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.

NASA's Artemis 1 mission will help return people to the Moon after a half-century break. The mission is a shakedown cruise for NASA's Space Launch System and Orion Crew Capsule.

The spaceship will visit the Moon, deploy satellites, and enter orbit. NASA wants to practice operating the spacecraft, test the conditions people will face on the Moon, and ensure a safe return to Earth.

We asked Jack Burns, a space scientist at the University of Colorado Boulder and former member of NASA's Presidential Transition Team, to describe the mission, explain what the Artemis program promises for space exploration, and reflect on how the space program has changed in the half-century since humans last set foot on the moon.

What distinguishes Artemis 1 from other rockets?

Artemis 1 is the Space Launch System's first launch. NASA calls this a "heavy-lift" vehicle. It will be more powerful than Apollo's Saturn V, which transported people to the Moon in the 1960s and 1970s.

It's a new sort of rocket system with two strap-on solid rocket boosters from the space shuttle. It's a mix of the shuttle and Saturn V.

The Orion Crew Capsule will be tested extensively. It'll spend a month in the high-radiation Moon environment. It will also test the heat shield, which protects the capsule and its occupants at 25,000 mph. The heat shield must work well because this is the fastest capsule descent since Apollo.

This mission will also carry miniature Moon-orbiting satellites. These will undertake vital precursor science, including as examining further into permanently shadowed craters where scientists suspect there is water and measuring the radiation environment to see long-term human consequences.

Artemis 1 will launch, fly to the Moon, place satellites, orbit it, return to Earth, and splash down in the ocean. NASA.

What's Artemis's goal? What launches are next?

The mission is a first step toward Artemis 3, which will lead to the first human Moon missions since 1972. Artemis 1 is unmanned.

Artemis 2 will have astronauts a few years later. Like Apollo 8, it will be an orbital mission that circles the Moon and returns. The astronauts will orbit the Moon longer and test everything with a crew.

Eventually, Artemis 3 will meet with the SpaceX Starship on the Moon's surface and transfer people. Orion will stay in orbit while the lunar Starship lands astronauts. They'll go to the Moon's south pole to investigate the water ice there.

Artemis is reminiscent of Apollo. What's changed in 50 years?

Kennedy wanted to beat the Soviets to the Moon with Apollo. The administration didn't care much about space flight or the Moon, but the goal would place America first in space and technology.

You live and die by the sword if you do that. When the U.S. reached the Moon, it was over. Russia lost. We planted flags and did science experiments. Richard Nixon canceled the program after Apollo 11 because the political goals were attained.

Large rocket with two boosters between two gates

NASA's new Space Launch System is brought to a launchpad. NASA

50 years later... It's quite different. We're not trying to beat the Russians, Chinese, or anyone else, but to begin sustainable space exploration.

Artemis has many goals. It includes harnessing in-situ resources like water ice and lunar soil to make food, fuel, and building materials.

SpaceX is part of this first journey to the Moon's surface, therefore the initiative is also helping to develop a lunar and space economy. NASA doesn't own the Starship but is buying seats for astronauts. SpaceX will employ Starship to transport cargo, private astronauts, and foreign astronauts.

Fifty years of technology advancement has made getting to the Moon cheaper and more practical, and computer technology allows for more advanced tests. 50 years of technological progress have changed everything. Anyone with enough money can send a spacecraft to the Moon, but not humans.

Commercial Lunar Payload Services engages commercial companies to develop uncrewed Moon landers. We're sending a radio telescope to the Moon in January. Even 10 years ago, that was impossible.

Since humans last visited the Moon 50 years ago, technology has improved greatly.

What other changes does Artemis have in store?

The government says Artemis 3 will have at least one woman and likely a person of color. 

I'm looking forward to seeing more diversity so young kids can say, "Hey, there's an astronaut that looks like me. I can do this. I can be part of the space program.”

The Lex Fridman podcast host has interviewed Elon Musk.

Lex is a minimalist YouTuber. His videos are sloppy. Suits are his trademark.

In a video, he shares a typical day. I've smashed my 6-month goals using its ideas.

Here's his schedule.

Morning Mantra

Not woo-woo. Lex's mantra reflects his practicality.

Four parts.

Rulebook

"I remember the game's rules," he says.

Among them:

• Sleeping 6–8 hours nightly

• 1–3 times a day, he checks social media.

• Every day, despite pain, he exercises. "I exercise uninjured body parts."

Visualize

He imagines his day. "Like Sims..."

He says three things he's grateful for and contemplates death.

"Today may be my last"

Objectives

Then he visualizes his goals. He starts big. Five-year goals.

Short-term goals follow. Lex says they're year-end goals.

Near but out of reach.

Principles

He lists his principles. Assertions. His goals.

He acknowledges his cliche beliefs. Compassion, empathy, and strength are key.

Here's my mantra routine:

Four-Hour Deep Work

Lex begins a four-hour deep work session after his mantra routine. Today's toughest.

AI is Lex's specialty. His video doesn't explain what he does.

Clearly, he works hard.

Before starting, he has water, coffee, and a bathroom break.

"During deep work sessions, I minimize breaks."

He's distraction-free. Phoneless. Silence. Nothing. Any loose ideas are typed into a Google doc for later. He wants to work.

"Just get the job done. Don’t think about it too much and feel good once it’s complete." — Lex Fridman

30-Minute Social Media & Music

After his first deep work session, Lex rewards himself.

10 minutes on social media, 20 on music. Upload content and respond to comments in 10 minutes. 20 minutes for guitar or piano.

"In the real world, I’m currently single, but in the music world, I’m in an open relationship with this beautiful guitar. Open relationship because sometimes I cheat on her with the acoustic." — Lex Fridman

Two-hour exercise

Then exercise for two hours.

