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

Market fraud

Due to its decentralized and fragmented character, the crypto market has integrity difficulties.

Cryptocurrencies are an immature sector, therefore market manipulation becomes a bigger issue. Many research have attempted to uncover these abuses. CryptoCompare's newest one highlights some of the industry's most typical scams.

Why are these concerns so common in the crypto market? First, even the largest centralized exchanges remain unregulated due to industry immaturity. A low-liquidity market segment makes an attack more harmful. Finally, market surveillance solutions not implemented reduce transparency.

In CryptoCompare's latest exchange benchmark, 62.4% of assessed exchanges had a market surveillance system, although only 18.1% utilised an external solution. To address market integrity, this measure must improve dramatically. Before discussing the report's malpractices, note that this is not a full list of attacks and hacks.

Clean Trading

An investor buys and sells concurrently to increase the asset's price. Centralized and decentralized exchanges show this misconduct. 23 exchanges have a volume-volatility correlation < 0.1 during the previous 100 days, according to CryptoCompares. In August 2022, Exchange A reported $2.5 trillion in artificial and/or erroneous volume, up from $33.8 billion the month before.

Spoofing

Criminals create and cancel fake orders before they can be filled. Since manipulators can hide in larger trading volumes, larger exchanges have more spoofing. A trader placed a 20.8 BTC ask order at $19,036 when BTC was trading at $19,043. BTC declined 0.13% to $19,018 in a minute. At 18:48, the trader canceled the ask order without filling it.

Front-Running

Most cryptocurrency front-running involves inside trading. Traditional stock markets forbid this. Since most digital asset information is public, this is harder. Retailers could utilize bots to front-run.

CryptoCompare found digital wallets of people who traded like insiders on exchange listings. The figure below shows excess cumulative anomalous returns (CAR) before a coin listing on an exchange.

Finally, LAYERING is a sequence of spoofs in which successive orders are put along a ladder of greater (layering offers) or lower (layering bids) values. The paper concludes with recommendations to mitigate market manipulation. Exchange data transparency, market surveillance, and regulatory oversight could reduce manipulative tactics.

A fascinating business conversation.

This week at Web Summit, I had mentor hour.

Mentor hour connects startups with experienced entrepreneurs.

The YC-selected founder who mentored me had grown his company to $100 million in 18 months.

I had 45 minutes to question him.

I've compiled this.

Context

Founder's name is Zack.

After working in private equity, Zack opted to acquire an MBA.

Surrounded by entrepreneurs at a prominent school, he decided to become one himself.

Unsure how to proceed, he bet on two horses.

On one side, he received an offer from folks who needed help running their startup owing to lack of time. On the other hand, he had an idea for a SaaS to start himself.

He just needed to validate it.

Validating

Since Zack's proposal helped companies, he contacted university entrepreneurs for comments.

He contacted university founders.

Once he knew he'd correctly identified the problem and that people were willing to pay to address it, he started developing.

He earned $100k in a university entrepreneurship competition.

His plan was evident by then.

The other startup's founders saw his potential and granted him $400k to launch his own SaaS.

Hiring

He started looking for a tech co-founder because he lacked IT skills.

He interviewed dozens and picked the finest.

As he didn't want to wait for his program to be ready, he contacted hundreds of potential clients and got 15 letters of intent promising they'd join up when it was available.

YC accepted him by then.

He had enough positive signals to raise.

Raising

He didn't say how many VCs he called, but he indicated 50 were interested.

He jammed meetings into two weeks to generate pressure and encourage them to invest.

Seed raise: $11 million.

Selling

His objective was to contact as many entrepreneurs as possible to promote his product.

He first contacted startups by scraping CrunchBase data.

Once he had more money, he started targeting companies with ZoomInfo.

His VC urged him not to hire salespeople until he closed 50 clients himself.

He closed 100 and hired a CRO through a headhunter.

Scaling

Three persons started the business.

1. He primarily works in sales.

2. Coding the product was done by his co-founder.

3. Another person performing operational duties.

He regretted recruiting the third co-founder, who was ineffective (could have hired an employee instead).

He wanted his company to be big, so he hired two young marketing people from a competing company.

After validating several marketing channels, he chose PR.

$100 Million and under

He developed a sales team and now employs 30 individuals.

He raised a $100 million Series A.

