Age-related differences in memory and executive functions in healthy APOE ɛ4 carriers: The contribution of individual differences in prefrontal volumes and systolic blood pressure

Bender, Andrew R.; Raz, Naftali

doi:10.1016/j.neuropsychologia.2011.12.025

Cited by 49 publications

(45 citation statements)

References 97 publications

(124 reference statements)

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“…In a large epidemiological study of over 500 subjects in Rotterdam, den Hiejer et al (2012) found a significant association between hippocampal volume, white matter lesions and diastolic blood pressure. This finding, however, has not been confirmed by other studies (Bender and Raz 2012; Gattringer et al 2012) which also examined blood pressure measures and in at least one study (Bender and Raz 2012) found associations with prefrontal regions, but not hippocampus.…”

Section: Hippocampal Volumecontrasting

confidence: 65%

Structural Imaging Measures of Brain Aging

2014

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During the course of normal aging, biological changes occur in the brain that are associated with changes in cognitive ability. This review presents data from neuroimaging studies of primarily “normal” or healthy brain aging. As such, we focus on research in unimpaired or nondemented older adults, but also include findings from lifespan studies that include younger and middle aged individuals as well as from populations with prodromal or clinically symptomatic disease such as cerebrovascular or Alzheimer’s disease. This review predominantly addresses structural MRI biomarkers, such as volumetric or thickness measures from anatomical images, and measures of white matter injury and integrity respectively from FLAIR or DTI, and includes complementary data from PET and cognitive or clinical testing as appropriate. The findings reveal highly consistent age-related differences in brain structure, particularly frontal lobe and medial temporal regions that are also accompanied by age-related differences in frontal and medial temporal lobe mediated cognitive abilities. Newer findings also suggest that degeneration of specific white matter tracts such as those passing through the genu and splenium of the corpus callosum may also be related to age-related differences in cognitive performance. Interpretation of these findings, however, must be tempered by the fact that comorbid diseases such as cerebrovascular and Alzheimer’s disease also increase in prevalence with advancing age. As such, this review discusses challenges related to interpretation of current theories of cognitive aging in light of the common occurrence of these later-life diseases. Understanding the differences between “Normal” and “Healthy” brain aging and identifying potential modifiable risk factors for brain aging is critical to inform potential treatments to stall or reverse the effects of brain aging and possibly extend cognitive health for our aging society.

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“…While previous studies have also shown that ApoE4 confers additional risk for poorer cognition, 21,22,32 the finding that those who were ApoE4- were more likely to produce erroneous content at verbal recall raises the question of a greater awareness of missing information, and the possible use of compensatory strategies that lead to more errors but better mask the lack of recalled information. Another interesting finding was that women who were ApoE4+ were significantly more likely to have more new verbal memory errors than ApoE4+ men, again suggesting a compensatory strategy for lower recall of presented information.…”

Section: Discussionmentioning

confidence: 89%

Mid-life Cardiovascular Risk Impacts Memory Function

Gupta

Preis

Beiser

et al. 2015

Alzheimer Disease &Amp; Associated Disorders

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Introduction This study incorporates unique error response analyses with traditional measures of memory to examine the association between mid-life cardiovascular risk factors (CVRF) and later-life memory function. Methods The Framingham Stroke Risk Profile (FSRP), a composite score of cardiovascular risk, was assessed in 1755 Framingham Offspring participants (54% women, mean age=54±9 years) from 1991-1995. Memory tests including Logical Memory (LM) and Visual Reproductions (VR) were administered from 2005-2008. Linear and logistic regression examined the association between FSRP and memory measures. Interaction between presence of the ApoE4 allele and each FSRP component on the memory measures was also assessed. Results FSRP and the individual components of age, sex, and smoking were related to lower standard scores of memory. The new error response analyses reinforced the standard analyses and also identified new relationships. Participants with diabetes were found to make more errors on LM, and those with a history of smoking were found to make more errors on VR. Lastly, ApoE4+ smokers experienced significant verbal memory loss whereas ApoE4- smokers did not. Conclusion Middle-aged healthy adults with CVRF including diabetes, history of smoking, and ApoE4 positivity were found to have greater later-life memory impairments.

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“…Bender and Raz [74] found than even young APOE4 carriers exhibited a higher vascular risk, poorer cognitive performance, and reduced prefrontal volumes, and this effect was more noticeable with age. The meta-analysis by Small et al [62] revealed APOE4 influences on a series of cognitive domains that were also modulated by age.…”

Section: Discussionmentioning

confidence: 99%

<b><i>APOE</i></b> ε4 Genotype and Cognitive Reserve Effects on the Cognitive Functioning of Healthy Elders

