Brain ageing acceleration ‘nearly inevitable’ with age

By Eleanor McDermid, Senior medwireNews Reporter

A large longitudinal study has charted the ages and rates at which people develop amyloidosis and neurodegeneration.

The results show that most brain ageing processes accelerate with age, except for the appearance of amyloidosis in people previously negative for brain ageing biomarkers. Instead, this is most common between the ages of about 60 and 75 years, after which rates plateau.

Clifford Jack Jr (Mayo Clinic and Foundation, Rochester, Minnesota, USA) and team studied the appearance of amyloidosis and neurodegeneration among 1541 participants of the Mayo Clinic Study of Aging who underwent regular neuroimaging.

Their findings show how “a very simple model for the rates of biomarker transitions can lead to a complex interplay of observed biomarker states”, they write in The Lancet Neurology.

“This is important because, unlike age-specific frequencies, state-to-state transition rates can be thought of as direct measures of underlying biological processes.”

With the exception of the appearance of amyloidosis in people previously negative for brain ageing markers, other changes occurred at rates that increased exponentially as participants got older.

The largest age-related increase was for neurodegeneration among people initially free of the brain ageing markers. This appeared at a rate of 1.6 per 100 person–years in people aged 65 years, compared with 17.2 per 100 person–years when participants were aged 85 years, representing an 11-fold increase. The steepest rise in transition to neurodegeneration occurred from the age of 75 years, contrasting with the younger age at which amyloidosis most commonly appeared in people previously free of either brain ageing marker.

Among people who already had amyloidosis, neurodegeneration appeared at rates of 6.1 and 20.8 per 100 person–years among those aged 65 and 85 years, respectively, giving a 3.4-fold increase. And among those who already had neurodegeneration, amyloidosis appeared at corresponding rates of 2.6 and 13.2 per 100 person–years, giving a fivefold increase.

In a related commentary, Stephanie Vos (Maastricht University, the Netherlands) and Anne Fagan (Washington University School of Medicine, Saint Louis, Missouri, USA) highlighted the rates of transition to dementia in the study cohort.

Among people with both amyloidosis and neurodegeneration, there was an 8.6-fold increase in transition rates to dementia between the ages of 65 and 85 years, but there was just a 2.6-fold increase among people with neurodegeneration only and no one with amyloidosis alone progressed to dementia.

This “is consistent with previous views and indicates that individuals with both β amyloidosis and neurodegeneration might be most suitable for clinical trials or need a close follow-up in clinical practice”, the editorialists write.

They say that the study “provides an important new step towards our understanding of dynamic processes taking place in the brain during normal ageing and in Alzheimer's disease and other neurodegenerative disorders.”

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