Hypertonie und ihre Behandlung in der Prävention der Alzheimerkrankheit – Auswirkung der Blutdruckwerte auf kognitive Funktionen

Arterielle Hypertonie im mittleren Lebensalter ist mit der Entwicklung einer Demenz im späteren Lebensalter assoziiert. Dies bezieht sich nicht nur auf vaskuläre Demenz, sondern auch auf die Alzheimerkrankheit. Bei alten Menschen sowie bei Patienten mit Alzheimer–Demenz ist diese Assoziation nicht eindeutig; im Gegenteil, es gibt Hinweise, dass sich bei diesen Personen zu niedrige Blutdruckwerte ungünstig auf die kognitiven Funktionen auswirken. Mehrere randomisierte Studien haben mögliche günstige Auswirkungen einer antihypertensiven Therapie auf die Entwicklung einer Demenz untersucht. Die Ergebnisse sind inkonklusiv, sodass bisher nicht sicher belegt ist, dass eine antihypertenisve Behandlung das Demenzrisiko senkt. Zahlreiche methodische Limitationen werden zur Erklärung der negativen Studienergebnisse herangezogen. Ebenso ist es nicht gesichert, dass bei Patienten mit manifester Demenz eine Blutdrucksenkung eine Verschlechterung der kognitiven Leistungen verursachen kann. Bei diesen Patienten, vor allem wenn eine vaskuläre Komponente vorliegt, sollte die Blutdrucksenkung behutsam unter Beobachtung der kognitiven Leistungsfähigkeit erfolgen.

Arterial hypertension has been associated with dementia in later life. This association has not only been described for vascular dementia, but also for Alzheimer's disease. In elderly people and in patients with Alzheimer's disease the association between hypertension and cognitive function is uncertain; on the contrary; in these persons, low blood pressure has been linked to poor cognitive function and a more rapid cognitive decline. Several randomized studies analysed the potential benefits of antihypertensive therapy on dementia risk. However, the results of these studies are inconclusive. Up to now, a protective effect of antihypertensive therapy on the incidence of dementia has not been firmly established. A variety of methodological limitations may explain these discouraging results. Several observational studies indicate that in patients with dementia, lowering blood pressure could cause or worsen cognitive decline. However, the results of the larger randomized studies did not confirm these findings. In particular in patients with cerebrovascular lesions, elevated blood pressure should be treated gradually under close observation of cognitive functions.

Key words

Alzheimer's disease - vascular dementia - arterial hypertension - antihypertensive therapy - risk factor

