Alzheimer's disease, and rivastigmine is also licensed for Parkinson's disease dementia. These drugs are prescribed to alleviate symptoms and delay disease progression in these and sometimes in other forms of dementia. There are uncertainties about the benefits and adverse effects of these drugs in the long term and in severe dementia, about effects of withdrawal, and about the most appropriate time to discontinue treatment.
Objectives
To evaluate the effects of withdrawal or continuation of cholinesterase inhibitors or memantine, or both, in people with dementia on: cognitive, neuropsychiatric and functional outcomes, rates of institutionalisation, adverse events, dropout from trials, mortality, quality of life and carer‐related outcomes.
Search methods
We searched the Cochrane Dementia and Cognitive Improvement Group’s Specialised Register up to 17 October 2020 using terms appropriate for the retrieval of studies of cholinesterase inhibitors or memantine. The Specialised Register contains records of clinical trials identified from monthly searches of a number of major healthcare databases, numerous trial registries and grey literature sources.
Selection criteria
We included all randomised, controlled clinical trials (RCTs) which compared withdrawal of cholinesterase inhibitors or memantine, or both, with continuation of the same drug or drugs.
Data collection and analysis
Two review authors independently assessed citations and full‐text articles for inclusion, extracted data from included trials and assessed risk of bias using the Cochrane risk of bias tool. Where trials were sufficiently similar, we pooled data for outcomes in the short term (up to 2 months after randomisation), medium term (3‐11 months) and long term (12 months or more). We assessed the overall certainty of the evidence for each outcome using GRADE methods.
Main results
We included six trials investigating cholinesterase inhibitor withdrawal, and one trial investigating withdrawal of either donepezil or memantine. No trials assessed withdrawal of memantine only. Drugs were withdrawn abruptly in five trials and stepwise in two trials. All participants had dementia due to Alzheimer's disease, with severities ranging from mild to very severe, and were taking cholinesterase inhibitors without known adverse effects at baseline. The included trials randomised 759 participants to treatment groups relevant to this review. Study duration ranged from 6 weeks to 12 months. There were too few included studies to allow planned subgroup analyses. We considered some studies to be at unclear or high risk of selection, performance, detection, attrition or reporting bias.
Compared to continuing cholinesterase inhibitors, discontinuing treatment may be associated with worse cognitive function in the short term (standardised mean difference (SMD) ‐0.42, 95% confidence interval (CI) ‐0.64 to ‐0.21; 4 studies; low certainty), but the effect in the medium term is very uncertain (SMD ‐0.40, 95% CI ‐0.87 to 0.07; 3 studies; very low certainty). In a sensitivity analysis omitting data from a study which only included participants who had shown a relatively poor prior response to donepezil, inconsistency was reduced and we found that cognitive function may be worse in the discontinuation group in the medium term (SMD ‐0.62; 95% CI ‐0.94 to ‐0.31). Data from one longer‐term study suggest that discontinuing a cholinesterase inhibitor is probably associated with worse cognitive function at 12 months (mean difference (MD) ‐2.09 Standardised Mini‐Mental State Examination (SMMSE) points, 95% CI ‐3.43 to ‐0.75; moderate certainty).
Discontinuation may make little or no difference to functional status in the short term (SMD ‐0.25, 95% CI ‐0.54 to 0.04; 2 studies; low certainty), and its effect in the medium term is uncertain (SMD ‐0.38, 95% CI ‐0.74 to ‐0.01; 2 studies; very low certainty). After 12 months, discontinuing a cholinesterase inhibitor probably results in greater functional impairment than continuing treatment (MD ‐3.38 Bristol Activities of Daily Living Scale (BADLS) points, 95% CI ‐6.67 to ‐0.10; one study; moderate certainty). Discontinuation may be associated with a worsening of neuropsychiatric symptoms over the short term and medium term, although we cannot exclude a minimal effect (SMD ‐ 0.48, 95% CI ‐0.82 to ‐0.13; 2 studies; low certainty; and SMD ‐0.27, 95% CI ‐0.47 to ‐0.08; 3 studies; low certainty, respectively). Data from one study suggest that discontinuing a cholinesterase inhibitor may result in little to no change in neuropsychiatric status at 12 months (MD ‐0.87 Neuropsychiatric Inventory (NPI) points; 95% CI ‐8.42 to 6.68; moderate certainty).
We found no clear evidence of an effect of discontinuation on dropout due to lack of medication efficacy or deterioration in overall medical condition (odds ratio (OR) 1.53, 95% CI 0.84 to 2.76; 4 studies; low certainty), on number of adverse events (OR 0.85, 95% CI 0.57 to 1.27; 4 studies; low certainty) or serious adverse events (OR 0.80, 95% CI 0.46 to 1.39; 4 studies; low certainty), and on mortality (OR 0.75, 95% CI 0.36 to 1.55; 5 studies; low certainty). Institutionalisation was reported in one trial, but it was not possible to extract data for the groups relevant to this review.
