A proposal, not yet a therapy. Pulsed sound waves carry a forty-beat-per-second rhythm deep into the brain, where flickering light and tones cannot reach. In mice bred for memory disease it clears protein deposits and improves memory. Not one person has yet received it. Some effects of pulsed brain ultrasound come from the audible buzz it makes. (Full Review)
| Marker | Target | Why |
|---|---|---|
| Plasma p-tau217 | Below assay-specific positivity threshold; stable or falling on repeat | Tracks Alzheimer's pathology and is the most responsive blood marker to disease-modifying effects |
| Plasma Aβ42/Aβ40 ratio | Above assay-specific threshold | Indicates whether amyloid pathology is present and therefore whether a plaque-directed mechanism has any substrate |
| Neurofilament light chain (NfL) | Age-adjusted; below the 75th percentile for age | General marker of neuronal injury; a rise would be the earliest signal of harm from an unvalidated exposure |
| Glial fibrillary acidic protein (GFAP) | Age-adjusted; stable across repeats | Marker of astrocyte activation; the closest blood proxy for the neuroinflammatory response the intervention is meant to reduce |
| High-sensitivity C-reactive protein (hs-CRP) | Below 1.0 mg/L | Systemic inflammatory load, which independently degrades cognition and would confound any inflammatory readout |
| Homocysteine | 5–8 µmol/L | Elevated levels accelerate brain atrophy and are a correctable competing driver of cognitive decline |
| Haemoglobin A1c (HbA1c) | 4.8–5.4% | Glycaemic control drives small-vessel disease and cognitive decline and is a far better-evidenced lever than any stimulation protocol |
| APOE genotype | Not a range; result is ε2/ε3/ε4 status | Determines vascular amyloid burden and therefore the risk tier for any amyloid-mobilising intervention |
| Cerebral microbleed count on susceptibility-weighted MRI | Zero to three; four or more is a conventional exclusion | Direct measure of the vascular fragility that determines haemorrhage risk |
| Resting EEG gamma power and 40 Hz entrainment response | Individually referenced; entrainment response present and stable or increasing | The only direct measure of whether the intended mechanism is engaged in that individual |
Cadence: Symptom log and scalp inspection after every session; EEG entrainment response and symptom review at 1 week and 4 weeks; cognitive battery and blood panel at 3 months and 6 months; susceptibility-weighted MRI at 6 months, or immediately if any new neurological symptom appears. Thereafter every 6–12 months for as long as sessions continue.