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.

SpaceX's Starship.

Launched last week.

Four minutes in:

SpaceX will succeed. When it does, its massiveness will matter.

Its payload will revolutionize space economics.

Civilization will shift.

We don't yet understand how this will affect space and Earth culture. Grab it.

The Cost of Space Transportation Has Decreased Exponentially

Space launches have increased dramatically in recent years.

We mostly send items to LEO, the green area below:

SpaceX's reusable rockets can send these things to LEO. Each may launch dozens of payloads into space.

With all these launches, we're sending more than simply things to space. Volume and mass. Since the 1980s, launching a kilogram of payload to LEO has become cheaper:

One kilogram in a large rocket cost over $75,000 in the 1980s. Carrying one astronaut cost nearly $5M! Falcon Heavy's $1,500/kg price is 50 times lower. SpaceX's larger, reusable rockets are amazing.

SpaceX's Starship rocket will continue. It can carry over 100 tons to LEO, 50% more than the current Falcon heavy. Thousands of launches per year. Elon Musk predicts Falcon Heavy's $1,500/kg cost will plummet to $100 in 23 years.

In context:

People underestimate this.

2. The Benefits of Affordable Transportation

Compare Earth's transportation costs:

It's no surprise that the US and Northern Europe are the wealthiest and have the most navigable interior waterways.

So what? since sea transportation is cheaper than land. Inland waterways are even better than sea transportation since weather is less of an issue, currents can be controlled, and rivers serve two banks instead of one for coastal transportation.

In France, because population density follows river systems, rivers are valuable. Cheap transportation brought people and money to rivers, especially their confluences.

How come? Why were humans surrounding rivers?

Imagine selling meat for $10 per kilogram. Transporting one kg one kilometer costs $1. Your margin decreases $1 each kilometer. You can only ship 10 kilometers. For example, you can only trade with four cities:

If instead, your cost of transportation is half, what happens? It costs you $0.5 per km. You now have higher margins with each city you traded with. More importantly, you can reach 20-km markets.

However, 2x distance 4x surface! You can now trade with sixteen cities instead of four! Metcalfe's law states that a network's value increases with its nodes squared. Since now sixteen cities can connect to yours. Each city now has sixteen connections! They get affluent and can afford more meat.

Rivers lower travel costs, connecting many cities, which can trade more, get wealthy, and buy more.

The right network is worth at least an order of magnitude more than the left! The cheaper the transport, the more trade at a lower cost, the more income generated, the more that wealth can be reinvested in better canals, bridges, and roads, and the wealth grows even more.

Throughout history. Rome was established around cheap Mediterranean transit and preoccupied with cutting overland transportation costs with their famous roadways. Communications restricted their empire.

The Egyptians lived around the Nile, the Vikings around the North Sea, early Japan around the Seto Inland Sea, and China started canals in the 5th century BC.

Transportation costs shaped empires.Starship is lowering new-world transit expenses. What's possible?

3. Change Organizations, Change Companies, Change the World

Starship is a conveyor belt to LEO. A new world of opportunity opens up as transportation prices drop 100x in a decade.

Satellite engineers have spent decades shedding milligrams. Weight influenced every decision: pricing structure, volumes to be sent, material selections, power sources, thermal protection, guiding, navigation, and control software. Weight was everything in the mission. To pack as much science into every millimeter, NASA missions had to be miniaturized. Engineers were indoctrinated against mass.

No way.

Starship is not constrained by any space mission, robotic or crewed.

Starship obliterates the mass constraint and every last vestige of cultural baggage it has gouged into the minds of spacecraft designers. A dollar spent on mass optimization no longer buys a dollar saved on launch cost. It buys nothing. It is time to raise the scope of our ambition and think much bigger. — Casey Handmer, Starship is still not understood

A Tesla Roadster in space makes more sense.

It went beyond bad PR. It told the industry: Did you care about every microgram? No more. My rockets are big enough to send a Tesla without noticing. Industry watchers should have noticed.

Most didn’t. Artemis is a global mission to send astronauts to the Moon and build a base. Artemis uses disposable Space Launch System rockets. Instead of sending two or three dinky 10-ton crew habitats over the next decade, Starship might deliver 100x as much cargo and create a base for 1,000 astronauts in a year or two. Why not? Because Artemis remains in a pre-Starship paradigm where each kilogram costs a million dollars and we must aggressively descope our objective.

