Treatment of hypertension a key factor in the prevention of dementia8 September 2008 Treatment of hypertension has been proved to reduce cardiovascular risk substantially, but a large proportion of people with hypertension in the general population are not even diagnosed or treated, writes Professor Ingmar Skoog, of the Institute of Neuroscience and Physiology, Göteborg University, Sweden. As a risk factor for stroke, ischemic brain lesions and silent brain infarcts, general atherosclerosis, myocardial infarction and cardiovascular morbidity, hypertension may also be a risk factor for dementia related to cerebrovascular disease. After a stroke event dementia occurs in up to 25–30% of patients above age 70. Dementia: a growing public health challenge Due to the aging population and the tragic effects of dementia, this age-related disease is a growing medical, social, and economic problem. Dementia is characterised by significant decline in memory and other cognitive abilities. It is a major cause of disability and mortality, and causes a high burden of suffering for patients and their families. It is one of the most common diseases in the elderly, with crude prevalence rates between 5.9–9.4% for subjects aged over 65 in the European Union (Berr et al., 2005). Dementia drastically affects daily life and everyday personal activities. Often the disease is associated with behavioural symptoms, personality change and numerous clinical complications, increasing the risk for urinary incontinence, hip fracture, and — most markedly — dependence on nursing care. Thus, it is not surprising that the costs of care for patients with dementia are immense. The two most common causes of dementia are Alzheimer's disease (AD) and vascular dementia. AD accounts for 50–70% of all cases of dementia, and about 20–30% have either vascular dementia or a combination of vascular dementia and AD (Boustani et al., 2003). In older patients, the brain lesions associated with each dementia type often occur together. AD and vascular brain lesions interact in important ways to impair cognition, suggesting common pathways of the two neurological diseases. In the absence of effective therapies (in terms of disease modification), it is essential that all potentially reversible causes of dementia be fully investigated. Dementia is one of the major challenges of the 21st century due to the enormous burden these disorders impose on healthcare systems. Searching for a breakthrough Today there is tremendous interest in developing effective treatments that will interfere with some step in the etiologic process or even prevent the clinical onset of dementia. With regard to AD, the sequence of the molecular and cellular events leading to progressive cognitive decline and the steps that are most amenable to intervention have been discussed controversially, but now there is substantial agreement that certain biochemical changes in the brain occur many years or decades before clinical symptoms. However, no effective prevention measures can be recommended so far. Advancing age is the major risk factor for dementia, with a doubling of risk every five years after the age of 65 (Jorm et al., 1987; Kawas, 2003). During the last decade, evidence has accumulated that high blood pressure may be a risk factor for both AD and vascular dementia, independent of the presence of cerebrovascular disease. Several longitudinal studies suggest an association between AD and previous hypertension. In addition, observational studies indicate that the use of antihypertensive drugs may reduce the incidence of AD and dementia. Conversely, no study reports that antihypertension treatment increases the risk for dementia. Treatment of hypertension might be a key factor in the prevention of dementia and cognitive decline. Risk and antihypertensive treatment Most trials of antihypertensive treatment in relation to dementia and cognitive decline have been accomplished as part of large trials where dementia is of secondary interest alongside the primary investigation of cardiovascular outcomes. So far five hypertension trials including in total approximately 22.600 patients have reported on dementia or cognitive function in association with antihypertensive treatment:
These trials observed significant reductions in cardiovascular outcomes, but only one study (Syst-Eur) reported a significantly reduced incidence of dementia under antihypertensive treatment. Regarding other cognitive outcomes, two studies reported a reduction of 11–19% for ‘significant cognitive decline’. Only one study (PROGRESS) showed a significantly lesser decline in cognitive function under antihypertensive treatment compared to placebo, while the other studies observed no differences between the groups in different cognitive tests. No study reported a higher risk for dementia or cognitive decline in the groups treated with antihypertensive drugs. With regard to subanalyses of these data, the PROGRESS study showed that dementia in combination with recurrent stroke was reduced by 34%. SCOPE found that cognitive function declined significantly less under antihypertensive treatment among patients with mild cognitive dysfunction (compared to controls). In SHEP, antihypertensive treatment reduced incidence of dementia if drop-outs were assigned a prevalence of 20–30% of dementia. Dementia prevention: is there hope for the future? The seemingly scanty findings from these trials could give rise to pessimism regarding the possibilities for dementia prevention. However, there are several methodological shortcomings that might explain some of the results and need to be considered in subsequent trials in order to achieve sound results:
In order to detect and substantiate an effect of antihypertensive treatment on dementia risk, patients have to be observed for more than 5 years.
The influence of dementia risk factors has to be clarified with regard to their roles in early, mid and late life, and relative to disease onset. In any case, early treatment of hypertension is essential. Clinical implications
Detection and treatment of hypertension in patients with dementia including Alzheimer's disease (AD) is important, as prevention of stroke and silent cerebrovascular disease may slow down the course of cognitive decline in AD. Acknowledgement This article was written for the 21st Congress of the European College of Neuropsychopharmacology, 2008, in Barcelona, Spain. www.ecnp.eu References 1. Berr C, Wancata J, Ritchie K. Prevalence of dementia in the elderly in Europe. European Neuropsychopharmacology 2005;15:463-471 2. Boustani M, Peterson B, Harris R, et al. Screening for Dementia. Systematic Evidence Review No. 20. Rockville, MD: Agency for Healthcare Research and Quality, June 2003 3. Jorm AF, Korten AE, Henderson AS. The prevalence of dementia: a quantitative integration of the literature. Acta Psychiatr Scand 1987;76:465-479 4. Kawas CH. Early Alzheimer´s disease. N Engl J Med 2003;349:1056-1063 5. Skoog I, Gustafson D. Update on hypertension and Alzheimer’s Disease. Neurological Research 2006;28:605-611 6. Skoog I, Lithell H, Hansson L, Elmfeldt D, Hofman A, Olofsson B, Trenkwalder P, Zanchetti A, for the SCOPE Study Group. Effect of baseline cognitive function on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE) – a randomized double-blind trial. Am J Hypertens. 2005;18:1052-1059 ![]() |
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