While our genes can't be changed easily, you can avoid some dementia risk factors. Today we discuss dementia and five drugs that may increase risk.

Memory loss appears to come with age, but we're not talking about forgetfulness. Sometimes losing your car keys isn't an indication of dementia. Dementia impairs the capacity to think, remember, or make judgments. Dementia hinders daily tasks.

Alzheimers is the most common dementia. Dementia is not normal aging, unlike forgetfulness. Aging increases the risk of Alzheimer's and other dementias. A family history of the illness increases your risk, according to the Mayo Clinic (USA).

Given that our genes are difficult to change (I won't get into epigenetics), what are some avoidable dementia risk factors? Certain drugs may cause cognitive deterioration.

Today we look at four drugs that may cause cognitive decline.

Dementia and benzodiazepines

Benzodiazepine sedatives increase brain GABA levels. Example benzodiazepines:

• Diazepam (Valium) (Valium)

• Alprazolam (Xanax) (Xanax)

• Clonazepam (Klonopin) (Klonopin)

Addiction and overdose are benzodiazepine risks. Yes! These medications don't raise dementia risk.

USC study: Benzodiazepines don't increase dementia risk in older adults.

Benzodiazepines can produce short- and long-term amnesia. This memory loss hinders memory formation. Extreme cases can permanently impair learning and memory. Anterograde amnesia is uncommon.

2. Statins and dementia

Statins reduce cholesterol. They prevent a cholesterol-making chemical. Examples:

• Atorvastatin (Lipitor) (Lipitor)

• Fluvastatin (Lescol XL) (Lescol XL)

• Lovastatin (Altoprev) (Altoprev)

• Pitavastatin (Livalo, Zypitamag) (Livalo, Zypitamag)

• Pravastatin (Pravachol) (Pravachol)

• Rosuvastatin (Crestor, Ezallor) (Crestor, Ezallor)

• Simvastatin (Zocor) (Zocor)

This finding is contentious. Harvard's Brigham and Womens Hospital's Dr. Joann Manson says:

“I think that the relationship between statins and cognitive function remains controversial. There’s still not a clear conclusion whether they help to prevent dementia or Alzheimer’s disease, have neutral effects, or increase risk.”

This one's off the dementia list.

3. Dementia and anticholinergic drugs

Anticholinergic drugs treat many conditions, including urine incontinence. Drugs inhibit acetylcholine (a brain chemical that helps send messages between cells). Acetylcholine blockers cause drowsiness, disorientation, and memory loss.

First-generation antihistamines, tricyclic antidepressants, and overactive bladder antimuscarinics are common anticholinergics among the elderly.

Anticholinergic drugs may cause dementia. One study found that taking anticholinergics for three years or more increased the risk of dementia by 1.54 times compared to three months or less. After stopping the medicine, the danger may continue.

4. Drugs for Parkinson's disease and dementia

Cleveland Clinic (USA) on Parkinson's:

Parkinson's disease causes age-related brain degeneration. It causes delayed movements, tremors, and balance issues. Some are inherited, but most are unknown. There are various treatment options, but no cure.

Parkinson's medications can cause memory loss, confusion, delusions, and obsessive behaviors. The drug's effects on dopamine cause these issues.

A 2019 JAMA Internal Medicine study found powerful anticholinergic medications enhance dementia risk.

Those who took anticholinergics had a 1.5 times higher chance of dementia. Individuals taking antidepressants, antipsychotic drugs, anti-Parkinson’s drugs, overactive bladder drugs, and anti-epileptic drugs had the greatest risk of dementia.

Anticholinergic medicines can lessen Parkinson's-related tremors, but they slow cognitive ability. Anticholinergics can cause disorientation and hallucinations in those over 70.

5. Antiepileptic drugs and dementia

The risk of dementia from anti-seizure drugs varies with drugs. Levetiracetam (Keppra) improves Alzheimer's cognition.