Space agencies can deliver 100x more payload to space for the same budget with 100x lower costs and 100x higher transportation volumes. How can space economy saturate this new supply?

Before Starship, NASA supplied heavy equipment for Moon base construction. After Starship, Caterpillar and Deere may space-qualify their products with little alterations. Instead than waiting decades for NASA engineers to catch up, we could send people to build a space outpost with John Deere equipment in a few years.

History is littered with the wreckage of former industrial titans that underestimated the impact of new technology and overestimated their ability to adapt: Blockbuster, Motorola, Kodak, Nokia, RIM, Xerox, Yahoo, IBM, Atari, Sears, Hitachi, Polaroid, Toshiba, HP, Palm, Sony, PanAm, Sega, Netscape, Compaq, GM… — Casey Handmer, Starship is still not understood

Everyone saw it coming, but senior management failed to realize that adaption would involve moving beyond their established business practice. Others will if they don't.

4. The Starship Possibilities

It's Starlink.

SpaceX invented affordable cargo space and grasped its implications first. How can we use all this inexpensive cargo nobody knows how to use?

Satellite communications seemed like the best way to capitalize on it. They tried. Starlink, designed by SpaceX, provides fast, dependable Internet worldwide. Beaming information down is often cheaper than cable. Already profitable.

Starlink is one use for all this cheap cargo space. Many more. The longer firms ignore the opportunity, the more SpaceX will acquire.

What are these chances?

Satellite imagery is outdated and lacks detail. We can improve greatly. Synthetic aperture radar can take beautiful shots like this:

Have you ever used Google Maps and thought, "I want to see this in more detail"? What if I could view Earth live? What if we could livestream an infrared image of Earth?

We could launch hundreds of satellites with such mind-blowing visual precision of the Earth that we would dramatically improve the accuracy of our meteorological models; our agriculture; where crime is happening; where poachers are operating in the savannah; climate change; and who is moving military personnel where. Is that useful?

What if we could see Earth in real time? That affects businesses? That changes society?

I started smoking in 2002 at IIT BHU. Most of us thought it was enjoyable at first. I didn't realize the cost later.

In 2005, during my final semester, I lost my father. Suddenly, I felt more accountable for my mother and myself.

I quit before starting my first job in Bangalore. I didn't see any smoking friends in my hometown for 2 months before moving to Bangalore.

For the next 5-6 years, I had no regimen and smoked only when drinking.

Due to personal concerns, I started smoking again after my 2011 marriage. Now smoking was a constant guilty pleasure.

I smoked 3-4 cigarettes a day, but never in front of my family or on weekends. I used to excuse this with pride! First office ritual: smoking. Even with guilt, I couldn't stop this time because of personal concerns.

After 8-9 years, in mid 2019, a personal development program solved all my problems. I felt complete in myself. After this, I just needed one cigarette each day.

The hardest thing was leaving this final cigarette behind, even though I didn't want it.

James Clear's Atomic Habits was published last year. I'd only read 2-3 non-tech books before reading this one in August 2021. I knew everything but couldn't use it.

In April 2022, I realized the compounding effect of a bad habit thanks to my subconscious mind. 1 cigarette per day (excluding weekends) equals 240 = 24 packs per year, which is a lot. No matter how much I did, it felt negative.

Then I applied the 2nd principle of this book, identifying the trigger. I tried to identify all the major triggers of smoking. I found social drinking is one of them & If I am able to control it during that time, I can easily control it in other situations as well. Going further whenever I drank, I was pre-determined to ignore the craving at any cost. Believe me, it was very hard initially but gradually this craving started fading away even with drinks.

I've been smoke-free for 3 months. Now I know a bad habit's effects. After realizing the power of habits, I'm developing other good habits which I ignored all my life.

My colleague Ilana Ovental and I examined pandemic media coverage of education at the end of last year. That analysis examined coverage changes. We tracked K-12 topic attention over the previous two decades using Lexis Nexis. See the results here.

I was struck by how cleanly the past two decades can be divided up into three (or three and a half) eras of school reform—a framing that can help us comprehend where we are and how we got here. In a time when epidemic, political unrest, frenetic news cycles, and culture war can make six months seem like a lifetime, it's worth pausing for context.

