Diseases & Longevity · File 02

Dementia. The system diagnosed 10 years after it starts.

Dementia and Alzheimer's disease are top 3 cause of death in high-income countries and the main contributor to prolonged disability. The neurodegenerative trajectory begins two to three decades before the first clinical symptom — and the Lancet Commission 2024 estimates 45% of risk is attributable to 14 modifiable factors. That is the window where longevity medicine operates.

Why measure the trajectory before symptoms

The deposition of brain amyloid begins, in many cases, two to three decades before the first clinical symptom of Alzheimer's. By the time clear cognitive decline appears, substantial structural damage already exists. That is the basic mechanic that makes dementia an early longevity disease, not an old-age one.

The Lancet Commission 2024 on dementia prevention identifies 14 modifiable factors explaining approximately 45% of population risk — from uncorrected hearing loss, hypertension, and obesity to physical inactivity, social isolation, and untreated depression. That figure is why a serious longevity program measures and discusses cognitive trajectory long before the classical neurology consultation.

When the symptom appears, two decades of biology already lie beneath. Longevity medicine operates in that window, not after.
Lancet Commission · 2024

Of risk is attributable to modifiable factors

The Lancet Commission on Dementia Prevention, Intervention, and Care (Livingston et al., 2024 update) synthesized the best available evidence on modifiable factors across the life course. It is the editorial reference that any serious longevity clinic must be able to cite — and operationalize.

  • Global burden

    Top 3 muerte HIC

    In Scandinavia, UK, and US (2019), dementia is top 3 cause of death and top 1 contributor to prolonged disability alongside ischemic heart disease.
    — Eriksen et al., Sci Rep 2025; WHO GHE 2020

  • Modifiable factors

    14 dianas

    Hearing loss, hypertension, obesity, smoking, depression, social isolation, physical inactivity, T2D, air pollution, low education, excessive alcohol, traumatic brain injury, high LDL cholesterol, and uncorrected visual loss.
    — Lancet Commission 2024

  • AMBAR study

    Fase IIb/III · 496 pacientes

    Plasma exchange with albumin replacement in mild-moderate Alzheimer's. In the moderate Alzheimer subgroup at baseline: 61% slowing of functional decline (ADCS-ADL) vs placebo (p<0.05). Did not obtain regulatory approval; did establish a clinically relevant signal.
    — Boada et al., Alzheimer's & Dementia 2020

  • Peripheral sink

    Base mecanística · 2001

    DeMattos showed that reducing plasma Aβ induces a gradient that extracts Aβ from the central nervous system. It is the same mechanistic base for anti-amyloid monoclonals (lecanemab, donanemab) and for plasma exchange with albumin.
    — DeMattos et al., PNAS 2001

Chap. 03 · Preclinical latency

The invisible years where the trajectory is decided

Ten to twenty years of biological changes precede clinical diagnosis. In that window we measure and modulate — not after.

  • Loss of autonomy

    AVD progresivas

    Established cognitive decline progressively reduces capacity for activities of daily living (ADL). Caregiver burden accumulates years of family disability.
    — GBD 2019

  • MCI → dementia

    30–50% en 5 años

    Mild cognitive impairment (MCI) progresses to clinical dementia in 30–50% of cases within 5 years. Identifying MCI early opens the intervention window.
    — GBD 2019

  • Comorbidity

    Depresión + osteoartritis

    Typical neurodegenerative cluster: dementia + depression + osteoarthritis with falls. Major depression is bidirectional and doubles cognitive progression risk.
    — Eriksen 2025; GBD 2019

  • Family cost

    Hospitalización ↑↑

    Hospital days per year increase ~2.5× in the worst health score (Eriksen 2025). Advanced dementia is one of the main generators of service utilization.
    — Eriksen et al., Sci Rep 2025

What we don't offer — and what we do

Wellness Care does not treat Alzheimer's disease. Clinical dementia diagnosis belongs to the neurologist; approved monoclonals (lecanemab, donanemab) are the specialist's responsibility; plasma exchange with albumin does not have regulatory approval as Alzheimer's treatment in the United States or Europe. AMBAR generated an interesting signal, not an approval.

What we do: evaluate patients with subjective cognitive concern, family history, or risk factors through advanced biomarker panel — inflammaging, neuro-specific profile (p-tau, NfL where applicable), brain metabolic profile, microbiota. We design individualized protocols acting on the 14 modifiable factors identified by the Lancet Commission. More clinical detail in the dedicated Alzheimer and AMBAR study category.

We don't promise to prevent Alzheimer's. What we do hold: 45% of risk is modifiable, and that is measured and worked on before the first symptom.
How we measure it

The layers of neurodegeneration
risk assessment

Before proposing any intervention: we measure. Cognitive risk assessment is built from four convergent layers, each with its own science and reading.