One study linked different anti-seizure medications to dementia. Anti-epileptic medicines increased the risk of Alzheimer's disease by 1.15 times in the Finnish sample and 1.3 times in the German population. Depakote, Topamax are drugs.

“I think if I had time to do something else, I would be so excited to go after this company right now.”

Sam Altman, CEO of Open AI, recently discussed AI's present and future.

Open AI is important. They're creating the cyberpunk and sci-fi worlds.

They use the most advanced algorithms and data sets.

GPT-3...sound familiar? Open AI built most copyrighting software. Peppertype, Jasper AI, Rytr. If you've used any, you'll be shocked by the quality.

Open AI isn't only GPT-3. They created DallE-2 and Whisper (a speech recognition software released last week).

What will they do next? What's the next great chance?

Sam Altman, CEO of Open AI, recently gave a lecture about the next trillion-dollar AI opportunity.

Who is the organization behind Open AI?

Open AI first. If you know, skip it.

Open AI is one of the earliest private AI startups. Elon Musk, Greg Brockman, and Rebekah Mercer established OpenAI in December 2015.

OpenAI has helped its citizens and AI since its birth.

They have scary-good algorithms.

Their GPT-3 natural language processing program is excellent.

The algorithm's exponential growth is astounding. GPT-2 came out in November 2019. May 2020 brought GPT-3.

Massive computation and datasets improved the technique in just a year. New York Times said GPT-3 could write like a human.

Same for Dall-E. Dall-E 2 was announced in April 2022. Dall-E 2 won a Colorado art contest.

Open AI's algorithms challenge jobs we thought required human innovation.

So what does Sam Altman think?

The Present Situation and AI's Limitations

During the interview, Sam states that we are still at the tip of the iceberg.

So I think so far, we’ve been in the realm where you can do an incredible copywriting business or you can do an education service or whatever. But I don’t think we’ve yet seen the people go after the trillion dollar take on Google.

He's right that AI can't generate net new human knowledge. It can train and synthesize vast amounts of knowledge, but it simply reproduces human work.

“It’s not going to cure cancer. It’s not going to add to the sum total of human scientific knowledge.”

But the key word is yet.

And that is what I think will turn out to be wrong that most surprises the current experts in the field.

Reinforcing his point that massive innovations are yet to come.

But where?

The Next $1 Trillion AI Company

Sam predicts a bio or genomic breakthrough.

There’s been some promising work in genomics, but stuff on a bench top hasn’t really impacted it. I think that’s going to change. And I think this is one of these areas where there will be these new $100 billion to $1 trillion companies started, and those areas are rare.

Avoid human trials since they take time. Bio-materials or simulators are suitable beginning points.

AI may have a breakthrough. DeepMind, an OpenAI competitor, has developed AlphaFold to predict protein 3D structures.

It could change how we see proteins and their function. AlphaFold could provide fresh understanding into how proteins work and diseases originate by revealing their structure. This could lead to Alzheimer's and cancer treatments. AlphaFold could speed up medication development by revealing how proteins interact with medicines.

Deep Mind offered 200 million protein structures for scientists to download (including sustainability, food insecurity, and neglected diseases).

Being in AI for 4+ years, I'm amazed at the progress. We're past the hype cycle, as evidenced by the collapse of AI startups like C3 AI, and have entered a productive phase.

We'll see innovative enterprises that could replace Google and other trillion-dollar companies.

What happens after AI adoption is scary and unpredictable. How will AGI (Artificial General Intelligence) affect us? Highly autonomous systems that exceed humans at valuable work (Open AI)

My guess is that the things that we’ll have to figure out are how we think about fairly distributing wealth, access to AGI systems, which will be the commodity of the realm, and governance, how we collectively decide what they can do, what they don’t do, things like that. And I think figuring out the answer to those questions is going to just be huge. — Sam Altman CEO

Understanding your own energy depletion and restoration is how to truly optimize

Hack has meant many bad things for centuries. In the 1800s, a hack was a meager horse used to transport goods.

