The role of
            <i>APOE</i>
            -ε4 in longitudinal cognitive decline

Bretsky, Philip; Guralnik, Jack M.; Launer, Lenore J.; Albert, Marilyn; Seeman, Teresa E.

doi:10.1212/01.wnl.0000055875.26908.24

Cited by 249 publications

(178 citation statements)

References 39 publications

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“…Although this finding has generated fewer biological insights than has the identification, through pedigree studies, of genes implicated in rare, mendelian forms of Alzheimer disease 78 , it has transformed epidemiological and clinical investigation of dementia and related phenotypes. Consequently, it is now known that ApoE4 is associated with the age of onset of Alzheimer disease 95 , the process of cognitive decline in 'normal' aging 96 , altered magnetic resonance imaging findings in asymptomatic individuals 97,98 , risk of chronic traumatic brain injury in boxers 99 and clinical outcome in survivors of traumatic brain injury 100 .…”

Section: Association Studiesmentioning

confidence: 99%

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

2004

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Efforts to identify gene variants associated with susceptibility to common diseases use three approaches: pedigree and affected sib-pair linkage studies and association studies of population samples. The different aims of these study designs reflect their derivation from biological versus epidemiological traditions. Similar principles regarding determination of the evidence levels required to consider the results statistically significant apply to both linkage and association studies, however. Such determination requires explicit attention to the prior probability of particular findings, as well as appropriate correction for multiple comparisons. For most common diseases, increasing the sample size in a study is a crucial step in achieving statistically significant genetic mapping results. Recent studies suggest that the technology and statistical methodology will soon be available to make wellpowered studies feasible using any of these approaches.

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Section: Association Studiesmentioning

confidence: 99%

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

2004

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“…Whereas the APOE2 protein may exert a protective effect from Alzheimer's disease, 4 the APOE4 isoform has been related to reduced neuronal survival and cognitive impairment. 5,6 Although individuals carrying at least one copy of the APOE E4 allele have an increased risk of developing Alzheimer's disease, it is less clear whether the APOE genotype may also be involved in non-pathological cognitive ageing: several studies indicate that possession of the APOE E4 allele relates to increased cognitive decline during normal ageing, [7][8][9][10][11][12][13][14] but other studies do not find evidence for such an association. [15][16][17][18] Various explanations for these conflicting results may be put forward.…”

Section: Introductionmentioning

confidence: 99%

“…However, such studies have not unequivocally offered support for the possible involvement of APOE E4 carrier status in age-related cognitive decline. [7][8][9]12,14,18,19 Second, in light of the involvement of the APOE E4 allele in Alzheimer's disease, it is important to exclude from the study participants with possible dementia, in order to avoid overestimating the association between APOE E4 status and non-pathological age-related cognitive decline. Failing to exclude cases of incipient dementia, particularly at follow-up, was an important limitation of some of the above-mentioned longitudinal studies.…”

Section: Introductionmentioning

confidence: 99%

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

et al. 2011

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Carriers of the APOE E4 allele have an increased risk of developing Alzheimer's disease. However, it is less clear whether APOE E4 status may also be involved in non-pathological cognitive ageing. The present study investigated the associations between APOE genotypes and cognitive change over 8 years in older community-dwelling individuals. APOE genotype was determined in 501 participants of the Lothian Birth Cohort 1921, whose intelligence had been measured in childhood in the Scottish Mental Survey 1932. A polymorphic variant of TOMM40 (rs10524523) was included to differentiate between the effects of the APOE E3 and E4 allelic variants. Cognitive performance on the domains of verbal memory, abstract reasoning and verbal fluency was assessed at mean age 79 years (n = 501), and again at mean ages of 83 (n = 284) and 87 (n = 187). Using linear mixed models adjusted for demographic variables, vascular risk factors and IQ at age 11 years, possession of the APOE E4 allele was associated with a higher relative rate of cognitive decline over the subsequent 8 years for verbal memory and abstract reasoning. Individuals with the long allelic variant of TOMM40, which is linked to APOE E4, showed similar results. Verbal fluency was not affected by APOE E4 status. APOE E2 status was not associated with change in cognitive performance over 8 years. In nondemented older individuals, possession of the APOE E4 allele predicted a higher rate of cognitive decline on tests of verbal memory and abstract reasoning between 79 and 87 years. Thus, possession of the APOE E4 allele may not only predispose to Alzheimer's disease, but also appears to be a risk factor for non-pathological decline in verbal memory and abstract reasoning in the ninth decade of life.

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“…The ε4 allele of the apolipoprotein E (ApoE) gene is the genetic risk factor most robustly associated with sporadic AD as well as a higher rate of incidence in some families (Bretsky et al, 2003;Saunders et al, 1993). The ε4 allele has been associated with increased risk of AD (Corder et al, 1993;Saunders et al, 1993) as well as an earlier age of disease onset (Corder et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

“…The ε4 allele has been associated with increased risk of AD (Corder et al, 1993;Saunders et al, 1993) as well as an earlier age of disease onset (Corder et al, 1993). Some studies have shown an association between the ε4 allele and increased risk of cognitive decline through measurements on a variety of cognitive tests in a normal elderly population (Bretsky et al, 2003;Dik et al, 2001). These findings suggest the involvement of the ε4 allele in the initial neurodegenerating changes associated with AD in individuals at risk for AD.…”

Section: Introductionmentioning

confidence: 99%

The effect of hormone therapy on olfactory sensitivity is dependent on apolipoprotein E genotype

Sundermann

Gilbert

Murphy

2008

Hormones and Behavior

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Patients with Alzheimer's disease (AD) show a deficit in olfactory threshold sensitivity. The Apolipoprotein E (ApoE) ε4 allele is associated with increased risk of AD and earlier symptom onset. Hormone therapy (HT) may exert neuroprotective effects on brain areas affected by AD. The current study investigated the effect of HT on performance on an olfactory threshold test in ε4 positive and ε4 negative non-hysterectomized, non-demented, elderly females and AD patients. Among the non-demented participants, ε4 positive females who had received HT performed 1) significantly better than those without HT, and 2) at levels similar to those of ε4 negative females. In contrast, those without HT who were ε4 positive performed significantly worse than those who were ε4 negative. HT had no effect on performance in AD patients regardless of ε4 status. These results suggest that HT may offer protection against loss of olfactory function in ε4 positive individuals in preclinical stages of AD. Future research is warranted in order to investigate further the neuroprotective role of HT on sensory and cognitive functions in non-demented aging individuals.

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The role of APOE -ε4 in longitudinal cognitive decline

Cited by 249 publications

References 39 publications

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

The use of pedigree, sib-pair and association studies of common diseases for genetic mapping and epidemiology

APOE E4 status predicts age-related cognitive decline in the ninth decade: longitudinal follow-up of the Lothian Birth Cohort 1921

The effect of hormone therapy on olfactory sensitivity is dependent on apolipoprotein E genotype

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