Effect of gender and apolipoprotein E genotype on response to anticholinesterase therapy in Alzheimer's disease

Abstract

Background. Anticholinesterase therapies offer modest benefit to subgroups of AD sufferers. However, there has previously been no way of predicting which patients will respond to any of the drugs. Objective. To discover if gender and/or apolipoprotein E genotype can be used as predictors of response in the clinical setting. Design. 107 patients from the Bristol Memory Disorders Clinic took part in a double‐blinded or open label trial of tacrine therapy for between 3 and 12 months or an open label trial of galanthamine therapy for 3 months. Results. After 3 months of therapy, gender was found to be the only significant influence on the number of responders to anticholinesterase therapy. Men had a 73% greater chance of responding than women (p=0·012). While ApoE genotype did not modify response to therapy in the short term, there are indications that it may affect response over the longer term (up to 12 months), and also that the initial advantage of male gender may not be maintained after 3 months. Conclusion. Gender is likely to be a more powerful determinant of outcome of anticholinesterase treatment than apolipoprotein E status in the short term. © 1998 John Wiley & Sons, Ltd.

Effect of apolipoprotein E and butyrylcholinesterase genotypes on cognitive response to cholinesterase inhibitor treatment at different stages of Alzheimer's disease

“…16 Another report found the e4 allele to confer cognitive benefit after 12 months of treatment with tacrine. 17 These studies used change in MMSE as the measure of response, but did not report baseline MMSE. Oddoze et al 18 showed that an improved early response to donepezil occurred in those subjects carrying an e4 allele.…”

“…However, our finding of an improved response to ChEI treatment with APOE e4 carriage is plausible and consistent with other subsequent treatment studies. [16][17][18][19][20] APOE e4 carriers have higher levels of acetylcholinesterase, 65 and the cholinergic deficit is less marked in AD, potentially leading to better response to treatment than in non-APOE e4 carriers.…”

“…15 However, other researchers have reported that the presence of APOE e4 is associated with improved outcome with ChEI therapy. [16][17][18][19][20] Several studies did not find that APOE genotype influenced treatment response. [21][22][23][24][25][26][27][28] Gender, either alone or in interaction with APOE genotype, was not found to influence response to ChEIs.…”

Gender-Dependent Levels of Hyaluronic Acid in Cerebrospinal Fluid of Patients with Neurodegenerative Dementia

“…Whether the gender differences are due to the fact that women live longer than men, is still a subject of debate, however several meta-studies have shown that women indeed have an increased risk of developing AD (19)(20)(21). Moreover, there are two studies showing that men with AD respond better to cholinesterase inhibitors treatment than women (22,23). Dementia with Lewy bodies, on the other hand, is a male-dominant disease (2), which further indicates that the mechanisms underlying these two neurodegenerative diseases differ.…”

Does gender play a role in Alzheimer therapy?

“…MacGowan et al claimed a better response of men to acetylcholine esterase therapy [18]. In contrast, Rigaud et al observed equivalent response to tacrine therapy in men and women [19].…”