Authors' conclusions
This review suggests that discontinuing cholinesterase inhibitors may result in worse cognitive, neuropsychiatric and functional status than continuing treatment, although this is supported by limited evidence, almost all of low or very low certainty. As all participants had dementia due to Alzheimer's disease, our findings are not transferable to other dementia types. We were unable to determine whether the effects of discontinuing cholinesterase inhibitors differed with baseline dementia severity. There is currently no evidence to guide decisions about discontinuing memantine. There is a need for further well‐designed RCTs, across a range of dementia severities and settings. We are aware of two ongoing registered trials. In making decisions about discontinuing these drugs, clinicians should exercise caution, considering the evidence from existing trials along with other factors important to patients and their carers.
Physician-scientists are critical members of the biomedical workforce. The combination of rigorous scientific training and clinical skills uniquely positions them to bridge clinical needs with ...investigational pursuits by identifying important clinical questions that drive basic discoveries and translating those into therapeutics that improve patient outcomes. The impact of physician-scientists on biomedical science has been profound. Here, Permar describes innovative strategies implemented at three academic medical centers in the US that are working to fill the physician-scientist pipeline.
Previous studies identified shifts in gut microbiota associated with atypical antipsychotic (AAP) treatment that may link AAPs to metabolic burden. Dietary prebiotics such as resistant starch may be ...beneficial in obesity and glucose regulation, but little is known mechanistically about their ability to modify gut microbiota in AAP-treated individuals. This investigation was undertaken to delineate mechanistically the effects of AAP treatment and resistant starch supplementation on gut microbiota in a psychiatric population.
Cross-sectional cohort study.
The study was performed in an outpatient setting.
A total of 37 adults with a diagnosis of bipolar disorder or schizophrenia who were treated with an AAP (clozapine, olanzapine, risperidone, quetiapine, or ziprasidone 21 patients) or lithium and/or lamotrigine (16 patients) for at least 6 months.
Patients in the AAP group received raw unmodified potato starch (resistant starch) daily for 14 days.
Of the 37 patients, the mean ± SD age was 52.2 ± 12.5 years, and 57% were male. The primary outcome was gut microbiome DNA composition. Microbiome DNA obtained from stool samples from all patients was subject to 16S ribosomal RNA (rRNA) gene sequencing before and during resistant starch supplementation. Inter- and intragroup microbial diversity measures were performed by permutational multivariate analysis of variance and the Inverse Simpson Diversity Index, respectively. Differentially abundant organisms were detected by using linear discriminant analysis effect size. Although no significant difference in overall microbiota composition was detected at baseline between AAP users and nonusers, non-AAP users showed increased fractional representation of Alistipes. AAP-treated women exhibited decreased diversity compared with non-AAP-treated women. Although the microbiome of AAP-treated patients varied with resistant starch administration, an increased abundance of the Actinobacteria phylum was observed.
These data suggest that AAP treatment is associated with measurable differences in gut microbiota, particularly in female AAP-treated patients in whom reduced species richness was observed. Additionally, variable microbiome responses to resistant starch supplementation were seen, with a significant increase in starch degraders.
Purpose
Physical health-related quality of life (HRQoL) is associated with adverse health outcomes, including hospitalizations and all-cause mortality. However, little is known about how physical ...HRQoL changes over time in older people and the predictors of this trajectory. This study (a) identified trajectories of physical HRQoL among older people and (b) explored whether economic factors, social health or stressful life events impact physical HRQoL trajectories.
Method
A cohort of 12,506 relatively ‘healthy’ community-dwelling Australians aged ≥ 70 years (54.4% females), enrolled in the ASPREE Longitudinal Study of Older Persons (ALSOP) study and was followed for six years. Economic factors, social health and life events in the last 12 months were assessed through a questionnaire at baseline. Physical HRQoL was measured by using the 12-item short form at baseline and annual follow-ups. Growth mixture and structural equation modelling were used to identify physical HRQoL trajectories and their predictors.
Results
Four physical HRQoL trajectories were identified—stable low (7.1%), declining (9.0%), stable intermediate (17.9%) and stable high (66.0%). Living in more disadvantaged areas, having a lower household income, no paid work, no voluntary work, loneliness and stressful life events (i.e. spousal illness, friend/family illness, financial problem) were associated with a 10%–152% higher likelihood of being in the stable low or declining physical HRQoL trajectory than the stable high group.
Conclusion
Specific stressful life events had a greater impact on adverse physical HRQoL trajectories in older people than other factors. Volunteering may prevent physical HRQoL decline and requires further investigation.
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