DR ANTON KRIGE FUNCTIONAL MEDICINE

Reversing Early Dementia? A New Randomised Trial of Precision Functional Medicine in Alzheimer’s Disease

8/5/2026

A recently published preprint has reported striking results from a randomised controlled trial using a personalised precision medicine approach in people with mild cognitive impairment or early Alzheimer’s disease. The study, titled “Precision Medicine Treatment of Alzheimer’s Disease: Successful Randomised Controlled Trial”, was posted on Preprints.org on 30 December 2025 and is explicitly marked as not yet peer reviewed, so the findings are important but should still be interpreted with appropriate scientific caution.
The reason this study is so interesting is that it did not use a single drug targeting a single disease pathway. Instead, it used a functional medicine style model: a broad assessment of the individual’s biology, followed by a personalised programme designed to address potential contributors to cognitive decline such as inflammation, insulin resistance, vascular risk, sleep-related oxygen problems, hormone imbalance, nutrient deficiency, toxin exposure, chronic infection, dysbiosis and immune dysfunction.
Functional medicine focuses on function at multiple levels, rather than simply applying a single treatment to a single diagnosis. In cognitive decline, this matters because the brain depends on multiple interacting systems: blood sugar regulation, vascular health, immune balance, sleep quality, mitochondrial function, hormones, nutrient status, detoxification capacity, gut health, and inflammatory signalling, all of which influence the environment in which brain cells either struggle or recover.
What did the study actually do? The trial included 73 people aged 45 to 76 with mild cognitive impairment or early dementia, with Montreal Cognitive Assessment scores of 18 or higher. Participants were randomised to either a personalised precision medicine protocol or standard-of-care treatment, and cognition and symptoms were assessed at baseline, three months, six months, and nine months.
The personalised group underwent a very comprehensive assessment. This included markers of inflammation, chronic infection, dysbiosis, immune dysfunction, insulin resistance, glycation, vascular disease, nocturnal hypoxaemia, hormone dysregulation, nutrient deficiency, toxicant exposure, genetic factors, epigenetic factors, Alzheimer ’s-associated biomarkers and MRI brain volumetrics.
The intervention was not a simple “take this supplement” protocol. It included diet, exercise, sleep optimisation, stress regulation, brain training, targeted nutrient and hormone support where indicated, gastrointestinal treatment, inflammation resolution, infection treatment, toxin-reduction strategies, and selected adjunctive therapies, depending on the individual’s findings.
This is important because it reflects the core functional medicine principle that the patient’s story, signs, symptoms and biological imbalances need to be integrated into a comprehensive plan. Two patients may both carry the label “early Alzheimer’s disease”, but one may have dominant insulin resistance and sleep apnoea, another may have inflammatory and toxicant drivers, and another may have vascular, hormonal and nutrient-related contributors.
What were the results? Compared with standard care, the precision medicine group showed statistically significant incremental improvements in broad neurocognitive function, composite memory, executive function, processing speed, cognitive symptom severity and Alzheimer’s disease symptom severity. The study also reported improvements in overall health markers, including blood pressure, body mass index, glycaemic markers, lipid profiles and methylation status.
One of the most striking findings was the difference in cognitive trajectory reported over the nine-month study period. In the precision medicine group, MoCA scores improved by an average of 3.8 points over nine months, while the standard care group improved by 2.6 points; however, the interaction p-value for MoCA was 0.154, indicating that the between-group difference on this measure did not reach conventional statistical significance.
The more sensitive computerised cognitive testing appeared more impressive in this trial. The paper reports significant benefits in CNS Vital Signs measures, including neurocognitive index, composite memory, executive function and processing speed, with the authors arguing that these changes are unlikely to be explained simply by practice effects.
The metabolic changes are also clinically relevant. The precision medicine group improved multiple cardiometabolic and inflammatory risk markers, including body mass index, blood pressure, HbA1c, insulin resistance, triglyceride-to-HDL ratio, homocysteine and vitamin D status.
This is highly consistent with what many functional medicine clinicians see in practice: the same biological terrain that affects cardiovascular risk, metabolic syndrome, immune resilience and inflammation may also affect brain resilience. Cognitive decline is not separate from the rest of the body.
Why this matters. Most conventional Alzheimer’s drug trials have focused on one dominant pathway, particularly amyloid. Some newer anti-amyloid drugs can slow decline in selected patients, but they do not usually produce cognitive improvement and may carry risks such as brain swelling or microhaemorrhage in some patients.
This point has become even more relevant following a recent Cochrane review of amyloid-beta-targeting monoclonal antibodies in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease. The review included 17 studies and 20,342 participants, and concluded that these drugs probably make little to no difference to memory and thinking decline or dementia symptom severity at 18 months, while increasing the risk of amyloid-related imaging abnormalities such as brain swelling and microbleeds.
The most important conclusion was not simply that these drugs have side effects. It was that the successful removal of amyloid proteins from the brain did not appear to be associated with clinically meaningful improvement in people with mild cognitive impairment or mild dementia due to Alzheimer’s disease.
The Cochrane news summary put this in very direct terms: anti-amyloid drugs can remove amyloid proteins from the brain, but this does not translate into meaningful clinical benefit, and future Alzheimer’s research should focus on other mechanisms.
