Carriers of apolipoprotein E “∈“4 allele seem particularly susceptible to their effects

Editor—We agree with Rupert McShane and colleagues that there is evidence for an association between treatment with neuroleptic drugs and a more rapid cognitive decline in dementia, but we would also point out an additional association with the apolipoprotein “∈“4 allele.1 We followed up 135 subjects from the Camberwell dementia case register.2 The patients all fulfilled the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria for Alzheimer's disease and had an initial score on the mini mental state examination of “≥“5 points (to avoid floor effects) over one year. Throughout this period 23 took neuroleptics and 112 had no evidence of use of neuroleptics. Neither age; sex; initial score on the minimental state examination; nor previous evidence of hallucinations, persecutory ideation, aggression, or sleep disturbance had any significant relation with the rate of cognitive decline over this period. The subjects who took neuroleptics, however, had a greater rate of cognitive decline than those who did not (mean (SE) 6.2 (1.0) v 2.1 (0.4) points a year, P < 0.0001).

One hundred of these subjects consented to apolipoprotein E genotyping. The presence of the apolipoprotein E “∈“4 gene alone was not associated with a greater rate of cognitive decline (2.7 (0.6) v 2.1 (0.7) points a year, P = 0.50), which was in keeping with earlier findings.3 A comparison of rates of cognitive decline by neuroleptic use according to the presence or absence of the apolipoprotein E “∈“4 allele showed that neuroleptic use was not associated with a greater rate of decline in the 41 subjects not carrying the allele (4.2 (2.4) v 1.8 (0.6) points a year, P = 0.2) but was associated with a …