Picture: Imaging signature of Alzheimer's disease in adults with Down's syndrome for brain structure, glucose metabolism, and amyloid β deposition
A study with CPFT has shown how people with Down's syndrome can develop the brain changes associated with Alzheimer’s disease by their forties, with no clinical symptoms to help detect them.
Researchers in Cambridge and Spain collaborated for the first time to investigate the development of Alzheimer's disease in people with Down's syndrome. Their findings have now been published in The Lancet.
Dr Shahid Zaman, CPFT 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.
Shahid 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.”
The researchers found that the cognitive and biochemical changes in Alzheimer’s disease start more than 20 years before clinical symptoms present in people with Down's syndrome. In this long preclinical phase, imaging biomarkers change following a predictable sequence, which is surprisingly similar to the way Alzheimer’s disease develops in the general population.
Shahid 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. This form also has an early onset, often before the age of 55.”
The earliest changes detected by the study started in adults with Down's syndrome at age 30, and the findings can now inform the development of future clinical trials. Understanding exactly what happens in this preclinical phase is essential to be able to prevent or moderate the progression of Alzheimer’s disease in Down's syndrome.
Shahid said: “Thank you to everyone who took part in this research. Clinicians are now a step closer to measuring this silent, pre-symptomatic stage of the disease in people with Down's syndrome. Hopefully, this study will help provide outcome measures for preventative clinical trials, which is the next stage we are planning.”
The biomarkers described by this research could help to select therapeutic targets and monitor the response to a potential treatment. Clinical trials to prevent Alzheimer’s disease are essential to reduce mortality for people with Down's syndrome, and could prove beneficial for the general population.
This study was supported in the UK by the Medical Research Council, the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, the NIHR Collaboration for Leadership in Applied Health Research and Care (CLAHRC) for the East of England (now the NIHR Applied Research Collaboration East of England), the NIHR Cambridge Dementia Biomedical Research Unit, the Down Syndrome Association, and the Health Foundation.
Funding and support in Spain was provided by the Fondo de Investigaciones Sanitario, Instituto de Salud Carlos III, and the CIBERNED programme, partly jointly funded by the EU European Regional Development Fund.