This is exactly where the precision functional medicine model becomes highly relevant. Amyloid plaque formation may be one visible downstream feature of Alzheimer’s disease, but it may not be the primary driver in every patient, and simply clearing plaque may not correct the upstream biological environment that allowed neurodegeneration to develop.
This new precision medicine trial is different because it asks a different question. Instead of asking, “Which single drug blocks one pathway?”, it asks, “What are the modifiable contributors to this individual’s cognitive decline, and what happens if we address as many of them as possible?”
That question is central to a personalised functional medicine approach. The brain is not an isolated organ. It is affected by insulin signalling, vascular supply, inflammatory tone, sleep architecture, gut-derived immune activation, hormone balance, nutrient availability, toxic exposures, infections, oxidative stress and mitochondrial function.
If several of these systems are out of balance simultaneously, it is unlikely that a single isolated intervention will fully restore function. A systems problem usually requires a systems solution.
In that context, amyloid may be better understood as part of the downstream disease picture rather than the whole explanation. A personalised upstream approach attempts to change the conditions that drive neuronal stress: insulin resistance, vascular insufficiency, chronic inflammation, immune activation, poor sleep oxygenation, nutrient insufficiency, hormonal dysregulation, dysbiosis, toxin burden, oxidative stress and impaired repair signalling.
The trial was not double blind, because participants could not realistically be blinded to major lifestyle and treatment changes. The neuropsychological and neuroimaging assessments were blinded, but patients and treating clinicians were not.
The study also did not include people with more advanced dementia. Patients with MoCA scores of 17 or lower were excluded, so the findings apply only to mild cognitive impairment and early dementia, not to moderate or advanced Alzheimer’s disease.
Another limitation is that the MRI volumetric results did not show significant differences between the two treatment groups, and several Alzheimer ’s-related blood biomarkers did not show significant between-group changes. The study therefore provides stronger evidence for functional and cognitive improvements than for structural or biomarker reversal.
The programme was also intensive, requiring detailed testing, regular clinical input and significant behavioural change. The authors themselves acknowledge that the trial suggests reversal may be possible in some cases, but it does not yet prove that this approach is easy, scalable or practical for all patients.
What does this mean for patients and families? The most important message is that early cognitive symptoms should be taken seriously and assessed properly. Memory loss, word-finding difficulty, reduced executive function, loss of mental clarity, impaired navigation, reduced processing speed or unexplained changes in confidence and function should not simply be dismissed as “normal ageing”.
Early assessment matters because this study focused on people with mild cognitive impairment or early dementia. In functional medicine, this is the stage where there may be the greatest opportunity to identify and address modifiable contributors before decline becomes more established.
A comprehensive cognitive health assessment should consider much more than memory testing alone. It should include metabolic health, insulin resistance, vascular risk, sleep quality, inflammation, thyroid and hormone status, nutrient sufficiency, medication effects, alcohol intake, toxin exposure, chronic infections, gut health, stress physiology, exercise capacity, genetics and family history.
This does not mean that every patient needs every test or every intervention. It means that a careful clinician should ask: “Why is this person’s brain struggling, and what can be changed?”
A functional medicine view of cognitive declineFrom a functional medicine perspective, dementia is not viewed only as a disease label. It is also a final common pathway that may emerge when multiple protective systems fail over time.
Those systems include energy production, detoxification, vascular delivery, immune regulation, glycaemic control, hormonal signalling, sleep restoration, synaptic plasticity and nutrient availability. When several of these systems are impaired, the brain may lose resilience.
The hopeful part is that many of these systems are modifiable. Blood sugar can be improved, sleep apnoea can be treated, nutrient deficiencies can be corrected, inflammation can be investigated, vascular risk can be addressed, toxins can be reduced, gut dysfunction can be treated and exercise can be used as a powerful brain-supportive intervention.
This is not a promise of cure. It is a rational, personalised and biologically grounded approach to improving the terrain in which the brain functions.
Final thoughts:
This new preprint randomised trial is one of the most encouraging pieces of research yet for those interested in personalised, precision and functional medicine approaches to early cognitive decline. It suggests that some people with mild cognitive impairment or early Alzheimer’s disease may improve when multiple underlying contributors are identified and addressed together.
However, the findings need peer review, replication, longer follow-up and further independent trials. Patients should not stop prescribed treatment or attempt complex protocols without appropriate medical supervision.
For patients and families, the practical message is clear: do not wait until cognitive decline is advanced before asking deeper questions. If memory, focus, processing speed or executive function are changing, a comprehensive functional medicine assessment may help identify modifiable factors that are contributing to brain vulnerability.

At Best You Functional Health Clinic, the aim is to integrate the patient’s story, symptoms, medical history and biological imbalances into a personalised plan to improve physiological function. Cognitive health is no exception.
If you or a family member are concerned about early cognitive changes and would like to explore a personalised functional medicine approach, you can arrange a free discovery call to discuss whether this type of assessment may be appropriate.

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