Impact of APOE status on cognitive maintenance in healthy elderly persons

Zehnder, Antoinette E.; Bläsi, Stefan; Berres, Manfred; Monsch, Andreas U.; Stähelin, Hannes; Spiegel, René

doi:10.1002/gps.2080

Cited by 43 publications

(33 citation statements)

References 41 publications

(45 reference statements)

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“…Additionally, Martin and colleagues [3] conducted a systematic review of the cognitive training intervention effects on various cognitive functioning domains (i.e., memory, EF, attention, and processing speed), finding that, versus a non-treatment control condition, cognitively intact older adults receiving cognitive training significantly improved their immediate and delayed verbal recall scores. Our results also contradict those obtained by Zehnder et al [45], which indicated that practice effects in APOE 4 allele carriers were inferior in most tested areas compared to the effects found in the noncarriers, especially in episodic memory functions (immediate verbal learning and delayed recall).…”

Section: Discussioncontrasting

confidence: 99%

“…Moreover, they observed that the noncarriers in the cognitively healthy NDFAM group benefited from CS, as evidenced by improved cognitive performance (particularly, in visuospatial memory function), whereas the APOE 4 carriers showed no significant improvement. Finally, a study carried out by Zehnder et al [45] measured the practice effect on cognitive performance by applying two neuropsychological assessment instruments in physically and mentally cognitively intact aged people (with a mean age of 70 years): initially at baseline and then, two years later. Their results indicated that the 4 allele of the APOE gene had a negative impact on cognitive performance, notably on episodic memory tasks (such as immediate verbal learning and delayed recall).…”

Section: Introductionmentioning

confidence: 99%

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APOE ε4 Modulation of Training Outcomes in Several Cognitive Domains in a Sample of Cognitively Intact Older Adults

López-Higes

Rodríguez-Rojo

Prados

et al. 2017

JAD

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Abstract.Background: Most research points to the 4 allele of the apolipoprotein E (APOE) gene as the most recognizable genetic risk factor associated with Alzheimer's disease pathogenesis. It has been also suggested that the APOE 4 allele has a negative influence on cognitive functioning, which begins long before cognitive impairment becomes manifest. However, still, little is known about the APOE 4 interaction with cognitive intervention programs. Objective: The main goal of this study was to explore whether there was a differential APOE genotype modulation effect after cognitive training in different domains, such as language comprehension, executive functions, and memory. Contrary to other studies, hippocampal volume was controlled for. Methods: Fifty older adults (65+ years; 30 women and 20 men) participated in a multi-domain cognitive training that involved 30 sessions taking place over 12 weeks. Half of the participants were APOE 4 carriers. The control group was matched in age, gender, normalized hippocampal volume, cognitive reserve, Mini-Mental State Examination score, and Geriatric Depression Scale-Short Version. Results: The study revealed that there were consistent treatment benefits in complex sentence comprehension (noncanonical sentences and sentences with two propositions), a domain that was not directly trained, but only in the APOE 4 noncarrier group. Conclusion: Genetic profile modulates training outcomes in sentence comprehension.

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Section: Discussioncontrasting

confidence: 99%

Section: Introductionmentioning

confidence: 99%

APOE ε4 Modulation of Training Outcomes in Several Cognitive Domains in a Sample of Cognitively Intact Older Adults

López-Higes

Rodríguez-Rojo

Prados

et al. 2017

JAD

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“…The lifetime risk of AD at the age of 85 years without reference to APOE genotype is about five-fold lower than that for ApoE 4 carriers [57]. Moreover, APOE 4 possession is associated with earlier and faster cognitive decline in patients with AD [58], and may impact cognitive performance, notably episodic memory functions, in cognitively healthy aged persons [59]. APOE-status is therefore a critical selection and matching variable in longitudinal studies of dementia.…”

Section: Discussionmentioning

confidence: 99%

Neuropsychological Signs of Alzheimer's Disease 8 Years Prior to Diagnosis

Schmid¹,

Taylor

Foldi

et al. 2013

JAD

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Abstract. We investigated the earliest neuropsychological changes in Alzheimer's disease (AD) by comparing the baseline performance of 29 individuals who subsequently developed AD within an average of 7.91 ± 2.70 years with 29 pairwisematched individuals who remained cognitively healthy (NC). We hypothesized that subtle, qualitative changes in cognition precede clinical AD by several years, and therefore examined subjective as well as standard quantitative measures of cognition, in addition to subjective estimates of mood and medical status. Participants were selected from the 825 members of the longitudinal BASEL study (BAsel Study on the ELderly), all of whom had been ApoE-genotyped and received comprehensive bi-annual neuropsychological assessments. Within 13 years, 29 were diagnosed with probable AD. Each individual who progressed to AD (AD-P) was pairwise matched to a NC participant based on age, education, demographic status, observation period, and, importantly, ApoE genotype. A regression analysis using the lasso technique identified which of 115 neuropsychological variables best discriminated baseline NC from baseline AD-P performance. This analysis yielded eleven neuropsychological variables that optimally discriminated the two groups (correct classification rate: 60.4%): 1) Intrusions and 2) response bias in verbal learning and memory tasks; 3) delayed figure recall; 4-6) three Wechsler Adult Intelligence Scale (WAIS) Block Design subtest variables; 7-8) number of errors and repetitions on letter fluency; and 9-11) self-report of memory problems, a feeling of sadness, and cardiac problems. These results suggest that the preclinical neuropsychological cascade to AD includes subtle but identifiable qualitative impairments in verbal and visual memory, visuospatial processing, error control, and subjective neuropsychological complaints.

