# Alzheimers and Parkinsons What Treatment Actually Exists

> Alzheimer's and Parkinson's: What Treatment Actually Exists is a plain inventory of the two most common neurodegenerative diseases and what can be done about them today, separated strictly into…

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Last updated: 2026-10-04
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**Alzheimer's and Parkinson's: What Treatment Actually Exists** is a plain inventory of the two most common neurodegenerative diseases and **what can be done about them today**, separated strictly into **approved**, **investigational** and **unproven**. Both diseases attract an enormous volume of hopeful writing, and the reason to be severe about the tiers is that **families make real decisions off these sentences**. Nothing here is individual medical advice; it is the map of the territory so that a conversation with a neurologist starts further along.

## 1. What the two diseases are

- **Alzheimer's disease** — a **proteinopathy** with two signatures: **extracellular amyloid-β plaques** and **intracellular hyperphosphorylated tau tangles**, plus synapse loss and neuroinflammation. Clinically it begins as **episodic-memory** failure. **Pathology precedes symptoms by 15–20 years**, which is the single most important fact for understanding why treatments fail: by the time anyone is diagnosed, a great deal is already gone.
- **Parkinson's disease** — loss of **dopaminergic neurons in the substantia nigra pars compacta**, with **α-synuclein** aggregated into **Lewy bodies**. Motor signs (bradykinesia, rigidity, rest tremor, postural instability) appear once roughly **50–60% of nigral neurons** are already lost. The **non-motor** disease often comes first by years — **REM sleep behaviour disorder**, **constipation**, **anosmia** (loss of smell), depression — and is frequently what reduces quality of life most.
- **They are not one thing.** "Parkinsonism" includes **progressive supranuclear palsy**, **multiple system atrophy**, **corticobasal degeneration** and **drug-induced** parkinsonism, which respond differently or not at all. **Dementia with Lewy bodies** sits between the two diseases on this page. An accurate diagnosis changes everything that follows.

## 2. Alzheimer's — what is approved

### Symptomatic (decades old, modest, real)

- **Cholinesterase inhibitors** — **donepezil**, **rivastigmine**, **galantamine**. They raise synaptic acetylcholine by blocking its breakdown. **Effect size is modest** and they do not alter the disease course, but the effect is real and measurable. Side effects are cholinergic: nausea, diarrhoea, bradycardia, vivid dreams.
  * **Galantamine** is also a **nicotinic allosteric modulator**, which is why it appears in the nootropic literature as well — see Galantamine and Cholinergic Neurotransmission and Cholinesterase Inhibition.
- **Memantine** — a **low-affinity, uncompetitive NMDA antagonist**, used in moderate-to-severe disease, often with a cholinesterase inhibitor. The low affinity is the point: it blocks pathological tonic glutamate signalling while letting physiological bursts through.
- **Brexpiprazole** is approved for **agitation** in Alzheimer's dementia. Symptom management, with the antipsychotic class risks.

### Disease-modifying — the anti-amyloid antibodies

This is the genuinely new thing, and it needs stating with its costs.
- **Lecanemab** (Leqembi) — approved in the US in 2023 — and **donanemab** (Kisunla) — 2024 — are **monoclonal antibodies that clear amyloid** from the brain. **They work**: amyloid is measurably removed, and both slowed cognitive decline in phase III.
- **How much?** Roughly a **25–35% slowing** on the trial scales over 18 months. **That is a slowing, not a stopping, and not a reversal.** Whether it is clinically perceptible to a family is **actively debated by people who are not hostile to the drugs**.
- **The risk is real and named: ARIA** — **amyloid-related imaging abnormalities**, meaning **brain oedema (ARIA-E) and microhaemorrhage (ARIA-H)**. Usually asymptomatic and detected on surveillance MRI; **occasionally severe, and deaths have occurred**, particularly with anticoagulation.
- **Genotype decides the risk.** **APOE4 homozygotes** have substantially higher ARIA rates, which is why **APOE testing before treatment** is now part of the pathway. This is **real pharmacogenomics in routine neurology** — see Skin Hair and Eye Colour Ancestry and Genetics for the population-genetics background on how such alleles distribute.
- **Aducanumab** (Aduhelm) is the cautionary tale: approved in 2021 on an **amyloid surrogate endpoint** over the objection of the FDA's own advisory committee, never shown convincingly to help patients, and **discontinued in 2024**.
- **The honest summary:** **the amyloid hypothesis has finally produced drugs that do something.** The effect is small, the infusion burden and MRI surveillance are heavy, the cost is high, and **the window is early disease only**. It is a beginning, and it is not a cure.

