ApoE epsilon 4 allele and cognitive decline in patients with Alzheimer's disease

Abstract

Many clinical and basic studies have confirmed an association between the apolipoprotein E (apoE) €4 allele and the development of Alzheimer's disease (AD). Corder et al.' reported that survival from onset was unrelated to €4 gene dose. In this issue, Kurz et al.' report that no association of the apoE €4 allele with cognitive decline was found in AD subjects. We examined the relationship between apoE alleles and the rate of cognitive decline in a longitudinal study of up to 3 years.Between February and October 1992, 105 subjects with probable AD diagnosed on the basis of NINCDS-ADRDA3 criteria entered the study. All the subjects underwent a baseline examination consisting of an interview, physical and mental examination, and laboratory tests. Although we were able to perform autopsies on only four of 27 subjects who died during the follow-up, we confirmed the pathologic diagnoses of AD in all of them. The instruments used to evaluate cognitive function were Hasegawa's Dementia Screening-Revised4 (HDSR, maximum score: 30) and the Clinical Dementia Rating (CDR) (score: 0 = no impairment, 18 = most severe impairment). Thereafter, we made annual evaluations using the scales. Between April and July 1994, we asked the subjects still participating for blood samples for apoE genotyping.To examine the relationship between apoE alleles and the rate of cognitive decline, we used the data for 70 subjects (21 men, 49 women) who fulfilled the criterion of availability of apoE genotyping, evaluated on a t least two occasions. Baseline characteristics for the 70 subjects were: age at onset, 75.1 2 8.1 (55 to 89) yr; age at entry, 77.4 2 8.2 (55 to 90) yr; years of education, 8.8 t 2.5 (6 to 15); Barthel score (ADL), 88.7 t 17.4 (37 to 100); place of residence, home = 51, nursing home = 19. The frequencies of the apoE alleles were: 2/3, N = 2; 2/4, N = 1; 3/3, N = 31; 3/4, N = 32; 4/4, N = 4. The number of annual evaluations for the subjects was 3.24 2 0.75 ( 2 to 4). The outcomes, i.e., the rates of decline for the total scores of the two scales, were estimated using least-squares regression for each subject, based on the subject's longitudinal data. To calculate the rates for the two scales, only the data obtained prior to the examination on which a subject showed the floor score (0 on the HDSR, 18 on the CDR) were used. Methods and results.To analyze the outcome for HDSR, we employed the abovedescribed baseline data and HDSR score a t entry, as well as the presence of the €4 allele, as explanatory variables. The stepwise procedure of multiple regression analysis revealed the final results, which do not support the contribution of the €4 allele to outcome (table, part A). The contribution was also not supported by analysis for CDR using the same method (table, part B). Unexpectedly, the same analyses for HDSR and CDR, in which the presence of the €2 allele instead of the €4 allele was employed as the explanatory variable, revealed that €2 was associated with accelerated decline (table, parts C,D).Discussion. There appears to b...

Evidence from case–control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity

“…The APOE ε4 haplotype is by far the most validated genetic variation and has repeatedly been associated with human longevity (e.g., Asada et al 1996;Bathum et al 2006;Deelen et al 2011;Gerdes et al 2000;McKay et al 2011;Nebel et al 2011;Schachter et al 1994), whereas one study has found association of rs2542052 in APOC3 with longevity (Atzmon et al 2006). The APOE polymorphism was recently reviewed in (Seripa et al 2011).…”

APOE ε4 allele predicts faster cognitive decline in mild Alzheimer disease

“…ε4 carriers have been found to demonstrate both slower (4)(5)(6) and faster rates of decline (7)(8)(9)(10)(11)(12)(13), potentially reflecting methodological differences in recruitment techniques, the measurement of cognition, followup time, and participants' stage of dementia. A subset of studies has also demonstrated nondifferential rates of decline in relation to ε4 status (14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24); however, most of these studies had relatively small sample sizes which may have limited their ability to detect differential change over time.…”

Differences in the Association Between Apolipoprotein E Genotype and Mortality Across Populations

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