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.

German stellarator revamped to run longer, hotter, compete with tokamaks

Tokamaks have dominated the search for fusion energy for decades. Just as ITER, the world's largest and most expensive tokamak, nears completion in southern France, a smaller, twistier testbed will start up in Germany.

If the 16-meter-wide stellarator can match or outperform similar-size tokamaks, fusion experts may rethink their future. Stellarators can keep their superhot gases stable enough to fuse nuclei and produce energy. They can theoretically run forever, but tokamaks must pause to reset their magnet coils.

The €1 billion German machine, Wendelstein 7-X (W7-X), is already getting "tokamak-like performance" in short runs, claims plasma physicist David Gates, preventing particles and heat from escaping the superhot gas. If W7-X can go long, "it will be ahead," he says. "Stellarators excel" Eindhoven University of Technology theorist Josefine Proll says, "Stellarators are back in the game." A few of startup companies, including one that Gates is leaving Princeton Plasma Physics Laboratory, are developing their own stellarators.

W7-X has been running at the Max Planck Institute for Plasma Physics (IPP) in Greifswald, Germany, since 2015, albeit only at low power and for brief runs. W7-X's developers took it down and replaced all inner walls and fittings with water-cooled equivalents, allowing for longer, hotter runs. The team reported at a W7-X board meeting last week that the revised plasma vessel has no leaks. It's expected to restart later this month to show if it can get plasma to fusion-igniting conditions.

Wendelstein 7-X's water-cooled inner surface allows for longer runs.

HOSAN/IPP

Both stellarators and tokamaks create magnetic gas cages hot enough to melt metal. Microwaves or particle beams heat. Extreme temperatures create a plasma, a seething mix of separated nuclei and electrons, and cause the nuclei to fuse, releasing energy. A fusion power plant would use deuterium and tritium, which react quickly. Non-energy-generating research machines like W7-X avoid tritium and use hydrogen or deuterium instead.

Tokamaks and stellarators use electromagnetic coils to create plasma-confining magnetic fields. A greater field near the hole causes plasma to drift to the reactor's wall.

Tokamaks control drift by circulating plasma around a ring. Streaming creates a magnetic field that twists and stabilizes ionized plasma. Stellarators employ magnetic coils to twist, not plasma. Once plasma physicists got powerful enough supercomputers, they could optimize stellarator magnets to improve plasma confinement.

W7-X is the first large, optimized stellarator with 50 6- ton superconducting coils. Its construction began in the mid-1990s and cost roughly twice the €550 million originally budgeted.

The wait hasn't disappointed researchers. W7-X director Thomas Klinger: "The machine operated immediately." "It's a friendly machine." It did everything we asked." Tokamaks are prone to "instabilities" (plasma bulging or wobbling) or strong "disruptions," sometimes associated to halted plasma flow. IPP theorist Sophia Henneberg believes stellarators don't employ plasma current, which "removes an entire branch" of instabilities.

In early stellarators, the magnetic field geometry drove slower particles to follow banana-shaped orbits until they collided with other particles and leaked energy. Gates believes W7-X's ability to suppress this effect implies its optimization works.

W7-X loses heat through different forms of turbulence, which push particles toward the wall. Theorists have only lately mastered simulating turbulence. W7-X's forthcoming campaign will test simulations and turbulence-fighting techniques.

A stellarator can run constantly, unlike a tokamak, which pulses. W7-X has run 100 seconds—long by tokamak standards—at low power. The device's uncooled microwave and particle heating systems only produced 11.5 megawatts. The update doubles heating power. High temperature, high plasma density, and extensive runs will test stellarators' fusion power potential. Klinger wants to heat ions to 50 million degrees Celsius for 100 seconds. That would make W7-X "a world-class machine," he argues. The team will push for 30 minutes. "We'll move step-by-step," he says.

W7-X's success has inspired VCs to finance entrepreneurs creating commercial stellarators. Startups must simplify magnet production.

