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Having the brain changes of Alzheimer's disease is not necessarily associated with dementia in very elderly people, according to a new study.

The paper suggests we need to be cautious about assuming that the presence of particular biomarkers means that someone will inevitably develop dementia in these age groups.

Professor Carol Brayne

Emphasis on diagnostic indicators developed on the younger old may lead to overdiagnosis and overtreatment in the older population.

Scientists studied 456 brains donated to the Medical Research Council Cognitive Function and Ageing Study from people aged 69 to 103 at time of death. The research paper, Age, Neuropathology, and Dementia, will appear in The New England Journal of Medicine.

They studied the effect of age on the relationship between neuropathological features and dementia. This study followed a representative sample of more than 18,000 people since the 1980s.

Researchers observed that although the relationship between cerebral atrophy and dementia persisted into the older age group (about 95 years), the strength of the association between the pathological features of Alzheimer's disease and clinical dementia diminished after age 75.

Research into Alzheimer's disease is generally focused on younger old people, whereas studies involving very old people report weakened relationships between the features of Alzheimer's and dementia.

Professor Carol Brayne, Director of the Institute of Public Health at the University of Cambridge, said the evidence pointed towards a more complex relationship between brain function and brain pathology than is usually assumed in dementia research.

"We wanted to see whether the pathology that is associated with dementia is different in older people. In the age group at greatest risk, having dementia by the time of death is much more loosely related to the usual suspects in terms of neuropathology than it is at younger ages. This means that approaches to early detection using markers for those usual suspects could, in future, lead to considerable overtreatment, expense and potential harm to individuals who would have died without ever developing dementia in life."

"The paper suggests we need to be cautious about assuming that the presence of particular biomarkers means that someone will inevitably develop dementia in these age groups."

Professor Paul Ince, Head of Pathology at the University of Sheffield, said: "We need to look at measures of pathology that are not presently part of the conventional protocols used for evaluating brain disease in dementia.

"A major strategy in dementia research has to be towards delaying the onset of dependency. If we could push back the age of onset by five years on average we would prevent a huge amount of the medical and social burden of dementia."

The study included research partners from the Department of Public Health and Primary Care, Institute of Public Health, Cambridge University; Academic Unit of Pathology, Sheffield University; MRC Biostatistics Unit, Institute of Public Health, University of Liverpool, University of Newcastle, University of Nottingham and the University of Oxford.


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