Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins

Carmelli, Dorit; Swan, Gary E.; Reed, Terry; Miller, Barney E.; Wolf, P. A.; Jarvik, Gail P.; Schellenberg, G. D.

doi:10.1212/wnl.50.6.1580

Cited by 132 publications

(91 citation statements)

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“…Although the results need to be replicated and extended, it is notable that these findings were obtained in a relatively young group of adults who showed no deficits on standard neuropsychological tests. These attentional changes must also be examined in relation to other conditions (e.g., cerebrovascular disease) that can affect cognitive functioning in older adults, particularly in those with the ApoE-ɛ4 gene (Carmelli et al, 1998). Because individuals with cerebrovascular disease were excluded from the previously described studies of attention in ApoE-ɛ4 carriers without dementia, the attentional changes associated with ApoE cannot be attributed to the influence of vascular disease.…”

Section: Greenwoodmentioning

confidence: 99%

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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Section: Greenwoodmentioning

confidence: 99%

The apolipoprotein E gene, attention, and brain function.

Parasuraman¹,

Greenwood²,

Sunderland³

2002

Neuropsychology

108

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“…Several studies have noted that blood pressure during middle age is associated with later cognitive dysfunction. [2][3][4][5][6][7][8] None of these studies measured cognition in mid life, however, so the temporal relationship between hypertension and cognitive impairment has not been clear. Studies have also shown clear relationships between diabetes mellitus, cognitive decline, and dementia (usually vascular dementia).…”

mentioning

confidence: 99%

“…Three studies in older subjects 3,4,6 have found that mid-life hypertension was associated with diminished cognitive performance in later life. Our study measured blood pressure at nearly as young an age as that performed in the Honolulu Heart Study 4 or the Framingham Heart Study, 3 but not as young as a study of twins by Carmelli et al 6 Our study design enabled us to detect an association with cognitive decline at a younger age than these three other studies.…”

mentioning

confidence: 99%

Cardiovascular risk factors and cognitive decline in middle-aged adults

Knopman¹,

Boland²,

Mosley³

et al. 2001

Neurology

778

505

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“…In brains of individuals with AD, de novo synthesis of cholesterol and lipid molecules was reduced in cortical and hippocampal areas, and neurons were dependent upon the internalization of exogenous ApoE-rich lipoprotein complexes as a source for such lipids. The ApoE4-induced cognitive decline in AD seemed to be exacerbated in patients with concurrent cerebrovascular disease [87], hypertension, diabetes, hypercholesterolemia, or atherosclerosis [88][89][90][91], partially due to dysregulation of intracellular lipid trafficking [92][93][94].…”

Section: Role Of Apolipoprotein E In Admentioning

confidence: 99%

Alzheimer’s Disease Risk Genes and Lipid Regulators

Gaamouch

Jing

Xia

et al. 2016

JAD

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Abstract. Brain lipid homeostasis plays an important role in Alzheimer's disease (AD) and other neurodegenerative disorders. Aggregation of amyloid-␤ peptide is one of the major events in AD. The complex interplay between lipids and amyloid-␤ accumulation has been intensively investigated. The proportions of lipid components including phospholipids, sphingolipids, and cholesterol are roughly similar across different brain regions under physiological conditions. However, disruption of brain lipid homeostasis has been described in AD and implicated in disease pathogenesis. Moreover, studies suggest that analysis of lipid composition in plasma and cerebrospinal fluid could improve our understanding of the disease development and progression, which could potentially serve as disease biomarkers and prognostic indicators for AD therapies. Here, we summarize the functional roles of AD risk genes and lipid regulators that modulate brain lipid homeostasis including different lipid species, lipid complexes, and lipid transporters, particularly their effects on amyloid processing, clearance, and aggregation, as well as neuro-toxicities that contribute to AD pathogenesis.

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Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins

Abstract: ApoE4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater vascular or degenerative damage among subjects with ApoE4.

Cited by 132 publications

References 0 publications

The apolipoprotein E gene, attention, and brain function.

The apolipoprotein E gene, attention, and brain function.

Cardiovascular risk factors and cognitive decline in middle-aged adults

Alzheimer’s Disease Risk Genes and Lipid Regulators

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Midlife cardiovascular risk factors, ApoE, and cognitive decline in elderly male twins

Abstract: ApoE*4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater vascular or degenerative damage among subjects with ApoE*4.

Cited by 132 publications

References 0 publications

The apolipoprotein E gene, attention, and brain function.

The apolipoprotein E gene, attention, and brain function.

Cardiovascular risk factors and cognitive decline in middle-aged adults

Alzheimer’s Disease Risk Genes and Lipid Regulators

Contact Info

Product

Resources

About

Abstract: ApoE4 and midlife cardiovascular risk factors may have a synergistic effect on decline in cognitive function. This effect may be due to greater vascular or degenerative damage among subjects with ApoE4.