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.

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)

ERC165 (or EIP-165) is a standard utilized by various open-source smart contracts like Open Zeppelin or Aavegotchi.

What's it? You must implement? Why do we need it? I'll describe the standard and answer any queries.

What is ERC165

ERC165 detects and publishes smart contract interfaces. Meaning? It standardizes how interfaces are recognized, how to detect if they implement ERC165, and how a contract publishes the interfaces it implements. How does it work?

Why use ERC165? Sometimes it's useful to know which interfaces a contract implements, and which version.

Identifying interfaces

An interface function's selector. This verifies an ABI function. XORing all function selectors defines an interface in this standard. The following code demonstrates.

// SPDX-License-Identifier: UNLICENCED
pragma solidity >=0.8.0 <0.9.0;

interface Solidity101 {
    function hello() external pure;
    function world(int) external pure;
}

contract Selector {
    function calculateSelector() public pure returns (bytes4) {
        Solidity101 i;
        return i.hello.selector ^ i.world.selector;
        // Returns 0xc6be8b58
    }

    function getHelloSelector() public pure returns (bytes4) {
        Solidity101 i;
        return i.hello.selector;
        // Returns 0x19ff1d21
    }

    function getWorldSelector() public pure returns (bytes4) {
        Solidity101 i;
        return i.world.selector;
        // Returns 0xdf419679
    }
}

This code isn't necessary to understand function selectors and how an interface's selector can be determined from the functions it implements.

Run that sample in Remix to see how interface function modifications affect contract function output.

Contracts publish their implemented interfaces.

We can identify interfaces. Now we must disclose the interfaces we're implementing. First, import IERC165 like so.

pragma solidity ^0.4.20;

interface ERC165 {
    /// @notice Query if a contract implements an interface
    /// @param interfaceID The interface identifier, as specified in ERC-165
    /// @dev Interface identification is specified in ERC-165. 
    /// @return `true` if the contract implements `interfaceID` and
    ///  `interfaceID` is not 0xffffffff, `false` otherwise
    function supportsInterface(bytes4 interfaceID) external view returns (bool);
}

We still need to build this interface in our smart contract. ERC721 from OpenZeppelin is a good example.

// SPDX-License-Identifier: MIT
// OpenZeppelin Contracts (last updated v4.5.0) (token/ERC721/ERC721.sol)

pragma solidity ^0.8.0;

import "./IERC721.sol";
import "./extensions/IERC721Metadata.sol";
import "../../utils/introspection/ERC165.sol";
// ...

contract ERC721 is Context, ERC165, IERC721, IERC721Metadata {
  // ...

  function supportsInterface(bytes4 interfaceId) public view virtual override(ERC165, IERC165) returns (bool) {
    return
      interfaceId == type(IERC721).interfaceId ||
      interfaceId == type(IERC721Metadata).interfaceId ||
      super.supportsInterface(interfaceId);
  }
  
  // ...
}

I deleted unnecessary code. The smart contract imports ERC165, IERC721 and IERC721Metadata. The is keyword at smart contract declaration implements all three.

Kind (interface).

Note that type(interface).interfaceId returns the same as the interface selector.

We override supportsInterface in the smart contract to return a boolean that checks if interfaceId is the same as one of the implemented contracts.

Super.supportsInterface() calls ERC165 code. Checks if interfaceId is IERC165.

function supportsInterface(bytes4 interfaceId) public view virtual override returns (bool) {
    return interfaceId == type(IERC165).interfaceId;
}

So, if we run supportsInterface with an interfaceId, our contract function returns true if it's implemented and false otherwise. True for IERC721, IERC721Metadata, andIERC165.

Conclusion

I hope this post has helped you understand and use ERC165 and why it's employed.

Have a great day, thanks for reading!

His success was unforeseeable.

2014 saw Facebook's $2.3 billion purchase of Oculus VR.