### What is coming

- **Blood biomarkers** — **plasma p-tau217** is accurate enough to be changing diagnosis in practice, which matters more than it sounds: **early, cheap, accurate diagnosis is the precondition for every early treatment.**
- **Anti-tau** approaches, **active vaccines**, and combination amyloid-plus-tau regimens are in trials.

## 3. Parkinson's — what is approved

### Dopamine replacement, which still dominates

- **Levodopa with carbidopa** remains **the most effective symptomatic treatment**, sixty years on. Carbidopa is a **peripheral decarboxylase inhibitor** — it does not cross the blood-brain barrier and exists purely to stop levodopa being converted to dopamine before it gets to the brain. **That is combination pharmacology in its clearest form** — see Inert Alone, Active Together.
- **The long-term problem is kinetics, not efficacy**: **wearing off**, **on-off fluctuations** and **levodopa-induced dyskinesia** emerge as the storage capacity of surviving neurons declines and plasma levels start to matter directly. **Most of modern Parkinson's pharmacology is an attempt to smooth that curve.**
- **Protein competes with levodopa** for the same intestinal and blood-brain-barrier amino-acid transporter, which is why dose timing relative to meals is a real clinical variable.
- **Mucuna Pruriens** contains natural levodopa, and the library has a page on it. **Variable content, no decarboxylase inhibitor** — which means more peripheral dopamine, so more nausea and more cardiovascular effect per unit of benefit. **That is a pharmacological argument, not a naturalistic one.**

### Extending and smoothing it

- **COMT inhibitors** — **entacapone**, **opicapone** — block the other peripheral degradation route and extend each levodopa dose.
- **MAO-B inhibitors** — **selegiline**, **rasagiline**, **safinamide** — slow central dopamine breakdown. Note that these are **B-selective**, which is why they lack the dietary tyramine problem of the **A**-selective and non-selective MAOIs discussed in Monoamine Oxidase Inhibitors and Neurotransmitter Systems — **at licensed doses only; selectivity is dose-dependent.**
- **Dopamine agonists** — **pramipexole**, **ropinirole**, **rotigotine** patch. Useful, and with a side effect that must be stated because it destroys lives quietly: **impulse control disorders** — pathological gambling, compulsive shopping, hypersexuality, binge eating. **Patients and families are frequently not warned. Warn them.**
- **Amantadine** is the main drug for **dyskinesia** itself (weak NMDA antagonism among other actions).
- **Istradefylline** is an **adenosine A2A antagonist** for off episodes — a genuinely non-dopaminergic mechanism, and the same receptor caffeine antagonises, which is part of why **caffeine consumption is epidemiologically associated with lower Parkinson's risk**.
- **Apomorphine** is the **rescue** therapy: a **non-selective dopamine agonist** given **subcutaneously** for sudden off periods, working in minutes. **It is not an opiate** — the name is a chemical accident of its synthesis from morphine, and it has **no opioid activity**. It is also the drug behind the **emetic** history and the apomorphine material in Spiced Wine, Bitters and the Colas. **Severe nausea** is the limiting feature, usually pre-treated.
- **Continuous delivery**: **levodopa-carbidopa intestinal gel** via PEG-J, and the newer **subcutaneous foslevodopa/foscarbidopa** infusion, both aimed at eliminating the peaks and troughs rather than adding potency.

### Device therapy, which is often underused

- **Deep brain stimulation** of the **subthalamic nucleus** or **globus pallidus interna** is **well established** for patients with good levodopa response and troublesome fluctuations. It is not a last resort and it is not experimental; the common error is referring too late.
- **MRI-guided focused ultrasound** makes a lesion without opening the skull — approved for **tremor** and for Parkinson's with specific indications, including staged bilateral treatment. **Irreversible**, unlike DBS.