Daily runs six miles. Then he chooses how far to go. Run time is an hour.

He does bodyweight exercises. Every minute for 15 minutes, do five pull-ups and ten push-ups. It's David Goggins-inspired. He aims for an hour a day.

He's hungry. Before running, he takes a salt pill for electrolytes.

He'll then take a one-minute cold shower while listening to cheesy songs. Afterward, he might eat.

Four-Hour Deep Work

Lex's second work session.

He works 8 hours a day.

Again, zero distractions.

Eating

The video's meal doesn't look appetizing, but it's healthy.

It's ground beef with vegetables. Cauliflower is his "ground-floor" veggie. "Carrots are my go-to party food."

Lex's keto diet includes 1800–2000 calories.

He drinks a "nutrient-packed" Atheltic Greens shake and takes tablets. It's:

• One daily tablet of sodium.

• Magnesium glycinate tablets stopped his keto headaches.

• Potassium — "For electrolytes"

• Fish oil: healthy joints

“So much of nutrition science is barely a science… I like to listen to my own body and do a one-person, one-subject scientific experiment to feel good.” — Lex Fridman

Four-hour shallow session

This work isn't as mentally taxing.

Lex planned to:

• Finish last session's deep work (about an hour)

• Adobe Premiere podcasting (about two hours).

• Email-check (about an hour). Three times a day max. First, check for emergencies.

If he's sick, he may watch Netflix or YouTube documentaries or visit friends.

“The possibilities of chaos are wide open, so I can do whatever the hell I want.” — Lex Fridman

Two-hour evening reading

Nonstop work.

Lex ends the day reading academic papers for an hour. "Today I'm skimming two machine learning and neuroscience papers"

This helps him "think beyond the paper."

He reads for an hour.

“When I have a lot of energy, I just chill on the bed and read… When I’m feeling tired, I jump to the desk…” — Lex Fridman

Takeaways

Lex's day-in-the-life video is inspiring.

He has positive energy and works hard every day.

Schedule:

• Mantra Routine includes rules, visualizing, goals, and principles.

• Deep Work Session #1: Four hours of focus.

• 10 minutes social media, 20 minutes guitar or piano. "Music brings me joy"

• Six-mile run, then bodyweight workout. Two hours total.

• Deep Work #2: Four hours with no distractions. Google Docs stores random thoughts.

• Lex supplements his keto diet.

• This four-hour session is "open to chaos."

• Evening reading: academic papers followed by fiction.

"I value some things in life. Work is one. The other is loving others. With those two things, life is great." — Lex Fridman

I've written a lot about Y Combinator's success, but as any startup founder or investor knows, many startups fail.

Rebel Fund invests in the top 5-10% of new Y Combinator startups each year, so we focus on identifying and supporting the most promising technology startups in our ecosystem. Given the power law dynamic and asymmetric risk/return profile of venture capital, we worry more about our successes than our failures. Since the latter still counts, this essay will focus on the proportion of YC startups that fail.

Since YC's launch in 2005, the figure below shows the percentage of active, inactive, and public/acquired YC startups by batch.

As more startups finish, the blue bars (active) decrease significantly. By 12 years, 88% of startups have closed or exited. Only 7% of startups reach resolution each year.

YC startups by status after 12 years:

Half the startups have failed, over one-third have exited, and the rest are still operating.

In venture investing, it's said that failed investments show up before successful ones. This is true for YC startups, but only in their early years.

Below, we only present resolved companies from the first chart. Some companies fail soon after establishment, but after a few years, the inactive vs. public/acquired ratio stabilizes around 55:45. After a few years, a YC firm is roughly as likely to quit as fail, which is better than I imagined.

I prepared this post because Rebel investors regularly question me about YC startup failure rates and how long it takes for them to exit or shut down.

Early-stage venture investors can overlook it because 100x investments matter more than 0x investments.

YC founders can ignore it because it shouldn't matter if many of their peers succeed or fail ;)

Three Arrows Capital's Google search volume rose over 5,000%.

Three Arrows Capital, a Singapore-based cryptocurrency hedge fund, filed for Chapter 15 bankruptcy last Friday to protect its U.S. assets from creditors.

• Three Arrows filed for bankruptcy on July 1 in New York.

• Three Arrows was ordered liquidated by a British Virgin Islands court last week after defaulting on a $670 million loan from Voyager Digital. Three days later, the Singaporean government reprimanded Three Arrows for spreading misleading information and exceeding asset limits.

• Three Arrows' troubles began with Terra's collapse in May, after it bought US$200 million worth of Terra's LUNA tokens in February, co-founder Kyle Davies told the Wall Street Journal. Three Arrows has failed to meet multiple margin calls since then, including from BlockFi and Genesis.

• Three Arrows Capital, founded by Kyle Davies and Su Zhu in 2012, manages $10 billion in crypto assets.

• Bitcoin's price fell from US$20,600 to below US$19,200 after Three Arrows' bankruptcy petition. According to CoinMarketCap, BTC is now above US$20,000.

What does it mean?

Every action causes an equal and opposite reaction, per Newton's third law. Newtonian physics won't comfort Three Arrows investors, but future investors will thank them for their overconfidence.

Regulators are taking notice of crypto's meteoric rise and subsequent fall. Historically, authorities labeled the industry "high risk" to warn traditional investors against entering it. That attitude is changing. Regulators are moving quickly to regulate crypto to protect investors and prevent broader asset market busts.

The EU has reached a landmark deal that will regulate crypto asset sales and crypto markets across the 27-member bloc. The U.S. is close behind with a similar ruling, and smaller markets are also looking to improve safeguards.

For many, regulation is the only way to ensure the crypto industry survives the current winter.