Longitudinal Memory Performance During Normal Aging: Twin Association Models of APOE and Other Alzheimer Candidate Genes

Reynolds, Chandra A.; Prince, Jonathan A.; Feuk, Lars; Brookes, Anthony J.; Gatz, Margaret; Pedersen, Nancy L.

doi:10.1007/s10519-005-9027-6

Cited by 35 publications

(33 citation statements)

References 46 publications

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“…These results echo the findings of a meta-analysis of cross-sectional studies by, 11 which concluded that, in the general aging population, the influence of apolipoprotein E genotype is small in magnitude and specific to certain domains of cognitive function. The findings of the current study, together with other, 11,15 but not all, 13,20 comparable observations, raise the possibility that apolipoprotein E 4 is a determinant of the trajectory of memory loss (and consequent cognitive decline) in the elderly general population. Table 1 for baseline models and Table 2 for change models.…”

Section: Discussionsupporting

confidence: 77%

“…[10][11][12][13][14][15] The underlying mechanism is thought in part to be more beta-amyloid deposits in the presence of E 4 than with other isoforms of the apolipoprotein, 8,43 although it is increasingly clear that apolipoprotein E phenotype has multiple effects on neurobiology. 21 Alzheimer's disease, characterized by episodic memory loss, is likely to be the end result of a long subclinical degenerative process, and the question arises as to when and how apolipoprotein E 4 contributes to this less-obvious pathology.…”

Section: Discussionmentioning

confidence: 99%

“…10,11 Longitudinal data also show good evidence of an association between E 4 and risk of Alzheimer's disease and dementia, 12,13 although the rela-tionship between the E 4 genotype and age-associated cognitive decline without dementia has been less clear. 14 One study 15 found a link in twins between E 4 and deterioration of working memory, and others have reported greater decline in verbal memory and executive function in those with E 4 . [16][17][18] In contrast, another study 13 found that possession of E 4 did not modify progression of cognitive decline in the preclinical period of Alzheimer's disease, and a third study 19 reported slower rates of memory decline in E 4 carriers.…”

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confidence: 99%

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Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Packard

Westendorp

Stott

et al. 2007

J American Geriatrics Society

114

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OBJECTIVE:To determine the influence of apolipoprotein E on cognitive decline in a cohort of elderly men and women. DESIGN: Prospective study. SETTING: Scotland, Ireland, and the Netherlands. PARTICIPANTS: Five thousand eight hundred four subjects aged 70 to 82 from the Prospective Study of Pravastatin in the Elderly at Risk (PROSPER). MEASUREMENTS: Subjects were assessed at baseline and over a mean 3.2-year (range 0.7-4.2) follow-up for memory (Picture-Word Recall), speed of information processing (Stroop and Letter-Digit Coding), global cognitive function (Mini-Mental State Examination), and activities of daily living. RESULTS: At baseline, subjects with apolipoprotein E 4 versus those without E 4 had poorer memory performance (mean score difference À 0.20 (95% confidence interval (CI) 5 À 0.31 to À 0.09) for immediate recall and À 0.32 (95% CI 5 À 0.48 to À 0.16) for delayed recall and slower information processing (difference in Stroop, 2.79 seconds, (95% CI 5 1.20-4.28); Letter-Digit score, À 0.36, (95% CI 5 À 0.77-0.05). Subjects with apolipoprotein E 4 showed a greater decline in immediate ( À 0.22, 95% CI 5 À 0.33 to À 0.11) and delayed ( À 0.30, 95% CI 5 À 0.46 to À 0.15) memory scores but no significant change in speed of information processing (Stroop, P 5.17; Letter-Digit, P 5.06). Memory scores decreased 2.5% from baseline in those without E 4 , 4.3% in E 4 heterozygotes (P 5.01 for immediate and P 5.03 for delayed, vs no E 4 ) and 8.9% to 13.8% in E 4 homozygotes (P 5.04 for immediate and P 5.004 for delayed, vs heterozygotes). Apolipoprotein E 4 was associated with greater decline in instrumental activities of daily living (Po.001). Cognitive decline was not associated with lipoprotein levels. CONCLUSION: Findings in PROSPER indicate that E 4 is associated with more-rapid cognitive decline and may, therefore, predispose to dementia. J Am Geriatr Soc 55:1777-1785, 2007. Key words: memory; dementia; trial; statin A major challenge in the quest to promote healthy aging is to uncover the determinants of cognitive decline in the general population and the risk factors that lead to the development of frank dementia. Although age is the main predictor of cognitive function, investigators have also reported that a history of hypertension, diabetes mellitus, stroke, depression, and lack of physical activity are factors. [1][2][3][4][5][6] The apolipoprotein E phenotype (apolipoprotein E is coded by a gene (e) that exhibits allelic variants e 2 , e 3 , and e 4 ) has been linked consistently and strongly to the appearance of Alzheimer's disease and to some aspects of cognitive decline in elderly cohorts. 1,2,[5][6][7][8][9] Inheritance of E 4 (the product of e 4 ) especially in the homozygous form, has been associated in cross-sectional studies with risk of Alzheimer's disease and poorer global cognitive function, episodic memory, and executive function, although the magnitude of the effect is modest. 10,11 Longitudinal data also show good evidence of an association between E 4 and risk of Alzheimer's diseas...

