Tests you need to catch early cognitive decline 🧠

Try This fam!

I heard you guys loud and clear in our recent survey! One of the things you care A LOT about is doing whatever you can to prevent cognitive decline.

I’m right there with you. Even though I’m only in my mid 40’s, it’s a topic that I’m personally invested in. I have a grandfather and other elders in my family who suffered from dementia, and it's one of the scariest diseases out there.

So, I hope you find today’s guest article on all things cognitive decline and Alzheimer's particularly helpful and hopeful. Because so much of addressing this disease is catching it early.

Here with us today is my friend and personal functional medicine doctor: Elroy Vojdani, MD. He’s discussing which tests and markers we should be looking at to assess and prevent early cognitive decline. 

You might be shocked by some of this information because we’re not talking about brain scans.

We’re talking about assessing your metabolic health, inflammation, hormones, and more…. because diseases of the brain actually start in the body.

Now, this list of markers and tests might feel overwhelming. But the goal here isn't to run every single one of these tomorrow. The goal is to understand the pathways that drive this disease so you can have smarter conversations with your doctor and know what questions to ask. More thoughts on this in my conclusion.

By the way, this guest article can be found on Dr. Vojdani's fantastic Substack newsletter, The Inflamed Generation. If you’re interested in this topic, consider subscribing to his Substack—it’s one of my go-tos! 

Now, let’s get into it:

Alzheimer’s doesn’t start in the brain. It starts in the body.

Long before memory slips, the earliest changes show up in metabolism, inflammation, hormones, sleep patterns, gut integrity, and environmental load. Your brain simply becomes the place where those signals finally become visible.

Seeing Alzheimer’s as an immunometabolic disease reshapes the prevention conversation. You realize you don’t have to wait for symptoms. You don’t need a PET scan. You don’t need a specialist.

You can measure the earliest risk markers decades before memory changes.

Let’s walk through what actually matters—in plain language.

1. The First Red Flags Show Up in Metabolism

The earliest changes in Alzheimer’s are metabolic, not cognitive. Before memory slips, the brain becomes less efficient at using glucose.

Alzheimer’s often begins as a fuel problem, not a memory problem.

Here are the most meaningful metabolic markers—with optimal ranges:

• Fasting glucose: 75–85 mg/dL
• Fasting insulin: 2–5 μIU/mL
• HOMA-IR: <1.0
• Hemoglobin A1c: 4.8–5.2%
• Triglycerides: <80 mg/dL
• HDL: >55 mg/dL (men); >65 mg/dL (women)
• ApoB: <80 mg/dL (ideal brain-protective range)

APOE4 carriers are more sensitive to glucose variability, but metabolic drift matters for everyone.

2. Inflammation: The Center of Gravity in Modern Alzheimer’s Research

This is the biggest shift in the field:
Alzheimer’s is increasingly understood as a disease of chronic immune activation.

Microglia, the brain’s immune cells, become “primed,” meaning they overreact to everyday signals and begin shifting the brain into a low-level inflammatory state.

Amyloid doesn’t cause inflammation. Inflammation triggers amyloid.

The most useful cytokines to measure are:

Core cytokines:
• IL-6: optimal <1 pg/mL
• TNF-α: optimal <2 pg/mL
• IL-1β: optimal as low as possible/undetectable
• IL-10: healthy adequate levels (anti-inflammatory “brake”)

Additional helpful markers:
• IFN-γ: low to low-normal
• IL-8: low
• MCP-1: low

These are not Alzheimer’s-specific tests—they’re metabolic and immune tests that reveal the terrain the brain is operating in.

And if you want a deeper look at gut–brain immune activation:

• Cyrex Array 2 → intestinal permeability
• Cyrex Array 20 → blood–brain barrier immune reactivity

When these markers drift upward, the brain is already feeling it—even if you feel “fine.”

Note from Dhru: I’ve done these labs through Dr. Vojandi’s clinic, Regenera Medical in Los Angeles, but ask your local functional medicine doctor if they can order and interpret these tests for you.