### The non-motor disease, which deserves equal billing

**Constipation, orthostatic hypotension, REM sleep behaviour disorder, depression, apathy, pain, drooling, and the cognitive end of the disease.** Each has its own management, and together they often matter more to a patient than tremor does. **A treatment plan that only addresses movement is half a plan.**

### Exercise, which is the most under-prescribed intervention in either disease

**For Parkinson's, exercise has better evidence than any supplement on the internet.** High-intensity aerobic training, resistance training, and **amplitude-based** programmes (LSVT BIG, boxing-style classes, tango) all have trial support for function, and the **SPARX** line of trials has been testing whether high-intensity endurance exercise is **disease-modifying**. **It is the one thing on this page that is free, available today, and unambiguously worth doing.** See Routes for Backpacking Pilgrimages and Building Muscle Tissue.

## 4. The investigational tier, including the failures that teach most

- **⚠️ GLP-1 agonists — exenatide FAILED.** This is the most important recent result in Parkinson's. Early-phase data were genuinely exciting and the hypothesis was good. The **phase 3 Exenatide-PD3 trial** (194 patients, 96 weeks, six UK centres) was **published in *The Lancet* in February 2025 and met neither its primary nor its secondary endpoints**. **No benefit over placebo.** Trials of **semaglutide** and **liraglutide** continue, and they may yet differ, **but the honest state of GLP-1 for Parkinson's today is "the biggest trial was negative."**
- **α-synuclein** is the main disease-modifying target: aggregation inhibitors, immunotherapies (prasinezumab and others, with equivocal results so far), and **reducing synuclein production**. **Machine learning has genuinely accelerated the search for aggregation inhibitors** — the Vendruscolo group's 2024 *Nature Chemical Biology* work screened millions of compounds, reporting ~10× faster screening at ~1000× lower cost and hits **hundreds of times more potent** than previous ones. **And separately**, **olive-oil tyrosols** (hydroxytyrosol acetate, DOPAC) and **oleuropein aglycone** turn out to inhibit α-synuclein aggregation **in vitro and in a *C. elegans* model**. **A worm is not a person, and no olive-oil intervention has shown benefit in human Parkinson's.** The full version of this, and why the "an AI discovered olive oil" headline conflates two separate true things, is in Cannabinoids in the Hospital §6.
- **GBA1 and LRRK2** — the two most important genetic subtypes, each with targeted drugs in trials. **This is where precision medicine in Parkinson's will start**, because a genetically defined subgroup is a tractable trial population.
- **Cell therapy** — dopaminergic neurons from stem cells, in early human trials after decades of fetal-graft work. Early, and not nothing.
- **For Alzheimer's**: anti-tau, **GLP-1 (semaglutide EVOKE)**, anti-inflammatory and metabolic approaches, and **40 Hz sensory gamma entrainment** — see §6.

## 5. The unproven tier, stated as such

These appear constantly and each gets one honest line.
- **Coconut oil / MCT ketones for Alzheimer's** — plausible mechanism (the Alzheimer's brain is glucose-hypometabolic but can burn ketones), **weak and inconsistent human data**, and the caprylic-acid medical-food result was **positive only in APOE4-negative** patients. **Widely overstated; traceable in its viral form to a single anecdote.**
- **Coenzyme Q10 for Parkinson's** — large trial, **futile**. Stopped early for lack of benefit.
- **Creatine for Parkinson's** — large NIH trial (NET-PD LS-1), **no benefit**. Creatine has good evidence for other things — see Creatine — **just not this**.
- **Vitamin E, ginkgo, DHA** for Alzheimer's prevention — repeatedly tested, **not supported**.
- **Curcumin** — poor bioavailability, no convincing clinical result despite excellent cell data. See Black Pepper for the bioavailability part.
- **Nicotine** — the epidemiology (smokers get less Parkinson's) is robust and genuinely puzzling, but the **nicotine patch trial in early Parkinson's was negative**. **An epidemiological association is a hypothesis, not a treatment.**
- **Cannabinoids** — no treatment for either disease. Possibly useful for **symptoms** (sleep, agitation, pain). Details in Cannabinoids in the Hospital.
- **What *is* supported for risk reduction** — and this list is unglamorous and real: **treat hypertension**, **treat hearing loss** (one of the largest modifiable dementia risk factors), **exercise**, **don't smoke**, **limit alcohol**, **treat diabetes**, **stay socially and cognitively engaged**, **protect your head**. The **Lancet Commission on dementia prevention** estimates a substantial fraction of cases are attributable to modifiable factors. **Nothing in a bottle competes with that list.**

