<i>APOE</i>*<i>E4</i>Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline

Haller, Sven; Montandon, ML; Rodriguez, Cristelle; Ackermann, Marine; Herrmann, Françoís; Giannakopoulos, Pantéleimon

doi:10.3174/ajnr.a5184

Cited by 31 publications

(29 citation statements)

References 46 publications

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“…In contrast, none of our carriers, who were exclusively heterozygotes (ε3/ε4), converted to MCI at 18 months, emphasizing the need for a lengthier followup interval in carriers with a single ε4 allele. In contrast, no baseline differences in cognitive performance were observed by Haller et al (2017). Unlike our study and that of Stonnington et al (2018), the criterion for change in Haller et al (2017) was not MCI conversion but cognitive decline on neuropsychological test performance.…”

Section: Discussioncontrasting

confidence: 93%

“…In contrast, no baseline differences in cognitive performance were observed by Haller et al (2017). Unlike our study and that of Stonnington et al (2018), the criterion for change in Haller et al (2017) was not MCI conversion but cognitive decline on neuropsychological test performance. Like our study, the majority of their carriers were heterozygotes.…”

Section: Discussioncontrasting

confidence: 93%

“…Two previous longitudinal studies (Haller et al, 2017;Stonnington et al, 2018) have examined possible baseline differences in cognitive performance between ε4 carriers who subsequently experience a deterioration in cognition and those that do not. Like our study, Stonnington et al (2018) found poorer baseline performance on episodic memory measures in their MCI converters relative to non-converters.…”

Section: Discussionmentioning

confidence: 99%

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Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Abraham

Seidenberg

Kelly

et al. 2020

J Int Neuropsychol Soc

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Objective: The Apolipoprotein (APOE) ε4 allele increases the risk for mild cognitive impairment (MCI) and dementia, but not all carriers develop MCI/dementia. The purpose of this exploratory study was to determine if early and subtle preclinical signs of cognitive dysfunction and medial temporal lobe atrophy are observed in cognitively intact ε4 carriers who subsequently develop MCI. Methods: Twenty-nine healthy, cognitively intact ε4 carriers (ε3/ε4 heterozygotes; ages 65–85) underwent neuropsychological testing and MRI-based measurements of medial temporal volumes over a 5-year follow-up interval; data were converted to z-scores based on a non-carrier group consisting of 17 ε3/ε3 homozygotes. Results: At follow-up, 11 ε4 carriers (38%) converted to a diagnosis of MCI. At study entry, the MCI converters had significantly lower scores on the Mini-Mental State Examination, Rey Auditory Verbal Learning Test (RAVLT) Trials 1–5, and RAVLT Immediate Recall compared to non-converters. MCI converters also had smaller MRI volumes in the left subiculum than non-converters. Follow-up logistic regressions revealed that left subiculum volumes and RAVLT Trials 1–5 scores were significant predictors of MCI conversion. Conclusions: Results from this exploratory study suggest that ε4 carriers who convert to MCI exhibit subtle cognitive and volumetric differences years prior to diagnosis.

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Section: Discussioncontrasting

confidence: 93%

Section: Discussioncontrasting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

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Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Abraham

Seidenberg

Kelly

et al. 2020

J Int Neuropsychol Soc

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“…In healthy elderly subjects, the APOE-ε4 effect on brain structure remains unclear. In previous contributions, decreased gray-matter volume was found in the posterior cingulate cortex [47], right cingulate and insula [48], hippocampus [49], and AD-sensitive regions [50]. However, negative data were also reported [7,[51][52][53][54].…”

Section: Discussionmentioning

confidence: 83%

Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

Haller¹,

Montandon

Rodriguez

et al. 2019

Neurodegener Dis

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Background: Hippocampal volume loss (HVL), PET-documented brain amyloid accumulation, and APOE-ε4 status are predictive biomarkers of the transition from mild cognitive impairment to Alzheimer disease (AD). In asymptomatic cases, the role of these biomarkers remains ambiguous. In contrast to the idea that HVL occurs in late phases of neurodegeneration, recent contributions indicate that it might occur before abnormal amyloid PET occurrence in elderly subjects and that its severity could be only marginally related to APOE variants. Using a longitudinal design, we examined the determinants of HVL in our sample, i.e., brain amyloid burden and the presence of APOE-ε4, and made a longitudinal assessment of cognitive functions. Methods: We performed a 4.5-year longitudinal study on 81 elderly community dwellers (all right-handed;, 48 (59.3%) women; mean age 73.7 ± 3.7 years) including MRI at baseline and follow-up, PET amyloid during follow-up, neuropsychological assessment at 18 and 54 months, and APOE genotyping. All cases were assessed using a continuous cognitive score (CCS) that took into account the global evolution of neuropsychological performance. Linear regression models were used to identify predictors of HVL. Results: There was a negative association between the CCS and HVL bilaterally. In multivariate models adjusting for demographic variables, the presence of APOE-ε4 was related to increased HVL bilaterally. A trend of significance was observed with respect to the impact of amyloid positivity on HVL in the left hemisphere. No significant interaction was found between amyloid positivity and the APOE-ε4 allele. Conclusion: The progressive decrement of neuropsychological performance is associated with HVL long before the emergence of clinically overt symptoms. In this cohort of healthy individuals, the presence of the APOE-ε4 allele was shown to be an independent predictor of worst hippocampal integrity in asymptomatic cases independently of amyloid positivity.

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“…The study encompassed a comprehensive neuropsychological evaluation, as described in detail previously. 13 The final sample included 87 participants, classified as cognitively healthy controls (mean age, 78.7 Ϯ 3.8 years; 49 women). All participants gave written informed consent after formal approval by the local ethics committee.…”

Section: Participantsmentioning

confidence: 99%

Brain Perfusion Measurements Using Multidelay Arterial Spin-Labeling Are Systematically Biased by the Number of Delays

Thiel

Rodriguez

Giannakopoulos

et al. 2018

AJNR Am J Neuroradiol

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*APOE**E4Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline

Cited by 31 publications

References 46 publications

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

Brain Perfusion Measurements Using Multidelay Arterial Spin-Labeling Are Systematically Biased by the Number of Delays

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APOE*E4Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline

Cited by 31 publications

References 46 publications

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Episodic Memory and Hippocampal Volume Predict 5-Year Mild Cognitive Impairment Conversion in Healthy Apolipoprotein ε4 Carriers

Hippocampal Volume Loss, Brain Amyloid Accumulation, and APOE Status in Cognitively Intact Elderly Subjects

Brain Perfusion Measurements Using Multidelay Arterial Spin-Labeling Are Systematically Biased by the Number of Delays

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*APOE**E4Is Associated with Gray Matter Loss in the Posterior Cingulate Cortex in Healthy Elderly Controls Subsequently Developing Subtle Cognitive Decline