I’m not going to do some sort of victory dance, because (once again) this is bad news for Alzheimer’s patients and for their families. I know that I have written many times that I thought this program would fail – I was cautious in 2015, cautious earlier last year, and much more than cautious just a few weeks later. My views on amyloid antibodies are well known, for the little that’s worth. I had no real expectations that aducanumab would work, despite all the attempts at positive spin over the years, and by golly, it doesn’t work. That doesn’t make me a prophet – I think any objective observer would have to have come to the same conclusion. Biogen and Eisai put themselves into this situation, although they definitely made it worse by trying to pretend that things were going differently than they have for every single other amyloid antibody program ever. They have all failed. One after another, again and again.--Derek Lowe

Aging leads to atrophy and reduced function of most organs throughout the body, including the brain. Lifestyle choices have measurable positive and negative effects on aging such that healthful eating habits and regular physical and mental exercise help preserve cognitive function, whereas poor lifestyle choices accelerate physical and functional aging.

Furthermore, aging is the most consistent and dominant risk factor for neurodegeneration. One of the main difference between aging and neurodegeneration is that with aging, the brain exhibits modest degrees of atrophy and functional loss over a period of years, whereas in AD, the declines are swifter and relentless, driving formerly fully functioning people to eventual end-stage vegetative states.

​These concepts suggest that lifestyle measures that either curtail or exacerbate the aging process may also modulate risk and rates of developing AD as well as other neurodegenerative diseases--S.M. de La Monte

​“Anyone with a brain is at risk for Alzheimer’s.” —Richard Isaacson

There is perhaps no better demonstration of the folly of human conceits than this distant image of our tiny world--Carl Sagan 

 Economists have a name for these activities: they call them rent seeking, getting income not as a reward to creating wealth but by trapping a larger share of the wealth that would otherwise have been produced without their effort. Those at the top have learned to suck out money from the rest in ways that the rest are hardly aware of - that is their true innovation.--The Price of Inequality, Joseph E. Stiglitz

As the drug industry has come back down to earth, the returns of the 46 middlemen on the list have soared. Fifteen years ago they accounted for a fifth of industry profits; now their share is 41%. Health-insurance companies generate abnormally high returns, but so do the wholesalers, the benefit managers and the pharmacies.

In total middlemen capture $126 of excess profits a year per American, or about two-thirds of the whole industry’s excess profits. Express Scripts earns billions while having less than $1bn of physical plants and no disclosed investment in R&D. ​This year the combined profits of three wholesalers that few outsiders have heard of are expected to exceed those of Starbucks. The dark view is that pockets of rent-seeking have become endemic in America’s economy. Wherever products are too complex for customers to understand, and where subsidies and complex regulation add to the muddle, huge profits can opaquely be made. Remember mortgage-backed securities?--The Economist, Which firms profit most from America’s health-care system

It is not sufficient, he argues, to simply collect and store massive amounts of data; they must be intelligently curated, and that requires a global framework. “We have all the pieces of the puzzle — now how do we actually assemble them so we can see the big picture?”--The Mathematical Shape of Big Science Data--Jennifer Ouellette

"After accounting for non-independence between risk factors, around a third of Alzheimer's diseases cases worldwide might be attributable to potentially modifiable risk factors. Alzheimer's disease incidence might be reduced through improved access to education and use of effective methods targeted at reducing the prevalence of vascular risk factors (eg, physical inactivity, smoking, midlife hypertension, midlife obesity, and diabetes) and depression."--The Lancet Neurology volume 13, issue 8, August 2014

“Now we have this new multimodal data [gleaned] from biological systems and human social systems, and the data is gathered before we even have a hypothesis.” The data is there in all its messy, multi-dimensional glory, waiting to be queried, but how does one know which questions to ask when the scientific method has been turned on its head?--The Mathematical Shape of Big Science Data

Everyone is hurling content over the pay-wall. In a time when we should be diffusing knowledge, the monetization beckons and many move deeper into their echo chamber. That is why my favorite read has been QuantaMagazine. Light-Triggered Genes Reveal the Hidden Workings of Memory saved my morning.

Study 201 (ClinicalTrials.gov identifier NCT01767311) is a placebo-controlled, double-blind, parallel-group, randomized study in patients with prodromal or mild Alzheimer’s disease (collectively known as early Alzheimer’s disease) and with positive biomarkers for brain amyloid pathology.

"You have a nearly 50 percent chance of developing the disease if you live into your mid-80s. In the United States, it is the only cause of death in the top 10 without any meaningful treatments that becomes more prevalent each year. That trend will likely continue as baby boomers age, which means that more families will watch their loved ones suffer from cognitive decline and slowly disappear. Despite this growing burden, scientists have yet to figure out what exactly causes Alzheimer’s or how to stop the disease from destroying the brain."--Why I'm Digging Deep Into Alzheimer's, Bill Gates

The researchers who publish the annual World Happiness Report found that about three-quarters of human happiness is driven by six factors: strong economic growth, healthy life expectancy, quality social relationships, generosity, trust, and freedom to live the life that’s right for you. These factors don’t materialize by chance; they are intimately related to a country’s government and its cultural values. In other words the happiest places incubate happiness for their people-- Dan Buettner

Ranking of Happiness 2014-2016 -- World Happiness Report (Chapter 2)

These Are the World’s Happiest Places--National Geographic Magazine

I guess we all realize there is no money to be had in prevention. At least not of the global scale witnessed by limited curative therapies and bottomless R&D efforts, especially in neurodegenerative diseases--I am talking to you Alzheimer's disease. Shareholders are mesmerized by "expanding market share" and the financial opportunities on the horizon. The rest of us scratch our heads and wonder--wouldn't prevention be a better service? What is causing the expanding "customer base" for Pharma and how can we mitigate the tide or better yet reverse the trends?

We are observing the rise of obesity and metabolic derangements in lock step with projected increases in rates of Alzheimer's disease. Perhaps the 90+ billion investment in commodity farming is suspect? I would be remiss if I didn't mention the US farm bill. Simply put the bill is a comprehensive, multi-year legislation that includes "federal farm, food, fiber, forestry, and rural policies and programs". And yes the Supplemental Nutrition Assistance Program (SNAP) is the largest part of the Nutrition Title. Okay hats off for investing in economic benefits for our domestic hunger safety net but look at the proportion of crops assigned to vegetables and healthy alternatives. Data Products USDA

Metabolic derangements mediate cognitive impairment and Alzheimer's disease: role of peripheral insulin-resistance diseases

Alzheimer's disease (AD) should be regarded as a degenerative metabolic disease caused by brain insulin resistance and deficiency, and overlapping with the molecular, biochemical, pathophysiological, and metabolic dysfunctions in diabetes mellitus, non-alcoholic fatty liver disease, and metabolic syndrome.

Although most of the diagnostic and therapeutic approaches over the past several decades have focused on amyloid-beta (Aβ42) and aberrantly phosphorylated tau, which could be caused by consequences of brain insulin resistance, the broader array of pathologies including white matter atrophy with loss of myelinated fibrils and leukoaraiosis, non-Aβ42 microvascular disease, dysregulated lipid metabolism, mitochondrial dysfunction, astrocytic gliosis, neuro-inflammation, and loss of synapses vis-à-vis growth of dystrophic neurites, is not readily accounted for by Aβ42 accumulations, but could be explained by dysregulated insulin/IGF-1 signaling with attendant impairments in signal transduction and gene expression.

​This review covers the diverse range of brain abnormalities in AD and discusses how insulins, incretins, and insulin sensitizers could be utilized to treat at different stages of neurodegeneration.