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

The company seeking 24/7 ultra-powerful solar electricity.

We're rushing to adopt low-carbon energy to prevent a self-made doomsday. We're using solar, wind, and wave energy. These low-carbon sources aren't perfect. They consume large areas of land, causing habitat loss. They don't produce power reliably, necessitating large grid-level batteries, an environmental nightmare. We can and must do better than fossil fuels. Longi, one of the world's top solar panel producers, is creating a low-carbon energy source. Solar-powered spacecraft. But how does it work? Why is it so environmentally harmonious? And how can Longi unlock it?

Space-based solar makes sense. Satellites above Medium Earth Orbit (MEO) enjoy 24/7 daylight. Outer space has no atmosphere or ozone layer to block the Sun's high-energy UV radiation. Solar panels can create more energy in space than on Earth due to these two factors. Solar panels in orbit can create 40 times more power than those on Earth, according to estimates.

How can we utilize this immense power? Launch a geostationary satellite with solar panels, then beam power to Earth. Such a technology could be our most eco-friendly energy source. (Better than fusion power!) How?

Solar panels create more energy in space, as I've said. Solar panel manufacture and grid batteries emit the most carbon. This indicates that a space-solar farm's carbon footprint (which doesn't need a battery because it's a constant power source) might be over 40 times smaller than a terrestrial one. Combine that with carbon-neutral launch vehicles like Starship, and you have a low-carbon power source. Solar power has one of the lowest emissions per kWh at 6g/kWh, so space-based solar could approach net-zero emissions.

Space solar is versatile because it doesn't require enormous infrastructure. A space-solar farm could power New York and Dallas with the same efficiency, without cables. The satellite will transmit power to a nearby terminal. This allows an energy system to evolve and adapt as the society it powers changes. Building and maintaining infrastructure can be carbon-intensive, thus less infrastructure means less emissions.

Space-based solar doesn't destroy habitats, either. Solar and wind power can be engineered to reduce habitat loss, but they still harm ecosystems, which must be restored. Space solar requires almost no land, therefore it's easier on Mother Nature.

Space solar power could be the ultimate energy source. So why haven’t we done it yet?

Well, for two reasons: the cost of launch and the efficiency of wireless energy transmission.

Advances in rocket construction and reusable rocket technology have lowered orbital launch costs. In the early 2000s, the Space Shuttle cost $60,000 per kg launched into LEO, but a SpaceX Falcon 9 costs only $3,205. 95% drop! Even at these low prices, launching a space-based solar farm is commercially questionable.

Energy transmission efficiency is half of its commercial viability. Space-based solar farms must be in geostationary orbit to get 24/7 daylight, 22,300 miles above Earth's surface. It's a long way to wirelessly transmit energy. Most laser and microwave systems are below 20% efficient.

Space-based solar power is uneconomical due to low efficiency and high deployment costs.

Longi wants to create this ultimate power. But how?

They'll send solar panels into space to develop space-based solar power that can be beamed to Earth. This mission will help them design solar panels tough enough for space while remaining efficient.

Longi is a Chinese company, and China's space program and universities are developing space-based solar power and seeking commercial partners. Xidian University has built a 98%-efficient microwave-based wireless energy transmission system for space-based solar power. The Long March 5B is China's super-cheap (but not carbon-offset) launch vehicle.

Longi fills the gap. They have the commercial know-how and ability to build solar satellites and terrestrial terminals at scale. Universities and the Chinese government have transmission technology and low-cost launch vehicles to launch this technology.

It may take a decade to develop and refine this energy solution. This could spark a clean energy revolution. Once operational, Longi and the Chinese government could offer the world a flexible, environmentally friendly, rapidly deployable energy source.

Should the world adopt this technology and let China control its energy? I'm not very political, so you decide. This seems to be the beginning of tapping into this planet-saving energy source. Forget fusion reactors. Carbon-neutral energy is coming soon.

There’s a funny part of ‘Steve Jobs’ by Walter Isaacson where Jobs says that Bill Gates was more a copier than an innovator:

“Bill is basically unimaginative and has never invented anything, which is why I think he’s more comfortable now in philanthropy than technology. He just shamelessly ripped off other people’s ideas….He’d be a broader guy if he had dropped acid once or gone off to an ashram when he was younger.”

