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.

Orion's red supergiant Betelgeuse erupted. This is astronomers' most magnificent occurrence.

Betelgeuse, a supergiant star in Orion, garnered attention in 2019 for its peculiar appearance. It continued to dim in 2020.

The star was previously thought to explode as a supernova. Studying the event has revealed what happened to Betelgeuse since it happened.

Astronomers saw that the star released a large amount of material, causing it to lose a section of its surface.

They have never seen anything like this and are unsure what caused the star to release so much material.

According to Harvard-Smithsonian Center for Astrophysics astrophysicist Andrea Dupre, astronomers' data reveals an unexplained mystery.

They say it's a new technique to examine star evolution. The James Webb telescope revealed the star's surface features.

Corona flares are stellar mass ejections. These eruptions change the Sun's outer atmosphere.

This could affect power grids and satellite communications if it hits Earth.

Betelgeuse's flare ejected four times more material than the Sun's corona flare.

Astronomers have monitored star rhythms for 50 years. They've seen its dimming and brightening cycle start, stop, and repeat.

Monitoring Betelgeuse's pulse revealed the eruption's power.

Dupre believes the star's convection cells are still amplifying the blast's effects, comparing it to an imbalanced washing machine tub.

The star's outer layer has returned to normal, Hubble data shows. The photosphere slowly rebuilds its springy surface.

Dupre noted the star's unusual behavior. For instance, it’s causing its interior to bounce.

This suggests that the mass ejections that caused the star's surface to lose mass were two separate processes.

Researchers hope to better understand star mass ejection with the James Webb Space Telescope.

The 2008 Bitcoin white paper solves the classic computer science consensus problem.

Issue Statement

The Byzantine Generals Problem (BGP) is called after an allegory in which several generals must collaborate and attack a city at the same time to win (figure 1-left). Any general who retreats at the last minute loses the fight (figure 1-right). Thus, precise messengers and no rogue generals are essential. This is difficult without a trusted central authority.

In their 1982 publication, Leslie Lamport, Robert Shostak, and Marshall Please termed this topic the Byzantine Generals Problem to simplify distributed computer systems.

Consensus in a distributed computer network is the issue. Reaching a consensus on which systems work (and stay in the network) and which don't makes maintaining a network tough (i.e., needs to be removed from network). Challenges include unreliable communication routes between systems and mis-reporting systems.

Solving BGP can let us construct machine learning solutions without single points of failure or trusted central entities. One server hosts model parameters while numerous workers train the model. This study describes fault-tolerant Distributed Byzantine Machine Learning.

Bitcoin invented a mechanism for a distributed network of nodes to agree on which transactions should go into the distributed ledger (blockchain) without a trusted central body. It solved BGP implementation. Satoshi Nakamoto, the pseudonymous bitcoin creator, solved the challenge by cleverly combining cryptography and consensus mechanisms.

Disclaimer

This is not financial advice. It discusses a unique computer science solution.

Bitcoin

Bitcoin's white paper begins:

“A purely peer-to-peer version of electronic cash would allow online payments to be sent directly from one party to another without going through a financial institution.” Source: https://www.ussc.gov/sites/default/files/pdf/training/annual-national-training-seminar/2018/Emerging_Tech_Bitcoin_Crypto.pdf

Bitcoin's main parts:

1. The open-source and versioned bitcoin software that governs how nodes, miners, and the bitcoin token operate.

2. The native kind of token, known as a bitcoin token, may be created by mining (up to 21 million can be created), and it can be transferred between wallet addresses in the bitcoin network.

3. Distributed Ledger, which contains exact copies of the database (or "blockchain") containing each transaction since the first one in January 2009.

4. distributed network of nodes (computers) running the distributed ledger replica together with the bitcoin software. They broadcast the transactions to other peer nodes after validating and accepting them.