19-year-old Palmer Luckey founded Oculus. He quit journalism school. His parents worried about his college dropout.

Facebook bought Oculus VR in less than 2 years.

Palmer Luckey started Anduril Industries. Palmer has raised $385 million with Anduril.

The Oculus journey began in a trailer

Palmer Luckey, 19, owned the trailer.

Luckey had his trailer customized. The trailer had all six of Luckey's screens. In the trailer's remaining area, Luckey conducted hardware tests.

At 16, he became obsessed with virtual reality. Virtual reality was rare at the time.

Luckey didn't know about VR when he started.

Previously, he liked "portabilizing" mods. Hacking ancient game consoles into handhelds.

In his city, fewer portabilizers actively traded.

Luckey started "ModRetro" for other portabilizers. Luckey was exposed to VR headsets online.

Luckey:

“Man, ModRetro days were the best.”

Palmer Luckey used VR headsets for three years. His design had 50 prototypes.

Luckey used to work at the Long Beach Sailing Center for minimum salary, servicing diesel engines and cleaning boats.

Luckey worked in a USC Institute for Creative Technologies mixed reality lab in July 2011. (ICT).

Luckey cleaned the lab, did reports, and helped other students with VR projects.

Luckey's lab job was dull.

Luckey chose to work in the lab because he wanted to engage with like-minded folks.

By 2012, Luckey had a prototype he hoped to share globally. He made cheaper headsets than others.

Luckey wanted to sell an easy-to-assemble virtual reality kit on Kickstarter.

He realized he needed a corporation to do these sales legally. He started looking for names. "Virtuality," "virtual," and "VR" are all taken.

Hence, Oculus.

If Luckey sold a hundred prototypes, he would be thrilled since it would boost his future possibilities.

John Carmack, legendary game designer

Carmack has liked sci-fi and fantasy since infancy.

Carmack loved imagining intricate gaming worlds.

His interest in programming and computer science grew with age.

He liked graphics. He liked how mismatching 0 and 1 might create new colors and visuals.

Carmack played computer games as a teen. He created Shadowforge in high school.

He founded Id software in 1991. When Carmack created id software, console games were the best-sellers.

Old computer games have weak graphics. John Carmack and id software developed "adaptive tile refresh."

This technique smoothed PC game scrolling. id software launched 3-D, Quake, and Doom using "adaptive tile refresh."

These games made John Carmack a gaming star. Later, he sold Id software to ZeniMax Media.

How Palmer Luckey met Carmack

In 2011, Carmack was thinking a lot about 3-D space and virtual reality.

He was underwhelmed by the greatest HMD on the market. Because of their flimsiness and latency.

His disappointment was partly due to the view (FOV). Best HMD had 40-degree field of view.

Poor. The best VR headset is useless with a 40-degree FOV.

Carmack intended to show the press Doom 3 in VR. He explored VR headsets and internet groups for this reason.

Carmack identified a VR enthusiast in the comments section of "LEEP on the Cheap." "PalmerTech" was the name.

Carmack approached PalmerTech about his prototype. He told Luckey about his VR demos, so he wanted to see his prototype.

Carmack got a Rift prototype. Here's his May 17 tweet.

John Carmack tweeted an evaluation of the Luckey prototype.

Dan Newell, a Valve engineer, and Mick Hocking, a Sony senior director, pre-ordered Oculus Rift prototypes with Carmack's help.

Everyone praised Luckey after Carmack demoed Rift.

Palmer Luckey received a job offer from Sony.

• It was a full-time position at Sony Computer Europe.

• He would run Sony’s R&D lab.

• The salary would be $70k.

Who is Brendan Iribe?

Brendan Iribe started early with Startups. In 2004, he and Mike Antonov founded Scaleform.

Scaleform created high-performance middleware. This package allows 3D Flash games.

In 2011, Iribe sold Scaleform to Autodesk for $36 million.

How Brendan Iribe discovered Palmer Luckey.