Gates lacked flavor. Nobody ever got excited about a Microsoft launch, despite their good products. Jobs had the world's best product taste. Apple vs. Microsoft.

A CEO's core job functions are all driven by taste: recruiting, vision, and company culture all require good taste. Depending on the type of company you want to build, know where you stand between Microsoft and Apple.

How can you improve your product judgment? How to acquire taste?

Test and refine

Product development follows two parallel paths: the ‘customer obsession’ path and the ‘taste and iterate’ path.

The customer obsession path involves solving customer problems. Lean Startup frameworks show you what to build at each step.

Taste-and-iterate doesn't involve the customer. You iterate internally and rely on product leaders' taste and judgment.

Creative Selection by Ken Kocienda explains this method. In Creative Selection, demos are iterated and presented to product leaders. Your boss presents to their boss, and so on up to Steve Jobs. If you have good product taste, you can be a panelist.

The iPhone follows this path. Before seeing an iPhone, consumers couldn't want one. Customer obsession wouldn't have gotten you far because iPhone buyers didn't know they wanted one.

In The Hard Thing About Hard Things, Ben Horowitz writes:

“It turns out that is exactly what product strategy is all about — figuring out the right product is the innovator’s job, not the customer’s job. The customer only knows what she thinks she wants based on her experience with the current product. The innovator can take into account everything that’s possible, but often must go against what she knows to be true. As a result, innovation requires a combination of knowledge, skill, and courage.“

One path solves a problem the customer knows they have, and the other doesn't. Instead of asking a person what they want, observe them and give them something they didn't know they needed.

It's much harder. Apple is the world's most valuable company because it's more valuable. It changes industries permanently.

If you want to build superior products, use the iPhone of your industry.

How to Improve Your Taste

I. Work for a company that has taste.

People with the best taste in products, markets, and people are rewarded for building great companies. Tasteful people know quality even when they can't describe it. Taste isn't writable. It's feel-based.

Moving into a community that's already doing what you want to do may be the best way to develop entrepreneurial taste. Most company-building knowledge is tacit.

Joining a company you want to emulate allows you to learn its inner workings. It reveals internal patterns intuitively. Many successful founders come from successful companies.

Consumption determines taste. Excellence will refine you. This is why restauranteurs visit the world's best restaurants and serious painters visit Paris or New York. Joining a company with good taste is beneficial.

2. Possess a wide range of interests

“Edwin Land of Polaroid talked about the intersection of the humanities and science. I like that intersection. There’s something magical about that place… The reason Apple resonates with people is that there’s a deep current of humanity in our innovation. I think great artists and great engineers are similar, in that they both have a desire to express themselves.” — Steve Jobs

I recently discovered Edwin Land. Jobs modeled much of his career after Land's. It makes sense that Apple was inspired by Land.

A Triumph of Genius: Edwin Land, Polaroid, and the Kodak Patent War notes:

“Land was introverted in person, but supremely confident when he came to his ideas… Alongside his scientific passions, lay knowledge of art, music, and literature. He was a cultured person growing even more so as he got older, and his interests filtered into the ethos of Polaroid.”

Founders' philosophies shape companies. Jobs and Land were invested. It showed in the products their companies made. Different. His obsession was spreading Microsoft software worldwide. Microsoft's success is why their products are bland and boring.

Experience is important. It's probably why startups are built by generalists and scaled by specialists.

Jobs combined design, typography, storytelling, and product taste at Apple. Some of the best original Mac developers were poets and musicians. Edwin Land liked broad-minded people, according to his biography. Physicist-musicians or physicist-photographers.

Da Vinci was a master of art, engineering, architecture, anatomy, and more. He wrote and drew at the same desk. His genius is remembered centuries after his death. Da Vinci's statue would stand at the intersection of humanities and science.

We find incredibly creative people here. Superhumans. Designers, creators, and world-improvers. These are the people we need to navigate technology and lead world-changing companies. Generalists lead.