3. The Hormone Shift No One Talks About—Especially for Women

Two-thirds of Alzheimer’s patients are women. This isn’t random. It aligns with the drop in estrogen during perimenopause and menopause, because estrogen plays a major role in:

• glucose metabolism in the brain

• mitochondrial energy production

• synaptic repair

• microglial stability

• blood–brain barrier strength

Menopause isn’t just a reproductive transition. It’s a neurological transition.

Here are the hormones worth measuring in midlife:

• Estradiol
• Progesterone
• Thyroid panel (TSH, free T3, free T4)
• SHBG
• DHEA-S
• Testosterone (total + free)
• Pregnenolone

The goal isn’t “high” hormones—it’s stable, supported signaling.

4. APOE4: A Different Operating Manual, Not a Destined Diagnosis

APOE4 has been painted as a deterministic “Alzheimer’s gene,” but that’s misleading.

APOE4 doesn’t doom you. It just changes what your brain needs.

The APOE4 brain:

• is more sensitive to glucose spikes

• is more responsive to inflammation

• relies more on ketones for backup energy

• is more impacted by sleep disruption

• reacts differently to hormonal shifts

But there’s an upside:

APOE4 carriers often respond more dramatically when these pathways are optimized.

Sensitivity can be leveraged into prevention.

5. The Quiet Predictors: Sleep, Gut, and Environment

If there’s one pattern I see across hundreds of patients, it’s this:

Your brain is downstream of everything else in your body.

Sleep: Deep sleep is when the brain clears metabolic waste, including amyloid. If deep sleep is disrupted, the brain’s nightly cleanup slows.

Gut: Leaky gut increases systemic inflammation. Systemic inflammation primes microglia.
Cyrex Array 2 and 20 help identify this pattern.

Environment: Mold exposure, air pollution, heavy metals—none of this is fringe anymore. These are well-established contributors to neuroinflammation.

This isn’t a fear-based narrative.
It’s a connected one.

6. The Point of All This: Early Changes Are Measurable and Fixable

Here’s the part I want people to remember: You don’t have to wait for symptoms to know your trajectory.

The earliest signs show up in:

• metabolic markers

• inflammatory markers

• hormone changes

• sleep architecture

• gut integrity

• immune balance

And the same markers that predict Alzheimer’s also predict:

• cardiovascular disease

• diabetes

• autoimmune drift

• chronic inflammation

• hormonal instability

• reduced resilience

Protect your metabolism, your inflammation pathways, your sleep, your hormones—and you’re protecting your brain at the same time.

Once you know what to look for, you’re no longer guessing.

You’re steering.

My (Dhru’s) Thoughts: I told you at the top that I'd share some additional thoughts.

Dr. Vojdani paints a clear picture. What happens in our bodies impacts our brain. But you don't need to run every test on this list to start making real shifts in your brain health.

If you zoom out, the big picture version of the details in the list is: don't overeat, stay active and metabolically healthy, be protective of your sleep, filter your water and air, and for women specifically, understand the role that menopause plays in the brain.

If you want to go deeper and look under the hood, start with the metabolic basics. Fasting glucose, fasting insulin, and hemoglobin A1c can be ordered by most GPs.

For more advanced markers, such as cytokine panels and hormone testing, you'll likely need a functional medicine or integrative doctor.

Dr. Dale Bredesen (past podcast guest) has a directory of practitioners trained in his cognitive health protocols, which is a good place to start your search. And companies like Superhuman (no affiliation) and others offer direct-to-consumer lab panels if you want to take matters into your own hands.

Lastly, if you want full access to this series where Dr. Vojdani breaks down the most important things to know about brain health, check out his Substack here, where you can find references for this info and more.

Much love, 

Dhru Purohit

The information in this newsletter is for educational purposes only and should not be construed as medical advice; please consult a qualified healthcare professional before making any health-related decisions.