5. Proof of work (PoW) is a cryptographic requirement that must be met in order for a miner to be granted permission to add a new block of transactions to the blockchain of the cryptocurrency bitcoin. It takes the form of a valid hash digest. In order to produce new blocks on average every 10 minutes, Bitcoin features a built-in difficulty adjustment function that modifies the valid hash requirement (length of nonce). PoW requires a lot of energy since it must continually generate new hashes at random until it satisfies the criteria.

6. The competing parties known as miners carry out continuous computing processing to address recurrent cryptography issues. Transaction fees and some freshly minted (mined) bitcoin are the rewards they receive. The amount of hashes produced each second—or hash rate—is a measure of mining capacity.

Cryptography, decentralization, and the proof-of-work consensus method are Bitcoin's most unique features.

Bitcoin uses encryption

Bitcoin employs this established cryptography.

1. Hashing

2. digital signatures based on asymmetric encryption

Hashing (SHA-256) (SHA-256)

Hashing converts unique plaintext data into a digest. Creating the plaintext from the digest is impossible. Bitcoin miners generate new hashes using SHA-256 to win block rewards.

A new hash is created from the current block header and a variable value called nonce. To achieve the required hash, mining involves altering the nonce and re-hashing.

The block header contains the previous block hash and a Merkle root, which contains hashes of all transactions in the block. Thus, a chain of blocks with increasing hashes links back to the first block. Hashing protects new transactions and makes the bitcoin blockchain immutable. After a transaction block is mined, it becomes hard to fabricate even a little entry.

Asymmetric Cryptography Digital Signatures

Asymmetric cryptography (public-key encryption) requires each side to have a secret and public key. Public keys (wallet addresses) can be shared with the transaction party, but private keys should not. A message (e.g., bitcoin payment record) can only be signed by the owner (sender) with the private key, but any node or anybody with access to the public key (visible in the blockchain) can verify it. Alex will submit a digitally signed transaction with a desired amount of bitcoin addressed to Bob's wallet to a node to send bitcoin to Bob. Alex alone has the secret keys to authorize that amount. Alex's blockchain public key allows anyone to verify the transaction.

Solution

Now, apply bitcoin to BGP. BGP generals resemble bitcoin nodes. The generals' consensus is like bitcoin nodes' blockchain block selection. Bitcoin software on all nodes can:

Check transactions (i.e., validate digital signatures)

2. Accept and propagate just the first miner to receive the valid hash and verify it accomplished the task. The only way to guess the proper hash is to brute force it by repeatedly producing one with the fixed/current block header and a fresh nonce value.

Thus, PoW and a dispersed network of nodes that accept blocks from miners that solve the unfalsifiable cryptographic challenge solve consensus.

Suppose:

1. Unreliable nodes

2. Unreliable miners

Bitcoin accepts the longest chain if rogue nodes cause divergence in accepted blocks. Thus, rogue nodes must outnumber honest nodes in accepting/forming the longer chain for invalid transactions to reach the blockchain. As of November 2022, 7000 coordinated rogue nodes are needed to takeover the bitcoin network.

Dishonest miners could also try to insert blocks with falsified transactions (double spend, reverse, censor, etc.) into the chain. This requires over 50% (51% attack) of miners (total computational power) to outguess the hash and attack the network. Mining hash rate exceeds 200 million (source). Rewards and transaction fees encourage miners to cooperate rather than attack. Quantum computers may become a threat.

Visit my Quantum Computing post.

Quantum computers—what are they? Quantum computers will have a big influence. towardsdatascience.com

Nodes have more power than miners since they can validate transactions and reject fake blocks. Thus, the network is secure if honest nodes are the majority.

Summary

Table 1 compares three Byzantine Generals Problem implementations.

Bitcoin white paper and implementation solved the consensus challenge of distributed systems without central governance. It solved the illusive Byzantine Generals Problem.