Princeton Stellarators, created by Gates and colleagues this year, has $3 million to build a prototype reactor without W7-X's twisted magnet coils. Instead, it will use a mosaic of 1000 HTS square coils on the plasma vessel's outside. By adjusting each coil's magnetic field, operators can change the applied field's form. Gates: "It moves coil complexity to the control system." The company intends to construct a reactor that can fuse cheap, abundant deuterium to produce neutrons for radioisotopes. If successful, the company will build a reactor.

Renaissance Fusion, situated in Grenoble, France, raised €16 million and wants to coat plasma vessel segments in HTS. Using a laser, engineers will burn off superconductor tracks to carve magnet coils. They want to build a meter-long test segment in 2 years and a full prototype by 2027.

Type One Energy in Madison, Wisconsin, won DOE money to bend HTS cables for stellarator magnets. The business carved twisting grooves in metal with computer-controlled etching equipment to coil cables. David Anderson of the University of Wisconsin, Madison, claims advanced manufacturing technology enables the stellarator.

Anderson said W7-X's next phase will boost stellarator work. “Half-hour discharges are steady-state,” he says. “This is a big deal.”

Better technology and lower launch costs revive science-fiction tech.

Airbus engineers showed off sustainable energy's future in Munich last month. They captured sunlight with solar panels, turned it into microwaves, and beamed it into an airplane hangar, where it lighted a city model. The test delivered 2 kW across 36 meters, but it posed a serious question: Should we send enormous satellites to capture solar energy in space? In orbit, free of clouds and nighttime, they could create power 24/7 and send it to Earth.

Airbus engineer Jean-Dominique Coste calls it an engineering problem. “But it’s never been done at [large] scale.”

Proponents of space solar power say the demand for green energy, cheaper space access, and improved technology might change that. Once someone invests commercially, it will grow. Former NASA researcher John Mankins says it might be a trillion-dollar industry.

Myriad uncertainties remain, including whether beaming gigawatts of power to Earth can be done efficiently and without burning birds or people. Concept papers are being replaced with ground and space testing. The European Space Agency (ESA), which supported the Munich demo, will propose ground tests to member nations next month. The U.K. government offered £6 million to evaluate innovations this year. Chinese, Japanese, South Korean, and U.S. agencies are working. NASA policy analyst Nikolai Joseph, author of an upcoming assessment, thinks the conversation's tone has altered. What formerly appeared unattainable may now be a matter of "bringing it all together"

NASA studied space solar power during the mid-1970s fuel crunch. A projected space demonstration trip using 1970s technology would have cost $1 trillion. According to Mankins, the idea is taboo in the agency.

Space and solar power technology have evolved. Photovoltaic (PV) solar cell efficiency has increased 25% over the past decade, Jones claims. Telecoms use microwave transmitters and receivers. Robots designed to repair and refuel spacecraft might create solar panels.

Falling launch costs have boosted the idea. A solar power satellite large enough to replace a nuclear or coal plant would require hundreds of launches. ESA scientist Sanjay Vijendran: "It would require a massive construction complex in orbit."

SpaceX has made the idea more plausible. A SpaceX Falcon 9 rocket costs $2600 per kilogram, less than 5% of what the Space Shuttle did, and the company promised $10 per kilogram for its giant Starship, slated to launch this year. Jones: "It changes the equation." "Economics rules"

Mass production reduces space hardware costs. Satellites are one-offs made with pricey space-rated parts. Mars rover Perseverance cost $2 million per kilogram. SpaceX's Starlink satellites cost less than $1000 per kilogram. This strategy may work for massive space buildings consisting of many identical low-cost components, Mankins has long contended. Low-cost launches and "hypermodularity" make space solar power economical, he claims.

Better engineering can improve economics. Coste says Airbus's Munich trial was 5% efficient, comparing solar input to electricity production. When the Sun shines, ground-based solar arrays perform better. Studies show space solar might compete with existing energy sources on price if it reaches 20% efficiency.

