Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer’s disease

Hashimoto, Mamoru; Yasuda, Minoru; Tanimukai, Satoshi; Matsui, Masami; Hirono, Nobutsugu; Kazui, Hiroaki; Mori, Etsuro

doi:10.1212/wnl.57.8.1461

Cited by 133 publications

(118 citation statements)

References 42 publications

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“…One may assume that sample characteristics, such as age, gender or cognitive status may contribute to discrepancies between studies. However, age, gender and MMSE scores were matched between the AD patients with and without ApoE4 genotype both in our sample and in the previous study showing a significant effect of ApoE4 [19]. Similar to us, one earlier study found no effect of ApoE4 genotype on amygdala volume [30] in AD patients.…”

Section: Discussionsupporting

confidence: 86%

“…This argument does not hold, however, given the subject numbers in this and one previous study [23]. Cohens d in one relatively large positive study comprising 138 patients was 0.55 [19]. Our study was powered to detect an effect size of 0.55 at 80% power and a p value of 0.05 in the AD group.…”

Section: Discussionmentioning

confidence: 63%

“…Findings from earlier studies are ambiguous. Some studies, did not find an effect of ApoE4 genotype [23], other studies reported significant effects of ApoE4 genotype on hippocampus volume in AD [19,30]. To explain this discrepany, it has been argued that subject numbers had been too low in the negative studies.…”

Section: Discussionmentioning

confidence: 99%

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Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Teipel

Ewers

Wolf

et al. 2010

Psychiatry Research: Neuroimaging

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MRI based volumetry of the hippocampus and amygdala has been suggested as a biomarker of Alzheimer's disease (AD). For validation of the candidate marker, however, effects of multicentre acquisition on measurement variability have to be considered. In the present study we determined effects of multicentre acqusitions of MRI data across 12 clinical sites within the German Competence Network on Dementias in 113 patients with clinically probable AD and 150 patients with amnestic mild cognitive impairment (MCI). Hippocampus and amygdala volumes were significantly reduced in AD compared to MCI patients using data pooled across centres. The between-centre effect accounted for 5 to 15% of within-centre variability. Using mixed effects regression, we found specific correlations between delayed recall of verbal and non-verbal material and global cognitive measures with hippocampus and amygdala volumes. In contrast drawing performance was not correlated with volume measures. ApoE4 genotype had no effect on volumetric measures. Power analysis for the detection of a difference in the volumes between AD and MCI patients across centres showed that multicentre variability did not significantly affect effect sizes. The total sample size needed is N= 58 for hippocampus and N= 158 for amygdala volumes. Our data indicate that multicentre acquisition of MRI data using manual volumetry is reliable and feasible for diagnostic trials and replicates essential findings from smaller scale monocentre studies.3

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 63%

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Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Teipel

Ewers

Wolf

et al. 2010

Psychiatry Research: Neuroimaging

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“…One in vivo SPECT study has suggested that delusions in AD may be associated with hypoperfusion in the temporal lobes (Starkstein et al, 1994), and some (Lee et al, 2003) but not all (van Dyck et al, 1998) functional imaging studies have shown that AD patients who carry the e4 allele have reduced temporal lobe function. The structural MRI literature is more unified in showing greater medial temporal lobe atrophy in association with the e4 allele in AD (Lehtovirta et al, 1996b;Hashimoto et al, 2001;Basso et al, in press). …”

Section: Interpretation Of An Increased Risk Of Psychosis In Apoe E4 mentioning

confidence: 99%

“…Among the three major isoforms of ApoE (e2, e3, and e4), the e4 allele has been reported to increase an individual's risk of developing AD, and decrease age of disease onset, in proportion to the number of e4 alleles present (Corder et al, 1993;Farrer et al, 1997). The search for phenotypic correlates of e4 has included neuropathological studies of the rate of b-amyloid (Ab) deposition Nagy et al, 1995;Norrman et al, 1995;Gomez-Isla et al, 1996), neurofibrillary tangle formation Nagy et al, 1995;Norrman et al, 1995;Gomez-Isla et al, 1996), cholinergic markers (Poirier et al, 1995;Soininen et al, 1995), and medial temporal lobe atrophy (Lehtovirta et al, 1996b;Hashimoto et al, 2001;Basso et al, in press).…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Zdanys

Kleiman

MacAvoy

et al. 2006

Neuropsychopharmacol

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The apolipoprotein E (ApoE) e4 allele is a well-documented genetic risk factor for sporadic Alzheimer's disease (AD). Its association with psychopathology among AD patients has been the subject of discrepant reports. We aimed to determine whether ApoE e4 + and e4-AD patients exhibit a different risk profile for psychotic symptoms and other behavioral disturbances. The Neuropsychiatric Inventory (NPI) was administered to determine the frequency and severity of psychotic and other behavioral symptoms in a sample of n ¼ 266 AD patients who had been genotyped for ApoE. Multiple logistic regression models were used to calculate the association between the ApoE e4 allele and the presence of psychotic symptoms (delusions or hallucinations). Exploratory analyses were also conducted to determine the impact of disease severity on e4 effects and to examine the association between e4 and other behavioral symptoms. ApoE e4 was significantly associated with psychotic symptoms (odds ratio (OR) ¼ 1.87, 95% CI ¼ 1.07-3.29, P ¼ 0.029), adjusting for age, sex, education, and MMSE score. More stringent definitions of clinically significant psychosis yielded similar results. Exploratory analyses suggested that this effect accrued specifically from patients with severe-stage AD and primarily from an association between e4 and delusions. The e4 allele did not appear to influence the development of most other behavioral symptoms in our sample. In conclusion, AD patients who carry the ApoE e4 allele are at greater risk than noncarriers for developing psychotic symptoms, particularly as the severity of their dementia progresses.

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Influence of Apolipoprotein E ϵ4 Genotype on Brain Tissue Integrity in Relapsing-Remitting Multiple Sclerosis

Stefano¹,

Bartolozzi²,

Nacmias³

et al. 2004

Arch Neurol

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Apolipoprotein E ε4 and the pattern of regional brain atrophy in Alzheimer’s disease

Abstract: Different patterns of regional brain atrophy were found among patients of different APOE genotypes. The effect of APOE epsilon 4 allele on the brains of AD patients may have regional specificity.

Cited by 133 publications

References 42 publications

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Multicentre variability of MRI-based medial temporal lobe volumetry in Alzheimer's disease

Apolipoprotein E ɛ4 Allele Increases Risk for Psychotic Symptoms in Alzheimer's Disease

Influence of Apolipoprotein E ϵ4 Genotype on Brain Tissue Integrity in Relapsing-Remitting Multiple Sclerosis

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