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Dietary supplement with olive polyphenols and bioavailable glutathione could be useful for patients diagnosed with mild AD.

Dietary supplement with olive polyphenols and bioavailable glutathione could be useful for patients diagnosed with mild AD.

The reporting of approaches facilitating the most efficient and timely recruitment of Alzheimer's disease (AD) patients into pharmacologic trials is fundamental to much-needed therapeutic progress.

T2 Protect AD (T2), a phase 2 randomized placebo-controlled trial of troriluzole in mild to moderate AD, used multiple recruitment strategies.

T2 exceeded its recruitment target, enrolling 350 participants between July 2018 and December 2019 (randomization rate 0.87 randomizations/site/month, or 3-fold greater than recent trials of mild to moderate AD). The vast majority (98%) of participants were enrolled during a 10-month window of intense promotion in news media, TV and radio advertisements, and social media. The distribution of primary recruitment sources included existing patient lists at participating sites (72.3%), news media (12.3%), physician referral (6.0%), word of mouth (3.1%), and paid advertising (2.9%).

The rapid recruitment of participants with mild to moderate AD was achieved through a range of approaches with varying success.

The rapid recruitment of participants with mild to moderate AD was achieved through a range of approaches with varying success.

Cerebral glucose and insulin metabolism is impaired in Alzheimer's disease (AD). Ketones provide alternative energy. Will medium chain triglyceride (MCT) oil, a nutritional source of ketones, impact cognition in AD?

This was a 6-month randomized, double-blind, placebo-controlled, crossover study, with 6-month open-label extension in probable AD subjects, on stable medications. MCT dose was 42g/day, or maximum tolerated. Cognition was assessed with Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and Cognigram®.

Twenty subjects, average age 72.6 years, 45% women, 70% university educated had baseline MMSE 22.6/30 (10-29); MoCA 15.6/30 (4-27); baseline Cognigram® Part 1 65-106, Part 2 48-107. Average MCT oil consumption was 1.8 tablespoons/day (25.2g, 234kcal). Eighty percent remained stable or improved. Longer MCT exposure and age>73, resulted in higher final MMSE (

<.001) and Cognigram® 1 scores.

This is the longest duration MCT AD study to date. Eighty percent had stabilization or improvement in cognition, and better response with 9-month continual MCT oil.

This is the longest duration MCT AD study to date. Eighty percent had stabilization or improvement in cognition, and better response with 9-month continual MCT oil.

Allopregnanolone (ALLO), an endogenous neurosteroid, promoted neurogenesis and oligogenesis and restored cognitive function in animal models of Alzheimer's disease (AD). Based on these discovery research findings, we conducted a randomized-controlled phase 1b/2a multiple ascending dose trial of ALLO in persons with early AD (NCT02221622) to assess safety, tolerability, and pharmacokinetics. Exploratory imaging outcomes to determine whether ALLO impacted hippocampal structure, white matter integrity, and functional connectivity are reported.

Twenty-four individuals participated in the trial (

=6 placebo;

=18 ALLO) and underwent brain magnetic resonance imaging (MRI) before and after 12weeks of treatment. Hippocampal atrophy rate was determined from volumetric MRI, computed as rate of change, and qualitatively assessed between ALLO and placebo sex, apolipoprotein E (

) ε4 allele, and ALLO dose subgroups. White matter microstructural integrity was compared between placebo and ALLO using fractional and quious preclinical studies and these exploratory MRI-based outcomes from this phase 1b/2a clinical cohort support advancement to a phase 2 proof-of-concept efficacy clinical trial of ALLO as a regenerative therapeutic for mild AD (REGEN-BRAIN study; NCT04838301).

Indicators of regeneration from previous preclinical studies and these exploratory MRI-based outcomes from this phase 1b/2a clinical cohort support advancement to a phase 2 proof-of-concept efficacy clinical trial of ALLO as a regenerative therapeutic for mild AD (REGEN-BRAIN study; NCT04838301).

Research suggests that incident dementia is decreasing, yet research on secular trends of prodromal dementia such as mild cognitive impairment (MCI) is lacking.

To determine change of MCI prevalence over time and potential explanatory factors, four baseline samples (years 2001-2020) of Swedish participants (

= 3910) aged 60 and 81 at examination were compared.

An overall drop of 9 to 10 percentage points in MCI prevalence between 2001 and 2020 was observed, with lower odds ratios (OR) for MCI in the latest birth cohorts compared to earliest (e.g., ORs for 60-year-olds in latest born = 0.53; 95% confidence interval [CI] 0.37-0.76). Adjustments for sociodemographic (e.g., education), lifestyle, vascular and metabolic health and depression could not fully explain the observed MCI decline (e.g., 60-year-olds, OR = 0.59; 95% CI 0.40-0.88).

Studies like this are imperative as even a slight postponement in the onset of dementia could have a substantial impact on future public health burden.

Studies like this are imperative as even a slight postponement in the onset of dementia could have a substantial impact on future public health burden.