Resources

Resources

1. https://en.wikipedia.org/wiki/Byzantine_fault

2. Source-code for Bitcoin Core Software — https://github.com/bitcoin/bitcoin

3. Bitcoin white paper — https://bitcoin.org/bitcoin.pdf

4. https://en.wikipedia.org/wiki/Bitcoin

5. https://www.microsoft.com/en-us/research/publication/byzantine-generals-problem/

6. https://www.microsoft.com/en-us/research/uploads/prod/2016/12/The-Byzantine-Generals-Problem.pdf

7. https://en.wikipedia.org/wiki/Hash_function

8. https://en.wikipedia.org/wiki/Merkle_tree

9. https://en.wikipedia.org/wiki/SHA-2

10. https://en.wikipedia.org/wiki/Public-key_cryptography

11. https://en.wikipedia.org/wiki/Digital_signature

12. https://en.wikipedia.org/wiki/Proof_of_work

13. https://en.wikipedia.org/wiki/Quantum_cryptography

14. https://dci.mit.edu/bitcoin-security-initiative

15. https://dci.mit.edu/51-attacks

16. Genuinely Distributed Byzantine Machine Learning, El-Mahdi El-Mhamdi et al., 2020. ACM, New York, NY, https://doi.org/10.1145/3382734.3405695

Google announced 6% layoffs recently (or 12,000 people). This aligns it with most tech companies. A publicly contrite CEO explained that they had overhired during the COVID-19 pandemic boom and had to address it, but they were sorry and took full responsibility. I thought this was "bullshit" too. Meta, Amazon, Microsoft, and others must feel similarly. I spent 10 years at Google, and these things don't reflect well on the company's leaders.

All publicly listed companies have a fiduciary duty to act in the best interests of their shareholders. Dodge vs. Ford Motor Company established this (1919). Henry Ford wanted to reduce shareholder payments to offer cheaper cars and better wages. Ford stated.

My ambition is to employ still more men, to spread the benefits of this industrial system to the greatest possible number, to help them build up their lives and their homes. To do this we are putting the greatest share of our profits back in the business.

The Dodge brothers, who owned 10% of Ford, opposed this and sued Ford for the payments to start their own company. They won, preventing Ford from raising prices or salaries. If you have a vocal group of shareholders with the resources to sue you, you must prove you are acting in their best interests. Companies prioritize shareholders. Giving activist investors a stick to threaten you almost enshrines short-term profit over long-term thinking.

This underpins Google's current issues. Institutional investors who can sue Google see it as a wasteful company they can exploit. That doesn't mean you have to maximize profits (thanks to those who pointed out my ignorance of US corporate law in the comments and on HN), but it allows pressure. I feel for those navigating this. This is about unrestrained capitalism.

When Google went public, Larry Page and Sergey Brin knew the risks and worked hard to keep control. In their Founders' Letter to investors, they tried to set expectations for the company's operations.

Our long-term focus as a private company has paid off. Public companies do the same. We believe outside pressures lead companies to sacrifice long-term opportunities to meet quarterly market expectations.

The company has transformed since that letter. The company has nearly 200,000 full-time employees and a trillion-dollar market cap. Large investors have bought company stock because it has been a good long-term bet. Why are they restless now?

Other big tech companies emerged and fought for top talent. This has caused rising compensation packages. Google has also grown rapidly (roughly 22,000 people hired to the end of 2022). At $300,000 median compensation, those 22,000 people added $6.6 billion in salary overheads in 2022. Exorbitant. If the company still makes $16 billion every quarter, maybe not. Investors wonder if this value has returned.

Investors are right. Google uses people wastefully. However, by bluntly reducing headcount, they're not addressing the root causes and hurting themselves. No studies show that downsizing this way boosts productivity. There is plenty of evidence that they'll lose out because people will be risk-averse and distrust their leadership.

The company's approach also stinks. Finding out that you no longer have a job because you can’t log in anymore (sometimes in cases where someone is on call for protecting your production systems) is no way to fire anyone. Being with a narcissistic sociopath is like being abused. First, you receive praise and fancy perks for making the cut. You're fired by text and ghosted. You're told to appreciate the generous severance package. This firing will devastate managers and teams. This type of firing will take years to recover self-esteem. Senior management contributed to this. They chose the expedient answer, possibly by convincing themselves they were managing risk and taking the Macbeth approach of “If it were done when ’tis done, then ’twere well It were done quickly”.

