Combination treatment needed to fight dementia

Combination therapies to tackle multiple changes in the brain may be needed to combat the growing problem of dementia in ageing societies, according to a study by the University of Sheffield.

The findings, which were published this week in the open access journal PLoS Medicine, show that multiple abnormal (pathological) processes in the brain are often involved in cases of dementia, and that the drugs currently in development to treat individual brain pathologies may have a limited impact on the overall burden of dementia in the population.

Dementia – which can involve problems with memory, language and judgement – is a growing social and clinical problem affecting a quarter of people 85 years or older and an estimated 35 million people worldwide.

Professor Paul Ince, from the University of Sheffield´s Medical School, along with colleagues at the University of Cambridge, conducted the study to estimate the relative contribution of known causes of dementia in the brain to dementia at death. Their research drew upon data from the Medical Research Council´s Cognitive Function and Ageing Study – a major investigation into dementia in England and Wales that began in 1990 in which researchers used statistical methods to establish the proportion of dementia directly attributed to each specific change in the brain and other factors.

In this study by the Medical Research Council, 456 people donated their brains for post-mortem examination after death. This enabled researchers at the University of Sheffield and the University of Cambridge to make an estimation of the contribution of each type of pathology to dementia in the population as a whole. The main pathological contributors to dementia were clumps of proteins called plaques and neurofibrillary tangles (19 per cent) – which are regarded as the hallmarks of Alzheimer´s disease –and blood vessel disease (21 per cent). Other factors contributing to the risk of dementia across the population included age (18 per cent), and markers of reduced brain size (atrophy) including lower brain weight (compared to people of the same sex; 17 per cent) and atrophy of a structure called the hippocampus (16 per cent) which is involved in learning and memory.

Researchers concluded that dementia is often associated with a mixture of pathological changes, meaning that at death, many people had changes in the brain consistent with both Alzheimer´s and vascular dementia. The findings represent the current best estimation of the pattern of dementia for the living population because many changes in the brain, and especially mixed pathology, can only be established by post-mortem.

The research also suggests that individual use of drugs focusing on specific pathologies – whilst possibly having a profound effect in the smaller proportion of cases in which a single disease process predominates – may do little to reduce the overall burden of dementia in societies with ageing populations. An effective strategy for the population will need a range of protective strategies linked to biomarkers for each major risk factor.

Professor Paul Ince, from the School of Medicine and Biomedical Sciences at the University of Sheffield, said: "This research shows that the assertion that Alzheimer's Disease is the commonest form of dementia is simplistic, but it also raises important issues about what factors determine whether a person becomes demented or not in the face of accumulating brain disease in old age.

"Some people seem to retain their intellect despite high levels of pathology. Knowing why would open new avenues in developing therapies to delay dementia onset."

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