Additionally, he stated

• He’s been rejected a lot. Like, a lot.

• Two great books to read: Steve Jobs by Isaacson, and Why Startups Fail by Tom Eisenmann.

• The best skill to learn for non-tech founders is “telling stories”, which means sales. A founder’s main job is to convince: co-founders, employees, investors, and customers. Learn code, or learn sales.

Conclusion

I often read about these stories but hardly take them seriously.

Zack was amazing.

Three things about him stand out:

1. His vision. He possessed a certain amount of fire.

2. His vitality. The man had a lot of enthusiasm and spoke quickly and decisively. He takes no chances and pushes the envelope in all he does.

3. His Rolex.

He didn't do all this in 18 months.

Not really.

He couldn't launch his company without private equity experience.

These accounts disregard entrepreneurs' original knowledge.

Hormozi will tell you how he founded Gym Launch, but he won't tell you how he had a gym first, how he worked at uni to pay for his gym, or how he went to the gym and learnt about fitness, which gave him the idea to open his own.

Nobody knows nothing. If you scale quickly, it's probable because you gained information early.

Lincoln said, "Give me six hours to chop down a tree, and I'll spend four sharpening the axe."

Sharper axes cut trees faster.

We're opening up Maki through a series of Medium posts. We'll describe what Maki is building and how. We'll explain how we built a SaaS in 100 days. This isn't a step-by-step guide to starting a business, but a product philosophy to help you build quickly.

Focus on end-users.

This may seem obvious, but it's important to talk to users first. When we started thinking about Maki, we interviewed 100 HR directors from SMBs, Next40 scale-ups, and major Enterprises to understand their concerns. We initially thought about the future of employment, but most of their worries centered on Recruitment. We don't have a clear recruiting process, it's time-consuming, we recruit clones, we don't support diversity, etc. And as hiring managers, we couldn't help but agree.

Co-create your product with your end-users.

We went to the drawing board, read as many books as possible (here, here, and here), and when we started getting a sense for a solution, we questioned 100 more operational HR specialists to corroborate the idea and get a feel for our potential answer. This confirmed our direction to help hire more objectively and efficiently.

Back to the drawing board, we designed our first flows and screens. We organized sessions with certain survey respondents to show them our early work and get comments. We got great input that helped us build Maki, and we met some consumers. Obsess about users and execute alongside them.

Don’t shoot for the moon, yet. Make pragmatic choices first.

Once we were convinced, we began building. To launch a SaaS in 100 days, we needed an operating principle that allowed us to accelerate while still providing a reliable, secure, scalable experience. We focused on adding value and outsourced everything else. Example:

Concentrate on adding value. Reuse existing bricks.

When determining which technology to use, we looked at our strengths and the future to see what would last. Node.js for backend, React for frontend, both with typescript. We thought this technique would scale well since it would attract more talent and the surrounding mature ecosystem would help us go quicker.

We explored for ways to bootstrap services while setting down strong foundations that might support millions of users. We built our backend services on NestJS so we could extend into microservices later. Hasura, a GraphQL APIs engine, automates Postgres data exposing through a graphQL layer. MUI's ready-to-use components powered our design-system. We used well-maintained open-source projects to speed up certain tasks.

We outsourced important components of our platform (Auth0 for authentication, Stripe for billing, SendGrid for notifications) because, let's face it, we couldn't do better. We choose to host our complete infrastructure (SQL, Cloud run, Logs, Monitoring) on GCP to simplify our work between numerous providers.

Focus on your business, use existing bricks for the rest. For the curious, we'll shortly publish articles detailing each stage.

Most importantly, empower people and step back.

We couldn't have done this without the incredible people who have supported us from the start. Since Powership is one of our key values, we provided our staff the power to make autonomous decisions from day one. Because we believe our firm is its people, we hired smart builders and let them build.

Nicolas left Spendesk to create scalable interfaces using react-router, react-queries, and MUI. JD joined Swile and chose Hasura as our GraphQL engine. Jérôme chose NestJS to build our backend services. Since then, Justin, Ben, Anas, Yann, Benoit, and others have followed suit.

If you consider your team a collective brain, you should let them make decisions instead of directing them what to do. You'll make mistakes, but you'll go faster and learn faster overall.

Invest in great talent and develop a strong culture from the start. Here's how to establish a SaaS in 100 days.