APOE Gene Polymorphism and Drug-Induced Cognitive Toxicity
In their recent and important article, Ancelin and colleagues1
described a number of age-related pharmacokinetic factors, including
slower metabolism and drug elimination, that may increase significant
cognitive toxicity among the elderly during ongoing treatment with drugs
having central anticholinergic effects. We would like to call attention to
emerging evidence that polymorphism of the APOE gene may also contribute
to individual variability in sensitivity to drug-induced cognitive
toxicity in the elderly.
As previously reported, we found that in healthy non-demented
elderly, possession of the APOE e4 allele, which is a well-established
risk factor for late-onset Alzheimer’s disease, was associated with
greater sensitivity or more persistent memory deficits than those observed
in individuals without this allele following acute administration of
single oral doses of trihexyphenidyl (2 mg) or lorazepam (1 mg).2, 3 Since
the APOE e4 allele has a frequency of 25% in the general population, it
would be of considerable interest if future studies in elderly populations
such as that conducted by Ancelin and colleagues (2006) examined the
influence of this genetic factor in the cognitive toxicity associated with
long-term use of commonly prescribed anticholinergic medications.
References:
1. Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K.
Non-degenerative mild cognitive impairment in elderly people and use of
anticholinergic drugs: longitudinal cohort study. BMJ 2006;332:455-9.
2. Pomara N, Willoughby LM, Wesnes K, Sidtis JJ. Increased
anticholinergic challenge-induced memory impairment associated with the APOE-e4 allele in the
elderly: a controlled pilot study. Neuropsychopharmacology 2004;29:403-9.
3. Pomara N, Willoughby L, Wesnes K, Greenblatt DJ, Sidtis JJ.
ApolipoproteinE e4 allele and lorazepam effects on memory in high-functioning older
adults. Arch Gen Psychiatry 2005;62:209-16.
Competing interests:
None declared
Competing interests:
No competing interests
03 March 2006
Nunzio Pomara
Professor & Director Geriatric Psychiatry Division
John J Sidtis
NYU School of Medicine & Nathan Kline Institute, Orangeburg, New York, 10962
Rapid Response:
APOE Gene Polymorphism and Drug-Induced Cognitive Toxicity
In their recent and important article, Ancelin and colleagues1
described a number of age-related pharmacokinetic factors, including
slower metabolism and drug elimination, that may increase significant
cognitive toxicity among the elderly during ongoing treatment with drugs
having central anticholinergic effects. We would like to call attention to
emerging evidence that polymorphism of the APOE gene may also contribute
to individual variability in sensitivity to drug-induced cognitive
toxicity in the elderly.
As previously reported, we found that in healthy non-demented
elderly, possession of the APOE e4 allele, which is a well-established
risk factor for late-onset Alzheimer’s disease, was associated with
greater sensitivity or more persistent memory deficits than those observed
in individuals without this allele following acute administration of
single oral doses of trihexyphenidyl (2 mg) or lorazepam (1 mg).2, 3 Since
the APOE e4 allele has a frequency of 25% in the general population, it
would be of considerable interest if future studies in elderly populations
such as that conducted by Ancelin and colleagues (2006) examined the
influence of this genetic factor in the cognitive toxicity associated with
long-term use of commonly prescribed anticholinergic medications.
References:
1. Ancelin ML, Artero S, Portet F, Dupuy AM, Touchon J, Ritchie K.
Non-degenerative mild cognitive impairment in elderly people and use of
anticholinergic drugs: longitudinal cohort study. BMJ 2006;332:455-9.
2. Pomara N, Willoughby LM, Wesnes K, Sidtis JJ. Increased
anticholinergic challenge-induced memory impairment associated with the APOE-e4 allele in the
elderly: a controlled pilot study. Neuropsychopharmacology 2004;29:403-9.
3. Pomara N, Willoughby L, Wesnes K, Greenblatt DJ, Sidtis JJ.
ApolipoproteinE e4 allele and lorazepam effects on memory in high-functioning older
adults. Arch Gen Psychiatry 2005;62:209-16.
Competing interests:
None declared
Competing interests: No competing interests