People with Down’s syndrome can develop brain changes associated with Alzheimer’s disease by their forties, with no clinical symptoms to help detect them, new research suggests.

The study found that cognitive and biochemical changes in Alzheimer’s disease start more than 20 years before clinical symptoms appear in people with Down’s syndrome.

In adults with the syndrome, the earliest changes detected by researchers were at the age of 30.

Scientists say the findings can now inform the development of future clinical trials.

Alzheimer’s disease and its complications are known to be the leading cause of death in adults with Down’s syndrome

Understanding what happens in the preclinical phase is essential to be able to prevent or moderate the progression of Alzheimer’s disease in Down’s syndrome.

Dr Shahid Zaman, Cambridgeshire and Peterborough NHS Foundation consultant psychiatrist and researcher with the Cambridge Intellectual and Developmental Disabilities Research Group, worked with neurologist Dr Juan Fortea and his team at the Sant Pau Memory Unit in Barcelona.

Dr Zaman said: “Alzheimer’s disease and its complications are known to be the leading cause of death in adults with Down’s syndrome.

“This work confirms the shocking fact that the neuropathology of Alzheimer’s disease occurs several years before the onset of symptoms in patients.”

According to the study published in The Lancet, in the long period before symptoms appear brain imaging biomarkers change following a predictable sequence, which is similar to the way Alzheimer’s disease develops in the general population.

Dr Zaman added: “The order and timing of these changes follows a similar pattern to those described in autosomal dominant Alzheimer’s disease, a very rare hereditary form of the disease caused by mutations in some genes – including the amyloid precursor protein gene.

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“This form also has an early onset, often before the age of 55.”

Between February 1, 2013, and June 28, 2019, in Barcelona, and between June 1, 2009, and Dec 31, 2014 in Cambridge, researchers included 388 participants with Down’s syndrome.

Of them 257 were asymptomatic, 48 had with prodromal Alzheimer’s disease – a very early form of the disease when memory is deteriorating but a person remains functionally independent, and 83 with Alzheimer’s disease dementia.

Researchers found changes in the brains of individuals with Down’s syndrome as early as the third decade of life.

Prodromal Alzheimer’s was diagnosed at a median age of 50.2 years, and Alzheimer’s disease dementia at 53.7 years.

Symptomatic Alzheimer’s disease prevalence increased with age in individuals with Down’s syndrome, reaching 90–100% in the seventh decade of life.


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