5 VC investment criteria

I reviewed 200 startup business concepts last week. Brainache.

The enterprises sold various goods and services. The concepts were achingly similar: give us money, we'll produce a product, then get more to expand. No different from daily plans and pitches.

Most of those 200 plans sounded plausible. But 10% looked venture-worthy. 90% of startups need alternatives to venture finance.

With the success of VC-backed businesses and the growth of venture funds, a common misperception is that investors would fund any decent company idea. Finding investors that believe in the firm and founders is the key to funding.

Incorrect. Venture capital needs investing in certain enterprises. If your startup doesn't match the model, as most early-stage startups don't, you can revise your business plan or locate another source of capital.

Before spending six months pitching angels and VCs, make sure your startup fits these criteria.

Likely to generate $100 million in sales

First, I check the income predictions in a pitch deck. If it doesn't display $100M, don't bother.

The math doesn't work for venture financing in smaller businesses.

Say a fund invests $1 million in a startup valued at $5 million that is later acquired for $20 million. That's a win everyone should celebrate. Most VCs don't care.

Consider a $100M fund. The fund must reach $360M in 7 years with a 20% return. Only 20-30 investments are possible. 90% of the investments will fail, hence the 23 winners must return $100M-$200M apiece. $15M isn't worth the work.

Angel investors and tiny funds use the same ideas as venture funds, but their smaller scale affects the calculations. If a company can support its growth through exit on less than $2M in angel financing, it must have $25M in revenues before large companies will consider acquiring it.

Aiming for Hypergrowth

A startup's size isn't enough. It must expand fast.

Developing a great business takes time. Complex technology must be constructed and tested, a nationwide expansion must be built, or production procedures must go from lab to pilot to factories. These can be enormous, world-changing corporations, but venture investment is difficult.

The normal 10-year venture fund life. Investments are made during first 3–4 years.. 610 years pass between investment and fund dissolution. Funds need their investments to exit within 5 years, 7 at the most, therefore add a safety margin.

Longer exit times reduce ROI. A 2-fold return in a year is excellent. Loss at 2x in 7 years.

Lastly, VCs must prove success to raise their next capital. The 2nd fund is raised from 1st fund portfolio increases. Third fund is raised using 1st fund's cash return. Fund managers must raise new money quickly to keep their jobs.

Branding or technology that is protected

No big firm will buy a startup at a high price if they can produce a competing product for less. Their development teams, consumer base, and sales and marketing channels are large. Who needs you?

Patents, specialist knowledge, or brand name are the only answers. The acquirer buys this, not the thing.

I've heard of several promising startups. It's not a decent investment if there's no exit strategy.

A company that installs EV charging stations in apartments and shopping areas is an example. It's profitable, repeatable, and big. A terrific company. Not a startup.

This building company's operations aren't secret. No technology to protect, no special information competitors can't figure out, no go-to brand name. Despite the immense possibilities, a large construction company would be better off starting their own.

Most venture businesses build products, not services. Services can be profitable but hard to safeguard.

Probable purchase at high multiple

Once a software business proves its value, acquiring it is easy. Pharma and medtech firms have given up on their own research and instead acquire startups after regulatory permission. Many startups, especially in specialized areas, have this weakness.

That doesn't mean any lucrative $25M-plus business won't be acquired. In many businesses, the venture model requires a high exit premium.

A startup invents a new glue. 3M, BASF, Henkel, and others may buy them. Adding more adhesive to their catalogs won't boost commerce. They won't compete to buy the business. They'll only buy a startup at a profitable price. The acquisition price represents a moderate EBITDA multiple.

The company's $100M revenue presumably yields $10m in profits (assuming they’ve reached profitability at all). A $30M-$50M transaction is likely. Not terrible, but not what venture investors want after investing $25M to create a plant and develop the business.

Private equity buys profitable companies for a moderate profit multiple. It's a good exit for entrepreneurs, but not for investors seeking 10x or more what PE firms pay. If a startup offers private equity as an exit, the conversation is over.

Constructed for purchase

The startup wants a high-multiple exit. Unless the company targets $1B in revenue and does an IPO, exit means acquisition.