If you look at the peaks in the above graph, the 21st century looks to be divided into periods. The decade-long rise and fall of No Child Left Behind began during the Bush administration. In a few years, NCLB became the dominant K-12 framework. Advocates and financiers discussed achievement gaps and measured success with AYP.

NCLB collapsed under the weight of rigorous testing, high-stakes accountability, and a race to the bottom by the Obama years. Obama's Race to the Top garnered attention, but its most controversial component, the Common Core State Standards, rose quickly.

Academic standards replaced assessment and accountability. New math, fiction, and standards were hotly debated. Reformers and funders chanted worldwide benchmarking and systems interoperability.

We went from federally driven testing and accountability to government encouraged/subsidized/mandated (pick your verb) reading and math standardization. Last year, Checker Finn and I wrote The End of School Reform? The 2010s populist wave thwarted these objectives. The Tea Party, Occupy Wall Street, Black Lives Matter, and Trump/MAGA all attacked established institutions.

Consequently, once the Common Core fell, no alternative program emerged. Instead, school choice—the policy most aligned with populist suspicion of institutional power—reached a half-peak. This was less a case of choice erupting to prominence than of continuous growth in a vacuum. Even with Betsy DeVos' determined, controversial efforts, school choice received only half the media attention that NCLB and Common Core did at their heights.

Recently, culture clash-fueled attention to race-based curriculum and pedagogy has exploded (all playing out under the banner of critical race theory). This third, culture war-driven wave may not last as long as the other waves.

Even though I don't understand it, the move from slow-building policy debate to fast cultural confrontation over two decades is notable. I don't know if it's cyclical or permanent, or if it's about schooling, media, public discourse, or all three.

One final thought: After doing this work for decades, I've noticed how smoothly advocacy groups, associations, and other activists adapt to the zeitgeist. In 2007, mission statements focused on accomplishment disparities. Five years later, they promoted standardization. Language has changed again.

Part of this is unavoidable and healthy. Chasing currents can also make companies look unprincipled, promote scepticism, and keep them spinning the wheel. Bearing in mind that these tides ebb and flow may give educators, leaders, and activists more confidence to hold onto their values and pause when they feel compelled to follow the crowd.

Christopher Janz of Point Nine Capital created the SaaS napkin in 2016. This post shows how founders have raised cash in the last 6 years. View raw data.

Round size

Unsurprisingly, round sizes have expanded and will taper down in 2022. In 2016, pre-seed rounds were $200k to $500k; currently, they're $1-$2m. Despite the macroeconomic scenario, Series A have expanded from $3m to $12m in 2016 to $6m and $18m in 2022.

Valuation

There are hints that valuations are rebounding this year. Pre-seed valuations in 2022 are $12m from $3m in 2016, and Series B prices are $270m from $100m in 2016.

Compared to public SaaS multiples, Series B valuations more closely reflect the market, but Seed and Series A prices seem to be inflated regardless of the market.

I'd like to know how each annual cohort performed for investors, based on the year they invested and the valuations. I can't access this information.

ARR

Seed firms' ARR forecasts have risen from $0 to $0.6m to $0 to $1m. 2016 expected $1.2m to $3m, 2021 $0.5m to $4m, and this year $0.5m to $2.5m, suggesting that Series A firms may raise with less ARR today. Series B minutes fell from $4.2m to $3m.

Capitalization Rate

2022 is the year that VCs start discussing capital efficiency in portfolio meetings. Given the economic shift in the markets and the stealthy VC meltdown, it's not surprising. Christopher Janz added capital efficiency to the SaaS Napkin as a new statistic for Series A (3.5x) and Series B. (2.5x). Your investors must live under a rock if they haven't asked about capital efficiency. If you're unsure:

The Capital Efficiency Ratio is the ratio of how much a company has spent growing revenue and how much they’re receiving in return. It is the broadest measure of company effectiveness in generating ARR

What next?

No one knows what's next, including me. All startup and growing enterprises around me are tightening their belts and extending their runways in anticipation of a difficult fundraising ride. If you're wanting to raise money but can wait, wait till the market is more stable and access to money is easier.