López

Turrero

Delgado

et al. 2017

Dement Geriatr Cogn Disord

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Aim: To test the association between cognitive performance and APOE genotype, and to assess potential modifications of this association by sociodemographic and neuroanatomical factors in a sample of 74 healthy elders. Methods: Firstly, we explored the isolated role of the APOE ɛ4 genotype (i.e., APOE4) in different neuropsychological tests, and then the effects of its interaction with sociodemographic (i.e., age, gender, and educational level) and neuroanatomical (i.e., hippocampal volumes) variables. Subsequently, we performed the same analyses after dividing the sample into two subgroups according to their Mini-Mental State Examination scores (control-high group ≥29 and control-low group < 29). Results: In the whole group, APOE4 carriers exhibited a significantly poorer execution in several cognitive domains including global cognitive functioning, episodic memory, verbal fluency, and naming. This effect was more noticeable in older and less educated subjects. The separated analyses revealed that APOE4 carriers in the control-low group exhibited lower scores in global cognitive functioning and episodic memory, while no effects were observed in the control-high group. Neither gender nor hippocampal volumes showed a significant interaction effect with APOE genotype. Conclusions: Current results point out that APOE4 genotype influences healthy aged cognition, although factors such age or educational attainment seem to modulate its effects.

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“…For example, we did not account for ApoE genotype, which may explain a significant proportion of variance in regional hippocampal volumes and memory by itself (Mueller & Weiner, 2009) or in interaction with elevated vascular risk (Bender & Raz, 2012a, 2012b. In light of the power limitations in this study, we restricted the number of variables and estimated parameters to test specific hypotheses regarding associations between CA1-2 and CA3-4/DG subfield volumes and memory.…”

Section: Limitations and Future Directionsmentioning

confidence: 99%

Vascular Risk Moderates Associations between Hippocampal Subfield Volumes and Memory

Bender

Daugherty

Raz

2013

Journal of Cognitive Neuroscience

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Advanced age and vascular risk negatively affect episodic memory. The hippocampus (HC) is a complex structure, and little is known about the roles of different HC regions in age-related memory declines. Using data from an ongoing longitudinal study, we investigated whether memory functions are related to volumes of specific HC subregions (CA1-2, CA3-4/dentate gyrus, and subiculum). Furthermore, we inquired if arterial hypertension, a common age-related vascular risk factor, modifies age-related differences in HC regional volumes, concurrent memory performance, and improvement in memory over multiple administrations. Healthy adults (n = 49, 52-82 years old) completed associative recognition and free recall tasks. In grouped path models, covariance structures differed between hypertensive and normotensive participants. Whereas larger CA3-4/dentate gyrus volumes predicted greater improvement in associative memory over repeated tests regardless of vascular risk, CA1-2 volumes were associated with improvement in noun recall only in hypertensive participants. Only among hypertensive participants, CA1-2 volumes negatively related to age and CA3-4/dentate gyrus and CA1-2 volumes were associated with performance at the last measurement occasion. These findings suggest that relatively small regions of the HC may play a role in age-related memory declines and that vascular risk factors associated with advanced age may modify that relationship.

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“…Data from literature identify APOE genotype as a strong genetic risk factor for various ageing-related diseases, including dementia. Carriers of ε4 allele have an increased risk of developing cognitive disabilities [3,4], whereas ε2 allele carriers are relatively protected [5,6].…”

Section: Introductionmentioning

confidence: 99%

Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment

Niculescu¹,

Toma²,

Ianăş

et al. 2012

Open Life Sciences

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The association of cholesteryl ester transfer protein (CETP) and apolipoprotein E (APOE) gene polymorphisms with mild cognitive impairment (MCI) is under debate. Our aim was to evaluate the relationship between APOE and CETP genotypes with healthy ageing. We analysed 267 elderly subjects (55 to 80+ years), 163 with MCI and 104 healthy, and 50 healthy control subjects (35 to 55 years) from a Romanian population. Biochemical parameters and thyroid hormones were assayed in plasma. APOE and CETP TaqIB gene polymorphisms were determined. Elderly subjects had higher frequency of ɛ3/ɛ2 genotype (14.6% vs. 4%, P<0.001) than controls. Elderly subjects with MCI had lower high density lipoproteins (HDL) cholesterol (P=0.031), apoA-I (P=0.018), T3 (P=0.002), T4 (P=0.028) and TSH (P=0.001) hormone levels, higher systolic blood pressure (P=0.005), lower frequency of CETP B2 allele than the age-matched subjects. Healthy elderly subjects had CETP B2 allele associated with higher plasma apoA-I (P=0.021), lower circulating collagen (P=0.001) levels, and an increased frequency of the combined APOE ɛ2- CETP B2 genotype (18.3%) relative to MCI elderly subjects (7.6%, P=0.011). Healthy elderly subjects are characterized by higher HDL cholesterol, apoA-I levels and higher frequency of the combined APOE ɛ2 and CETP B2 alleles, indicating this pattern as representative for healthy ageing.

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Age-related differences in memory and executive functions in healthy APOE ɛ4 carriers: The contribution of individual differences in prefrontal volumes and systolic blood pressure

Cited by 49 publications

References 97 publications

Structural Imaging Measures of Brain Aging

Mid-life Cardiovascular Risk Impacts Memory Function

<b><i>APOE</i></b> ε4 Genotype and Cognitive Reserve Effects on the Cognitive Functioning of Healthy Elders

Vascular Risk Moderates Associations between Hippocampal Subfield Volumes and Memory

Gene polymorphisms of CETP and apolipoprotein E in elderly subjects with cognitive impairment

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