Narcissus and Daffodil

Clinical trials of galanthamine 359
Table 14.1 Key instruments used to assess AD symptoms in trials with galanthamine
Instrument (reference) Description
MMSE (Folstein et al., 1975) Mini Mental State Examination: standardised and
validated test of cognitive function, covering memory,
orientation, language and praxis. On a scale of 0–30,
mild to moderate cognitive impairment is indicated by
a score between 26 and 10. Less than 10 implies severe
impairment. Score is influenced by age, socio-economic
and educational status.
ADAS-Cog (Rosen et al., 1984) Alzheimer’s Disease Assessment Scale – cognitive sub-scale:
standardised scale, examining aspects of cognitive
performance including memory, language and praxis.
On a scale of 0–70, cognitive impairment is directly
related to score. Typically, patients with mild to moderate
disease progress by approximately 7–11 units per year.
CIBIC-Plus (Jann, 1998) Clinician’s Interview-based Impression of Change scale:
non-standardised scale assessing changes in patient
performance in general, cognitive, behavioural and daily
living activities; ranging from 1 – markedly improved,
to 7 – markedly worse.
Around the same time, a German group (Thomsen and Kewitz, 1989; Thomsen
et al., 1990) reported on a 60-year-old female, suffering from advanced AD with a
five-year history, who was given oral galanthamine hydrobromide in divided
doses varying between 15 and 55 mg daily over a 120-day period. This included
a 14-day washout period to examine the effects of drug withdrawal. Perhaps due
to the advanced nature of her disease, the results of standard psychometric tests,
including the widely accepted Mini Mental State Examination (MMSE) (Folstein
et al., 1975; see Table 14.1), showed no appreciable improvement with therapy
but neither was clinical deterioration observed over the extended period. Her
doctor and spouse noted subjective improvement in the patient’s appearance
and performance in daily tasks. Interestingly, cholinesterase inhibition in the
patient’s erythrocytes was monitored throughout treatment, and these improvements
corresponded with high-dose phases of therapy and a cholinesterase
inhibition of 50–70%. Incidentally, the technique of titrating individual galanthamine
doses to achieve a target level of erythrocyte cholinesterase inhibition
was used in some, but not all, subsequent clinical trials. Galanthamine appeared
to be well tolerated, without side effects except for transient tachycardia, excitation
and headache that appeared upon re-introduction of the drug after the
washout period.
A second Austrian study (Dal-Bianco et al., 1991) examined 18 patients with
the diagnosis of possible AD, made according to criteria defined by the National
Institute of Neurological and Communicative Disorders and Stroke with the
Alzheimer’s Disease and Related Disorders Association (NINCDS-ADRDA or
simply NINCDS criteria; McKhann et al., 1984). Eighteen individuals, aged between
53 and 83 years, were given galanthamine, 30–50 mg/day for periods ranging
from 2–16 months. In this rather incompletely reported study, there were no