Tolerance to tacrine, arterial hypotension and leuko-araiosis in Alzheimer's disease

SIR—The baroreflex regulation of blood pressure is modulated by cholinergic systems [1]. Alzheimer's disease (AD) is more often associated with sympathetic dysfunction than fronto-temporal lobe dementia, in which the cholinergic system is relatively spared [2]. In patients with AD, orthostatic hypotension is associated with the severity of the cognitive decline—possibly because of chronic hypoperfusion of the white matter [3]. Orthostatic hypotension could also influence the response to cholinesterase inhibitors; Velnacrine non-responders had a more severe decrease in systolic postural blood pressure before treatment than responders [4]. Amar et al. [5] reported a high rate of withdrawal from tacrine in patients with AD with leuko-araiosis, especially because of agitation. We examined a possible relationship between tolerance to tacrine, orthostatic blood pressure and leuko-araiosis in patients with AD. Forty-one consecutive patients with AD with mild or moderate dementia were included. They were free from heart disease, diabetes mellitus or delirium. They were not taking any drugs with hypotensive side effects. Drug dosage had been stable for at least 1 month before the start of the study. Median age was 739 years (range 57-88), the median Mini-Mental State Examination score [6] was 196 (range 29-9) at baseline. Leuko-araiosis was assessed on computed tomography scan using Rezek's score [7].