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.

Perovskite solar cells will revolutionize everything.

Humanity is in a climatic Armageddon. Our widespread ecological crimes of the previous century are catching up with us, and planet-scale karma threatens everyone. We must adjust to new technologies and lifestyles to avoid this fate. Even solar power, a renewable energy source, has climate problems. A recent discovery could boost solar power's eco-friendliness and affordability. Perovskite solar cells are amazing.

Perovskite is a silicon-like semiconductor. Semiconductors are used to make computer chips, LEDs, camera sensors, and solar cells. Silicon makes sturdy and long-lasting solar cells, thus it's used in most modern solar panels.

Perovskite solar cells are far better. First, they're easy to make at room temperature, unlike silicon cells, which require long, intricate baking processes. This makes perovskite cells cheaper to make and reduces their carbon footprint. Perovskite cells are efficient. Most silicon panel solar farms are 18% efficient, meaning 18% of solar radiation energy is transformed into electricity. Perovskite cells are 25% efficient, making them 38% more efficient than silicon.

However, perovskite cells are nowhere near as durable. A normal silicon panel will lose efficiency after 20 years. The first perovskite cells were ineffective since they lasted barely minutes.

Recent research from Princeton shows that perovskite cells can endure 30 years. The cells kept their efficiency, therefore no sacrifices were made.

No electrical or chemical engineer here, thus I can't explain how they did it. But strangely, the team said longevity isn't the big deal. In the next years, perovskite panels will become longer-lasting. How do you test a panel if you only have a month or two? This breakthrough technique needs a uniform method to estimate perovskite life expectancy fast. The study's key milestone was establishing a standard procedure.

Lab-based advanced aging tests are their solution. Perovskite cells decay faster at higher temperatures, so scientists can extrapolate from that. The test heated the panel to 110 degrees and waited for its output to reduce by 20%. Their panel lasted 2,100 hours (87.5 days) before a 20% decline.

They did some math to extrapolate this data and figure out how long the panel would have lasted in different climates, and were shocked to find it would last 30 years in Princeton. This made perovskite panels as durable as silicon panels. This panel could theoretically be sold today.

This technology will soon allow these brilliant panels to be released into the wild. This technology could be commercially viable in ten, maybe five years.

Solar power will be the best once it does. Solar power is cheap and low-carbon. Perovskite is the cheapest renewable energy source if we switch to it. Solar panel manufacturing's carbon footprint will also drop.

Perovskites' impact goes beyond cost and carbon. Silicon panels require harmful mining and contain toxic elements (cadmium). Perovskite panels don't require intense mining or horrible materials, making their production and expiration more eco-friendly.

Solar power destroys habitat. Massive solar farms could reduce biodiversity and disrupt local ecology by destroying vital habitats. Perovskite cells are more efficient, so they can shrink a solar farm while maintaining energy output. This reduces land requirements, making perovskite solar power cheaper, and could reduce solar's environmental impact.

Perovskite solar power is scalable and environmentally friendly. Princeton scientists will speed up the development and rollout of this energy.

Why bother with fusion, fast reactors, SMRs, or traditional nuclear power? We're close to developing a nearly perfect environmentally friendly power source, and we have the tools and systems to do so quickly. It's also affordable, so we can adopt it quickly and let the developing world use it to grow. Even I struggle to justify spending billions on fusion when a great, cheap technology outperforms it. Perovskite's eco-credentials and cost advantages could save the world and power humanity's future.

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)

Writing for readers:

14 years of daily writing.

I post practically everything on social media. I authored hundreds of articles, thousands of tweets, and numerous volumes to almost no one.

Tens of thousands of readers regularly praise me.

I despised writing. I'm stuck now.

I've learned what readers like and what doesn't.

Here are some essential guidelines for writing with impact:

Readers won't understand your work if you can't.

Though obvious, this slipped me up. Share your truths.

Stories engage human brains.

Showing the journey of a person from worm to butterfly inspires the human spirit.

Overthinking hinders powerful writing.

The best ideas come from inner understanding in between thoughts.

Avoid writing to find it. Write.

Writing a masterpiece isn't motivating.

Write for five minutes to simplify. Step-by-step, entertaining, easy steps.

Good writing requires a willingness to make mistakes.

So write loads of garbage that you can edit into a good piece.

Courageous writing.

A courageous story will move readers. Personal experience is best.

Go where few dare.

Templates, outlines, and boundaries help.

Limitations enhance writing.

Excellent writing is straightforward and readable, removing all the unnecessary fat.

Use five words instead of nine.

Use ordinary words instead of uncommon ones.

Readers desire relatability.

Too much perfection will turn it off.

Write to solve an issue if you can't think of anything to write.

Instead, read to inspire. Best authors read.

Every tweet, thread, and novel must have a central idea.

What's its point?

This can make writing confusing.

️ Don't direct your reader.

Readers quit reading. Demonstrate, describe, and relate.

Even if no one responds, have fun. If you hate writing it, the reader will too.

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.

Japan's startup challenge: 7 reasons

Every day, another Silicon Valley business is bought for a billion dollars, making its founders rich while growing the economy and improving consumers' lives.

Google, Amazon, Twitter, and Medium dominate our daily lives. Tesla automobiles and Moderna Covid vaccinations.

The startup movement started in Silicon Valley, California, but the rest of the world is catching up. Global startup buzz is rising. Except Japan.