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Section: Discussionsupporting

confidence: 77%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Packard

Westendorp

Stott

et al. 2007

J American Geriatrics Society

114

View full text Add to dashboard Cite

show abstract

“…However, in the former study the amplified decline was observed for e4 homozygotes, whereas in the present study we considered e4 heteroand homzygotes together for sample size considerations. Similarly, A2M and 5HTR2A were associated with mean differences in episodic figural recognition change over age (Thurstone Picture Memory) in prior studies (Reynolds, Jansson, et al, 2006;Reynolds, Prince, et al, 2006) but in the present case neither were identified as 'variability genes' for episodic figural recognition change.…”

Section: Discussionsupporting

confidence: 53%

Genotype–Environment Interactions: Cognitive Aging and Social Factors

Reynolds¹,

Gatz

Berg

et al. 2007

Twin Res Hum Genet

Self Cite

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The possibility of genotype–environment interaction for memory performance and change was examined in 150 monozygotic (MZ) twin pairs from the Swedish Adoption Twin Study of Aging (SATSA). We used an MZ twin pair difference approach to examine the possibility that genotype was associated with intrapair variability and thus suggestive of genotype–nonshared environment interactions. Multiple ‘variability genes’ were found for longitudinal change in a semantic memory task including candidates coding for apolipoprotein E (APOE) and estrogen receptor alpha (ESR1) as well as serotonin candidates (HTR2A and 5HTT). One candidate also related to variability in change in episodic memory (5HTT). Of the significant associations observed, generally results indicated that MZ pairs who carry putative risk alleles were less variable than noncarriers, suggesting that noncarriers may be more sensitive to environmental contexts. We sought to ‘contextualize’ the possible nonshared environmental influences for found gene–environment (G × E) effects by considering intrapair differences in measured social and stress factors, including social support, life events and depressive symptoms. Results suggested that nonshared environmental influences associated with depressive symptoms may moderate the G × E relationship observed for ESR1 and APOE and longitudinal semantic memory change whereby noncarriers of putative risk alleles may be relatively more sensitive to depressionevoking environmental contexts than carriers of the risk allele. Thus, the contexts that facilitate or reduce depressive symptoms may affect semantic memory resiliency dependent on genotype. Further work ought to consider larger sample sizes as well as consider additional social and contextual factors.

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“…Variation in DRD4 and COMT (a gene involved in metabolizing dopamine) is implicated in better attentional control and working memory performance, as well as stronger neural activation in these frontal regions. 79,80 In addition, although it has been studied in regards to dementia in adulthood, the APOE gene (apolipoprotein E) has been implicated in typical variation in adults' working memory performance as well 81,82 and may emerge as a gene that explains variation in working memory performance even in childhood.…”

Section: Self-regulation and Genetic Mechanismsmentioning

confidence: 99%

Biological Systems and the Development of Self-Regulation: Integrating Behavior, Genetics, and Psychophysiology

Bell

Deater‐Deckard

2007

Journal of Developmental &Amp; Behavioral Pediatrics

142

124

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Self-regulation is the ability to control inner states or responses with respect to thoughts, emotions, attention, and performance. As such, it is a critical aspect of development and fundamental to personality and behavioral adjustment. In this review, we focus on attentional, cognitive, and emotional control as we discuss the genetic mechanisms and brain mechanisms that contribute to individual differences in self-regulation. We conclude with a discussion of the implications for deviations in the development of this complex construct and suggestions for future research. (J Dev Behav Pediatr 28:409-420, 2007) Index terms: self-regulation, controlled attention, temperament, brain mechanisms, genetic mechanisms Whatexpl ains the remarkable variation between children in how well they adapt to their ever changing environments? In part, the answer lies in self-regulation, a critical aspect of development in infancy, early childhood, and beyond. A set of developing regulatory processes appears to be fundamental to individual differences in personality development and behavioral adjustment 1-3 and includes biological components such as physiology, neurobiology, and genes, and situational components such as parenting, environment, and experience. 4,5 As such, self-regulation can be examined at many different levels and can have multiple definitions. 6 This necessarily makes self-regulation a complex construct and developmentalists have typically simplified the study of self-regulation by focusing only on one or two of these conceptual levels at a time, such as the regulation of emotion. 2,7 There is general agreement, however, that self-regulation operates at the physiological, attentional, emotional, cognitive, and behavioral levels. 1,8,9 In this review, we define self-regulation as the ability to control inner states or responses with respect to thoughts, emotions, attention, and performance. 6 Thus, our conceptualization of self-regulation could be described as cognitive control and emotion control. Within this conceptualization, we highlight attentional control as the mechanism for early developing self-regulation in both the cognitive and emotional domains. 10 -12 As such, we go beyond the typical focus on relationships between either cognitive functioning or attentional control and consequential emotion regulation 5,7 and provide a more dynamic view of self-regulatory processes. 11 Our focus in this review is on the biological components of developing self-regulation, as the situational and contextual components have been reviewed elsewhere. 6,7 We begin by highlighting the psychobiological framework that we use in conceptualizing regulatory processes. Then we discuss biological mechanisms of selfregulation associated with the development of specific cognitive and emotion behaviors. Because of our focus on psychobiology, we next examine genetic and brain mechanisms of self-regulation processes by integrating the functions associated with central nervous system and autonomic nervous system networks tha...

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Longitudinal Memory Performance During Normal Aging: Twin Association Models of APOE and Other Alzheimer Candidate Genes

Cited by 35 publications

References 46 publications

Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Genotype–Environment Interactions: Cognitive Aging and Social Factors

Biological Systems and the Development of Self-Regulation: Integrating Behavior, Genetics, and Psychophysiology

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Longitudinal Memory Performance During Normal Aging: Twin Association Models of APOE and Other Alzheimer Candidate Genes

Cited by 35 publications

References 46 publications

Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults

Association Between Apolipoprotein E4 and Cognitive Decline in Elderly Adults

Genotype–Environment Interactions: Cognitive Aging and Social Factors

Biological Systems and the Development of Self-Regulation: Integrating Behavior, Genetics, and Psychophysiology

Contact Info

Product

Resources

About

Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults

Association Between Apolipoprotein E₄ and Cognitive Decline in Elderly Adults