Cognitive Function and Apolipoprotein E in Very Old Adults: Findings From the Nun Study

Riley, Kathryn; Snowdon, David A.; Saunders, Ann M.; Roses, Allen D.; Mortimer, James A.; Nanayakkara, Nuwan D.

doi:10.1093/geronb/55.2.s69

Cited by 55 publications

(34 citation statements)

References 46 publications

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“…Flory, Manuck, Ferrell, Ryan, and Muldoon (2000) extended these findings to middle-aged adults by showing that ApoE-ɛ4 carriers with a mean age of 46 had lower verbal memory performance than those with the ApoE-ɛ2 or ApoE-ɛ3 alleles. Also consistent with these results linking ApoE and cognition is the finding that the absence of the ApoE ɛ4 allele is associated with higher levels of cognitive functioning in very old (75-98 years) adults (Riley et al, 2000).However, some studies finding no differences in neuropsychological test performance as a function of ApoE genotype have also been reported (Plassman et al, 1997;Reiman et al, 1996; B. J. Small et al, 2000; G. E. Smith et al, 1998).…”

supporting

confidence: 71%

The apolipoprotein E gene, attention, and brain function.

Parasuraman¹,

Greenwood²,

Sunderland³

2002

Neuropsychology

108

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The ɛ4 allele of the apolipoprotein E (ApoE) gene is associated with alterations in brain function and is a risk factor for Alzheimer's disease (AD). Changes in components of visuospatial attention with ApoE-ɛ4, aging, and AD are described. Healthy middle-aged adults without dementia who have the ApoE-ɛ4 gene show deficits in spatial attention and working memory that are qualitatively similar to those seen in clinically diagnosed AD patients. The findings support an association between ApoE polymorphism and specific components of visuospatial attention. Molecular mechanisms that may mediate the ApoE-attention link by modulating cholinergic neurotransmission to the posterior parietal cortex are discussed. Studies of attention and brain function in ApoE-ɛ4 carriers without dementia can advance knowledge of the genetics of visual attention, may enhance understanding of the preclinical phase of AD, and may lead to better methods for early AD detection.Apolipoprotein E (ApoE) is an amino acid glycoprotein that is important in lipid storage, transport, and metabolism (Mahley, 1988). Although synthesized mainly in the liver, ApoE is also found in the peripheral and central nervous systems, including the brain. ApoE has long been of interest in medicine, but its importance in neuroscience increased dramatically with the identification of the ɛ4 allele of the ApoE gene on chromosome 19 as a major risk factor for the development of late-onset Alzheimer's disease (AD) in older adults Strittmatter et al., 1993). This discovery led to a growing number of studies examining the role of the ApoE gene in normal brain function and cognition, as well as in disorders such as AD, brain injury, and stroke (Higgins, Large, Rupniak, & Barnes, 1997;Horsburgh, McCarron, White, & Nicol, 2000; J. D. Smith, 2000).Polymorphisms of the ApoE gene are associated with significant alterations in brain morphology (Plassman et al., 1997) and cognitive functioning, including attention (Greenwood, Sunderland, Friz, & Parasuraman, 2000) and memory (Bondi et al., 1995). Studies of ApoE may thus reveal information relevant to the genetics of attention and memory in normal individuals. At the same time, such studies may identify cognitive and neural changes that may be characteristic of preclinical stages of AD. In this article, we review the role of the ApoE gene in normal cognition and in the development of deficits indicative of early AD.Currently, no reliable methods exist for the early detection and treatment of AD. New techniques for preventing, slowing the progression of, and treating AD are being urgently sought. Such efforts would be aided considerably if AD could be detected prior to the clinical diagnosis of AD and before irreversible brain changes occur (Daffner & Scinto, 2000). Postmortem studies show that neuropathological changes occur decades before the onset of NIH Public Access Author ManuscriptNeuropsychology. Author manuscript; available in PMC 2006 January 25. Published in final edited form as:Neuropsychology. 2002 April ; ...

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supporting

confidence: 71%

The apolipoprotein E gene, attention, and brain function.

Parasuraman¹,

Greenwood²,

Sunderland³

2002

Neuropsychology

108

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“…Subsequently, APOE4 has been associated with neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) 32 – 34. Consistent with these findings, APOE4 has been associated with the decline of cognitive function during ageing35 and with age of onset of AD and PD 36 37. Because these disorders are more common in older people, it is expected that the APOE4 allele may play a part in ageing and may affect quality of life in older people in many ways.…”

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confidence: 71%

Apolipoprotein E polymorphism, life stress and self-reported health among older adults

Zhang

Lewis

Yang

et al. 2008

Journal of Epidemiology & Community Health

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The APOE4 allele and life-stress factors are associated with SRH, especially in women. Physical exercise is good for health, but benefits may be attenuated among APOE4 allele carriers. This is the first evidence associating a genetic factor and an interaction between APOE4 and physical exercise with SRH. We suggest that well studied genetic factors should be included in health research to control potential heterogeneity.

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“…The unexpected findings of APOE e4 heterozygotes and A2M ins/del heterozygotes showing comparable or better expected performance than noncarriers leads to speculation about antagonistic pleiotropy (Williams, 1957 as cited in Finch andTanzi, 1997) where the same gene may have deleterious outcomes at certain ages and yet be advantageous at other ages (e.g., attenuation of APOE e4 effect after age 80, see Riley et al, 2000) or for other traits.…”

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confidence: 99%

Longitudinal Memory Performance During Normal Aging: Twin Association Models of APOE and Other Alzheimer Candidate Genes

et al. 2006

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The APOE gene (apolipoprotein E) is a major risk factor for Alzheimer's Disease (AD) but has been inconsistently associated with memory in nondemented adults. Two other genes with mixed support as genetic risk factors for AD, A2M (alpha-2-macroglobulin) and LRP (low-density lipoprotein receptor-related protein), have not been studied in relation to memory among nondemented adults. The present study examined these three genes and latent growth parameters estimated from memory performance spanning 13 years in 478 twins from the Swedish Adoption/Twin Study of Aging (SATSA). APOE was associated with working and recall memory ability levels and working memory rate of change, with e4 homozygotes exhibiting the worst performance at all ages. Homozygotes for the rare A2M insertion/deletion variant exhibited accelerating decline on delayed figural recognition. There were no significant findings for LRP. Dominance, often untested in previous studies, was important in the current study's findings.

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Cognitive Function and Apolipoprotein E in Very Old Adults: Findings From the Nun Study

Cited by 55 publications

References 46 publications

The apolipoprotein E gene, attention, and brain function.

The apolipoprotein E gene, attention, and brain function.

Apolipoprotein E polymorphism, life stress and self-reported health among older adults

Longitudinal Memory Performance During Normal Aging: Twin Association Models of APOE and Other Alzheimer Candidate Genes

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