Modern usage describes a butcher or ax murderer's cleaver chop. The 1980s programming boom distinguished elegant code from "hacks". Both got you to your goal, but the latter made any programmer cringe and mutter about changing the code. From this emerged the hacker trope, the friendless anti-villain living in a murky hovel lit by the computer monitor, eating junk food and breaking into databases to highlight security system failures or steal hotdog money.

Now, start-a-billion-dollar-business-from-your-garage types have shifted their sights from app development to DIY biology, coining the term "bio-hack". This is a required keyword and meta tag for every fitness-related podcast, book, conference, app, or device.

Bio-hacking involves bypassing your body and mind's security systems to achieve a goal. Many biohackers' initial goals were reasonable, like lowering blood pressure and weight. Encouraged by their own progress, self-determination, and seemingly exquisite control of their biology, they aimed to outsmart aging and death to live 180 to 1000 years (summarized well in this vox.com article).

With this grandiose north star, the hunt for novel supplements and genetic engineering began.

Companies selling do-it-yourself biological manipulations cite lab studies in mice as proof of their safety and success in reversing age-related diseases or promoting longevity in humans (the goal changes depending on whether a company is talking to the federal government or private donors).

The FDA is slower than science, they say. Why not alter your biochemistry by buying pills online, editing your DNA with a CRISPR kit, or using a sauna delivered to your home? How about a microchip or electrical stimulator?

What could go wrong?

I'm not the neo-police, making citizen's arrests every time someone introduces a new plumbing gadget or extrapolates from animal research on resveratrol or catechins that we should drink more red wine or eat more chocolate. As a scientist who's spent her career asking, "Can we get better?" I've come to view bio-hacking as misguided, profit-driven, and counterproductive to its followers' goals.

We're creatures of nature. Despite all the new gadgets and bio-hacks, we still use Roman plumbing technology, and the best way to stay fit, sharp, and happy is to follow a recipe passed down since the beginning of time. Bacteria, plants, and all natural beings are rhythmic, with alternating periods of high activity and dormancy, whether measured in seconds, hours, days, or seasons. Nature repeats successful patterns.

During the Upstate, every cell in your body is naturally primed and pumped full of glycogen and ATP (your cells' energy currencies), as well as cortisol, which supports your muscles, heart, metabolism, cognitive prowess, emotional regulation, and general "get 'er done" attitude. This big energy release depletes your batteries and requires the Downstate, when your subsystems recharge at the cellular level.

Downstates are when you give your heart a break from pumping nutrient-rich blood through your body; when you give your metabolism a break from inflammation, oxidative stress, and sympathetic arousal caused by eating fast food — or just eating too fast; or when you give your mind a chance to wander, think bigger thoughts, and come up with new creative solutions. When you're responding to notifications, emails, and fires, you can't relax.

Downstates aren't just for consistently recharging your battery. By spending time in the Downstate, your body and brain get extra energy and nutrients, allowing you to grow smarter, faster, stronger, and more self-regulated. This state supports half-marathon training, exam prep, and mediation. As we age, spending more time in the Downstate is key to mental and physical health, well-being, and longevity.

When you prioritize energy-demanding activities during Upstate periods and energy-replenishing activities during Downstate periods, all your subsystems, including cardiovascular, metabolic, muscular, cognitive, and emotional, hum along at their optimal settings. When you synchronize the Upstates and Downstates of these individual rhythms, their functioning improves. A hard workout causes autonomic stress, which triggers Downstate recovery.

By choosing the right timing and type of exercise during the day, you can ensure a deeper recovery and greater readiness for the next workout by working with your natural rhythms and strengthening your autonomic and sleep Downstates.

Morning cardio workouts increase deep sleep compared to afternoon workouts. Timing and type of meals determine when your sleep hormone melatonin is released, ushering in sleep.

