Effect of baseline cognitive function and antihypertensive treatment on cognitive and cardiovascular outcomes: Study on COgnition and Prognosis in the Elderly (SCOPE)

The Study on COgnition and Prognosis in the Elderly (SCOPE) is a multicentre, prospective, randomized, double-blind, parallel-group study designed to compare the effects of candesartan cilexetil and placebo in elderly patients with mild hypertension. The primary objective of the study is to assess the effect of candesartan cilexetil on major cardiovascular events. The secondary objectives of the study are to assess the effect of candesartan cilexetil on cognitive function and on total mortality, cardiovascular mortality, myocardial infarction, stroke, renal function, hospitalization, quality of life and health economics. Male and female patients aged between 70 and 89 years, with a sitting systolic blood pressure (SBP) of 160-179 mmHg and/or diastolic blood pressure (DBP) of 90-99 mmHg, and a Mini-Mental State Examination (MMSE) score of 24 or above, are eligible for the study. The overall target study population is 4000 patients, at least 1000 of whom are also to be assessed for quality of life and health economics data. After an open run-in period lasting 1-3 months, during which patients are assessed for eligibility and those who are already on antihypertensive therapy at enrolment are switched to hydrochlorothiazide 12.5 mg o.d., patients are randomized to receive either candesartan cilexetil 8 mg once daily (o.d.) or matching placebo o.d. At subsequent study visits, if SBP remains >160 mmHg, or has decreased by <10 mmHg since the randomization visit, or DBP is >85 mmHg, study treatment is doubled to candesartan cilexetil 16 mg o.d. or two placebo tablets o.d. Recruitment was completed in January 1999. At that time 4964 patients had been randomized. All randomized patients will be followed for an additional 2 years. If the event rate is lower than anticipated, the follow-up will be prolonged.

[1]  A. Hofman,et al.  Antihypertensive drugs and incidence of dementia: the Rotterdam Study , 2001, Neurobiology of Aging.

[2]  A. Hofman,et al.  Blood Pressure and Risk of Dementia: Results from the Rotterdam Study and the Gothenburg H-70 Study , 2000, Dementia and Geriatric Cognitive Disorders.

[3]  K. Hall,et al.  The Association Between Vascular Risk Factor‐Mediating Medications and Cognition and Dementia Diagnosis in a Community‐Based Sample of African‐Americans , 2000, Journal of the American Geriatrics Society.

[4]  B. Winblad,et al.  Incidence of stroke in relation to cognitive function and dementia in the Kungsholmen Project , 2000, Neurology.

[5]  I. Skoog,et al.  A Longitudinal Population Study of the Mini-Mental State Examination in the Very Old: Relation to Dementia and Education , 2000, Dementia and Geriatric Cognitive Disorders.

[6]  R. Havlik,et al.  Midlife blood pressure and dementia: the Honolulu–Asia aging study☆ , 2000, Neurobiology of Aging.

[7]  J. Swales.  Current clinical practice in hypertension: the EISBERG (Evaluation and Interventions for Systolic Blood pressure Elevation-Regional and Global) project. , 1999, American heart journal.

[8]  B. Winblad,et al.  Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use. , 1999, Archives of neurology.

[9]  J. Tuomilehto,et al.  Prevention of dementia in randomised double-blind placebo-controlled Systolic Hypertension in Europe (Syst-Eur) trial , 1998, The Lancet.

[10]  D. Jolley,et al.  Cost benefits of a medically supervised day treatment program for patients with Alzheimer's disease and other forms of dementia , 1989 .

[11]  Ingmar Skoog,et al.  A Review on Blood Pressure and Ischaemic White Matter Lesions , 1998, Dementia and Geriatric Cognitive Disorders.

[12]  Joël Ménard,et al.  Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial , 1998, The Lancet.

[13]  L. Hansson,et al.  Hypertension is related to cognitive impairment: a 20-year follow-up of 999 men. , 1998, Hypertension.

[14]  I. Skoog.  Status of Risk Factors for Vascular Dementia , 1998, Neuroepidemiology.

[15]  Jan A Staessen,et al.  Randomised double-blind comparison of placebo and active treatment for older patients with isolated systolic hypertension , 1997, The Lancet.

[16]  G. Mcinnes,et al.  The efficacy and tolerability of candesartan cilexetil in an elderly hypertensive population. , 1997, Journal of human hypertension.