Literatur

• 1 Plouin PF, Rossignol P, Bobrie G.. Hypertension in the elderly.  Bull Acad Natl Med. 2006;  190 793-805
• 2 Sytkowski PA, D'Agostino RB, Belanger AJ, Kannel WB.. Secular trends in long–term sustained hypertension, long–term treatment, and cardiovascular mortality. The Framingham Heart Study 1950 to 1990.  Circulation. 1996;  93 697-703
• 3 Rovio S, Kareholt I, Helkala EL. et al. . Leisure–time physical activity at midlife and the risk of dementia and Alzheimer's disease.  Lancet Neurol. 2005;  4 705-711
• 4 Patterson C, Feightner JW, Garcia A. et al. . Diagnosis and treatment of dementia: 1. Risk assessment and primary prevention of Alzheimer disease.  Cmaj. 2008;  178 548-556
• 5 Sorrentino G, Migliaccio R, Bonavita V.. Treatment of vascular dementia: the route of prevention.  Eur Neurol. 2008;  60 217-223
• 6 Kovacs GG, Alafuzoff I, Al–Sarraj S. et al. . Mixed brain pathologies in dementia: the BrainNet Europe consortium experience.  Dement Geriatr Cogn Disord. 2008;  26 343-350
• 7 Stein PS, Desrosiers M, Donegan SJ. et al. . Tooth loss, dementia and neuropathology in the Nun study.  J Am Dent Assoc. 2007;  138 1314-1322
• 8 Musicco M, Palmer K, Salamone G. et al. . Predictors of progression of cognitive decline in Alzheimer's disease: the role of vascular and sociodemographic factors.  J Neurol. 2009;  8
• 9 Kloppenborg RP, van den Berg E, Kappelle LJ, Biessels GJ.. Diabetes and other vascular risk factors for dementia: which factor matters most? A systematic review.  Eur J Pharmacol. 2008;  585 97-108
• 10 Seux ML, Thijs L, Forette F. et al. . Correlates of cognitive status of old patients with isolated systolic hypertension: the Syst–Eur Vascular Dementia Project.  J Hypertens. 1998;  16 963-969
• 11 Starr JM, Whalley LJ, Inch S, Shering PA.. Blood pressure and cognitive function in healthy old people.  J Am Geriatr Soc. 1993;  41 753-756
• 12 Scherr PA, Hebert LE, Smith LA, Evans DA.. Relation of blood pressure to cognitive function in the elderly.  Am J Epidemiol. 1991;  134 1303-1315
• 13 Coley N, Andrieu S, Gardette V. et al. . Dementia prevention: methodological explanations for inconsistent results.  Epidemiol Rev. 2008;  30 35-66
• 14 Skoog I, Lernfelt B, Landahl S. et al. . 15–year longitudinal study of blood pressure and dementia.  Lancet. 1996;  347 1141-1145
• 15 Launer LJ, Ross GW, Petrovitch H. et al. . Midlife blood pressure and dementia: the Honolulu–Asia aging study.  Neurobiol Aging. 2000;  21 49-55
• 16 Kivipelto M, Helkala EL, Laakso MP. et al. . Midlife vascular risk factors and Alzheimer's disease in later life: longitudinal, population based study.  Bmj. 2001;  322 1447-1451
• 17 Ruitenberg A, Skoog I, Ott A. et al. . Blood pressure and risk of dementia: results from the Rotterdam study and the Gothenburg H–70 Study.  Dement Geriatr Cogn Disord. 2001;  12 33-39
• 18 Verghese J, Lipton RB, Hall CB. et al. . Low blood pressure and the risk of dementia in very old individuals.  Neurology. 2003;  61 1667-1672
• 19 Guo Z, Fratiglioni L, Zhu L. et al. . Occurrence and progression of dementia in a community population aged 75 years and older: relationship of antihypertensive medication use.  Arch Neurol. 1999;  56 991-996
• 20 Qiu C, von Strauss E, Winblad B, Fratiglioni L.. Decline in blood pressure over time and risk of dementia: a longitudinal study from the Kungsholmen project.  Stroke. 2004;  35 1810-1815
• 21 Bellew KM, Pigeon JG, Stang PE. et al. . Hypertension and the rate of cognitive decline in patients with dementia of the Alzheimer type.  Alzheimer Dis Assoc Disord. 2004;  18 208-213
• 22 White L, Petrovitch H, Hardman J. et al. . Cerebrovascular pathology and dementia in autopsied Honolulu–Asia Aging Study participants.  Ann N Y Acad Sci. 2002;  977 9-23
• 23 Korf ES, White LR, Scheltens P, Launer LJ.. Midlife blood pressure and the risk of hippocampal atrophy: the Honolulu Asia Aging Study.  Hypertension. 2004;  44 29-34
• 24 den Heijer T, Launer LJ, Prins ND. et al. . Association between blood pressure, white matter lesions, and atrophy of the medial temporal lobe.  Neurology. 2005;  64 263-267
• 25 Korf ES, Scheltens P, Barkhof F, de Leeuw FE.. Blood pressure, white matter lesions and medial temporal lobe atrophy: closing the gap between vascular pathology and Alzheimer's disease?.  Dement Geriatr Cogn Disord. 2005;  20 331-337
• 26 Wiseman RM, Saxby BK, Burton EJ. et al. . Hippocampal atrophy, whole brain volume, and white matter lesions in older hypertensive subjects.  Neurology. 2004;  63 1892-1897
• 27 Skoog I, Andreasson LA, Landahl S, Lernfelt B.. A population–based study on blood pressure and brain atrophy in 85–year–lds.  Hypertension. 1998;  32 404-409
