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THE CASE Mr. AB was assessed at the McGill Centre for Studies in Aging in December 1995 at the age of 73 for a two year history of decreased recall for recent events and hesitation for words. University educated and active socially, living with his spouse there was some interference of these symptoms with daily life: he had to be reminded of appointments and used the expression “this thing” more and more in his spontaneous language. His medical background was unremarkable and an older brother was a little forgetful. The neurologic assessment showed a slight difficulty to draw a clock with instructions to put all the numbers and set the time at 11:10. He had no observable impairment of copying a cube The score on the Mini Mental State Examination (MMSE) (1) was 27/30, well into the normal range. Uninfused brain computer tomography (CT) imaging showed moderate diffuse brain atrophy evident by widening of the convolutional sulci and mild dilatation of the lateral ventricles. A diagnosis of dementia caused by Alzheimer’s disease (AD) was suspected but follow-up assessments were required for confirmation: six months later his family reported that he repeated questions often, with more hesitation for words leading to angry verbal outbursts; the MMSE score was the same. Nine months after the initial visit the MMSE score dropped to 24/30 and the repeat CT showed increasing atrophy. A diagnosis of AD was made, and explained to the patient and his family. He was offered to join a research protocol evaluating the safety and efficacy of Cerebrolysine, a mixture of peptides extracted from pig brain and having demonstrated in vitro neurotropic properties. Administered intravenously, the treatment allocation was randomized to placebo or active infusion once a day for 28 days at home. After five months of follow-up, there was no detectable change in clinical status and the MMSE score was 23/30. The patient elected to start donepezil (Aricept) therapy, a cholinesterase inhibitor acting by enhancing residual acetylcholine activity. Prior to treatment hobbies and interest were listed, including reading of newspapers intermittently and having stopped more complex tasks such as crossword puzzles and playing chess. After one month on donepezil 5 mg once a day, he described an improved recall for upcoming events, had played and won a chess game against his son (and remembered winning it), and his MMSE score had increased to 28/30. After two months of treatment, there was an apparent loss of clinical benefit, and the MMSE score was 24/30. The dose of donepezil was increased to 10 mg daily. After four months the family reported a decreased in the number of questions repeated, and the MMSE was 25/30. After six months, he is stable clinically. At no time did gastro-intestinal side-effects such as nausea, diarrhea or vomiting occur.

Clinical Assessment of Alzheimer’s Disease and Response to Donepezil Treatment