If they're constructing the business for acquisition or themselves, founders must decide.

If you want an indefinitely-running business, I applaud you. We need more long-term founders. Most successful organizations are founded around consumer demands, not venture capital's urge to grow fast and exit. Not venture funding.

if you don't match the venture model, what to do

VC funds moonshots. The 10% that succeed are extraordinary. Not every firm is a rocketship, and launching the wrong startup into space, even with money, will explode.

But just because your startup won't make $100M in 5 years doesn't mean it's a bad business. Most successful companies don't follow this model. It's not venture capital-friendly.

Although venture capital gets the most attention due to a few spectacular triumphs (and disasters), it's not the only or even most typical option to fund a firm.

Other ways to support your startup:

• Personal and family resources, such as credit cards, second mortgages, and lines of credit

• bootstrapping off of sales

• government funding and honors

• Private equity & project financing

• collaborating with a big business

• Including a business partner

Before pitching angels and VCs, be sure your startup qualifies. If so, include them in your pitch.

Are MVPs outdated and have no place in modern product culture?

Frank Robinson coined "MVP" in 2001. In the same year as the Agile Manifesto, the first Scrum experiment began. MVPs are old.

The concept was created to solve the waterfall problem at the time.

The market was still sour from the .com bubble. The tech industry needed a new approach. Product and Agile gained popularity because they weren't waterfall.

More than 20 years later, waterfall is dead as dead can be, but we are still talking about MVPs. Does that make sense?

What is an MVP?

Minimum viable product. You probably know that, so I'll be brief:

[…] The MVP fits your company and customer. It's big enough to cause adoption, satisfaction, and sales, but not bloated and risky. It's the product with the highest ROI/risk. […] — Frank Robinson, SyncDev

MVP is a complete product. It's not a prototype. It's your product's first iteration, which you'll improve. It must drive sales and be user-friendly.

At the MVP stage, you should know your product's core value, audience, and price. We are way deep into early adoption territory.

What about all the things that come before?

Modern product discovery

Eric Ries popularized the term with The Lean Startup in 2011. (Ries would work with the concept since 2008, but wide adoption came after the book was released).

Ries' definition of MVP was similar to Robinson's: "Test the market" before releasing anything. Ries never mentioned money, unlike Jobs. His MVP's goal was learning.

“Remove any feature, process, or effort that doesn't directly contribute to learning” — Eric Ries, The Lean Startup

Product has since become more about "what" to build than building it. What started as a learning tool is now a discovery discipline: fake doors, prototyping, lean inception, value proposition canvas, continuous interview, opportunity tree... These are cheap, effective learning tools.

Over time, companies realized that "maximum ROI divided by risk" started with discovery, not the MVP. MVPs are still considered discovery tools. What is the problem with that?

Time to Market vs Product Market Fit

Waterfall's Time to Market is its biggest flaw. Since projects are sliced horizontally rather than vertically, when there is nothing else to be done, it’s not because the product is ready, it’s because no one cares to buy it anymore.

MVPs were originally conceived as a way to cut corners and speed Time to Market by delivering more customer requests after they paid.

Original product development was waterfall-like.

Time to Market defines an optimal, specific window in which value should be delivered. It's impossible to predict how long or how often this window will be open.

Product Market Fit makes this window a "state." You don’t achieve Product Market Fit, you have it… and you may lose it.

Take, for example, Snapchat. They had a great time to market, but lost product-market fit later. They regained product-market fit in 2018 and have grown since.

An MVP couldn't handle this. What should Snapchat do? Launch Snapchat 2 and see what the market was expecting differently from the last time? MVPs are a snapshot in time that may be wrong in two weeks.

MVPs are mini-projects. Instead of spending a lot of time and money on waterfall, you spend less but are still unsure of the results.

MVPs aren't always wrong. When releasing your first product version, consider an MVP.

Minimum viable product became less of a thing on its own and more interchangeable with Alpha Release or V.1 release over time.

Modern discovery technics are more assertive and predictable than the MVP, but clarity comes only when you reach the market.

MVPs aren't the starting point, but they're the best way to validate your product concept.