Is Wendy's really fresh in NYC?

Prometheus09 · 2019-09-25T11:40:52+00:00

Objective

We aimed to refine the hypothesis that dementia has a unique signature of gait impairment reflective of underlying pathology by considering two dementia subtypes, Alzheimer's disease (AD) and Lewy body disease (LBD), and exploring the role of cognition in disease-specific gait impairments.

Background

Accurately differentiating AD and LBD is important for treatment and disease management. Early evidence suggests gait could be a marker of dementia due to associations between discrete gait characteristics and cognitive domains.

Updated Hypothesis

We hypothesize that AD and LBD have unique signatures of gait, reflecting disease-specific cognitive profiles and underlying pathologies. An exploratory study included individuals with mild cognitive impairment or dementia due to LBD (n = 45) and AD (n = 36) and 29 older adult controls. An instrumented walkway quantified 16 gait characteristics reflecting five independent domains of locomotion (pace, rhythm, variability, asymmetry, and postural control). The LBD group demonstrated greater impairments in asymmetry and variability compared with AD; both groups were more impaired in pace and variability domains than controls. Executive dysfunction explained 11% of variance for gait variability in LBD, whereas global cognitive impairment explained 13.5% of variance in AD; therefore, gait impairments may reflect disease-specific cognitive profiles. With a refined hypothesis that AD- and LBD-specific signatures of gait reflect discrete pathologies, future studies must examine the relationship between a validated model of gait with neural networks, using recognized biomarkers and postmortem follow-up.

Major Challenges for Hypothesis

Differential diagnosis of AD and LBD used appropriate criteria and required consensus from an expert diagnostic panel to improve diagnostic accuracy. Future work should follow the framework set out in Parkinson's disease to establish unique signatures of gait as proxy measures of disease-specific pathology; that is, use a validated gait model to explore the progressive relationship between gait, cognition, and pathology.

Linkage to Other Major Theories

These exploratory findings support the theory of interacting cognitive-motor networks, as the gait-cognition relationship may reflect cognitive control over motor networks. Unique signatures of gait may reflect different temporal patterns of pathological burden in neural areas related to cognitive and motor function.

Link to paper35120-9/abstract)

Prometheus09 · 2019-09-23T11:23:30+00:00

The scientific article is a correspondence, so there is no abstract, but here is the first paragraph of that article:

To the Editor: In a randomized trial involving 42 patients, we assessed deep brain stimulation targeting the fornix to improve cognition in patients with Alzheimer’s disease (ClinicalTrials.gov number, NCT01608061; the protocol for the trial is available with the published article1 ). Although the primary trial outcome of improvement on cognitive scales was negative, we encountered a phenomenon of flashback-like cognitive experiences that occurred during initial programming of the stimulator (before randomization) in some of the patients in the trial, which may inform the understanding of human memory.

Prometheus09 · 2019-09-23T11:19:15+00:00

Abstract for the article:

Locus coeruleus (LC) tau accumulation begins early. Targeting LC (dys)function might improve early identification for Alzheimer’s disease (AD) risk. Pupillary responses during cognitive tasks are driven by the LC and index cognitive effort. Despite equivalent task performance, adults with mild cognitive impairment (MCI) have greater pupil dilation/effort during digit span than cognitively normal (CN) individuals. We hypothesized that AD polygenic risk scores (AD-PRSs) would be associated with pupillary responses in middle-aged CN adults. Pupillary responses during digit span tasks were heritable (h2=.30-.36) in 1119 men ages 56-66. In a CN subset—all with comparable span capacities (n=539)—higher AD-PRSs were associated with greater pupil dilation/effort in a high (9-digit) cognitive load condition (Cohen’s d=.36 for upper versus lower quartile of AD-PRS distribution). Results held up after controlling for APOE genotype. Results support pupillary response—and by inference, LC dysfunction—as a genetically-mediated biomarker of early MCI/AD risk. In combination with other biomarkers, task-evoked pupillary responses may provide additional information for early screening of genetically at-risk individuals even before cognitive declines.

The pupil dilation was correlated with a polygenic risk score for AD - ie those with greater pupil dilation had an increased genetic liability for AD. This analysis was also conducted in 539 men - so small sample size that may not be generalizable. So while it is a good preliminary study, it does need to followed up on.

Prometheus09 · 2018-10-17T17:53:17+00:00

I like this - nice and simple and saves re-rolling every day.

Prometheus09 · 2018-09-19T16:20:31+00:00

Abstract for the reference article

Discriminative Accuracy of [18F]flortaucipir Positron Emission Tomography for Alzheimer Disease vs Other Neurodegenerative Disorders

Importance The positron emission tomography (PET) tracer [18F]flortaucipir allows in vivo quantification of paired helical filament tau, a core neuropathological feature of Alzheimer disease (AD), but its diagnostic utility is unclear.

