[34] A 32-year-long prospective study in approximately 2000 indiv

[34] A 32-year-long prospective study in approximately 2000 individuals, meanwhile, concluded that those who developed dementia had higher systolic blood pressure in early life, but that blood pressure then fell to a greater extent in the same individuals in later life[35] a finding partially

supported by Razay et al.[36] who, in a study of 235 control individuals, 141 patients with Alzheimer’s disease, 42 with mild cognitive impairment and 59 with other dementias, determined that faster cognitive decline over 5 years was associated with extremes of blood pressure, both high and low. Paradoxically four studies, LDE225 in vivo ranging from 327 to 6249 patients, showed that hypertension is associated with a decreased risk of all dementias[37–40] and hypotension associated with an increased risk.[38] A possible confounding factor in such studies is a history of antihypertensive medication. A small study in 321 memory-clinic patients showed that cognition, as assessed by the MMSE, was equal in individuals receiving

antihypertensive therapy and those not receiving such medication at the outset, but that at 3-year follow-up those receiving antihypertensives had better cognition.[41] Along the same lines, R428 cost Gao et al.[29] reported that hypertension caused a decrease in cognition, but that treated hypertensive patients were not significantly different from normotensive controls. In contradiction to this ‘normalizing effect’ of antihypertensive therapies, Hoffman et al.,[42] who undertook 291 post-mortem examinations, showed that a history of antihypertensive medication was associated with decreased Alzheimer-like neuropathological changes compared with normotensive controls. Hypertensive patients who had not received medication were similar to normotensive Bcl-w controls, who thus had more neuropathological changes than those individuals who had received antihypertensive medication. The antihypertensive therapies therefore are perhaps more ‘protective’ than ‘normalizing’. Two studies have been published recently: a study

of 1054 hypertensive individuals, 158 of whom developed dementia during the 6-year study,[43] and a study of 800 000 individuals receiving antihypertensive drugs, of whom 12 500 had Alzheimer’s disease and 44 500 had dementia.[44] In the first study[43] the class of antihypertensive most robustly associated with a protective effect against dementia was brain-penetrating ACEIs.[43] These results were first reported at a meeting of the American Geriatrics Society in 2007,[45] and they have been replicated in an independent Russian study.[46] Brain-penetrating ACEIs include captopril, fosinopril, lisinopril, perindopril, ramipril and trandolapril. Non-brain-penetrating ACEIs included benazepril, enalapril, moexipril and quinapril.

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