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Unraveling the pathology of 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 published this week in
the open access journal PLoS Medicine.
The study shows that multiple abnormal 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
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.
Paul Ince, of the University of Sheffield, and 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 this study, the researchers used statistical methods to
establish the proportion of dementia
directly attributed to each specific change
in the brain and other factors.
456 participants in the study donated their brains for
post-mortem examination which enabled
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%) – which are
regarded as the hallmarks of Alzheimer's
disease –and blood vessel disease (21%).
Other factors contributing to the risk of dementia across
the population included age, markers of
reduced brain size and atrophy of a
structure called the hippocampus which is
involved in learning and memory.
The researchers conclude that dementia is often associated
with mixed pathological changes – in other
words, at death many people had changes in
the brain consistent with Alzheimer's and
those linked to vascular dementia.
The findings may be difficult to extrapolate to the living
population because most changes in the brain
can only be established by post-mortem,
whilst the abnormal changes in the brains of
people living with dementia may alter over
Nevertheless, the findings suggest that drugs
focusing on specific pathologies – whilst
having a profound effect in some 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.