Context-specific memory and apolipoprotein E (ApoE) [varepsilon]4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease

Lévy, J; Bergeson, Judy; Putnam, Karen; Rosen, Virginia M.; Cohen, Robert M.; Lalonde, François; Mirza, Nadeem Q.; Linker, Gary; Sunderland, Trey

doi:10.1017/s1355617704103044

Cited by 42 publications

(33 citation statements)

References 87 publications

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“…A number of studies have shown that nondemented older adults with a positive family history for AD perform significantly worse than those with a negative family history on tests of episodic memory (Bondi et al 1994;Caselli et al 2004;La Rue et al 1992;Levy et al 2004). …”

Section: Neuropsychological Studies Of the Prodromal Period Of Alzheimentioning

confidence: 99%

Neuropsychological Contributions to the Early Identification of Alzheimer’s Disease

et al. 2008

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A wealth of evidence demonstrates that a prodromal period of Alzheimer's disease (AD) exists for some years prior to the appearance of significant cognitive and functional declines required for the clinical diagnosis. This prodromal period of decline is characterized by a number of different neuropsychological and brain changes, and reliable identification of individuals prior to the development of significant clinical symptoms remains a top priority of research. In this review we provide an overview of those neuropsychological changes. In particular, we examine specific domains of cognition that appear to be negatively affected during the prodromal period of AD, and we review newer analytic strategies designed to examine cognitive asymmetries or discrepancies between higher-order cognitive functions versus fundamental skills. Finally, we provide a critical examination of the clinical concept of Mild Cognitive Impairment and offer suggestions for an increased focus on the impact of cerebrovascular disease (CVD) and CVD risk during the prodromal period of AD.

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Section: Neuropsychological Studies Of the Prodromal Period Of Alzheimentioning

confidence: 99%

Neuropsychological Contributions to the Early Identification of Alzheimer’s Disease

et al. 2008

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“…For instance, ε3/3 homozygotes with a +FH have a 30% chance of developing AD, whereas ε3/4 heterozygotes with a +FH have a 46% lifetime risk and ε4/4 homozygotes with +FH have a 61% likelihood of developing AD . Cognitively, several studies have shown that nondemented older adults with a positive family history for AD perform significantly worse than those with a negative family history on tests of episodic memory (Bondi et al, 1994;Caselli et al, 2004;La Rue et al, 1992;Levy et al, 2004).…”

Section: Functional Mri Patterns Of Activity Associated With Risk Of mentioning

confidence: 99%

Use of Functional Magnetic Resonance Imaging in the Early Identification of Alzheimer's Disease

Wierenga

Bondi

2007

Neuropsychol Rev

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A growing body of evidence suggests that a preclinical phase of Alzheimer's disease (AD) exists several years or more prior to the overt manifestation of clinical symptoms and is characterized by subtle neuropsychological and brain changes. Identification of individuals prior to the development of significant clinical symptoms is imperative in order to have the greatest treatment impact by maintaining cognitive abilities and preserving quality of life. Functional magnetic resonance imaging (fMRI) offers considerable promise as a non-invasive tool for detecting early functional brain changes in asymptomatic adults. In fact, evidence to date indicates that functional brain decline precedes structural decline in preclinical samples. Therefore, fMRI may offer the unique ability to capture the dynamic state of change in the degenerating brain. This review examines the clinical utility of blood oxygen level dependent (BOLD) fMRI in those at risk for AD as well as in early AD. We provide an overview of fMRI findings in at-risk groups by virtue of genetic susceptibility or mild cognitive decline followed by an appraisal of the methodological issues concerning the diagnostic usefulness of fMRI in early AD. We conclude with a discussion of future directions and propose that BOLD-fMRI in combination with cerebral blood flow or diffusion techniques will provide a more complete accounting of the neurovascular changes that occur in preclinical AD and thus improve our ability to reliably detect early brain changes prior to disease onset.

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“…Cross-sectional studies provide evidence for lower cognitive test scores among ApoE -4 carriers vs. non-carriers. For example, cross-sectional studies of cognitively normal middle-aged and older adults have reported lower performance among ApoE -4 carriers compared to non-carriers on tests of episodic memory [17], verbal fluency [18], and attention [19]. However, cross-sectional cognitive differences as a function of ApoE genotype are not always evident, particularly in studies that largely focus on middle-aged (45 - 65 years) individuals [20-23].…”

Section: Introductionmentioning

confidence: 99%

Cognitive Changes Preceding Clinical Symptom Onset of Mild Cognitive Impairment and Relationship to ApoE Genotype

Albert¹,

Soldan²,

Gottesman³

et al. 2014

CAR

111

154

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Background This study had two goals (1) to evaluate changes in neuropsychological performance among cognitively normal individuals that might precede the onset of clinical symptoms, and (2) to examine the impact of Apolipoprotein E (ApoE) genotype on these changes. Methods Longitudinal neuropsychological, clinical assessments and consensus diagnoses were completed prospectively in 268 cognitively normal individuals. The mean duration of follow-up was 9.2 years (+/− 3.3). 208 participants remained normal and 60 developed cognitive decline, consistent with a diagnosis of MCI or dementia. Cox regression analyses were completed, for both baseline scores and rate of change in scores, in relation to time to onset of clinical symptoms. Analyses were completed both with and without ApoE-4 status included. Interactions with ApoE-4 status were also examined. Results Lower baseline test scores, as well as greater rate of change in test scores, were associated with time to onset of clinical symptoms (p<0.001). The mean time from baseline to onset of clinical symptoms was 6.15 (+/− 3.4) years. The presence of an ApoE-4 allele doubled the risk of progression. The rate of change in two of the test scores was significantly different in ApoE-4 carriers vs. non-carriers. Conclusions Cognitive performance declines prior to the onset of clinical symptoms that are a harbinger of a diagnosis of MCI. Cognitive changes in normal individuals who will subsequently decline may be observed at least 6.5 years prior to symptom onset. In addition, the risk of decline is doubled among individuals with an ApoE-4 allele.

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Context-specific memory and apolipoprotein E (ApoE) [varepsilon]4: Cognitive evidence from the NIMH prospective study of risk for Alzheimer's disease

Cited by 42 publications

References 87 publications

Neuropsychological Contributions to the Early Identification of Alzheimer’s Disease

Neuropsychological Contributions to the Early Identification of Alzheimer’s Disease

Use of Functional Magnetic Resonance Imaging in the Early Identification of Alzheimer's Disease

Cognitive Changes Preceding Clinical Symptom Onset of Mild Cognitive Impairment and Relationship to ApoE Genotype

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