Rhythm isn't a hack. It's not a way to cheat the system or the boss. Nature has honed its optimization wisdom over trillions of days and nights. Stop looking for quick fixes. You're a whole system made of smaller subsystems that must work together to function well. No one pill or subsystem will make it all work. Understanding and coordinating your rhythms is free, easy, and only benefits you.

Dr. Sara C. Mednick is a cognitive neuroscientist at UC Irvine and author of The Power of the Downstate (HachetteGO)

Economic mutual destruction.

Multibillion-dollar corporations never bothered with an independent audit, and they all lied about their balance sheets.

It's easy to forget that the Big Four accounting firms are lousy fraud enablers. Just because they sign off on your books doesn't mean you're not a hoax waiting to erupt.

This is *crazy* Capitalism depends on independent auditors. Rich folks need to know their financial advisers aren't lying. Rich folks usually succeed.

No accounting. EY, KPMG, PWC, and Deloitte make more money consulting firms than signing off on their accounts.

The Big Four sign off on phony books because failing to make friends with unscrupulous corporations may cost them consulting contracts.

The Big Four are the only firms big enough to oversee bankruptcy when they sign off on fraudulent books, as they did for Carillion in 2018. All four profited from Carillion's bankruptcy.

The Big Four are corrupt without any consequences for misconduct. Who can forget when KPMG's top management was fined millions for helping auditors cheat on ethics exams?

Consulting and auditing conflict. Consultants help a firm cover its evil activities, such as tax fraud or wage theft, whereas auditors add clarity to a company's finances. The Big Four make more money from cooking books than from uncooking them, thus they are constantly embroiled in scandals.

If a major scandal breaks, it may bring down the entire sector and substantial parts of the economy. Jim Peterson explains system risk for The Dig.

The Big Four are voluntary private partnerships where accountants invest their time, reputations, and money. If a controversy threatens the business, partners who depart may avoid scandal and financial disaster.

When disaster looms, each partner should bolt for the door, even if a disciplined stay-and-hold posture could weather the storm. This happened to Arthur Andersen during Enron's collapse, and a 2006 EU report recognized the risk to other corporations.

Each partner at a huge firm knows how much dirty laundry they've buried in the company's garden, and they have well-founded suspicions about what other partners have buried, too. When someone digs, everyone runs.

If a firm confronts substantial litigation damages or enforcement penalties, it could trigger the collapse of one of the Big Four. That would be bad news for the firm's clients, who would have trouble finding another big auditor.

Most of the world's auditing capacity is concentrated in four enormous, brittle, opaque, compromised organizations. If one of them goes bankrupt, the other three won't be able to take on its clients.

Peterson: Another collapse would strand many of the world's large public businesses, leaving them unable to obtain audit views for their securities listings and regulatory compliance.

Count Down: The Past, Present, and Uncertain Future of the Big Four Accounting Firms is in its second edition.

https://www.emerald.com/insight/publication/doi/10.1108/9781787147003

GM Friens

The space had better days. Those greenish spikes...oh wow, haven't felt that in ages. Cryptocurrencies and NFTs have lost popularity. Google agrees. Both are declining.

As seen below, crypto interest spiked in May because of the Luna fall. NFT interest is similar to early October last year.

This makes me think NFTs are mostly hype and FOMO. No art or community. I've seen enough initiatives to know that communities stick around if they're profitable. Once it starts falling, they move on to the next project. The space has no long-term investments. Flip everything.

OpenSea trading volume has stayed steady for months. May's volume is 1.8 million ETH ($3.3 billion).

Despite this, I think NFTs and crypto will stick around. In bad markets, builders gain most.

Only 4k developers are active on Ethereum blockchain. It's low. A great chance for the space enthusiasts.

An employee of OpenSea might get a 40-year prison sentence for insider trading using NFTs.

Nathaniel Chastian, an OpenSea employee, traded on insider knowledge. He'll serve 40 years for that.

Here's what happened if you're unfamiliar.

OpenSea is a secondary NFT marketplace. Their homepage featured remarkable drops. Whatever gets featured there, NFT prices will rise 5x.

