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.

The Kardashev scale grades civilizations from Type 1 to Type 3 based on energy harvesting.

How do technologically proficient civilizations emerge across timescales measuring in the tens of thousands or even millions of years? This is a question that worries me as a researcher in the search for “technosignatures” from other civilizations on other worlds. Since it is already established that longer-lived civilizations are the ones we are most likely to detect, knowing something about their prospective evolutionary trajectories could be translated into improved search tactics. But even more than knowing what to seek for, what I really want to know is what happens to a society after so long time. What are they capable of? What do they become?

This was the question Russian SETI pioneer Nikolai Kardashev asked himself back in 1964. His answer was the now-famous “Kardashev Scale.” Kardashev was the first, although not the last, scientist to try and define the processes (or stages) of the evolution of civilizations. Today, I want to launch a series on this question. It is crucial to technosignature studies (of which our NASA team is hard at work), and it is also important for comprehending what might lay ahead for mankind if we manage to get through the bottlenecks we have now.

The Kardashev scale

Kardashev’s question can be expressed another way. What milestones in a civilization’s advancement up the ladder of technical complexity will be universal? The main notion here is that all (or at least most) civilizations will pass through some kind of definable stages as they progress, and some of these steps might be mirrored in how we could identify them. But, while Kardashev’s major focus was identifying signals from exo-civilizations, his scale gave us a clear way to think about their evolution.

The classification scheme Kardashev employed was not based on social systems of ethics because they are something that we can probably never predict about alien cultures. Instead, it was built on energy, which is something near and dear to the heart of everybody trained in physics. Energy use might offer the basis for universal stages of civilisation progression because you cannot do the work of establishing a civilization without consuming energy. So, Kardashev looked at what energy sources were accessible to civilizations as they evolved technologically and used those to build his scale.

From Kardashev’s perspective, there are three primary levels or “types” of advancement in terms of harvesting energy through which a civilization should progress.

Type 1: Civilizations that can capture all the energy resources of their native planet constitute the first stage. This would imply capturing all the light energy that falls on a world from its host star. This makes it reasonable, given solar energy will be the largest source available on most planets where life could form. For example, Earth absorbs hundreds of atomic bombs’ worth of energy from the Sun every second. That is a rather formidable energy source, and a Type 1 race would have all this power at their disposal for civilization construction.

Type 2: These civilizations can extract the whole energy resources of their home star. Nobel Prize-winning scientist Freeman Dyson famously anticipated Kardashev’s thinking on this when he imagined an advanced civilization erecting a large sphere around its star. This “Dyson Sphere” would be a machine the size of the complete solar system for gathering stellar photons and their energy.

Type 3: These super-civilizations could use all the energy produced by all the stars in their home galaxy. A normal galaxy has a few hundred billion stars, so that is a whole lot of energy. One way this may be done is if the civilization covered every star in their galaxy with Dyson spheres, but there could also be more inventive approaches.

Implications of the Kardashev scale

Climbing from Type 1 upward, we travel from the imaginable to the god-like. For example, it is not hard to envisage utilizing lots of big satellites in space to gather solar energy and then beaming that energy down to Earth via microwaves. That would get us to a Type 1 civilization. But creating a Dyson sphere would require chewing up whole planets. How long until we obtain that level of power? How would we have to change to get there? And once we get to Type 3 civilizations, we are virtually thinking about gods with the potential to engineer the entire cosmos.

For me, this is part of the point of the Kardashev scale. Its application for thinking about identifying technosignatures is crucial, but even more strong is its capacity to help us shape our imaginations. The mind might become blank staring across hundreds or thousands of millennia, and so we need tools and guides to focus our attention. That may be the only way to see what life might become — what we might become — once it arises to start out beyond the boundaries of space and time and potential.

This is a summary. Read the full article here.

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)

We're opening up Maki through a series of Medium posts. We'll describe what Maki is building and how. We'll explain how we built a SaaS in 100 days. This isn't a step-by-step guide to starting a business, but a product philosophy to help you build quickly.

Focus on end-users.

This may seem obvious, but it's important to talk to users first. When we started thinking about Maki, we interviewed 100 HR directors from SMBs, Next40 scale-ups, and major Enterprises to understand their concerns. We initially thought about the future of employment, but most of their worries centered on Recruitment. We don't have a clear recruiting process, it's time-consuming, we recruit clones, we don't support diversity, etc. And as hiring managers, we couldn't help but agree.

Co-create your product with your end-users.

We went to the drawing board, read as many books as possible (here, here, and here), and when we started getting a sense for a solution, we questioned 100 more operational HR specialists to corroborate the idea and get a feel for our potential answer. This confirmed our direction to help hire more objectively and efficiently.

Back to the drawing board, we designed our first flows and screens. We organized sessions with certain survey respondents to show them our early work and get comments. We got great input that helped us build Maki, and we met some consumers. Obsess about users and execute alongside them.

Don’t shoot for the moon, yet. Make pragmatic choices first.

Once we were convinced, we began building. To launch a SaaS in 100 days, we needed an operating principle that allowed us to accelerate while still providing a reliable, secure, scalable experience. We focused on adding value and outsourced everything else. Example:

Concentrate on adding value. Reuse existing bricks.

When determining which technology to use, we looked at our strengths and the future to see what would last. Node.js for backend, React for frontend, both with typescript. We thought this technique would scale well since it would attract more talent and the surrounding mature ecosystem would help us go quicker.

