Introduction to the special issue on controversies in dementia

Dementia is among the most prevalent and feared health problems. In this edition of the International Review of Psychiatry, we examine and discuss issues that relate to dementia and that generate considerable controversy. These issues were chosen to be of great clinical importance, in urgent need of more confident answers, and open to debate. Hence we settled on controversies regarding the aspects of epidemiology, early cognitive symptoms, prevention by modifiable risks, depression before and after the onset of dementia, and medication development.

It is well known that treatments which prevent the development of pathology, control disease progression, or better manage dementia symptoms are much needed in the near future. Otherwise, we face a major dementia pandemic. Millions of people worldwide already live with dementia, with 4.6 million new cases annually. Two thirds live in low- and middle-income countries. The number of people affected is projected to double every 20 years to 81.1 million by 2040. While most people with dementia live in developing countries (60% in 2001, rising to 71% by 2040), rates of increase are not uniform across world regions. The number affected in developed countries is forecast to increase 100% by 2040, in contrast to 300% in India, China, and other southern Asian-Pacific nations (Ferri et al., [2005]). In poor but rapidly developing regions of the world people are living longer while high fat diets, smoking and sedentary lifestyles are becoming more common. Chronic non-communicable diseases linked to ageing–heart disease, stroke, cancer and dementia–are much more in evidence, and being recognized as a public health priority. This controversy is examined by Prince et al., in ‘Ageing and dementia in low- and middle-income countries–using research to engage with public and policymakers’.

While age is by far the greatest risk factor, an important proportion of dementia cases might be avoided if potentially reversible risk factors are modified on a large scale. The identification of preventable or modifiable risk factors for dementia development has become a major public health priority across the world. Brain vascular disease is an identifiable risk factor that may be responsive to intervention. Given that ‘vascular conditions’ represent a group of the major modifiable risk factors for dementia, a better understanding of the pathophysiology of dementia associated with brain vascular disease may guide the development of prophylactic and therapeutic strategies (O'Brien et al., [2003]). Stephan and Brayne present an excellent discussion of this controversy in ‘Vascular factors and prevention of dementia’.

Current knowledge is limited by not knowing exactly when the common brain diseases that cause dementia begin relative to the emergence of symptoms. Thus, an understanding of the pre-clinical or early clinical presentations of dementia is a significant priority since this will facilitate early detection and treatment, and lead to prevention. Mild cognitive impairment is hypothesized as different from normal ageing, representing those destined to develop Alzheimer's dementia (Petersen et al., [1999]). This controversy is addressed by Allegri et al. in ‘Mild cognitive impairment: Believe it or not?’

Tertiary prevention attempts to reduce dementia-associated symptoms including cognitive decline, functional disability and neuropsychiatric symptoms (NPS). Although there are many important care priorities in dementia, the most frequent current treatment issue for patients presenting to clinical services and their caregivers remains the management of NPS. Most professionals, and the majority of studies, suggest three main NPS syndromes: agitation, psychosis and mood disorders (Howard, Ballard, O'Brien, & Burns, [2001]; Lyketsos, [2006]). Understanding their natural course is essential, as this will optimize effective treatment targeting while avoiding needless, and at times risky, interventions. NPS are distressing both to the patients who experience them and to the family members who care for them. Therefore NPS should no longer be considered a secondary feature of dementia, but more accurately a central part of the dementia syndrome that is of critical importance to treatment. While Parkinson's disease (PD) has been conceptualized primarily based on motor impairments, increasing emphasis is being placed on the cognitive impairments and NPS caused by this brain disease. Depression, dementia, psychosis and impulse control disorders have a major impact on quality of life for both PD patients and their families (Schrag, Jahanshahi, & Quinn, [2000]). Moreover, there is growing evidence that the cognitive deficits associated with PD overlap with those of disseminated Lewy body disease and that these two conditions may represent different points on a spectrum of the same disease. These controversies are extensively discussed by Ballard et al. in ‘Neuropsychiatric symptoms in dementia: Importance and treatment considerations’, and by Merims and Freedman in ‘Cognitive and behavioural impairment in Parkinson's disease’.

Separating depression from dementia remains one of the most difficult clinical challenges for psychiatrists and other physicians caring for older adults. The relationship between late life depression and dementia is complex as clinicians often are faced with the question, ‘does this patient have depression or dementia?’ Why is there such a strong association to incident dementia? (Schweitzer, Tuckwell, O'Brien, & Ames, [2002]). For the clinician, a thoughtful approach that focuses separately on the onset, severity, and course of depressive or cognitive symptoms will improve diagnosis and better inform evaluation and treatment. Additionally, depression is one of the most frequent comorbid psychiatric disorders seen in Alzheimer's and other dementias. It is associated with poor quality of life, significant disability in activities of daily living, rapid cognitive decline, high rates of nursing home placement, and burden to caregivers (Kales, Chen, Blow, Welsh, & Mellow, [2005]). Depression in Alzheimer's disease is markedly under-diagnosed, and most patients with depression are either not treated or are on subclinical doses of antidepressants. These controversies are discussed in depth by Steffens in ‘Separating mood disturbance from mild cognitive impairment in geriatric depression’, and by Starkstein et al. in ‘Depression in Alzheimer's disease: Phenomenology, clinical correlates and treatment’.

Finally, we examine the issue of medication development. There has been important progress in understanding the molecular neurobiological basis of Alzheimer's disease, and there have also been promising developments with regard to other brain diseases that cause dementia. Studies of disease mechanisms have identified a number of potentially utilizable critical steps that may represent opportunities for treatment. Intervention at the level of amyloid beta processing, tau hyper-phosphorylation, excitotoxicity, inflammation, or apoptosis–or their combination–may result in preservation of nerve cells with a direct impact on disease onset or progression. Detection of the soluble form of membrane-bound aspartyl protease in CSF, may be useful for monitoring the effects of drug candidates in vivo (Verheijen, et al., [2006]). Clinical trials are advancing; biomarkers are being included in most trials, and innovative trial designs are being implemented to accelerate treatment development. Controversies surrounding treatment development are unmasked by Cummings in his paper ‘Controversies in Alzheimer's disease drug development’.

In summary, the aim of this issue is to offer evidence-based information of relevance to psychiatrists and the expertise of recognized authorities who have thought deeply about each of the selected controversies. Certainly, these experts have provided an in-depth, scholarly review of each topic.

Declaration of interest: The author report no conflicts of interest. The author alone is responsible for the content and writing of the paper.