Chastian was at OpenSea. He chose forthcoming NFTs for OpenSeas' webpage.

Using anonymous digital currency wallets and OpenSea accounts, he would buy NFTs before promoting them on the homepage, showcase them, and then sell them for at least 25 times the price he paid.

From June through September 2021, this happened. Later caught, fired. He's charged with wire fraud and money laundering, each carrying a 20-year maximum penalty.

Although web3 space is all about decentralization, a step like this is welcomed since it restores faith in the area. We hope to see more similar examples soon.

Here's the press release.

Understanding smart contracts

@cantino.eth has a Twitter thread on smart contracts. Must-read. Also, he appears educated about the space, so follow him.

Genius or lucky?

From the title, you might think I'm selling advertising for a financial influencer, a dubious trading site, or a training organization to attract clients. I'm suspicious. Better safe than sorry.

But not here.

Jake Freeman, 20, made $110 million in a month, according to the Financial Times. At 18, he ran for president. He made his name in markets, not politics. Two years later, he's Wall Street's prince. Interview requests flood the prodigy.

Jake Freeman bought 5 million Bed Bath & Beyond Group shares for $5.5 in July 2022 and sold them for $27 a month later. He thought the stock might double. Since speculation died down, he sold well. The stock fell 40.5% to 11 dollars on Friday, 19 August 2022. On August 22, 2022, it fell 16% to $9.

Smallholders have been buying the stock for weeks and will lose heavily if it falls further. Bed Bath & Beyond is the second most popular stock after Foot Locker, ahead of GameStop and Apple.

Jake Freeman earned $110 million thanks to a significant stock market flurry.

Online broker customers aren't the only ones with jitters. By June 2022, Ken Griffin's Citadel and Stephen Mandel's Lone Pine Capital held nearly a third of the company's capital. Did big managers sell before the stock plummeted?

Recent stock movements (derivatives) and rumors could prompt a SEC investigation.

Jake Freeman wrote to the board of directors after his investment to call for a turnaround, given the company's persistent problems and short sellers. The bathroom and kitchen products distribution group's stock soared in July 2022 due to renewed buying by private speculators, who made it one of their meme stocks with AMC and GameStop.

Second-quarter 2022 results and financial health worsened. He didn't celebrate his miraculous operation in a nightclub. He told a British newspaper, "I'm shocked." His parents dined in New York. He returned to Los Angeles to study math and economics.

Jake Freeman founded Freeman Capital Management with his savings and $25 million from family, friends, and acquaintances. They are the ones who are entitled to the $110 million he raised in one month. Will his investors pocket and withdraw all or part of their profits or will they trust the young prodigy for new stunts on Wall Street?

His operation should attract new clients. Well-known hedge funds may hire him.

Jake Freeman didn't listen to gurus or former traders. At 17, he interned at a quantitative finance and derivatives hedge fund, Volaris. At 13, he began investing with his pharmaceutical executive uncle. All countries have increased their Google searches for the young trader in the last week.

Naturally, his success has inspired resentment.

His success stirs jealousy, and he's attacked on social media. On Reddit, people who lost money on Bed Bath & Beyond, Jake Freeman's fortune, are mourning.

Several conspiracy theories circulate about him, including that he doesn't exist or is working for a Taiwanese amusement park.

If all 20 million American students had the same trading skills, they would have generated $1.46 trillion. Jake Freeman is unique. Apprentice traders' careers are often short, disillusioning, and tragic.

Two years ago, 20-year-old Robinhood client Alexander Kearns committed suicide after losing $750,000 trading options. Great traders start young. Michael Platt of BlueCrest invested in British stocks at age 12 under his grandmother's supervision and made a £30,000 fortune. Paul Tudor Jones started trading before he turned 18 with his uncle. Warren Buffett, at age 10, was discussing investments with Goldman Sachs' head. Oracle of Omaha tells all.