## 6. Where our own work touches this

We have a research line here and it should be described at its true strength, which is **early**.
- **40 Hz gamma sensory entrainment** — the MIT work (Tsai, Boyden and colleagues) showed that **40 Hz light and sound reduced amyloid and improved cognition in mouse models**, and human trials (the **Cognito Therapeutics** device line) have run with **mixed but non-trivial** results. **This is an investigational intervention, not a treatment**, and the library's pages say so: Gamma Entrainment · Hathor 40 Hz · Auditory Steady State Response · Invisible Spectral Flicker · Display Refresh and Flicker Delivery · The Medical Applications of Light.
- **Why we care about the delivery details** — refresh rate, flicker visibility, actual delivered modulation depth — is that **a mis-delivered 40 Hz is not 40 Hz**, and a trial that delivers the wrong stimulus tests nothing. That is an engineering problem we can actually work on.
- **The neuroplasticity and neurogenesis background**: Synaptogenesis Neuroplasticity and Brain Rewiring · Neurogenesis Neuroprotectants and Synaptogenesis · Building Brains · Brain Balance.

## 7. How to read a claim about either disease

1. **Approved, investigational or unproven?** Say which. Most writing on these diseases blurs the three deliberately.
1. **Slowing, stopping or reversing?** Nothing reverses either disease. **Lecanemab slows.**
1. **Which stage?** A drug for early Alzheimer's is useless in late Alzheimer's, and may be harmful.
1. **Species and endpoint.** Mouse amyloid is not human cognition. A worm is not a person.
1. **What did the biggest trial say?** Not the most exciting trial — **the biggest and most recent**. Exenatide, CoQ10, creatine, nicotine and aducanumab are all cases where the small hopeful result was followed by a large disappointing one.
1. **And remember who is reading.** Somebody searching these words at 2 a.m. has a parent who just got a diagnosis. **That is the reason the tiers are labelled, and the reason not to blur them.**

## Sources

- van Dyck C. H. et al., "Lecanemab in early Alzheimer's disease", *New England Journal of Medicine* 388 (2023).
- Sims J. R. et al., "Donanemab in early symptomatic Alzheimer disease (TRAILBLAZER-ALZ 2)", *JAMA* 330 (2023).
- Hampel H. et al. and Palmqvist S. et al., on plasma p-tau217 diagnostic accuracy.
- Livingston G. et al., "Dementia prevention, intervention, and care: 2024 report of the *Lancet* standing Commission".
- Vijiaratnam N. et al. / Foltynie T. et al., "Exenatide once a week versus placebo as a potential disease-modifying treatment for people with Parkinson's disease in the UK: a phase 3, multicentre, double-blind, parallel-group, randomised, placebo-controlled trial", *The Lancet* (2025).
- NINDS NET-PD LS-1 Investigators, "Effect of creatine monohydrate on clinical progression in patients with Parkinson disease", *JAMA* 313 (2015).
- Parkinson Study Group QE3 Investigators, "A randomized clinical trial of high-dosage coenzyme Q10 in early Parkinson disease: no evidence of benefit", *JAMA Neurology* 71 (2014).
- Iacono D. et al. and the nicotine-patch trial literature in early Parkinson's.
- Schapira A. H. V., Chaudhuri K. R. and Jenner P., "Non-motor features of Parkinson disease", *Nature Reviews Neuroscience* 18 (2017).
- Iaccarino H. F. et al., "Gamma frequency entrainment attenuates amyloid load and modifies microglia", *Nature* 540 (2016); Martorell A. J. et al., *Cell* 177 (2019).
- Vendruscolo M. group, machine-learning identification of α-synuclein aggregation inhibitors, *Nature Chemical Biology* (2024).
- "Olive oil tyrosols reduce α-synuclein aggregation *in vitro* and *in vivo* after ingestion in a *Caenorhabditis elegans* Parkinson's model" (2024), PMID 38817211.