Lack of association of apolipoprotein E allele ϵ4 with late‐onset Alzheimer's disease among Finnish centenarians

Abstract

No association between Alzheimer's disease (AD) and apolipoprotein E type epsilon 4 (ApoE epsilon 4) phenotype was found among centenarians in Finland (N = 179). The data are based on ascertainment of all centenarians in Finland in 1991. All examinations were conducted during 1991. The diagnoses of dementia and AD were based on clinical grounds, conforming to DSM-III-R and NINCDS-ADRDA criteria. The percentage of ApoE epsilon 4 alleles among the centenarians was 8.7% (31 of 358 alleles). This is significantly lower than percentages found in younger Finnish populations. Thirty (16.8%) of the 179 centenarians were epsilon 4 allele carriers. One hundred fifty-one (84.4%) of the centenarians were women. Twenty-eight (18.5%) of the women had at least one epsilon 4 allele, as did two (7.1%) of the men. The prevalence of clinically diagnosed AD was 26.8%; 44% of the subjects were cognitively normal, 23% had signs of cognitive decline or at most mild dementia (with no differential diagnosis), and 6% had a dementia clinically diagnosed as being due to some cause other than AD. For AD cases versus cognitively normal subjects, the odds ratio associated with being a carrier of the epsilon 4 allele was 1.34 (p = 0.64; 95% CI = [0.5, 3.3]). Among women, the odds ratio was 0.99 (p = 1.0; 95% CI = [0.4, 2.6]). There were fewer, but not significantly so, epsilon 4 carriers among subjects with cognitive decline or at most mild dementia (12.2%) than there were among the cognitively normal subjects (16.5%). The AD patients had no evidence of difficulty standing on a flat stationary surface unless the surface suddenly moved.(ABSTRACT TRUNCATED AT 250 WORDS)

Alzheimers and Dementia in the Oldest-Old: A Century of Challenges

“…Some studies of participants aged 85+ found the presence of an e4 allele to be related to prevalent AD [36][37][38] but this was not the case in a study of Finnish centenarians [39]. Furthermore, it is not known if agents that potentially confer protection in younger subjects such as folate, non-steroidal anti-inflammatory drugs, statins, antioxidants, estrogen therapy, and physical and cognitive activities are operative for individuals in extreme old age.…”

Effects of the APOE ε4 allele and education on cognitive function in Japanese centenarians

“…While there was a significant negative association between the ε4 allele and cognitive function among 103 Korean centenarians (Choi et al 2003), this finding was not observed in 179 Finnish (Sobel et al 1995) and 33 Japanese centenarians (Asada et al 1996).…”

“…In previous studies on centenarians, effects of the APOE ε4 allele on cognitive function have been inconsistent (Asada et al 1996;Choi et al 2003;Sobel et al 1995). These inconsistent findings could be attributed to common characteristics of centenarian studies: small sample size, skewed distribution of APOE genotype, and lesser attention of researchers with regard to the effect of life course environment on cognitive function in centenarian study (Hofer and Alwin 2008).…”

“…These inconsistent findings could be attributed to common characteristics of centenarian studies: small sample size, skewed distribution of APOE genotype, and lesser attention of researchers with regard to the effect of life course environment on cognitive function in centenarian study (Hofer and Alwin 2008). First, the number of participants which analyzed in the previous centenarian studies were small (N = 33, 103, and 179, respectively, Asada et al 1996;Choi et al 2003;Sobel et al 1995). Second, the APOE gene has been associated with longevity; centenarians tend not to have the APOE ε4 allele (Ewbank 2002;Farrer et al 1997).…”

Susceptibility Genetics in the Etiopathogenesis of Alzheimer's Disease: Role for Potential Confounding Factors

“…The extent of the ~4 effect is diminished in the very elderly (Rebeck et al, 1994;Sobel et al, 1995) and many can reach old age without cognitive impairment despite the inheritance of one or two APOE ~4 alleles (Hymanet al, 1996). Use of APOE genotype in predictive test situations, however, requires absolute risk information that can be obtained only from prospective cohort studies, a number of which are under way (Brayne et al, 1996;Feskens et al, 1994;Henderson et al, 1995;Hyman et al, 1996;Kuusisto et al, 1994;Myers et al, 1996;Petersen et al, 1995).…”