From cognitive assessments and imaging to advanced biomarkers and digital tools, much work is going into Alzheimer’s disease diagnosis. But is the search for new tests misdirected and potentially wasteful?

That’s the argument made by the Alzheimer’s Prevention Expert Group (APEG). They advocate for leveraging existing, cost-effective tools to identify individuals at risk and promote preventative measures.

Cognitive function
Our cognitive abilities are typically divided into several categories and subcategories, each representing a different aspect of mental functioning. For example, the broad category of Memory includes short-term, long-term, declarative, non-declarative, episodic, semantic, and others, and Executive Function includes planning, decision-making, problem-solving and inhibition. These varied abilities contribute to our overall cognitive functioning and are essential for daily activities, learning, and interaction with the environment.

Cognitive function declines steadily from the age of 18, making it possible to spot individuals dropping faster than average and encourage preventative actions. Cognitive Function Tests (CFT), such as those offered by the charity foodforthebrain.org, can identify declining cognitive function. Over the past decade, nearly half a million people have been tested using the CFT via foodforthebrain.org, allowing for early intervention through dietary and lifestyle changes.

Testing and diagnosis
Alzheimer’s, which makes up two-thirds of dementia cases, involves the shrinking of certain areas of the brain as neurons die off. Imaging can successfully diagnose Alzheimer’s and distinguish it from other forms of dementia. Magnetic Resonance Imaging (MRI) is commonly used to identify structural changes in the brain, particularly atrophy in the hippocampus, a region critical for memory. Positron Emission Tomography (PET) scans provide further insights by visualising brain metabolism and detecting amyloid plaques, a hallmark of Alzheimer’s.

However, APEG highlights that while these specialised brain scans can detect Alzheimer’s years before diagnosis, their high-cost limits widespread use, plus these scans are not guaranteed to be performed early enough to discover those ‘at risk’.

Biomarkers are another available tool for early diagnosis of Alzheimer’s disease. Cerebrospinal fluid (CSF) analysis can detect abnormal levels of beta-amyloid, total tau, and phosphorylated tau proteins, which are indicative of Alzheimer’s pathology. Although the toxic protein p-tau, can be found in CSF, detection via lumbar puncture is a risky and expensive process and certainly not suitable to test tens of thousands of people.

Work towards developing a blood test that could identify those heading towards Alzheimer’s earlier is exciting many in this field; this type of test could be a cheaper and less invasive alternative to expensive scans.

But APEG questions the pursuit of a blood test for Alzheimer’s, suggesting that it might be driven by pharmaceutical interests rather than patient benefit. They caution that such tests could lead to overdiagnosis and unnecessary treatment, similar to current practices with amyloid-targeting drugs, which have not shown significant clinical benefits and carry severe risks.

Leveraging Existing Knowledge
APEG advocates for a more pragmatic approach: using cost-effective, accessible tests to identify modifiable risk factors. For instance, homocysteine, a toxic amino acid, rises with age and insufficient intake of B vitamins (B6, folate, B12). Elevated homocysteine levels increase p-tau accumulation, but addressing vitamin deficiencies can reduce this risk.

The VITACOG trial, run by pharmacology professor David Smith (a member of APEG), demonstrated that high doses of B vitamins could slow brain cell death and arrest cognitive decline in individuals with Mild Cognitive Impairment (MCI) and high homocysteine levels.

Smith and his APEG colleagues favour using a Cognitive Function Test (which is free) to identify those at risk, followed by testing risk factors and biomarkers such as homocysteine to be included in the research funds being made available for testing blood biomarkers because this is one thing you can actually do something about.

Other useful tests for risk factors include omega-3 and vitamin D levels since low levels of these nutrients also increase risk; and HbA1c, the standard measure used to diagnose diabetes, since lower levels help protect the brain and high levels indicate those who need to reduce their intake of sugar and processed foods.

These tests are corroborative rather than diagnostic, but importantly, they identify prevention actions that people can take. This two-step paradigm of testing cognitive function early and then having further blood tests, such as homocysteine, omega-3, vitamin D and HBA1c for glucose control, helps guide diet and lifestyle prevention strategies. And they are available right now.

The charity foodforthebrain.org offers a free cognitive function test, plus a home test kit that measures all these risk factors with a pinprick blood test.

Conclusion
The landscape of Alzheimer’s disease diagnosis is evolving rapidly, with a range of current tests and promising new technologies on the horizon. However, the pursuit of new diagnostic methods should not overshadow the potential of existing, cost-effective tools and preventative strategies.

Early and accurate diagnosis, combined with actionable prevention measures, can significantly impact the management and progression of Alzheimer’s disease. As research continues, a balanced approach that integrates new technologies with practical prevention strategies will be crucial for improving outcomes for individuals at risk of Alzheimer’s.

About the Author
Patrick Holford is the founder of foodforthebrain.org, a not-for-profit independent registered charity, and Chair of the Alzheimer’s Expert Group.

Evidence/References:
The VITACOG trials, evidence for homocysteine as causal and lowering it with B vitamins as disease-modifying and a consensus statement regarding this evidence in the Journal of Alzheimer’s Disease is here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5836397/

The validation of foodforthebrain.org’s Cognitive Function Test in the International Journal of Geriatric Psychiatry is here: https://onlinelibrary.wiley.com/doi/abs/10.1002/gps.3993

The evidence in relation to p-tau and homocysteine is here: https://foodforthebrain.org/the-p-tau-delusion/