Advanced biomarkers

21 specialized panels across 8 clinical categories — biological age, inflammaging, metabolic profile, functional hormonal, microbiota. The quantitative layer.

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Alzheimer & AMBAR study

The largest Phase IIb/III trial of plasma exchange with albumin in Alzheimer's — Boada et al., Alzheimer's & Dementia 2020.

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Therapeutic plasma exchange

Spectra Optia, Buck Institute evidence (Fuentealba 2025), inflammaging modulation, and peripheral clearance.

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The Longevity Program

How this assessment integrates into the full program — from initial valuation to individualized protocol design under medical judgment.

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Featured evidence

The papers that sustain
the cognitive conversation

Three publications that structure evidence-based brain longevity medicine.

"45% of dementia risk is potentially modifiable through 14 factors across the life course, from hearing loss to physical inactivity, hypertension, depression, and untreated hypercholesterolaemia."
14 factores · life-course
Livingston et al.
Lancet Commission · 2024
"Plasma exchange with albumin replacement showed a 61% slowing of functional decline in moderate Alzheimer disease patients vs. placebo (ADCS-ADL, p<0.05)."
AMBAR · subgrupo moderado
Boada et al.
Alzheimer's & Dementia · 2020
"Dementia is the top 3 cause of death in high-income countries and the top 1 contributor to years lived with disability alongside ischemic heart disease."
WHO GHE · Eriksen cohort
Eriksen et al.
Scientific Reports · 2025

Frequently asked questions about dementia and Alzheimer's

The most recurrent questions about dementia, Alzheimer's, the 14 modifiable factors identified by the Lancet Commission, and how Wellness Care addresses cognitive risk before diagnosis. No overclaim, no marketing.

01

How much of dementia risk is modifiable?

The Lancet Commission on Dementia Prevention, Intervention, and Care (Livingston et al. 2024) estimates approximately 45% of dementia risk is attributable to 14 modifiable factors throughout life.

This does not mean 45% of cases are individually avoidable, but systematic work on those factors substantially reduces population risk.

Livingston et al. · Lancet Commission · 2024
02

What are the 14 modifiable factors?

The 14 modifiable factors identified by the Lancet Commission 2024:

· Uncorrected hearing loss
· Hypertension
· Central obesity
· Smoking
· Untreated depression
· Social isolation
· Physical inactivity
· Type 2 diabetes
· Air pollution
· Low early education
· Excessive alcohol
· Traumatic brain injury
· Elevated LDL cholesterol (added 2024)
· Uncorrected visual loss (added 2024)

03

When does Alzheimer's disease begin biologically?

Brain amyloid deposition, brain glucose metabolism changes (measurable by FDG-PET), and plasma markers (p-tau217, NfL) can be detected 15 to 25 years before the first evident cognitive symptom.

That preclinical window is the central target of any serious secondary prevention program.

04

What was the AMBAR study and what did it find?

AMBAR (Alzheimer Management by Albumin Replacement) is the largest Phase IIb/III clinical trial of plasma exchange with albumin replacement in mild-moderate Alzheimer's.

496 patients, 41 centers in Spain and US, sponsored by Grifols. The primary intention-to-treat endpoint did not reach statistical significance, but in the pre-specified moderate Alzheimer subgroup it showed 61% slowing of functional decline measured with ADCS-ADL (p<0.05).

It did not obtain regulatory approval. More in the dedicated category.

Boada et al. · Alzheimer's & Dementia · 2020
05

Does Wellness Care treat Alzheimer's?

No. Wellness Care does not treat Alzheimer's disease or propose unapproved treatments as substitutes for the neurological standard.

Clinical diagnosis, approved monoclonals (lecanemab, donanemab), and management of established dementia are the neurologist's responsibility.

What we do: evaluate patients with cognitive concern, family history, or risk factors, through advanced biomarkers, and design individualized secondary prevention protocols under medical judgment.

06

What is the link between depression and dementia?

Major depression is on the Lancet Commission 2024 list of 14 modifiable factors.

The association is bidirectional: untreated depression increases cognitive progression risk, and incipient dementia can manifest as depression.

Depression also accelerates all-cause mortality (−7 to −11 years of life expectancy per GBD 2019).

The first act of power

45% of dementia risk is modifiable — but only if it is worked on before the first symptom appears.

Measure cognitive biomarkers before diagnosis, identify the 14 modifiable factors from the Lancet Commission, intervene under indexed evidence — that is what we do. It is not preventing Alzheimer's. It is working with the biology we can actually measure.

Concerned about your brain health?

Book a neurodegeneration risk assessment

We evaluate clinical history, risk factors, inflammaging biomarkers, and neuro-specific profile. If you have subjective cognitive concern, family history of Alzheimer's, or want to understand your trajectory before symptoms — this is what we do.

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