The severity of amyloid deposition in the brain -- not just age -- may be key to determining who will benefit from new anti-amyloid therapies to delay the progression of Alzheimer’s disease, a new study has found.

Clinicians and scientists from the University of Pittsburgh in the US report that the accumulation of toxic amyloid beta clumps accelerates in old age but the baseline amyloid burden and the overall brain health going into this acceleration are more powerful predictors of who is most likely to progress to Alzheimer’s.

“Understanding the complexity of the increased amyloid accumulation, when individuals are cognitively normal, is critical for improved implementation of dementia treatments,” said Oscar Lopez, professor of neurology at Pitt and chief of cognitive and behavioural neurology at UPMC.

While people who are 80 and older have the highest prevalence of Alzheimer ’s-associated dementias, most studies that measured the A-beta burden in the brain using imaging techniques have focused on younger populations.

As such, the connection between A-beta and dementia in the oldest of the old has remained unclear, according to a paper published in the journal Neurology.

Lopez and his colleagues are set to change that by examining the relationship between A-beta deposition and new cases of dementia in 94 elderly individuals who were cognitively unimpaired when the study was launched.

The rate of amyloid deposition in the brain of these individuals was compared with a younger group from the Australian Imaging, Biomarker, and Lifestyle (AIBL) study.

Researchers observed a steady increase in A-beta accumulation in all participants over time, independent of their A-beta status at the beginning of the study.

However, this accumulation was significantly faster in patients in their 80s and older compared to participants in their late 60s, explaining the higher prevalence of A-beta in the oldest old.

In the end, very few participants developed dementia without having A-beta deposits in the brain. Importantly, individuals whose brain scans were positive for amyloid at the beginning of the study developed dementia two years earlier than those who were amyloid-negative.

Researchers also found that the short-term change in A-beta alone over 1.8 years could not predict the future risk of dementia.

“Our findings are consistent with studies showing that the amyloid accumulation in the brain takes decades to develop, and occurs in the context of other brain pathologies, specifically small vessel disease,” said Lopez.