Brendan Iribe's friend Laurent Scallie.

Laurent told Iribe about a potential opportunity.

Laurent promised Iribe VR will work this time. Laurent introduced Iribe to Luckey.

Iribe was doubtful after hearing Laurent's statements. He doubted Laurent's VR claims.

But since Laurent took the name John Carmack, Iribe thought he should look at Luckey Innovation. Iribe was hooked on virtual reality after reading Palmer Luckey stories.

He asked Scallie about Palmer Luckey.

Iribe convinced Luckey to start Oculus with him

First meeting between Palmer Luckey and Iribe.

The Iribe team wanted Luckey to feel comfortable.

Iribe sought to convince Luckey that launching a company was easy. Iribe told Luckey anyone could start a business.

Luckey told Iribe's staff he was homeschooled from childhood. Luckey took self-study courses.

Luckey had planned to launch a Kickstarter campaign and sell kits for his prototype. Many companies offered him jobs, nevertheless.

He's considering Sony's offer.

Iribe advised Luckey to stay independent and not join a firm. Iribe asked Luckey how he could raise his child better. No one sees your baby like you do?

Iribe's team pushed Luckey to stay independent and establish a software ecosystem around his device.

After conversing with Iribe, Luckey rejected every job offer and merger option.

Iribe convinced Luckey to provide an SDK for Oculus developers.

After a few months. Brendan Iribe co-founded Oculus with Palmer Luckey. Luckey trusted Iribe and his crew, so he started a corporation with him.

Crowdfunding

Brendan Iribe and Palmer Luckey launched a Kickstarter.

Gabe Newell endorsed Palmer's Kickstarter video.

Gabe Newell wants folks to trust Palmer Luckey since he's doing something fascinating and answering tough questions.

Mark Bolas and David Helgason backed Palmer Luckey's VR Kickstarter video.

Luckey introduced Oculus Rift during the Kickstarter campaign. He introduced virtual reality during press conferences.

Oculus' Kickstarter effort was a success. Palmer Luckey felt he could raise $250,000.

Oculus raised $2.4 million through Kickstarter. Palmer Luckey's virtual reality vision was well-received.

Mark Zuckerberg's Oculus discovery

Brendan Iribe and Palmer Luckey hired the right personnel after a successful Kickstarter campaign.

Oculus needs a lot of money for engineers and hardware. They needed investors' money.

Series A raised $16M.

Next, Andreessen Horowitz partner Brain Cho approached Iribe.

Cho told Iribe that Andreessen Horowitz could invest in Oculus Series B if the company solved motion sickness.

Mark Andreessen was Iribe's dream client.

Marc Andreessen and his partners gave Oculus $75 million.

Andreessen introduced Iribe to Zukerberg. Iribe and Zukerberg discussed the future of games and virtual reality by phone.

Facebook's Oculus demo

Iribe showed Zuckerberg Oculus.

Mark was hooked after using Oculus. The headset impressed him.

The whole Facebook crew who saw the demo said only one thing.

“Holy Crap!”

This surprised them all.

Mark Zuckerberg was impressed by the team's response. Mark Zuckerberg met the Oculus team five days after the demo.

First meeting Palmer Luckey.

Palmer Luckey is one of Mark's biggest supporters and loves Facebook.

Oculus Acquisition

Zuckerberg wanted Oculus.

Brendan Iribe had requested for $4 billion, but Mark wasn't interested.

Facebook bought Oculus for $2.3 billion after months of drama.

After selling his company, how does Palmer view money?

Palmer loves the freedom money gives him. Money frees him from small worries.

Money has allowed him to pursue things he wouldn't have otherwise.

“If I didn’t have money I wouldn’t have a collection of vintage military vehicles…You can have nice hobbies that keep you relaxed when you have money.”

He didn't start Oculus to generate money. His virtual reality passion spanned years.

He didn't have to lie about how virtual reality will transform everything until he needed funding.