We explored for ways to bootstrap services while setting down strong foundations that might support millions of users. We built our backend services on NestJS so we could extend into microservices later. Hasura, a GraphQL APIs engine, automates Postgres data exposing through a graphQL layer. MUI's ready-to-use components powered our design-system. We used well-maintained open-source projects to speed up certain tasks.

We outsourced important components of our platform (Auth0 for authentication, Stripe for billing, SendGrid for notifications) because, let's face it, we couldn't do better. We choose to host our complete infrastructure (SQL, Cloud run, Logs, Monitoring) on GCP to simplify our work between numerous providers.

Focus on your business, use existing bricks for the rest. For the curious, we'll shortly publish articles detailing each stage.

Most importantly, empower people and step back.

We couldn't have done this without the incredible people who have supported us from the start. Since Powership is one of our key values, we provided our staff the power to make autonomous decisions from day one. Because we believe our firm is its people, we hired smart builders and let them build.

Nicolas left Spendesk to create scalable interfaces using react-router, react-queries, and MUI. JD joined Swile and chose Hasura as our GraphQL engine. Jérôme chose NestJS to build our backend services. Since then, Justin, Ben, Anas, Yann, Benoit, and others have followed suit.

If you consider your team a collective brain, you should let them make decisions instead of directing them what to do. You'll make mistakes, but you'll go faster and learn faster overall.

Invest in great talent and develop a strong culture from the start. Here's how to establish a SaaS in 100 days.

A worldwide energy crisis might have hampered renewable energy and clean tech investment. Nope.

BNEF's 2023 Energy Transition Investment Trends study surprised and encouraged. Global energy transition investment reached $1 trillion for the first time ($1.11t), up 31% from 2021. From 2013, the clean energy transition has come and cannot be reversed.

BNEF Head of Global Analysis Albert Cheung said our findings ended the energy crisis's influence on renewable energy deployment. Energy transition investment has reached a record as countries and corporations implement transition strategies. Clean energy investments will soon surpass fossil fuel investments.

The table below indicates the tripping point, which means the energy shift is occuring today.

BNEF calls money invested on clean technology including electric vehicles, heat pumps, hydrogen, and carbon capture energy transition investment. In 2022, electrified heat received $64b and energy storage $15.7b.

Nonetheless, $495b in renewables (up 17%) and $466b in electrified transport (up 54%) account for most of the investment. Hydrogen and carbon capture are tiny despite the fanfare. Hydrogen received the least funding in 2022 at $1.1 billion (0.1%).

China dominates investment. China spends $546 billion on energy transition, half the global amount. Second, the US total of $141 billion in 2022 was up 11% from 2021. With $180 billion, the EU is unofficially second. China invested 91% in battery technologies.

The 2022 transition tipping point is encouraging, but the BNEF research shows how far we must go to get Net Zero. Energy transition investment must average $4.55 trillion between 2023 and 2030—three times the amount spent in 2022—to reach global Net Zero. Investment must be seven times today's record to reach Net Zero by 2050.

BNEF 2023 Energy Transition Investment Trends.

As shown in the graph above, BNEF experts have been using their crystal balls to determine where that investment should go. CCS and hydrogen are still modest components of the picture. Interestingly, they see nuclear almost fading. Active transport advocates like me may have something to say about the massive $4b in electrified transport. If we focus on walkable 15-minute cities, we may need fewer electric automobiles. Though we need more electric trains and buses.

Albert Cheung of BNEF emphasizes the challenge. This week's figures promise short-term job creation and medium-term energy security, but more investment is needed to reach net zero in the long run.

I expect the BNEF Energy Transition Investment Trends report to show clean tech investment outpacing fossil fuels investment every year. Finally saying that is amazing. It's insufficient. The planet must maintain its electric (not gas) pedal. In response to the research, Christina Karapataki, VC at Breakthrough Energy Ventures, a clean tech investment firm, tweeted: Clean energy investment needs to average more than 3x this level, for the remainder of this decade, to get on track for BNEFs Net Zero Scenario. Go!

The Federal Funds Rate (FFR) is the target interest rate set by the Federal Reserve System (Fed)'s policy-making body (FOMC). This target is the rate at which the Fed suggests commercial banks borrow and lend their excess reserves overnight to each other.

The FOMC meets 8 times a year to set the target FFR. This is supposed to promote economic growth. The overnight lending market sets the actual rate based on commercial banks' short-term reserves. If the market strays too far, the Fed intervenes.

Banks must keep a certain percentage of their deposits in a Federal Reserve account. A bank's reserve requirement is a percentage of its total deposits. End-of-day bank account balances averaged over two-week reserve maintenance periods are used to determine reserve requirements.

If a bank expects to have end-of-day balances above what's needed, it can lend the excess to another institution.

The FOMC adjusts interest rates based on economic indicators that show inflation, recession, or other issues that affect economic growth. Core inflation and durable goods orders are indicators.

In response to economic conditions, the FFR target has changed over time. In the early 1980s, inflation pushed it to 20%. During the Great Recession of 2007-2009, the rate was slashed to 0.15 percent to encourage growth.

Inflation picked up in May 2022 despite earlier rate hikes, prompting today's 0.75 percent point increase. The largest increase since 1994. It might rise to around 3.375% this year and 3.1% by the end of 2024.