Apolipoprotein E ϵ4 allele and hippocampal volume in twins with normal cognition

Plassman, Brenda L.; Welsh-Bohmer, Kathleen A.; Bigler, E. D.; Johnson, Sterling C.; Anderson, Christopher; Helms, Michael J.; Saunders, Ann M.; Breitner, John C.S.

doi:10.1212/wnl.48.4.985

Cited by 149 publications

(102 citation statements)

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“…These observations are important since previous work, including our own, has suggested that APOE may affect normal neurocognitive performance in aging in addition to being a risk factor for AD (e.g. Plassman et al, 1997;Reed et al, 1994). The current findings suggest that differences on memory measures may reflect very early, undetected disease rather than "normal" cognitive variability related to the different APOE polymorphisms (Smith et al, 1998;Bondi et al, 1999).…”

Section: Discussionsupporting

confidence: 55%

“…Some studies have shown lower cognitive function in non-demented individuals carrying one or more APOE ε4 alleles (e.g. Reed et al, 1994;Plassman et al, 1997;Caselli et al, 2004); whereas, others have suggested that group differences are related to the early AD phenotype and are not a function of normal cognitive aging (Smith et al, 1998). Data from the Cache County Study suggest that APOE genotype may play a role in the "timing" of AD onset (e.g.…”

Section: Introductionmentioning

confidence: 99%

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Neuropsychological performance in advanced age: Influences of Demographic factors and Apolipoprotein E: Findings from the Cache County Memory Study

Welsh-Bohmer

Østbye

Sanders

et al. 2009

The Clinical Neuropsychologist

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The Cache County Study of Memory in Aging (CCMS) is an epidemiological study of Alzheimer's disease (AD), mild cognitive disorders, and aging in a population of exceptionally long-lived individuals (7 th to 11 th decade). Observation of population members without dementia provides an opportunity for establishing the range of normal neurocognitive performance in a representative sample of the very old. We examined neurocognitive performance of the normal participants undergoing full clinical evaluations (n=507) and we tested the potential modifying effects of APOE genotype, a known genetic risk factor for the later development of AD. The results indicate that advanced age and low education are related to lower test scores across nearly all of the neurocognitive measures. Gender and APOE ε4 both had negligible and inconsistent influences, affecting only isolated measures of memory and expressive speech (in case of gender). The gender and APOE effects disappeared once age and education were controlled. The study of this exceptionally long-lived population provides useful normative information regarding the broad range of "normal" cognition seen in advanced age. Among elderly without dementia or other cognitive impairment, APOE does not appear to exert any major effects on cognition once other demographic influences are controlled.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

Neuropsychological performance in advanced age: Influences of Demographic factors and Apolipoprotein E: Findings from the Cache County Memory Study

Welsh-Bohmer

Østbye

Sanders

et al. 2009

The Clinical Neuropsychologist

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“…These early "preclinical" memory changes are more likely to occur in those with a genetic susceptibility marker for AD, the apolipoprotein E (APOE) ε4 allele [11,37], than in those without this risk factor. In parallel with these findings, structural [32,44] and functional [4,6,15,20,34,42] neuroimaging alterations are more evident in non-demented elderly with the ε4 allele than in those without this allele type.…”

Section: Introductionmentioning

confidence: 52%

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Han

Houston

Jak

et al. 2007

Neurobiology of Aging

139

114

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Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE ε4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-ε4 and 12 ε4 subjects. The ε4 group displayed greater activation than the non-ε4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE ε4-related deficiencies associated with verbal episodic memory encoding and consolidation.

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“…Previous reports concerning effects of APOE 4 on hippocampal atrophy from cross-sectional MRI are quite variable [23,33,39,45]. The longitudinal MRI study by Cohen et al showed that atrophy rate of hippocampus was higher in CN subjects with APOE 4 than those without APOE 4 [6].…”

Section: Discussionmentioning

confidence: 98%

Age effects on atrophy rates of entorhinal cortex and hippocampus

Schuff

Chao

et al. 2006

Neurobiology of Aging

188

150

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The effects of age, subcortical vascular disease, apolipoprotein E (APOE) 4 allele and hypertension on entorhinal cortex (ERC) and hippocampal atrophy rates were explored in a longitudinal MRI study with 42 cognitively normal (CN) elderly subjects from 58 to 87 years old. The volumes of the ERC, hippocampus, and white matter hyperintensities (WMH) and the presence of lacunes were assessed on MR images. Age was significantly associated with increased atrophy rates of 0.04 ± 0.02% per year for ERC and 0.05 ± 0.02% per year for hippocampus. Atrophy rates of hippocampus, but not that of ERC increased with presence of lacunes, in addition to age. WMH, APOE 4 and hypertension had no significant effect on atrophy rates. In conclusion, age and presence of lacunes should be taken into consideration in imaging studies of CN subjects and AD patients to predict AD progression and assess the response to treatment trials.

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Apolipoprotein E ϵ4 allele and hippocampal volume in twins with normal cognition

Cited by 149 publications

References 0 publications

Neuropsychological performance in advanced age: Influences of Demographic factors and Apolipoprotein E: Findings from the Cache County Memory Study

Neuropsychological performance in advanced age: Influences of Demographic factors and Apolipoprotein E: Findings from the Cache County Memory Study

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Age effects on atrophy rates of entorhinal cortex and hippocampus

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