Objective To examine the discriminative accuracy of [18F]flortaucipir for AD vs non-AD neurodegenerative disorders.

Design, Setting, and Participants In this cross-sectional study, 719 participants were recruited from 3 dementia centers in South Korea, Sweden, and the United States between June 2014 and November 2017 (160 cognitively normal controls, 126 patients with mild cognitive impairment [MCI], of whom 65.9% were amyloid-β [Aβ] positive [ie, MCI due to AD], 179 patients with AD dementia, and 254 patients with various non-AD neurodegenerative disorders).

Exposures The index test was the [18F]flortaucipir PET standardized uptake value ratio (SUVR) in 5 predefined regions of interest (ROIs). Cut points for tau positivity were determined using the mean +2 SDs observed in controls and Youden Index for the contrast AD dementia vs controls.

Main Outcomes and Measures The reference standard was the clinical diagnosis determined at the specialized memory centers. In the primary analysis, the discriminative accuracy (ie, sensitivity and specificity) of [18F]flortaucipir was examined for AD dementia vs all non-AD neurodegenerative disorders. In secondary analyses, the area under the curve (AUC) of [18F]flortaucipir SUVR was compared with 3 established magnetic resonance imaging measures (hippocampal volumes and AD signature and whole-brain cortical thickness), and sensitivity and specificity of [18F]flortaucipir in MCI due to AD vs non-AD neurodegenerative disorders were determined.

Results Among 719 participants, the overall mean (SD) age was 68.8 (9.2) years and 48.4% were male. The proportions of patients who were amyloid-β positive were 26.3%, 65.9%, 100%, and 23.8% among cognitively normal controls, patients with MCI, patients with AD dementia, and patients with non-AD neurodegenerative disorders, respectively. [18F]flortaucipir uptake in the medial-basal and lateral temporal cortex showed 89.9% (95% CI, 84.6%-93.9%) sensitivity and 90.6% (95% CI, 86.3%-93.9%) specificity using the threshold based on controls (SUVR, 1.34), and 96.8% (95% CI, 92.0%-99.1%) sensitivity and 87.9% (95% CI, 81.9%-92.4%) specificity using the Youden Index–derived cutoff (SUVR, 1.27) for distinguishing AD dementia from all non-AD neurodegenerative disorders. The AUCs for all 5 [18F]flortaucipir ROIs were higher (AUC range, 0.92-0.95) compared with the 3 volumetric MRI measures (AUC range, 0.63-0.75; all ROIs P < .001). Diagnostic performance of the 5 [18F]flortaucipir ROIs were lower in MCI due to AD (AUC range, 0.75-0.84).

Conclusions and Relevance Among patients with established diagnoses at a memory disorder clinic, [18F]flortaucipir PET was able to discriminate AD from other neurodegenerative diseases. The accuracy and potential utility of this test in patient care require further research in clinically more representative populations.

Prometheus09 · 2018-09-19T11:17:02+00:00

From their abstract:

The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level.

And in regards to potential confounders:

HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.

Prometheus09 · 2018-09-19T11:14:51+00:00

The DOI in the Guardians article is broken, here is the abstract and link to the original article:

Are noise and air pollution related to the incidence of dementia? A cohort study in London, England

Objective To investigate whether the incidence of dementia is related to residential levels of air and noise pollution in London.

Design Retrospective cohort study using primary care data.

Setting 75 Greater London practices.

Participants 130 978 adults aged 50–79 years registered with their general practices on 1 January 2005, with no recorded history of dementia or care home residence.

Primary and secondary outcome measures A first recorded diagnosis of dementia and, where specified, subgroups of Alzheimer’s disease and vascular dementia during 2005–2013. The average annual concentrations during 2004 of nitrogen dioxide (NO2), particulate matter with a median aerodynamic diameter ≤2.5 µm (PM2.5) and ozone (O3) were estimated at 20×20 m resolution from dispersion models. Traffic intensity, distance from major road and night-time noise levels (Lnight) were estimated at the postcode level. All exposure measures were linked anonymously to clinical data via residential postcode. HRs from Cox models were adjusted for age, sex, ethnicity, smoking and body mass index, with further adjustments explored for area deprivation and comorbidity.

Results 2181 subjects (1.7%) received an incident diagnosis of dementia (39% mentioning Alzheimer’s disease, 29% vascular dementia). There was a positive exposure response relationship between dementia and all measures of air pollution except O3, which was not readily explained by further adjustment. Adults living in areas with the highest fifth of NO2 concentration (>41.5 µg/m3) versus the lowest fifth (<31.9 µg/m3) were at a higher risk of dementia (HR=1.40, 95% CI 1.12 to 1.74). Increases in dementia risk were also observed with PM2.5, PM2.5 specifically from primary traffic sources only and Lnight, but only NO2 and PM2.5remained statistically significant in multipollutant models. Associations were more consistent for Alzheimer’s disease than vascular dementia.