The company's success was an unexpected bonus. He was merely passionate about a good cause.

After Oculus' $2.3 billion exit, what changed?

Palmer didn't mind being rich. He did similar things.

After Facebook bought Oculus, he moved to Silicon Valley and lived in a 12-person shared house due to high rents.

Palmer might have afforded a big mansion, but he prefers stability and doing things because he wants to, not because he has to.

“Taco Bell is never tasted so good as when you know you could afford to never eat taco bell again.”

Palmer's leadership shifted.

Palmer changed his leadership after selling Oculus.

When he launched his second company, he couldn't work on his passions.

“When you start a tech company you do it because you want to work on a technology, that is why you are interested in that space in the first place. As the company has grown, he has realized that if he is still doing optical design in the company it’s because he is being negligent about the hiring process.”

Once his startup grows, the founder's responsibilities shift. He must recruit better firm managers.

Recruiting talented people becomes the top priority. The founder must convince others of their influence.

A book that helped me write this:

The History of the Future: Oculus, Facebook, and the Revolution That Swept Virtual Reality — Blake Harris

*This post is a summary. Read the full article here.

This is how to build a car while driving.

Building a high-growth startup is compared to building a car while it's speeding down the highway.

How to plan without going crazy? Or, without losing team, board, and investor buy-in?

I just delivered our company's product roadmap for the rest of the year. Complete. Thorough. Page-long. I'm optimistic about its chances of surviving as everything around us changes, from internal priorities to the global economy.

It's tricky. This isn't the first time I've created a startup roadmap. I didn't invent a document. It took time to deliver a document that will be relevant for months.

Goals matter.

Although they never change, goals are rarely understood.

This is the third in a series about a startup's unique roadmapping needs. Velocity is the intensity at which a startup must produce to survive.

A high-growth startup moves at breakneck speed, which I alluded to when I said priorities and economic factors can change daily or weekly.

At that speed, a startup's roadmap must be flexible, bend but not break, and be brief and to the point. I can't tell you how many startups and large companies develop a product roadmap every quarter and then tuck it away.

Big, wealthy companies can do this. It's suicide for a startup.

The drawer thing happens because startup product roadmaps are often valid for a short time. The roadmap is a random list of features prioritized by different company factions and unrelated to company goals.

It's not because the goals changed that a roadmap is shelved or ignored. Because the company's goals were never communicated or documented in the context of its product.

In the previous post, I discussed how to turn company goals into a product roadmap. In this post, I'll show you how to make a one-page startup roadmap.

In a future post, I'll show you how to follow this roadmap. This roadmap helps you track company goals, something a roadmap must do.

Be vague for growth, but direct for execution.

Here's my plan. The real one has more entries and more content in each.

Let's discuss smaller boxes.

Product developers and engineers know that the further out they predict, the more wrong they'll be. When developing the product roadmap, this rule is ignored. Then it bites us three, six, or nine months later when we haven't even started.

Why do we put everything in a product roadmap like a project plan?

Yes, I know. We use it when the product roadmap isn't goal-based.

A goal-based roadmap begins with a document that outlines each goal's idea, execution, growth, and refinement.

Once the goals are broken down into epics, initiatives, projects, and programs, only the idea and execution phases should be modeled. Any goal growth or refinement items should be vague and loosely mapped.

Why? First, any idea or execution-phase goal will result in growth initiatives that are unimaginable today. Second, internal priorities and external factors will change, but the goals won't. Locking items into calendar slots reduces flexibility and forces deviation from the single source of truth.

No soothsayers. Predicting the future is pointless; just prepare.

A map is useless if you don't know where you're going.

As we speed down the road, the car and the road will change. Goals define the destination.

This quarter and next quarter's roadmap should be set. After that, you should track destination milestones, not how to get there.

When you do that, even the most critical investors will understand the roadmap and buy in. When you track progress at the end of the quarter and revise your roadmap, the destination won't change.