Apolipoprotein E ɛ4 influences on episodic recall and brain structures in aging pilots

Adamson, Maheen M.; Landy, Kelly M.; Duong, Susan; Fox-Bosetti, Sabrina; Ashford, J. Wesson; Murphy, Greer M.; Weiner, Michael W.; Taylor, Joy L.

doi:10.1016/j.neurobiolaging.2008.07.017

Cited by 28 publications

(32 citation statements)

References 37 publications

(46 reference statements)

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“…Together these variables predicted a significant amount of variance in episodic memory performance, R 2 = .183, p < .001. Replicating previous findings (e.g., Adamson et al, 2010; Backman et al, 2005; Bondi et al, 1995; Filippini et al, 2009; Nilsson et al, 2006; Pike et al, 2011; Schultz et al, 2008; Wisdom et al, 2011), episodic memory scores were significantly lower in older adults, β = −.367, p < .001, and in APOE ε4 carriers, β = .166, p = .015. The effect of APOE ε4 carrier status was larger in older than younger adults; however, the Age × APOE interaction was not significant, β = −.320, p = .142 (see Figure 1).…”

Section: Resultssupporting

confidence: 85%

“…Although no study has examined whether APOE ε4 carrier status influences everyday memory, a number of studies of memory for verbal and pictorial materials have shown that ε4 carrier status affects episodic memory in older adults (e.g., Adamson et al, 2010; Baxter, Caselli, Johnson, Reiman, & Osborne, 2003; Bondi et al, 1995; Caselli et al, 2009; Nilsson et al, 2006; Packard et al, 2007; Pike et al, 2011; Wisdom et al, 2011). APOE genotype interacts with age such that the effect of the ε4 allele is more detrimental in older adults, and is often absent Filippini et al, 2009) or even beneficial in younger adults (Alexander et al, 2007; Mondadori et al, 2007; Rusted, Evans, King, Dowell, Tabet, & Tofts, 2013).…”

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confidence: 99%

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APOE ε4genotype predicts memory for everyday activities

Bailey

Sargent

Flores

et al. 2015

Aging, Neuropsychology, and Cognition

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The apolipoprotein E (ApoE) ε4 allele is associated with neuropathological buildup of amyloid in the brain, and with lower performance on some laboratory measures of memory in some populations. In two studies, we tested whether ApoE genotype affects memory for everyday activities. In Study 1, participants aged 20-79 years old (n = 188) watched movies of actors engaged in daily activities and completed memory tests for the activities in the movies. In Study 2, cognitively healthy and demented older adults (n = 97) watched and remembered similar movies, and also underwent structural MRI scanning. All participants provided saliva samples for genetic analysis. In both samples we found that, in older adults, ApoE ε4 carriers demonstrated worse everyday memory performance than did ε4 non-carriers. In Study 2, ApoE ε4 carriers had smaller MTL volumes, and MTL volume mediated the relationship between ApoE genotype and everyday memory performance. These everyday memory tasks measure genetically-determined cognitive decline that can occur prior to a clinical diagnosis of dementia. Further, these tasks are easily administered and may be a useful clinical tool in identifying ε4 carriers who may be at risk for MTL atrophy and further cognitive decline that is a common characteristic of the earliest stages of Alzheimer's disease.

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Section: Resultssupporting

confidence: 85%

mentioning

confidence: 99%

APOE ε4genotype predicts memory for everyday activities

Bailey

Sargent

Flores

et al. 2015

Aging, Neuropsychology, and Cognition

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“…It is unclear whether healthy carriers of the APOEε4 variant have smaller hippocampal volumes. Several reports of negative effects of APOEε4 on the hippocampal volume in healthy participants (Chiang et al 2011; Cohen et al 2001; den Heijer et al 2012; Lind et al 2006; Lu et al 2011; Moffat et al 2000) are balanced by studies that failed to find such an association (Adamson et al 2010; Cherbuin et al 2008; Ferencz et al 2013; Hostage et al 2013; Lemaître et al 2005; Richter-Schmidinger et al 2011; Troyer et al 2012), with some finding the effect only for the homozygotes (Crivello et al 2010). …”

