Decreased hippocampal volume asymmetry on MRIs in nondemented elderly subjects carrying the apolipoprotein E ϵ4 allele

Soininen, Hilkka; Partanen, Kaarina; Pitkänen, A.; Hallikainen, Merja; Hänninen, Tuomo; Helisalmi, Seppo; Mannermaa, Arto; Ryynänen, Markku; Koiuisto, K.; Riekkinen, Paavo

doi:10.1212/wnl.45.2.391

Cited by 115 publications

(70 citation statements)

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“…These studies have shown atypical asymmetries in mesial temporal and parietal lobe regions in individuals at risk for AD (Reiman et al, 1996;Small et al, 1995;Soininen et al, 1994Soininen et al, , 1995. Findings of cognitive asymmetry in at-risk individuals also are consistent with the asymmetric neuropsychological profiles identified in mildly demented patients with AD (Albert et al, 1990;Delis et al, 1992).…”

Section: Discussionsupporting

confidence: 64%

“…There is also preliminary neuroimaging data suggesting that asymmetric structural and metabolic anomalies can be detected in nondemented elderly at risk for AD (Celsis et al, 1997;Grady et al, 1990;Reiman et al, 1996;Small et al, 1995;Soininen et al, 1994Soininen et al, , 1995. Given the strong evidence for asymmetry in early AD (Bugiani, Constantinidis, Ghetti, Bouras, & Tagliavini, 1991;Koss, Friedland, Ober, & Jagust, 1985), it is possible that subtle changes in verbal relative to visuospatial skills (or vice versa) could occur in a preclinical phase.…”

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confidence: 99%

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Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses.

Jacobson¹,

Delis²,

Bondi³

et al. 2002

Neuropsychology

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Attempts to identify cognitive markers of a preclinical phase of Alzheimer's disease (AD) have yielded inconsistent findings. The problem may stem in part from methodologies that are insensitive to potential subgroups within the at-risk, preclinical AD population (PCAD). The present study investigated the utility of asymmetric cognitive profiles in identifying individuals at risk for AD. Twenty elderly adults who were later diagnosed with AD (PCAD) and 20 matched control participants were compared on measures of cognitive asymmetry derived from difference scores on tests of verbal and visuospatial ability. Although both groups performed similarly on the individual tests, comparisons using difference scores revealed significantly larger discrepancies between naming and visuoconstruction skills in the PCAD group. The PCAD group also had a higher frequency of asymmetric cognitive profiles relative to a normative group.

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Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 99%

Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses.

Jacobson¹,

Delis²,

Bondi³

et al. 2002

Neuropsychology

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“…These early "preclinical" memory changes are more likely to occur in those with a genetic susceptibility marker for AD, the apolipoprotein E (APOE) ε4 allele [11,37], than in those without this risk factor. In parallel with these findings, structural [32,44] and functional [4,6,15,20,34,42] neuroimaging alterations are more evident in non-demented elderly with the ε4 allele than in those without this allele type.…”

Section: Introductionmentioning

confidence: 53%

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Han

Houston

Jak

et al. 2007

Neurobiology of Aging

139

114

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Previous studies of episodic memory report a greater extent of blood-oxygenation-level-dependent (BOLD) response in non-demented older adults with the apolipoprotein E epsilon-4 (APOE ε4) allele than in those without the allele. We conducted a functional MRI study to investigate whether APOE genotype is related to brain response to verbal paired-associate encoding and consolidation, particularly in the right hemisphere, among non-demented older adults. Structurally segmented volumes and BOLD response were measured in 13 non-ε4 and 12 ε4 subjects. The ε4 group displayed greater activation than the non-ε4 group in multiple right hemisphere regions for previously encoded word pairs relative to fixation. Activation within manually outlined hippocampal regions of interest also displayed genotype-specific dissociations consistent with whole brain analyses. Furthermore, this differential BOLD response occurred in the presence of equivalent behavioral and neuropsychological performances as well as comparable hippocampal and overall structural segmentation volumes between groups. Results implicate a widely distributed and interconnected network of right hemisphere brain regions that may be involved in compensating for APOE ε4-related deficiencies associated with verbal episodic memory encoding and consolidation.

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“…Other published findings, including a meta-analysis, support a right dominant hippocampal asymmetry in healthy adults (Pedraza et al 2004). The existence of such an asymmetry is of even greater interest given reports of changes in asymmetry in individuals at elevated risk for and diagnosed with AD (Soininen et al 1994;Soininen et al 1995;Barnes et al 2005) that may be related to concomitant cognitive changes (Finton et al 2003). …”

Section: Introductionmentioning

confidence: 99%

Feasibility of Multi-site Clinical Structural Neuroimaging Studies of Aging Using Legacy Data

et al. 2007

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The application of advances in biomedical computing to medical imaging research is enabling scientists to conduct quantitative clinical imaging studies using data collected across multiple sites to test new hypotheses on larger cohorts, increasing the power to detect subtle effects.Given that many research groups have valuable existing (legacy) data, one goal of the Morphometry Biomedical Informatics Research Network (BIRN) Testbed is to assess the feasibility of pooled analyses of legacy structural neuroimaging data in normal aging and Alzheimer's disease. Neuroinform (2007) 5:235-245 DOI 10.1007 Brad Dickerson and Randy L. Gollub contributed equally. The present study examined whether such data could be meaningfully reanalyzed as a larger combined data set by using rigorous data curation, image analysis, and statistical modeling methods; in this case, to test the hypothesis that hippocampal volume decreases with age and to investigate findings of hippocampal asymmetry. This report describes our work with legacy T1-weighted magnetic resonance (MR) and demographic data related to normal aging that have been shared through the BIRN by three research sites. Results suggest that, in the present application, legacy MR data from multiple sites can be pooled to investigate questions of scientific interest. In particular, statistical analyses suggested that a mixed-effects model employing site as a random effect best fits the data, accounting for site-specific effects while taking advantage of expected comparability of age-related effects. In the combined sample from three sites, significant age-related decline of hippocampal volume and right-dominant hippocampal asymmetry were detected in healthy elderly controls. These expected findings support the feasibility of combining legacy data to investigate novel scientific questions.

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Decreased hippocampal volume asymmetry on MRIs in nondemented elderly subjects carrying the apolipoprotein E ϵ4 allele

Cited by 115 publications

References 0 publications

Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses.

Do neuropsychological tests detect preclinical Alzheimer's disease: Individual-test versus cognitive-discrepancy score analyses.

Verbal paired-associate learning by APOE genotype in non-demented older adults: fMRI evidence of a right hemispheric compensatory response

Feasibility of Multi-site Clinical Structural Neuroimaging Studies of Aging Using Legacy Data

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