Memory problems at age 45 may herald Alzheimer's risk decades later. What researchers discovered in a simple blood test

Memory problems that appear around the age of 45 are, in most cases, consequences of fatigue, stress or lack of sleep. In some cases, however, they can be the first signs of a neurodegenerative disease that will only be diagnosed after 20 or 30 years, draws the attention of a team of researchers from the University of Otago, in New Zealand.

The scientists analyzed blood samples collected from 856 adults, all aged 45, to measure the level of the protein pTau181, a biomarker associated with Alzheimer's disease. Participants who reported memory problems in everyday life had, on average, higher levels of the pTau181 protein than those who did not report such problems, although standardized cognitive tests and magnetic resonance imaging of the brain still showed no differences.

The results, published in the journal GeroScience in May 2026, suggest that the biological processes associated with Alzheimer's disease may begin long before the onset of clinical symptoms that lead to the diagnosis – typically after the age of 70.

Current treatments for Alzheimer's dementia slow the progression of the disease, but have the best results if given in the early stages. So, identifying people at high risk through a simple blood test could become, in the coming years, a less invasive alternative to the diagnostic procedures used today.

“Biomarkers like pTau181 reflect risk, not certainty,” said Ashleigh Barrett-Young, the study's lead author and a researcher in the Department of Psychology at the University of Otago.

Participants, medically followed from birth

The data comes from one of the longest-running longitudinal medical studies. The Dunedin Multidisciplinary Health and Development Study enrolled, in 1972 and 1973, 1,037 newborns from the city of Dunedin in southern New Zealand. Since then, each of them has been periodically re-evaluated, through full batteries of medical tests, until today. The major stages of revaluation took place from 3 to 52 years, at intervals of 2-3 years.

The study has since become one of the world's most cited sources on aging, mental health, and cumulative risk factors. At the 45-year assessment, held between 2017 and 2019, 94% of those left alive returned. The researchers collected blood samples to measure pTau181 protein, performed brain MRIs, administered standardized cognitive assessment tests, and separately asked them to answer a questionnaire about their perception of their own cognitive function.

The Otago team then compared the results of the four types of investigations. People with higher levels of pTau181 were, on average, those who had reported memory problems or difficulty concentrating. In contrast, these differences were not yet seen in objective cognitive tests or MRI.

In other words, the first memory difficulties observed by the participants coincided with a biological marker associated with Alzheimer's disease, before cognitive tests or MRIs suggested clear changes.

Tau protein and abnormal deposits in the diseased brain

Alzheimer's disease is associated with the abnormal accumulation of two proteins in the brain. Beta-amyloid forms plaques between neurons, and tau protein forms clumps inside nerve cells. Over time, these deposits disrupt communication between neurons and lead to their death. This is how memory loss, language difficulties and problems in everyday activities gradually appear.

Tau protein normally has a supportive role inside neurons. In Alzheimer's disease, however, it undergoes a chemical change called phosphorylation and begins to accumulate abnormally. One of the modified forms, pTau181, can travel from the brain into the blood when neurons are damaged. Previous studies have shown that people diagnosed with Alzheimer's disease have higher levels of this protein than healthy people of the same age.

Currently, the precise diagnosis of Alzheimer's dementia can be established either by post-mortem pathological examination or, in living patients, by lumbar puncture, a procedure by which cerebrospinal fluid is collected for the dosage of proteins associated with the disease. The technique is safe, but invasive and difficult to access in routine practice. A blood test would, by comparison, be a quick and easier method to apply on a large scale.

When the patient first notices that something has changed

The study shows that 45-year-olds can notice subtle changes in memory before they are detected by regular tests. The researchers consider two explanations. The first would be that the pTau181 protein begins to increase in the early stages of the pathological process, when the person begins to notice slight changes, but before clinical tests or MRI can reveal them.

The second assumes that, at age 45, high levels of the protein may not be related to Alzheimer's disease, and the biomarker's utility would remain reserved for detection at older ages. The answer remains to be clarified in future reassessments of the same cohort, with the 52-year assessment already completed. Until then, experts recommend that forgetfulness and decreased ability to concentrate after age 45 be investigated.

The 14 modifiable risk factors identified by the Lancet Commission

The Lancet Commission for the Prevention of Dementia, which brings together some of the world's most important neurologists and epidemiologists, published in 2024 an update of its report that has become a reference in the field. The paper identifies 14 modifiable risk factors that, if addressed in time, could prevent or delay up to 45% of dementia cases worldwide.

For middle age, defined as the range between 40 and 65, the report indicates four main targets:

• blood pressure control,
• hearing loss correction,
• avoiding obesity,
• maintaining the level of LDL cholesterol within optimal limits.

The list goes on with measures valid at any age. Regular exercise, quality sleep, social relationships, treating depression, quitting smoking, limiting alcohol, reducing exposure to pollution, preventing head injuries and correcting vision problems also appear in the report.

Why testing is not recommended for all adults over 45

The study results do not, however, justify testing pTau181 levels in all 45-year-old adults at this time. The analysis is not a routine one, and its interpretation for the early detection of Alzheimer's disease in healthy individuals needs to be validated by other international studies, on diverse populations. The Dunedin cohort, although important in terms of length and rigor of follow-up, includes predominantly people of European New Zealand descent.

In practice, medical evaluation becomes warranted when episodes repeat, intensify, or are also observed by the family. The doctor may first check for common and treatable causes, such as sleep disorders, anxiety, depression, thyroid problems, vitamin B12 deficiency, or the effects of certain medications. If these explanations are not sufficient, the neurological consultation can determine whether monitoring, more detailed cognitive tests or further investigations are needed.