Recap. Google's leadership did a stupid thing—mass firing—in a stupid way. How do we get rid of enough people to make investors happier? and "have 6% less people." Empathetic leaders should not emulate Elon Musk. There is no humane way to fire 12,000 people, but there are better ways. Why is Google so wasteful?

Ambition answers this. There aren't enough VP positions for a group of highly motivated, ambitious, and (increasingly) ruthless people. I’ve loitered around the edges of this world and a large part of my value was to insulate my teams from ever having to experience it. It’s like Game of Thrones played out through email and calendar and over video call.

Your company must look a certain way to be promoted to director or higher. You need the right people at the right levels under you. Long-term, growing your people will naturally happen if you're working on important things. This takes time, and you're never more than 6–18 months from a reorg that could start you over. Ambitious people also tend to be impatient. So, what do you do?

Hiring and vanity projects. To shape your company, you hire at the right levels. You value vanity metrics like active users over product utility. Your promo candidates get through by subverting the promotion process. In your quest for growth, you avoid performance managing people out. You avoid confronting toxic peers because you need their support for promotion. Your cargo cult gets you there.

Its ease makes Google wasteful. Since they don't face market forces, the employees don't see it as a business. Why would you do when the ads business is so profitable? Complacency causes senior leaders to prioritize their own interests. Empires collapse. Personal ambition often trumped doing the right thing for users, the business, or employees. Leadership's ambition over business is the root cause. Vanity metrics, mass hiring, and vague promises have promoted people to VP. Google goes above and beyond to protect senior leaders.

The decision-makers and beneficiaries are not the layoffees. Stock price increase beneficiaries. The people who will post on LinkedIn how it is about misjudging the market and how they’re so sorry and take full responsibility. While accumulating wealth, the dark room dwellers decide who stays and who goes. The billionaire investors. Google should start by addressing its bloated senior management, but — as they say — turkeys don't vote for Christmas. It should examine its wastefulness and make tough choices to fix it. A 6% cut is a blunt tool that admits you're not running your business properly. why aren’t the people running the business the ones shortly to be entering the job market?

This won't fix Google's wastefulness. The executives may never regain trust after their approach. Suppressed creativity. Business won't improve. Google will have lost its founding vision and us all. Large investors know they can force Google's CEO to yield. The rich will get richer and rationalize leaving 12,000 people behind. Cycles repeat.

It doesn’t have to be this way. In 2013, Nintendo's CEO said he wouldn't fire anyone for shareholders. Switch debuted in 2017. Nintendo's stock has increased by nearly five times, or 19% a year (including the drop most of the stock market experienced last year). Google wasted 12,000 talented people. To please rich people.

From 1984 until 2011, he ran Apple using the same template.

What is a founder CEO's most crucial skill?

Presentation, communication, and sales

As a Business Angel Investor, I saw many pitch presentations and met with investors one-on-one to promote my companies.

There is always the conception of “Investors have to invest,” so there is no need to care about the presentation.

It's false. Nobody must invest. Many investors believe that entrepreneurs must convince them to invest in their business.

Sometimes — like in 2018–2022 — too much money enters the market, and everyone makes good money.

Do you recall the Buy Now, Pay Later Movement? This amazing narrative had no return potential. Only buyers who couldn't acquire financing elsewhere shopped at these companies.

Klarna's failing business concept led to high valuations.

Investors become more cautious when the economy falters. 2022 sees rising inflation, interest rates, wars, and civil instability. It's like the apocalypse's four horsemen have arrived.

Storytelling is important in rough economies.

When investors draw back, how can entrepreneurs stand out?

In Q2/2022, every study I've read said:

Investors cease investing

Deals are down in almost all IT industries from previous quarters.

What do founders need to do?

Differentiate yourself.

Storytelling talents help.

The Steve Jobs Way

Every time I watch a Steve Jobs presentation, I'm enthralled.