[17]  D. Elmfeldt,et al.  Candesartan cilexetil, a new generation angiotensin II antagonist, provides dose dependent antihypertensive effect. , 1997, Journal of human hypertension.

[18]  Alan D. Lopez,et al.  Mortality by cause for eight regions of the world: Global Burden of Disease Study , 1997, The Lancet.

[19]  H. Lithell,et al.  How do we treat, or not treat, high blood pressure in the oldest old? A practice study in Swedish geriatricians. , 1997, Blood pressure.

[20]  F. Messerli,et al.  Angiotensin II receptor inhibition. A new therapeutic principle. , 1996, Archives of internal medicine.

[21]  B. Lernfelt,et al.  High blood pressure and dementia , 1996, The Lancet.

[22]  B. Lernfelt,et al.  15-year longitudinal study of blood pressure and dementia , 1996, The Lancet.

[23]  M. Prince,et al.  Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's treatment trial of hypertension in older adults , 1996, BMJ.

[24]  C. Martyn,et al.  Cognitive impairment and mortality in a cohort of elderly people , 1996, BMJ.

[25]  D. W. Desmond,et al.  COGNITIVE IMPAIRMENT AND RISK OF STROKE IN THE OLDER POPULATION , 1996, Journal of the American Geriatrics Society.

[26]  M. Prince.  Vascular risk factors and atherosclerosis as risk factors for cognitive decline and dementia. , 1995, Journal of psychosomatic research.

[27]  O. Paulson,et al.  Cerebrovascular consequences of hypertension , 1994, The Lancet.

[28]  I. Skoog,et al.  The Prevalence of White-Matter Lesions on Computed Tomography of the Brain in Demented and Nondemented 85-Year-Olds , 1994, Journal of geriatric psychiatry and neurology.

[29]  J. J. Claus,et al.  Cardiovascular disease and distribution of cognitive function in elderly people: the Rotterdam study , 1994, BMJ.

[30]  J. Wright,et al.  Brain angiotensin receptor subtypes in the control of physiological and behavioral responses , 1994, Neuroscience & Biobehavioral Reviews.

[31]  A. Rodgers,et al.  The effects of antihypertensive treatment on vascular disease: Reappraisal of the evidence in 1994 , 1993 .

[32]  J. Monfort.  A population-based study of dementia in 85-year-olds. , 1993, The New England journal of medicine.

[33]  V. Hachinski.  Preventable senility: a call for action against the vascular dementias , 1992, The Lancet.

[34]  T. Tombaugh,et al.  The Mini‐Mental State Examination: A Comprehensive Review , 1992, Journal of the American Geriatrics Society.

[35]  R. Mayeux,et al.  Dementia after stroke , 1992, Neurology.

[36]  C. Dollery,et al.  Medical Research Council trial of treatment of hypertension in older adults: principal results. , 1992 .

[37]  B. Dahlöf,et al.  Morbidity and mortality in the Swedish Trial in Old Patients with Hypertension (STOP-Hypertension) , 1991, The Lancet.

[38]  B. Costall,et al.  Cognitive enhancing actions of PD123177 detected in a mouse habituation paradigm. , 1990, NeuroReport.

[39]  Anthony F Jorm.  The Epidemiology of Alzheimer's Disease and Related Disorders , 1991 .

[40]  Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension. Final results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group. , 1991, JAMA.

[41]  D. Sparks,et al.  Cortical senile plaques in coronary artery disease, aging and Alzheimer's disease , 1990, Neurobiology of Aging.

[42]  H. Morgenstern,et al.  Women, myocardial infarction, and dementia in the very old , 1990, Neurology.

[43]  D B Hier,et al.  Dementia in stroke survivors in the Stroke Data Bank cohort. Prevalence, incidence, risk factors, and computed tomographic findings. , 1990, Stroke.

[44]  R. Collins,et al.  Blood pressure, stroke, and coronary heart disease Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias , 1990, The Lancet.

[45]  B. Costall,et al.  Cognitive enhancing actions of DuP 753 detected in a mouse habituation paradigm. , 1990, Neuroreport.

[46]  B. Costall,et al.  Angiotensin II inhibits the release of [3H]acetylcholine from rat entorhinal cortex in vitro , 1989, Brain Research.

[47]  F. Caird,et al.  Chronic brain failure: the silent epidemic. , 1987, The New Zealand medical journal.

[48]  S. Folstein,et al.  "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician. , 1975, Journal of psychiatric research.