When is Alzheimer’s disease not dementia?

Jenny McCleery is a Consultant Old Age Psychiatrist and Terry Quinn is a Consultant Geriatrician and Senior Lecturer in Stroke Medicine. They are both editors of the Cochrane Dementia Group which exists to publish reviews of the evidence about diagnosis and treatment of dementia. In their Age and Ageing paper, they and colleagues discussed a new research framework for Alzheimer’s disease proposed by the National Institute of Ageing and the Alzheimer’s Association (NIA-AA) in the US .

How do we, or indeed how should we, define disease?  The boundary between normal ageing and disease is a blurred one. Joints and arteries stiffen, senses dull, kidneys get less efficient. It is not easy to decide at what point we should start to think of these changes as diseases. Much effort has gone into persuading the public that dementia is not an inevitable consequence of ageing, but is a disease (or set of diseases) which merits diagnosis and medical interest.

When a person presents with problems in memory or thinking, an important job for the clinical team is to determine whether these symptoms could be dementia (a disease) or not.  If we think that dementia is present, we spend time trying to determine the type of dementia. Is this Alzheimer’s disease, vascular dementia, or something rarer?

Even dementia specialists are not very good at classifying dementia. Up to 30% of people diagnosed with Alzheimer’s dementia turn out not to have brain changes suggestive of Alzheimer’s at post mortem. On the other hand, 30% of older people without any signs of dementia do have Alzheimer’s brain changes. Clearly, it is not just the presence of Alzheimer’s brain changes which determines problematic memory and thinking. Increasingly, we recognise that dementia in an older person typically results from a mixture of disease processes as well as other things, such as how much resilience their brain has built up, perhaps from good sleep or a lifetime of mental activity. We have called this the ‘messy reality’ of clinical dementia.

The US National Institutes of Ageing (NIA) and Alzheimer’s Association (AA) are important organisations that support dementia research.  The two groups recently issued a joint statement offering a new definition of Alzheimer’s disease. This aims to impose some order on the messy reality of dementia.  The NIA and AA suggest redefining Alzheimer’s disease as something which can be identified on the basis of abnormal biomarker tests.  These are tests which can be done in life to detect Alzheimer’s processes in the brain.  The new guidance suggests that a diagnosis of Alzheimer’s disease can be made solely on the basis of a lumbar puncture or brain scan regardless of whether or not a person has any problems with memory and thinking.

This proposal worries us for a number of reasons, and this was why we wrote our commentary article for Age and Ageing.  We do not think it is a good idea to start diagnosing Alzheimer’s disease in large numbers of older people who do not have, and may never develop, dementia.  The NIA and AA are keen to see new biomarkers for other forms of dementia, but the same argument holds.  Ultimately this approach could lead to the vast majority of older people being diagnosed with brain diseases.  Changing a definition to create lots of new cases comes with ethical, financial and societal implications.  Some other areas of medicine have intense debates about this and many people think there should be a move in the opposite direction so that fewer people with a low risk of developing symptoms of, for example, osteoporosis or prostate cancer are caught in the diagnostic ‘net’.

It remains true that effective treatments for dementia are lacking.  In order to deliver treatments that work, we believe it is important for a research framework to embrace fully the complexity of dementia.  The most productive way to think about dementia may be to focus less on individual diseases processes and more on ways to make the best predictions we can about how memory and thinking may change in individual patients. 

We recognise that this is a contentious area and not everyone will share our view.  However, this is such an important topic that we want at least to start the conversation.  We would be interested to hear your views and you can tweet us @CochraneDCIG

Read the Age and Ageing paper When is Alzheimer’s not dementia—Cochrane commentary on The National Institute on Ageing and Alzheimer’s Association Research Framework for Alzheimer’s Disease


I strongly support the authors of this commentary. I hope the UK doesn't follow the US method of relying solely on 'objective' evidence without due consideration to the patient's story. It has become clear in MSK medicine that solely depending on MRIs and X-rays to diagnose disc prolapses or arthritis respectively have led to numerous false positives. A comprehensive approach to diagnosis and treatment is really the sensible way forward.

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