With no treatment for dementia, there is a need to identify high risk cases to focus preventive strategies, particularly in low- and middle-income countries (LMICs) where the burden of dementia is greatest. We evaluated the risk of conversion from mild cognitive ompairment (MCI) to dementia in LMICs.

Medline, Embase, PsycINFO, and Scopus were searched from inception until June 30, 2020. The search was restricted to observational studies, conducted in population-based samples, with at least 1 year follow-up. There was no restriction on the definition of MCI used as long as it was clearly defined. PROSPERO registration CRD42019130958.

Ten thousand six hundred forty-seven articles were screened;

=11 retained. Of the 11 studies, most were conducted in China (

=7 studies), with only two studies from countries classified as low income. A qualitative analysis of

=11 studies showed that similar to high-income countries the conversion rate to dementia from MCI was variable (range 6







.





s with cognitive impairment who are at highest risk of dementia in LMICs is necessary for the development of risk reduction strategies that are contextualized to these unique settings.

MCI is associated with high, but variable, conversion to dementia in LMICs and may be influenced by demographic and health factors. There is a notable absence of data from low-income settings and countries outside of China. This highlights the urgent need for research investment into aging and dementia in LMIC settings. Being able to identify those individuals with cognitive impairment who are at highest risk of dementia in LMICs is necessary for the development of risk reduction strategies that are contextualized to these unique settings.

Age-related neuropathology associated with sporadic Alzheimer's disease (AD) often develops well before the onset of symptoms. Given AD's long preclinical period, translational models are needed to identify early signatures of pathological decline.

Using structural magnetic resonance imaging and cognitive assessments, we examined the relationships among age, cognitive performance, and neuroanatomy in 48 vervet monkeys (

) ranging from young adults to very old.

We found negative associations of age with cortical gray matter volume (

=.003) and the temporal-parietal cortical thickness meta-region of interest (

=.001). Additionally, cortical gray matter volumes predicted working memory at approximately 1-year follow-up (correct trials at the 20s delay [

=.008]; correct responses after longer delays [

=.004]).

Cortical gray matter diminishes with age in vervets in regions relevant to AD, which may increase risk of cognitive impairment. This study lays the groundwork for future investigations to test therapeutics to delay or slow pathological decline.

Cortical gray matter diminishes with age in vervets in regions relevant to AD, which may increase risk of cognitive impairment. This study lays the groundwork for future investigations to test therapeutics to delay or slow pathological decline.

Herpes simplex virus (HSV) may be involved in Alzheimer's disease (AD) pathophysiology. The antiviral valacyclovir inhibits HSV replication.

This phase-II pilot trial involved valacyclovir administration (thrice daily, 500mg week 1, 1000mg weeks 2-4) to persons aged ≥ 65 years with early-stage AD, anti-HSV immunoglobulin G, and apolipoprotein E ε4. Intervention safety, tolerability, feasibility, and effects on Mini-Mental State Examination (MMSE) scores and cerebrospinal fluid (CSF) biomarkers were evaluated.

Thirty-two of 33 subjects completed the trial on full dosage. Eighteen percent experienced likely intervention-related mild, temporary adverse events. CSF acyclovir concentrations were mean 5.29 ± 2.31μmol/L. U0126 cost CSF total tau and neurofilament light concentrations were unchanged; MMSE score and CSF soluble triggering receptor expressed on myeloid cells 2 concentrations increased (

=.02 and .03).

Four weeks of high-dose valacyclovir treatment was safe, tolerable, and feasible in early-stage AD. Our findings may guide future trial design.

Four weeks of high-dose valacyclovir treatment was safe, tolerable, and feasible in early-stage AD. Our findings may guide future trial design.Nonlinear dynamical behaviours with chaotic phenomena are commonly observed in a typical logistics model and supply chain system. Bullwhip effect has been widely recognized as one of the main issues on affecting the supply chain management. In essence, this phenomenon will lead to unnecessary consumption and waste of natural and social resources by demand variability amplification as moving up in the supply chain networks. However, traditional modelling approaches may become complicated in dealing with uncertainty and chaotic behaviour that are prevalent in real supply chains. System dynamics theory has been employed as a potentially effective strategy to cope with chaotic supply chains which are unpredictable behaviours in time. Four-dimensional differential equations which exhibit chaotic behaviours are constructed to describe a multi-echelon supply chain with bullwhip effect. Furthermore, modern control theory is applied to deal with the multi-stage supply chain optimization problems against disruptions. Specifically, the novel fractional order adaptive sliding mode control (FO-ASMC) algorithm has been implemented for ensuring efficient supply chain management. In addition, the chaos synchronization scheme is implemented in an attempt to regulate the supply chain systems under the impact of extensive uncertainties caused by tumultuous real market. It is found that the chaos synchronization is effectively realised by new FO-ASMC theory to manage advanced supply chain networks. Finally, this advanced management optimization offers a new class of intelligent applications that connects demand to supply and planning to execution across the entire supply chains.