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| Article | Sample | Methods used | Relevant findings |
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| Bloss et al. [8] | 147 youth, age 11–16 | Assessment of verbal cognition and visuospatial processing | APOE ε4 carriers performed better than ε2 carriers on a test of visuospatial processing |
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| Marchant et al. [9] | 156 college students, age 18–30 | Assessment of spatial working memory, estimated IQ, immediate verbal memory, verbal fluency, sustained attention, and decision-making ability | APOE ε4 carriers showed an advantage over noncarriers on tests of verbal fluency and decision-making |
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| Noé et al. [10] | 82 patients currently with post-traumatic amnesia (PTA; mean age = 31.5) and 107 patients without PTA (mean age = 29.5) | Assessment of PTA severity, verbal memory, and working memory | APOE ε4 carriers were more severe at baseline but exhibited a steeper rate of improvement in working memory over time than noncarriers |
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| Dennis et al. [11] | 24 young adults (mean age = 21.3) | Functional MRI during the encoding portion of an object memory task followed by a recall session 24 hours later, and an assessment of memory, processing speed, attention, and executive functioning | APOE ε4 carriers and noncarriers performed similarly on all cognitivetests, while ε4 carriers showed more bilateral MTL activity and functional connectivity of MTL and posterior cingulate and perilimbic structures during memory encoding |
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| Filbey et al. [12] | 36 healthy adults, age 50–75 and 16 adults, age 19–32 | Functional MRI during a visual working memory task and an assessment of global cognition | APOE ε4 carriers and noncarriers did not differ in cognitive performance, while ε4 carriers showed more medial frontal and MTL activity compared to noncarriers during the working memory task. Older ε4 carriers also showed decreased activation compared to noncarriers in several frontal, parietal, temporal, and cingulate cortices |
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| Hiekkanen et al. [13] | 33 mild TBI patients (mean age = 44.2) | Structural MRI, assessment of PTA, and Glasgow Coma Scale ratings over a one year follow-up period | While MRI findings and PTA severity predicted TBI outcome after one year, APOE genotype was unassociated with TBI outcome |
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| Luciano et al. [14] | 1,091 participants in the Lothian Birth Cohort | Assessment of IQ at age 11 and measures of global cognition, working memory, nonverbal reasoning, construction, verbal fluency, and processing speed at age 70 | APOE genotype was unrelated to IQ at age 11, yet the ε4 allele was associated with lower processing speed, nonverbal reasoning, and general cognition measured at age 70 |
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| Ruiz et al. [15] | 412 participants, age 13–18 | Assessment of verbal and quantitative skills and problem solving ability | APOE genotype was not associated with cognition, but ε4 carriers who also had the MTHFR 677TT allele had lower quantitative and reasoning abilities |
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| Bloss et al. [16] | 109 youth, age 11–16 | Assessment of verbal cognition and visuospatial processing | APOE genotype was not associated with cognition, but ε4 carriers who also had a family history of AD had lower verbal and visuospatial abilities |
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| Acevedo et al. [17] | 50 youth, age 7–10 | Assessment of general intelligence, memory, attention, executive functioning, and visuospatial processing | APOE ε4 carriers were more likely to have been placed in intensive care after birth and had lower spatial memory abilities, especially among girls |
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| Filippini et al. [18] | 36 adults, age 20–35 | Structural MRI, perfusion MRI at rest, and functional MRI at rest and during a memory encoding task | APOE ε4 carriers showed more connectivity among default-mode network regions and more hippocampal activation during the memory task than noncarriers |
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| Kukolja et al. [4] | 18 healthy older adults (mean age = 60.5) | Functional MRI during a spatial contextual memory task | APOE ε4 carriers had poorer memory performance than noncarriers. ε4 carriers also more strongly activated prefrontal, temporal, and parietal regions during encoding than did noncarriers but showed less activation in prefrontal cortex during retrieval |
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| Trivedi et al. [19] | 155 healthy adults, age 18–84 | Functional MRI during episodic encoding and metacognitive self-appraisal tasks | APOE ε4 carriers showed increasing hippocampal activation with age during the memory task, while noncarriers showed age-related reductions in hippocampal activity |
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| Wierenga et al. [20] | 22 healthy older adults (mean age = 78.10) | Functional MRI during an object naming task | APOE genotype was unrelated to naming ability, yet ε4 carriers exhibited greater activity in the left fusiform, right perisylvian cortex, and bilateral medial prefrontal cortex than noncarriers |
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| Seidenberg et al. [21] | 69 healthy older adults, age 65–85 | Functional MRI during a semantic memory task | Those with an ε4 allele and family history of AD showed greater activations in bilateral cingulate, temporoparietal, and prefrontal regions than those without risk factors. ε4 carriers also showed greater recruitment of right middle frontal regions |
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| Woodard et al. [22] | 57 older adults, age 65–85 with or without amnestic MCI | Functional MRI during a semantic memory task | Those with an ε4 allele and family history of AD displayed increased activation in temporoparietal, hippocampal, and posterior cingulate regions than those without risk factors. MCI patients showed similar patterns along with enhanced frontal recruitment |
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| Bartrés-Faz et al. [23] | 32 older adults with mild memory impairments (mean age = 66.83) | Functional MRI during a face-name learning task | APOE ε4 carriers showed increased connectivity of the hippocampus with anterior cingulate, postcentral gyrus, and caudate nucleus during encoding compared to noncarriers |
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| Borghesani et al. [24] | 14 healthy older adults | Functional MRI during a visuospatial memory task | APOE ε4 carriers showed less MTL activation during encoding than noncarriers despite equal performance |
