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Journal of Psychopharmacology
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A double-blind, placebo-controlled study of tacrine in patients with Alzheimer's disease using SPET

Neil Prentice

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Margaret Van Beck

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Nadine J. Dougall

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Anthony P. R. Moffoot

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Ronan E. O'Carroll

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Guy M. Goodwin

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Klaus P. Ebmeier

MRC Brain Metabolism Unit, Royal Edinburgh Hospital, Morningside Park, Edinburgh EH10 5HF, UK

Background: the effect of single-dose and long-term cholinergic enhancement with tacrine on regional cerebral perfusion was examined in patients with Alzheimer's disease using single-photon emission tomography (SPET). Method: 23 patients with probable Alzheimer's disease (DSM-III-R and NINCDS-ADRDA criteria) were scanned before and after a single oral dose of tacrine at the start of the study and again after 12 weeks of randomized, double-blind treatment with tacrine or placebo, using high resolution 99mTc-Exametazime SPET. Patients also underwent neuropsychological testing with the CAMCOG, the Mini-Mental State Examination and the Rivermead Behavioural Memory Test before and after 12 weeks of treatment. Results: occipital count ratios in all regions of interest declined by 3% over 12 weeks, indicating a progression of the disease. Acute tacrine challenge resulted in a 16% increase in the superior frontal and a 11% decrease in the anterior temporal cortex. The acute effects of tacrine were modified by 12 weeks of treatment, particularly in the medial frontal (cingulate) cortex where active treatment was associated with a reduced acute tacrine response. There were no changes in cognitive function associated with active treatment. Conclusion: the study demonstrates the sensitivity of cerebral perfusion measures to changes during acute and medium-term tacrine treatment.

Key Words: tacrine • Alzheimer's disease • double-blind treatment

Journal of Psychopharmacology, Vol. 10, No. 3, 175-181 (1996)
DOI: 10.1177/026988119601000301
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