Section: Discussionmentioning

confidence: 99%

Volume of the hippocampal subfields in healthy adults: differential associations with age and a pro-inflammatory genetic variant

et al. 2014

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The hippocampus is one of the most age-sensitive brain regions, yet the mechanisms of hippocampal shrinkage remain unclear. Recent studies suggest that hippocampal subfields are differentially vulnerable to aging and differentially sensitive to vascular risk. Promoters of inflammation are frequently proposed as major contributors to brain aging and vascular disease but their effects on hippocampal subfields are unknown. We examined the associations of hippocampal subfield volumes with age, a vascular risk factor (hypertension), and genetic polymorphisms associated with variation in pro-inflammatory cytokines levels (IL-1β C-511T and IL-6 C-174G) and risk for Alzheimer’s disease (APOEε4) in healthy adult volunteers (N = 80; age = 22-82 years). Volumes of three hippocampal subfields, cornu ammonis (CA) 1-2, CA3-dentate gyrus, and the subiculum were manually measured on high-resolution magnetic resonance images. Advanced age was differentially associated with smaller volume of CA1-2, whereas carriers of the T allele of IL-1β C-511T polymorphism had smaller volume of all hippocampal subfields than CC homozygotes did. Neither of the other genetic variants, nor diagnosis of hypertension was associated with any of the measured volumes. The results support the notion that volumes of age-sensitive brain regions may be affected by pro-inflammatory factors that may be targeted by therapeutic interventions.

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“…Intra- and inter-rater reliability coefficients are .90 or better (Hsu et al, 2002; Schuff et al, 2009b). The SNT method has been implemented by the Alzheimer’s Disease Neuroimaging Initiative (ADNI) (Schuff et al, 2009b), and SNT has been used in our prior work showing hippocampal volume correlates with memory performance ( r = .47) (Adamson et al, 2010). SNT total hippocampal volume, which includes hippocampal gray matter only and no nearby regions such as the parahippocampal gyrus (PHG), was chosen as the a priori primary ROI.…”

Section: Methodsmentioning

confidence: 99%

APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults older than 50 years

Taylor¹,

Scanlon²,

Farrell³

et al. 2014

Neurobiology of Aging

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Atrophy of the hippocampus and surrounding temporal regions occurs in Alzheimer’s disease (AD). APOE ε4, the major genetic risk factor for late-onset AD, has been associated with smaller volume in these regions before amyloidosis can be detected by AD biomarkers. To examine APOE ε4 effects in relation to aging, we performed a longitudinal MRI study involving cognitively normal adults (25 APOE ε4 carriers and 31 ε3 homozygotes), initially aged 51–75 years. We used growth curve analyses, which can provide information about APOE ε4-related differences initially and later in life. Hippocampal volume was the primary outcome; nearby medial temporal regions were secondary outcomes. BDNF val66met was a secondary covariate. APOE ε4 carriers had significantly smaller initial hippocampal volumes than ε3 homozygotes. Rate of hippocampal atrophy was not greater in the APOE ε4 group, even though age-related atrophy was detected in the overall sample. The findings add to the growing evidence that effects of APOE ε4 on hippocampal size begin early in life, underscoring the importance of early interventions to increase reserve.

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Apolipoprotein E ɛ4 influences on episodic recall and brain structures in aging pilots

Cited by 28 publications

References 37 publications

APOE ε4genotype predicts memory for everyday activities

APOE ε4genotype predicts memory for everyday activities

Volume of the hippocampal subfields in healthy adults: differential associations with age and a pro-inflammatory genetic variant

APOE-epsilon4 and aging of medial temporal lobe gray matter in healthy adults older than 50 years

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