Study Detects Early Alzheimer’s ‘Stealth’ Phase Before Symptoms Set In

Written by Katharine Lang — Fact checked by Kevin Cyr, MD

Alzheimer’s disease is the most common form of dementia — a progressive neurological disorder that affects memory, thinking and behavior, eventually interfering with daily life.

According to the World Health Organization (WHO), around 55 million people all over the Globe are living with dementia, and 10 million people are diagnosed with dementia each year around the world. Of these, up to 70% have Alzheimer’s disease.

Alzheimer’s generally starts with mild memory loss, and the symptoms worsen over time. People in the later stages of Alzheimer’s lose the ability to carry on a conversation and perform simple daily tasks, often needing round-the-clock care.

Symptoms are caused by changes in the brain, but new research has now found that some brain changes may begin long before any symptoms are seen.

The study, funded by the National Institutes of Health (NIH), suggests that the first slow, silent phase of Alzheimer’s occurs before any memory loss, with damage to just a few vulnerable cells in the brain. The second phase, which coincides with the development of symptoms, is more destructive and is characterized by the accumulation of plaques, tangles, and other Alzheimer’s hallmarks.

Igor Camargo Fontana, PhD, Alzheimer’s Association director of scientific conference programming, who was not involved in this study, told Medical News Today that:

“Alzheimer’s disease has a long pre-symptomatic period; Alzheimer ’s-related changes take place in the brain 10, 15, even 20 years before the onset of memory and thinking symptoms. This new paper may contribute to how these changes are understood. Only time will tell.”

Almost three-quarters (31 of 42) of high ADNC cases had dementia before death, as did one-third of the intermediate (7 of 21) and low (4 of 12) ADNC cases. None of those with no ADNC had dementia before death.

The researchers first used machine learning to quantify the progression of Alzheimer’s disease, including pTau — referring to levels of phosphorylated tau protein in plasma, a blood component — and beta-amyloid, for each donor.

Each was allocated a score between 0 and 1. The researchers found that a score of 0.4-0.6 was when pTau and beta-amyloid accumulation increased dramatically and cognitive deficits increased.

From the scores, they worked out that the severity of Alzheimer’s could be clearly defined in two phases:

1. an early phase where there were low levels of pathology, together with some evidence of neuronal loss and early amyloid pathology, but no cognitive effects
2. the later phase, where there were markedly increased levels of Alzheimer’s pathology, neuronal loss and cognitive impairment.

Richard J. Hodes, MD, director of the NIH National Institute on Aging, said in an NIH news release that “one of the challenges to diagnosing and treating Alzheimer’s is that much of the damage to the brain happens well before symptoms occur.“

“The ability to detect these early changes means that, for the first time, we can see what is happening to a person’s brain during the earliest periods of the disease,” he suggested.

“The authors propose that, in what they are calling the disease’s later phase, other brain cells associated with inflammation, called microglia and astrocytes, initiate a process to try to counteract these initial changes by releasing molecules or changing their form,” Fontana told MNT.

“Alterations in inflammatory cells and inhibitory neurons slowly evolve to demonstrate the well-known biological changes of Alzheimer’s, including the accumulation of amyloid plaques and formation of tau tangle pathology, culminating in a terminal state,” he added.

“The disease’s long pre-symptomatic period creates opportunities for early detection and early intervention/prevention of dementia symptoms,” he told MNT.

“If the findings in this new paper are confirmed by other labs, it raises the question of whether effectively addressing the brain changes that happen in what the authors call the first ‘quiet’ phase can slow, delay or prevent the second, more destructive phase,“ Fontana added.

“It will be important to evaluate the ‘quiet’ phase using a combination of diagnostic tools, and further investigate its associations with biomarkers of Alzheimer’s, such as amyloid and tau,” he emphasized.