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Forgetful and forgotten

Tor Atle Rosness (View bio)

Research on dementia receives well-deserved awards, but effective treatment of the condition is a long way off.

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Photo: Sivert Almvik

At the end of 2016 came the news that solanezumab did not meet expectations as an effective treatment for Alzheimer’s disease. Now another drug, verubecestat, can be added to the series of disappointments (1). Both these drugs reduce the accumulation of amyloid plaque in the brain, and were among those anticipated to slow the progress of the disease at an early stage. Five years ago, an editorial article in the Journal of the Norwegian Medical Association pointed out the ineffectiveness of treatment for dementia (2). In light of these discouraging results, that statement still holds true: there are as yet no drugs that prevent or significantly slow the progress of the disease. The problems in finding effective treatment may be partly due to the fact that the clinical symptoms in patients with dementia do not necessarily correspond to the degree of neurodegeneration, and reduction in the amount of plaque in the brain does not alone result in better memory (3).

In brief, the following treatment options for dementia are currently available: four anti-dementia drugs, antidepressants, antipsychotics, physical activity, environmental measures, support groups for relatives, day centres, support contacts, respite care and different institutional placements (4). These are good services – the problem is that none of them are either new, or very effective. Moreover, patients with dementia deteriorate over time, and the various services thus gradually become less relevant as the disease progresses. There is therefore a clear need for better treatment options than those that already exist.

However, after several unsuccessful pharmaceutical trials, it appears that for the moment a curative treatment is unachievable. This makes it easy to think that diagnosis of dementia is unnecessary in clinical practice – especially at an early stage – because there are no effective ways to treat the illness. Such attitudes are familiar in my own daily work as a nursing home doctor, and not only in that context, since according to a Norwegian study that included 1000 participants from 19 municipalities, only one out of five patients with dementia is diagnosed (5). However, when a person, even an 80-year-old, starts to become forgetful to the degree that it affects the normal ability to function, he or she should, in my opinion, always be assessed for dementia. Both patient and next of kin need the situation to be clarified. A diagnosis may mean that elderly persons with dementia receive better treatment and that the use of physical restraint is reduced, as shown by Swedish colleagues (6).

For busy doctors in clinical practice, whether in nursing homes, GP surgeries or hospitals, assessment for dementia is therefore understandably given less priority. For dementia researchers the situation is quite different. This year, the dementia research prize from the Norwegian Public Health Association was awarded to Professor Tormod Fladby (7). He has conducted research on biomarkers from blood and spinal fluid which render it possible to make a diagnosis before it becomes possible to detect dementia clinically. This brings hope of earlier initiation of treatment (8).

In theory, this type of knowledge may make it possible to predict whether a person is susceptible to dementia several years before the onset of symptoms (8). However, as yet there is no agreement on which biomarkers have the greatest prognostic significance (9). This presents ethical problems associated with making an early-stage diagnosis. As long as no possibilities exist to prevent the condition, any knowledge of future serious illness may in the worst case do more harm than good. This is further complicated by the fact that the overlap between normal ageing and dementia is not as unequivocal as was previously assumed (10).

Brain research, including research on memory and dementia, is highly esteemed among researchers as well as society at large. However, paradoxically, assessment and treatment of dementia disorders by no means enjoy the same status. Until we manage to develop more effective drugs, as researchers or clinicians we must none of us forget to diagnose, inform, look after and as far as possible treat this patient group.

We must not forget the forgetful.

1

Key Alzheimer’s drug show virtually no chance of working. www.newscientist.com/article/2121497-key-alzheimers-drug-shows-virtually-no-chance-of-working/ (27.1.2017).

2

Brean A. Når hjernen svikter. Tidsskr Nor Legeforen 2011; 121: 2227.

3

Sperling RA, Aisen PS, Beckett LA et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 2011; 7: 280 – 92. [PubMed] [CrossRef]

4

Laver K, Dyer S, Whitehead C et al. Interventions to delay functional decline in people with dementia: a systematic review of systematic reviews. BMJ Open 2016; 6: e010767. [PubMed] [CrossRef]

5

Wergeland JN, Selbæk G, Høgset LD et al. Dementia, neuropsychiatric symptoms, and the use of psychotropic drugs among older people who receive domiciliary care: a cross-sectional study. Int Psychogeriatr 2014; 26: 383 – 91. [PubMed] [CrossRef]

6

Pellfolk T, Sandman PO, Gustafson Y et al. Physical restraint use in institutional care of old people in Sweden in 2000 and 2007. Int Psychogeriatr 2012; 24: 1144 – 52. [PubMed] [CrossRef]

8

Dubois B, Feldman HH, Jacova C et al. Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria. Lancet Neurol 2014; 13: 614 – 29. [PubMed] [CrossRef]

9

Olsson B, Lautner R, Andreasson U et al. CSF and blood biomarkers for the diagnosis of Alzheimer’s disease: a systematic review and meta-analysis. Lancet Neurol 2016; 15: 673 – 84. [PubMed] [CrossRef]

10

Mattsson N, Zetterberg H, Janelidze S et al. Plasma tau in Alzheimer disease. Neurology 2016; 87: 1827 – 35. [PubMed] [CrossRef]

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