Lighter parts reduce costs. "Sandwich panels" with PV cells on one side, electronics in the middle, and a microwave transmitter on the other could help. Thousands of them build a solar satellite without heavy wiring to move power. In 2020, a team from the U.S. Naval Research Laboratory (NRL) flew on the Air Force's X-37B space plane.

NRL project head Paul Jaffe said the satellite is still providing data. The panel converts solar power into microwaves at 8% efficiency, but not to Earth. The Air Force expects to test a beaming sandwich panel next year. MIT will launch its prototype panel with SpaceX in December.

As a satellite orbits, the PV side of sandwich panels sometimes faces away from the Sun since the microwave side must always face Earth. To maintain 24-hour power, a satellite needs mirrors to keep that side illuminated and focus light on the PV. In a 2012 NASA study by Mankins, a bowl-shaped device with thousands of thin-film mirrors focuses light onto the PV array.

International Electric Company's Ian Cash has a new strategy. His proposed satellite uses enormous, fixed mirrors to redirect light onto a PV and microwave array while the structure spins (see graphic, above). 1 billion minuscule perpendicular antennas act as a "phased array" to electronically guide the beam toward Earth, regardless of the satellite's orientation. This design, argues Cash, is "the most competitive economically"

If a space-based power plant ever flies, its power must be delivered securely and efficiently. Jaffe's team at NRL just beamed 1.6 kW over 1 km, and teams in Japan, China, and South Korea have comparable attempts. Transmitters and receivers lose half their input power. Vijendran says space solar beaming needs 75% efficiency, "preferably 90%."

Beaming gigawatts through the atmosphere demands testing. Most designs aim to produce a beam kilometers wide so every ship, plane, human, or bird that strays into it only receives a tiny—hopefully harmless—portion of the 2-gigawatt transmission. Receiving antennas are cheap to build but require a lot of land, adds Jones. You could grow crops under them or place them offshore.

Europe's public agencies currently prioritize space solar power. Jones: "There's a devotion you don't see in the U.S." ESA commissioned two solar cost/benefit studies last year. Vijendran claims it might match ground-based renewables' cost. Even at a higher price, equivalent to nuclear, its 24/7 availability would make it competitive.

ESA will urge member states in November to fund a technical assessment. If the news is good, the agency will plan for 2025. With €15 billion to €20 billion, ESA may launch a megawatt-scale demonstration facility by 2030 and a gigawatt-scale facility by 2040. "Moonshot"

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.

The Top 8 Growth Hacking Techniques for Startups

These startups, and how they used growth-hack marketing to flourish, are some of the more ethical ones, while others are less so.

Before the 1970 World Cup began, Puma paid footballer Pele $120,000 to tie his shoes. The cameras naturally focused on Pele and his Pumas, causing people to realize that Puma was the top football brand in the world.

Early workers of Uber canceled over 5,000 taxi orders made on competing applications in an effort to financially hurt any of their rivals.

PayPal developed a bot that advertised cheap goods on eBay, purchased them, and paid for them with PayPal, fooling eBay into believing that customers preferred this payment option. Naturally, Paypal became eBay's primary method of payment.

Anyone renting a space on Craigslist had their emails collected by AirBnB, who then urged them to use their service instead. A one-click interface was also created to list immediately on AirBnB from Craigslist.

To entice potential single people looking for love, Tinder developed hundreds of bogus accounts of attractive people. Additionally, for at least a year, users were "accidentally" linked.

Reddit initially created a huge number of phony accounts and forced them all to communicate with one another. It eventually attracted actual users—the real meaning of "fake it 'til you make it"! Additionally, this gave Reddit control over the tone of voice they wanted for their site, which is still present today.

To disrupt the conferences of their main rival, Salesforce recruited fictitious protestors. The founder then took over all of the event's taxis and gave a 45-minute pitch for his startup. No place to hide!

When a wholesaler required a minimum purchase of 10, Amazon CEO Jeff Bezos wanted a way to purchase only one book from them. A wholesaler would deliver the one book he ordered along with an apology for the other eight books after he discovered a loophole and bought the one book before ordering nine books about lichens. On Amazon, he increased this across all of the users.

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