• 28 Viswanathan A, Rocca WA, Tzourio C.. Vascular risk factors and dementia: how to move forward?.  Neurology. 2009;  72 368-374
• 29 Esiri MM, Nagy Z, Smith MZ. et al. . Cerebrovascular disease and threshold for dementia in the early stages of Alzheimer's disease.  Lancet. 1999;  354 919-920
• 30 Schneider JA, Boyle PA, Arvanitakis Z. et al. . Subcortical infarcts, Alzheimer's disease pathology, and memory function in older persons.  Ann Neurol. 2007;  62 59-66
• 31 Cechetto DF, Hachinski V, Whitehead SN.. Vascular risk factors and Alzheimer's disease.  Expert Rev Neurother. 2008;  8 743-750
• 32 de la Torre JC.. Vascular basis of Alzheimer's pathogenesis.  Ann N Y Acad Sci. 2002;  977 196-215
• 33 Iadecola C, Davisson RL.. Hypertension and cerebrovascular dysfunction.  Cell Metab. 2008;  7 476-484
• 34 Di Bari M, Pahor M, Franse LV. et al. . Dementia and disability outcomes in large hypertension trials: lessons learned from the systolic hypertension in the elderly program (SHEP) trial.  Am J Epidemiol. 2001;  153 72-78
• 35 Staessen JA, Fagard R, Thijs L. et al. . Randomised double–blind comparison of placebo and active treatment for older patients with isolated systolic hypertension. The Systolic Hypertension in Europe (Syst–Eur) Trial Investigators.  Lancet. 1997;  350 757-764
• 36 Thijs L, Staessen JA, Beleva S. et al. . How well can blood pressure be controlled? Progress report on the Systolic Hypertension in Europe Follow–Up Study (Syst–Eur 2).  Curr Control Trials Cardiovasc Med. 2001;  2 298-306
• 37 Tzourio C, Anderson C, Chapman N. et al. . Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.  Arch Intern Med. 2003;  163 1069-1075
• 38 Dufouil C, Chalmers J, Coskun O. et al. . Effects of blood pressure lowering on cerebral white matter hyperintensities in patients with stroke: the PROGRESS (Perindopril Protection Against Recurrent Stroke Study) Magnetic Resonance Imaging Substudy.  Circulation. 2005;  112 1644-1650
• 39 Lithell H, Hansson L, Skoog I. et al. . The Study on Cognition and Prognosis in the Elderly (SCOPE): principal results of a randomized double–blind intervention trial.  J Hypertens. 2003;  21 875-886
• 40 Peters R, Beckett N, Forette F. et al. . Incident dementia and blood pressure lowering in the Hypertension in the Very Elderly Trial cognitive function assessment (HYVET–COG): a double–blind, placebo controlled trial.  Lancet Neurol. 2008;  7 683-689
• 41 McGuinness B, Todd S, Passmore P, Bullock R.. The effects of blood pressure lowering on development of cognitive impairment and dementia in patients without apparent prior cerebrovascular disease. Cochrane Database Syst 2006
• 42 Birns J, Morris R, Donaldson N, Kalra L.. The effects of blood pressure reduction on cognitive function: a review of effects based on pooled data from clinical trials.  J Hypertens. 2006;  24 1907-1914
• 43 Birkenhager WH, Staessen JA.. Progress in cardiovascular diseases: cognitive function in essential hypertension.  Prog Cardiovasc Dis. 2006;  49 1-10
• 44 Raspe E, Madsen L, Lefebvre AM. et al. . Modulation of rat liver apolipoprotein gene expression and serum lipid levels by tetradecylthioacetic acid (TTA) via PPARalpha activation.  J Lipid Res. 1999;  40 2099-2110
• 45 Moretti R, Torre P, Antonello RM. et al. . Risk factors for vascular dementia: hypotension as a key point.  Vasc Health Risk Manag. 2008;  4 395-402
• 46 Paran E, Anson O, Reuveni H.. Blood pressure and cognitive functioning among independent elderly.  Am J Hypertens. 2003;  16 818-826
• 47 van Dijk EJ, Breteler MM, Schmidt R. et al. . The association between blood pressure, hypertension, and cerebral white matter lesions: cardiovascular determinants of dementia study.  Hypertension. 2004;  44 625-630
• 48 Prince MJ, Bird AS, Blizard RA, Mann AH.. Is the cognitive function of older patients affected by antihypertensive treatment? Results from 54 months of the Medical Research Council's trial of hypertension in older adults.  Bmj. 1996;  312 801-805
• 49 Lasser NL, Nash J, Lasser VI. et al. . Effects of antihypertensive therapy on blood pressure control, cognition, and reactivity. A placebo–controlled comparison of prazosin, propranolol, and hydrochlorothiazide.  Am J Med. 1989;  86 98-103
• 50 Glynn RJ, Beckett LA, Hebert LE. et al. . Current and remote blood pressure and cognitive decline.  JAMA. 1999;  281 438-445
• 51 Bohannon AD, Fillenbaum GG, Pieper CF. et al. . Relationship of race/ethnicity and blood pressure to change in cognitive function.  J Am Geriatr Soc. 2002;  50 424-429
• 52 Skoog I.. Antihypertensive treatment and dementia prevention.  Lancet Neurol. 2008;  7 664-665

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