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| Xu et al. [25] | 74 healthy adults, age 50–65 | Functional MRI during an episodic face recognition task | APOE ε4 carriers showed reduced activation in posterior and anterior cingulate and precuneus than noncarriers during recall |
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| Suthana et al. [26] | 32 healthy older adults (mean age = 61.1) | Functional MRI during a word memory task | APOE ε4 carriers displayed reduced hippocampal activation during encoding than noncarriers |
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| Welsh-Bohmer et al. [27] | 507 healthy older adults, age 66–103 | Assessment of object naming, verbal fluency, memory, construction, processing speed, and global cognition | APOE genotype was unrelated to all measures of cognition |
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| Adamson et al. [28] | 50 healthy pilots, age 50–76 | Structural MRI and assessment of memory | APOE ε4 carriers performed more poorly on visual paired associate recall than noncarriers but showed no structural brain differences |
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| Debette et al. [29] | 717 healthy adult offspring from the Framingham cohort (mean age = 59) | Structural MRI, assessment of memory, abstract reasoning, and mental flexibility, and determination of parental dementia | APOE ε4 carriers were more likely to have a parent with dementia. Among ε4 carriers, parental dementia was associated with lower memory performance |
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| Honea et al. [30] | 53 healthy older adults age, 60 and older | Structural MRI, diffusion tensor imaging, and an assessment of memory, language, executive functioning, and visuospatial ability | APOE ε4 carriers performed more poorly on measures of memory and working memory and had smaller hippocampi and parahippocampal FA |
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| Caselli et al. [31] | 815 healthy adults age, 21–97 | A longitudinal assessment of long-term memory, global cognition, verbal fluency, and visuospatial abilities | APOE ε4 carriers were found to experience memory decline in their 50’s, while noncarriers did not show decline until their 70’s. A dose-dependent effect was found in which ε4 homozygotes displayed earlier memory decline than heterozygotes. ε4 carriers showed steeper decline than noncarriers in memory, global cognition, and visuospatial processing |
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| De Blasi et al. [32] | 620 healthy older adults, age 65–85 | Assessment of memory and global cognition | While APOE ε4 was associated with memory encoding and recall, it was unrelated to global cognition |
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| Knopman et al. [33] | 1130 adults (mean age = 59) | Assessment of memory, verbal fluency, processing speed, and vascular risk factors | APOE ε4 carriers exhibited increased decline in processing speed and memory compared to noncarriers |
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| Mungas et al. [34] | 369 older adults (mean age = 74.3) | Assessment of object naming, verbal fluency, memory, and working memory | APOE ε4 carriers exhibited lower episodic memory scores at baseline and increased decline in memory and executive functioning than noncarriers |
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| Walhovd et al. [35] | 161 older adults, age 55–90 | Structural MRI, FDG-PET, and an assessment of memory | APOE ε4 allele was associated with poorer recognition memory beyond imaging variables |
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| Hayden et al. [36] | 2957 older adults (mean age = 74) | Longitudinal assessment of global cognition and family history of dementia | APOE ε4 carriers had lower baseline global cognitionand steeper decline in cognition than noncarriers |
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| Whitehair et al. [37] | 516 amnestic MCI patients, age 55–90 | Longitudinal assessment of global cognition, memory, processing speed, verbal fluency, working memory, naming, and functioning | APOE ε4 carriers had lower baseline scores on nearly every assessment and also showed steeper declines in nearly every domain |
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| Yaffe et al. [38] | 2509 healthy older adults, age 70–79 | Longitudinal assessment of global cognition and health variables | APOE ε4 allele was associated with likelihood of cognitive decline |
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| Thambisetty et al. [39] | 94 healthy older adults (mean age = 69.2) | Longitudinal structural MRI, PET imaging, and assessment of memory, verbal intelligence, verbal fluency, attention, working memory, and executive functioning | APOE ε4 carriers performed more poorly on category fluency and also had greater decline in regional cerebral blood flow, particularly in areas commonly implicated in AD |
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| Raz et al. [40] | 189 healthy adults, age 18–82 | Assessment of fluid intelligence, memory, executive functioning, and processing speed | APOE ε4 carriers evidenced greater age-related interference effects in a Stroop task than noncarriers |
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| Barabash et al. [41] | 89 amnestic MCI patients (mean age = 79) and 90 healthy adults (mean age = 76) | Longitudinal assessment of cognitive diagnosis | APOE ε4 allele was associated with higher risk of developing MCI, but not AD |
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| Wang et al. [42] | 20 healthy older adults (mean age = 75) and 58 amnestic MCI patients (mean age = 76.6) | Longitudinal structural MRI and an assessment of global cognition, memory, attention, language, construction, and abstract thinking | APOE ε4 allele was unassociated with rate of decline in cognition or brain volumes |
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| Heun et al. [43] | 200 healthy older adults (mean age = 80.3) | Longitudinal assessment of cognitive diagnosis, global cognition, memory, construction, attention, and language | APOE ε4 allele was unassociated with likelihood of conversion to MCI |
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| Carrión-Baralt et al. [44] | 87 nonagenarians | Assessment of global cognition, memory, naming, verbal fluency, attention, and processing speed | APOE ε4 carriers displayed higher global cognition, attention, visuospatial processing, naming, praxis, and memory encoding than noncarriers |
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| Kozauer et al. [45] | 659 adults (mean age = 58.4) | Longitudinal assessment of global cognition and memory | APOE ε4 carriers in the younger cohort, who were in their 50’s, showed increased decline in memory and global cognition compared to noncarriers. However, older ε4 carriers in their 70’s showed no cognitive differences from noncarriers |
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