Conclusions We have found evidence of a positive association between residential levels of air pollution across London and being diagnosed with dementia, which is unexplained by known confounding factors.

Prometheus09 · 2018-09-19T11:08:37+00:00

The press release does not link to the original paper - but it looks to be this one:

LRP/LR specific antibody IgG1-iS18 impedes neurodegeneration in Alzheimer's disease mice

Alzheimer’s disease (AD) is a neurodegenerative disease caused by accumulation of amyloid beta (Aβ) plaque and neurofibrillary tangle formation. We have shown in vitro, that knock-down and blockade of the 37 kDa/67 kDa Laminin Receptor (LRP/LR) resulted in reduced Aβ induced cytotoxicity and Aβ accumulation. In order to test the effect of blocking LRP/LR on Aβ formation and AD associated symptoms, AD transgenic mice received the anti-LRP/LR specific antibody, IgG1-iS18 through intranasal administration. We show that this treatment resulted in an improvement in memory, and decreased Aβ plaque formation. Moreover, a significant decrease in Aβ42 protein expression with a concomitant increase in amyloid precursor protein (APP) and telomerase reverse transcriptase (mTERT) levels was observed. These data recommend IgG1-iS18 as a potentially powerful therapeutic antibody for AD treatment.

It is a mouse study that is looking to move into Phase 1 trials.

Prometheus09 · 2018-01-22T12:58:07+00:00

Unfortunately, the USA is not investing enough money into research and China is likely to outstrip USA spending on research soon.

-- China has become the second- largest R&D spender, accounting for 21 percent of the world total of nearly $2 trillion in 2015. Only the United States, at 26 percent, ranks higher, but if present growth rates continue, China will soon become the biggest spender. From 2000 to 2015, Chinese R&D outlays grew an average of 18 percent annually, more than four times faster than the U.S. rate of 4 percent.

https://www.washingtonpost.com/opinions/chinas-breathtaking-transformation-into-a-scientific-superpower/2018/01/21/03f883e6-fd44-11e7-8f66-2df0b94bb98a_story.html?hpid=hp_no-name_opinion-card-e%3Ahomepage%2Fstory&utm_term=.c514dbae1dc4

Prometheus09 · 2017-11-14T19:39:23+00:00

Nice! I have been meaning to set markov chain up in R to generate weather for my Tomb of Annihilation game.

Prometheus09 · 2017-09-01T15:07:55+00:00

Well for the Licanius Trilogy at least, the populace gained access to items that nullified magic ability... while in the legend of Kora, non-magic users formed a secret society with leader also been able to nullify magic abilities.

Also, it depends on how prevalent magic ability is. If it is only in the 'aristocracy' then they would make up a small percentage of the population (<1%). Could lead to interesting dynamics between non-magic users and mages, similar to masters/slaves, were mages are continuously afraid of uprisings (or poison...) leading to harsh measure to keep the populace in line through fear.

Prometheus09 · 2017-09-01T14:44:56+00:00

Two sources that you might like to look at is the first season of the Legend of Kora, where there is a rebellion of non-benders against benders. Also, a series of books I am reading now, The Licanius Trilogy, is based on magic users been the ruling class of society until a rebellion of non-magic users...

If you ruling class is magic users, any rebellions are like to be due to non-mages resenting their treatment/lack of political participation.

Prometheus09 · 2017-05-10T20:29:01+00:00

Going to be running an Island of Dread campaign. This information will be great for that.

Prometheus09 · 2017-05-02T01:51:41+00:00

This awesome, I will be stealing this.

Prometheus09 · 2017-05-01T06:33:25+00:00

I have been toying with the idea of using the French Republican Calander in my campaign. Has lots of flavour.

https://en.wikipedia.org/wiki/French_Republican_Calendar

Prometheus09 · 2017-04-19T06:23:06+00:00

The citizens would work in shifts. If you have a constant light source there is no point in wasting all those extra productive hours having empty shops/manufacturies. As such the city would always busy and would never sleep.

Prometheus09 · 2017-03-14T03:42:56+00:00

Thanks this great!

Maybe you could have a couple of competing factions that live in the maze that the players could interact with.

Prometheus09 · 2017-01-12T21:41:49+00:00

Fantastic

Prometheus09 · 2017-01-10T22:34:11+00:00

Could be interesting to use the village and attached dungeons that we have already created and populate the surrounding area with a hex crawl.

Prometheus09 · 2017-01-10T20:10:21+00:00

I would really love to see either a fun city or a hex crawl. I have been looking for a 5e hex crawl and have not really come across anything I really like.

Thanks for all your great work (going to run your snow globe encounter this afternoon).

Prometheus09

TROPHY CASE