644 of CB Insights' 1170 unicorns—successful firms valued at over $1 billion—are US-based. China follows with 302 and India third with 108.

Japan? 6!

1% of US startups succeed. The third-largest economy is tied with small Switzerland for startup success.

Mexico (8), Indonesia (12), and Brazil (12) have more successful startups than Japan (16). South Korea has 16. Yikes! Problem?

Why Don't Startups Exist in Japan More?

Not about money. Japanese firms invest in startups. To invest in startups, big Japanese firms create Silicon Valley offices instead of Tokyo.

Startups aren't the issue either. Local governments are competing to be Japan's Shirikon Tani, providing entrepreneurs financing, office space, and founder visas.

Startup accelerators like Plug and Play in Tokyo, Osaka, and Kyoto, the Startup Hub in Kobe, and Google for Startups are many.

Most of the companies I've encountered in Japan are either local offices of foreign firms aiming to expand into the Japanese market or small businesses offering local services rather than disrupting a staid industry with new ideas.

There must be a reason Japan can develop world-beating giant corporations like Toyota, Nintendo, Shiseido, and Suntory but not inventive startups.

Culture, obviously. Japanese culture excels in teamwork, craftsmanship, and quality, but it hates moving fast, making mistakes, and breaking things.

If you have a brilliant idea in Silicon Valley, quit your job, get money from friends and family, and build a prototype. To fund the business, you approach angel investors and VCs.

Most non-startup folks don't aware that venture capitalists don't want good, profitable enterprises. That's wonderful if you're developing a solid small business to consult, open shops, or make a specialty product. However, you must pay for it or borrow money. Venture capitalists want moon rockets. Silicon Valley is big or bust. Almost 90% will explode and crash. The few successes are remarkable enough to make up for the failures.

Silicon Valley's high-risk, high-reward attitude contrasts with Japan's incrementalism. Japan makes the best automobiles and cleanrooms, but it fails to produce new items that grow the economy.

Changeable? Absolutely. But, what makes huge manufacturing enterprises successful and what makes Japan a safe and comfortable place to live are inextricably connected with the lack of startups.

Barriers to Startup Development in Japan

These are the 7 biggest obstacles to Japanese startup success.

1. Unresponsive Employment Market

While the lifelong employment system in Japan is evolving, the average employee stays at their firm for 12 years (15 years for men at large organizations) compared to 4.3 years in the US. Seniority, not experience or aptitude, determines career routes, making it tough to quit a job to join a startup and then return to corporate work if it fails.

1. Conservative Buyers

Even if your product is buggy and undocumented, US customers will migrate to a cheaper, superior one. Japanese corporations demand perfection from their trusted suppliers and keep with them forever. Startups need income fast, yet product evaluation takes forever.

1. Failure intolerance

Japanese business failures harm lives. Failed forever. It hinders risk-taking. Silicon Valley embraces failure. Build another startup if your first fails. Build a third if that fails. Every setback is viewed as a learning opportunity for success.

4. No Corporate Purchases

Silicon Valley industrial giants will buy fast-growing startups for a lot of money. Many huge firms have stopped developing new goods and instead buy startups after the product is validated.

Japanese companies prefer in-house product development over startup acquisitions. No acquisitions mean no startup investment and no investor reward.

Startup investments can also be monetized through stock market listings. Public stock listings in Japan are risky because the Nikkei was stagnant for 35 years while the S&P rose 14x.

5. Social Unity Above Wealth

In Silicon Valley, everyone wants to be rich. That creates a competitive environment where everyone wants to succeed, but it also promotes fraud and societal problems.

Japan values communal harmony above individual success. Wealthy folks and overachievers are avoided. In Japan, renegades are nearly impossible.

6. Rote Learning Education System

Japanese high school graduates outperform most Americans. Nonetheless, Japanese education is known for its rote memorization. The American system, which fails too many kids, emphasizes creativity to create new products.

1. Immigration.

Immigrants start 55% of successful Silicon Valley firms. Some come for university, some to escape poverty and war, and some are recruited by Silicon Valley startups and stay to start their own.

Japan is difficult for immigrants to start a business due to language barriers, visa restrictions, and social isolation.

How Japan Can Promote Innovation

Patchwork solutions to deep-rooted cultural issues will not work. If customers don't buy things, immigration visas won't aid startups. Startups must have a chance of being acquired for a huge sum to attract investors. If risky startups fail, employees won't join.

Will Japan never have a startup culture?

Once a consensus is reached, Japan changes rapidly. A dwindling population and standard of living may lead to such consensus.

Toyota and Sony were firms with renowned founders who used technology to transform the world. Repeatable.

Silicon Valley is flawed too. Many people struggle due to wealth disparities, job churn and layoffs, and the tremendous ups and downs of the economy caused by stock market fluctuations.

The founders of the 10% successful startups are heroes. The 90% that fail and return to good-paying jobs with benefits are never mentioned.

Silicon Valley startup culture and Japanese corporate culture are opposites. Each have pros and cons. Big Japanese corporations make the most reliable, dependable, high-quality products yet move too slowly. That's good for creating cars, not social networking apps.

Can innovation and success be encouraged without eroding social cohesion? That can motivate software firms to move fast and break things while recognizing the beauty and precision of expert craftsmen? A hybrid culture where Japan can make the world's best and most original items. Hopefully.