I'm a techie. Everything technical interests me. But, I skim most presentations.

What's Steve Jobs's secret?

Steve Jobs created Apple in 1976 and made it a profitable software and hardware firm in the 1980s. Macintosh goods couldn't beat IBM's. This mistake sacked him in 1985.

Before rejoining Apple in 1997, Steve Jobs founded Next Inc. and Pixar.

From then on, Apple became America's most valuable firm.

Steve Jobs understood people's needs. He said:

“People don’t know what they want until you show it to them. That’s why I never rely on market research. Our task is to read things that are not yet on the page.”

In his opinion, people talk about problems. A lot. Entrepreneurs must learn what the population's pressing problems are and create a solution.

Steve Jobs showed people what they needed before they realized it.

I'll explain:

Present a Big Vision

Steve Jobs starts every presentation by describing his long-term goals for Apple.

1984's Macintosh presentation set up David vs. Goliath. In a George Orwell-style dystopia, IBM computers were bad. It was 1984.

Apple will save the world, like Jedis.

Why do customers and investors like Big Vision?

People want a wider perspective, I think. Humans love improving the planet.

Apple users often cite emotional reasons for buying the brand.

Revolutionizing several industries with breakthrough inventions

Establish Authority

Everyone knows Apple in 2022. It's hard to find folks who confuse Apple with an apple around the world.

Apple wasn't as famous as it is today until Steve Jobs left in 2011.

Most entrepreneurs lack experience. They may market their company or items to folks who haven't heard of it.

Steve Jobs presented the company's historical accomplishments to overcome opposition.

In his presentation of the first iPhone, he talked about the Apple Macintosh, which altered the computing sector, and the iPod, which changed the music industry.

People who have never heard of Apple feel like they're seeing a winner. It raises expectations that the new product will be game-changing and must-have.

The Big Reveal

A pitch or product presentation always has something new.

Steve Jobs doesn't only demonstrate the product. I don't think he'd skip the major point of a company presentation.

He consistently discusses present market solutions, their faults, and a better consumer solution.

No solution exists yet.

It's a multi-faceted play:

• It's comparing the new product to something familiar. This makes novelty and the product more relatable.

• Describe a desirable solution.

• He's funny. He demonstrated an iPod with an 80s phone dial in his iPhone presentation.

Then he reveals the new product. Macintosh presented itself.

Show the benefits

He outlines what Apple is doing differently after demonstrating the product.

How do you distinguish from others? The Big Breakthrough Presentation.

A few hundred slides might list all benefits.

Everyone would fall asleep. Have you ever had similar presentations?

When the brain is overloaded with knowledge, the limbic system changes to other duties, like lunch planning.

What should a speaker do? There's a classic proverb:

“Tell me and I forget, teach me and I may remember, involve me and I learn” (— Not Benjamin Franklin).

Steve Jobs showcased the product live.

Again, using ordinary scenarios to highlight the product's benefits makes it relatable.

The 2010 iPad Presentation uses this technique.

Invite the Team and Let Them Run the Presentation

CEOs spend most time outside the organization. Many companies elect to have only one presenter.

It sends the incorrect message to investors. Product presentations should always include the whole team.

Let me explain why.

Companies needing investment money frequently have shaky business strategies or no product-market fit or robust corporate structure.

Investors solely bet on a team's ability to implement ideas and make a profit.

Early team involvement helps investors understand the company's drivers. Travel costs are worthwhile.

But why for product presentations?

Presenters of varied ages, genders, social backgrounds, and skillsets are relatable. CEOs want relatable products.

Some customers may not believe a white man's message. A black woman's message may be more accepted.

Make the story relatable when you have the best product that solves people's concerns.

Best example: 1984 Macintosh presentation with development team panel.

What is the largest error people make when companies fail?

Saving money on the corporate and product presentation.

Invite your team to five partner meetings when five investors are shortlisted.

Rehearse the presentation till it's natural. Let the team speak.

Successful presentations require structure, rehearsal, and a team. Steve Jobs nailed it.