Early-onset Alzheimer's patients accumulate symptoms years before diagnosis

People who develop Alzheimer's disease before the age of 65 experience a growing range of health problems and increasing use of healthcare services years before diagnosis. However, the cardiovascular risk factors traditionally associated with Alzheimer's disease are no more common among those diagnosed at working age than among age- and sex-matched controls without neurodegenerative disease.

A study by the University of Oulu and the University of Eastern Finland found that people who developed Alzheimer’s disease before the age of 65 accumulated a wide range of health problems, particularly during the five years preceding diagnosis. Compared with matched controls, they were more likely to experience depression, dizziness, headaches, traumatic brain injuries, epilepsy, cerebrovascular disorders, thyroid diseases and problems related to heavy alcohol use. Tinnitus and hearing loss were already more common six to ten years before diagnosis.

One of the study’s most striking findings concerned cardiovascular risk factors, which, alongside advanced age, are among the best-known risk factors for Alzheimer’s disease. In contrast to late-onset Alzheimer’s disease, high blood pressure and hyperlipidemia were not more common among people with early-onset Alzheimer’s disease than among the control group.

The study examined diseases and health conditions occurring during the 15 years preceding an Alzheimer’s disease diagnosis in people who developed the disease before the age of 65.

Early-onset Alzheimer’s disease shows a distinct health profile

The researchers found no significant differences in morbidity 11 to 15 years before diagnosis, suggesting that identifiable changes begin to emerge mainly closer to disease onset. The findings indicate that early-onset Alzheimer’s disease may involve mechanisms that differ, at least in part, from those underlying late-onset Alzheimer’s disease.

“Our findings support the view that early-onset Alzheimer’s disease is not simply a younger-age version of late-onset Alzheimer’s disease. Rather than the familiar cardiovascular risk factors, we observed a range of other health problems becoming more common as diagnosis approached,” says Adjunct Professor Johanna Krüger, the study’s lead investigator from the University of Oulu.

Rising healthcare use may support earlier recognition

The researchers also found that healthcare utilisation increased markedly during the five years leading up to diagnosis, alongside a growing burden of health conditions. The steepest increase in healthcare visits occurred during the final year before Alzheimer’s disease was diagnosed.

Of course, no single disease or symptom predicts Alzheimer’s disease. Our results suggest that, in the years before diagnosis, patients may accumulate a variety of seemingly unrelated symptoms and healthcare encounters. Recognizing this overall pattern could help raise suspicion of a neurodegenerative disease earlier than is currently the case.”

Laura Leppänen, doctoral researcher, University of Oulu and study’s first author

According to Leppänen, the findings highlight the need to identify early-onset dementia and Alzheimer's disease among working-age adults at an earlier stage. Diagnosing early-onset Alzheimer’s disease remains challenging, and diagnosis is often delayed by several years after the first symptoms appear.

The findings are based on patient data from memory clinics at Oulu University Hospital and Kuopio University Hospital, combined with nationwide health register data. The study included 407 people with early-onset Alzheimer’s disease and compared their health records with those of more than 4,000 age- and sex-matched controls.