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“…In addition, more than a decade of research has also demonstrated deficits in various cognitive domains in non-demented ɛ4 carriers in comparison with non-ɛ4 carriers in middle and old adulthood (e.g., Berr et al, 1996;Cantu, 2000; De Blasi et al, 2009;Driscoll, McDaniel, & Guynn, 2005;Greenwood, Lambert, Sunderland, & Parasuraman, 2005;Helkala et al, 1995;Lavretsky et al, 2003;Negash et al, 2007; Packard et al, 2007;Reed et al, 1994;Small et al, 1999;Wetter et al, 2005;Zehnder et al, 2009). …”

Section: Discussionmentioning

confidence: 99%

APOE ε4 and cognitive function in early life: A meta-analysis.

Ihle¹,

Bunce²,

Kliegel³

2012

Neuropsychology

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Introduction. It is well established that the Apolipoprotein E (APOE) ε4 allele is associated with cognitive impairment and Alzheimer's disease in old age. By contrast, several studies have demonstrated cognitive benefits in young ε4 carriers. It is therefore possible that the ε4 allele exhibits a pleiotropic association with cognition across the lifespan where ε4-related benefits in youth reverse in later life to become risk factors for cognitive impairment and dementia in later life. To date though, there has been no broad quantitative review of work assessing APOE-cognition associations in children, adolescents and young adults.Methods. Based on 20 studies investigating cognitive performance in ε4 carrying young persons and their non-ε4 counterparts, a meta-analytic study was conducted to examine APOE ε 4-related differences in cognitive performance. Additionally, we assessed whether the level of executive demands affected the strength of association between the ε4 allele and cognitive measure.Results. In all analyses, estimated APOE ε4 related population effect sizes did not reliably differ from zero. Furthermore, the level of executive demands of the task did not affect this finding. Conclusion.We found no APOE ε4-related cognitive benefits in young adults, adolescents, and children and findings were not moderated by the level of executive demands in a cognitive task. Given the current empirical evidence therefore, suggestions that APOE ε4 exhibits a pleiotropic association with cognition across the lifespan should be treated with caution.Key words: Apolipoprotein E; APOE; cognition; cognitive performance; executive processes; young adults; adolescence; childhood; meta-analysis 3 Apolipoprotein E (APOE) is a protein that plays an important role in cholesterol transportation (for reviews of the mechanisms and functions of APOE in the nervous system, see Czyzewski, Pfeffer, & Barcikowska, 1998; Harris et al., 2003;Lahiri, Sambamurti, & Bennett, 2004;Mahley, 1988;Menzel, Kladetzky, & Assmann, 1983;Rocchi, Pellegrini, Siciliano, & Murri, 2003;Rubinsztein, 1995). The gene coding for APOE is located on chromosome 19 and has three alleles, ɛ2, ɛ3, and ɛ4.APOE ɛ4 is well established as a risk factor for Alzheimer's disease (AD: Corder et al., 1993; Saunders et al, 1993), where persons possessing the ɛ4 allele have a three to four times higher risk for developing AD (see also Farrer et al., 1997, for a meta-analysis on effects of age, sex, and ethnicity on the association between APOE genotype and AD).Moreover, various studies have found that APOE ɛ4 is strongly associated with cognitive decline among persons who have been diagnosed with AD (e.g., Hirono, Hashimoto, Yasuda, Kazui, & Mori, 2003;Marra et al., 2004;Martins, Oulhaj, De Jager, & Williams, 2005;Plassman & Breitner, 1996). In addition, more than a decade of research has also demonstrated deficits in various cognitive domains in non-demented ɛ4 carriers in comparison with non-ɛ4 carriers in middle and old adulthood (e.g., Berr et al., 1996;Cantu, ...

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Impact of APOE status on cognitive maintenance in healthy elderly persons

Cited by 43 publications

References 41 publications

APOE ε4 Modulation of Training Outcomes in Several Cognitive Domains in a Sample of Cognitively Intact Older Adults

APOE ε4 Modulation of Training Outcomes in Several Cognitive Domains in a Sample of Cognitively Intact Older Adults

Neuropsychological Signs of Alzheimer's Disease 8 Years Prior to Diagnosis

APOE ε4 and cognitive function in early life: A meta-analysis.

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