Analysis of the MIRIAD Data Shows Sex Differences in Hippocampal Atrophy Progression

Ardekani, Babak A.; Convit, Antonio; Bachman, Alvin H.

doi:10.3233/jad-150780

Cited by 116 publications

(97 citation statements)

References 48 publications

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“…While men are at greater risk of developing MCI (Petersen et al, ), women are more likely to develop AD (Alzheimer's Association, ), possibly due to sex‐related differences in the rate of progression from MCI to probable AD. In patients with MCI and AD, brain volumes, particularly hippocampal, have been found to decline faster in women than men (Ardekani, Convit, & Bachman, ; Skup et al, ), supporting the evidence of faster progression of women from MCI to AD. Furthermore, genes implicated in dementias have been found to increase risk and progression of AD in women; the effect of the APOE ε4 genotype is more pronounced in women (Altmann et al, ), while the MET66 allele of BDNF (brain‐derived neurotrophic factor) is selectively associated with increased risk of AD in women but not in men (Fukumoto et al, ).…”

Section: Discussionmentioning

confidence: 90%

ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training

et al. 2018

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Using high‐resolution resting state functional magnetic resonance imaging (fMRI), the present study tested the hypothesis that ABCA7 genetic risk differentially affects intra‐medial temporal lobe (MTL) functional connectivity between MTL subfields, versus internetwork connectivity of the MTL with the medial prefrontal cortex (mPFC), in nondemented older African Americans. Although the association of ABCA7 risk variants with Alzheimer's disease (AD) has been confirmed worldwide, its effect size on the relative odds of being diagnosed with AD is significantly higher in African Americans. However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to AD risk conferred by ABCA7. In a case–control fMRI study of 36 healthy African Americans, we observed ABCA7 related impairments in behavioral generalization that was mediated by dissociation in entorhinal cortex (EC) resting state functional connectivity. Specifically, ABCA7 risk variant was associated with EC‐hippocampus hyper‐synchronization and EC‐mPFC hypo‐synchronization. Carriers of the risk genotype also had a significantly smaller anterolateral EC, despite our finding no group differences on standardized neuropsychological tests. Our findings suggest a model where impaired cortical connectivity leads to a more functionally isolated EC at rest, which translates into aberrant EC‐hippocampus hyper‐synchronization resulting in generalization deficits. While we cannot identify the exact mechanism underlying the observed alterations in EC structure and network function, considering the relevance of Aβ in ABCA7 related AD pathogenesis, the results of our study may reflect the synergistic reinforcement between amyloid and tau pathology in the EC, which significantly increases tau‐induced neuronal loss and accelerates synaptic alterations. Finally, our results add to a growing literature suggesting that generalization of learning may be a useful tool for assessing the mild cognitive deficits seen in the earliest phases of prodromal AD, even before the more commonly reported deficits in episodic memory arise.

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Section: Discussionmentioning

confidence: 90%

ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training

et al. 2018

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“…Steps (4)–(7) were repeated for the left and right hippocampi independently to obtain HI for both sides. More details about this methodology can be found in [6]. The software for HI estimation (kaiba) is freely available online at: www.nitrc.org/projects/art.…”

Section: Methodsmentioning

confidence: 99%

“…As an alternative, Ardekani et al [6] have proposed a measure of hippocampal volumetric integrity (HI) based on the notion that cerebrospinal fluid (CSF) replaces brain parenchyma in the process of neurodegeneration. Therefore, in given standardized regions-of-interest (ROIs), the ratio of parenchyma volume over total volume (parenchyma plus CSF) would decrease as a result of neuronal loss.…”

Section: Introductionmentioning

confidence: 99%

Hippocampal volume and integrity as predictors of cognitive decline in intact elderly

et al. 2016

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Risk of Alzheimer’s disease (AD) can be predicted by volumetric analyses of MRI data in the medial temporal lobe. The present study compared a volumetric measurement of the hippocampus to a novel measure of hippocampal integrity derived from the ratio of parenchyma volume over total volume. Participants were cognitively intact and aged 60 or older at baseline, and were tested twice, roughly three years apart. Participants had been recruited for a study on late-life major depression (LLMD) and were evenly split between depressed and controls. Linear regression models were applied to the data with a cognitive composite score as outcome, and hippocampal integrity (HI) and volume (HV), together or separately, as predictors. Subsequent cognitive performance was predicted well by models that include an interaction between HI and LLMD-status, such that lower HI scores predicted more cognitive decline in depressed subjects. More research is needed, but tentative results from this study appear to suggest that the newly introduced measure HI is an effective tool for the purpose of predicting future changes in general cognitive ability, and especially so in individuals with LLMD.

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“…This female-bias is not seen in any other types of dementias [92], although some have reasoned that it is a result of women living longer than men [93]. Women AD patients exhibit faster rate of hippocampal atrophy and greater neurofibrillary tangles than men with AD [94,95]. Women also show more rapid loss of autonomy, greater disability and more rapid cognitive decline whilst men have a higher mortality and comorbidity and later onset [79,96,97].…”

Section: Female-biased Brain Disordersmentioning

confidence: 99%

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

et al. 2018

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Males and females sometimes significantly differ in their propensity to develop neurological disorders. Females suffer more from mood disorders such as depression and anxiety, whereas males are more susceptible to deficits in the dopamine system including Parkinson’s disease (PD), attention-deficit hyperactivity disorder (ADHD) and autism. Despite this, biological sex is rarely considered when making treatment decisions in neurological disorders. A better understanding of the molecular mechanism(s) underlying sex differences in the healthy and diseased brain will help to devise diagnostic and therapeutic strategies optimal for each sex. Thus, the aim of this review is to discuss the available evidence on sex differences in neuropsychiatric and neurodegenerative disorders regarding prevalence, progression, symptoms and response to therapy. We also discuss the sex-related factors such as gonadal sex hormones and sex chromosome genes and how these might help to explain some of the clinically observed sex differences in these disorders. In particular, we highlight the emerging role of the Y-chromosome gene, SRY, in the male brain and its potential role as a male-specific risk factor for disorders such as PD, autism, and ADHD in many individuals.

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Analysis of the MIRIAD Data Shows Sex Differences in Hippocampal Atrophy Progression

Cited by 116 publications

References 48 publications

ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training

ABCA7 risk variant in healthy older African Americans is associated with a functionally isolated entorhinal cortex mediating deficient generalization of prior discrimination training

Hippocampal volume and integrity as predictors of cognitive decline in intact elderly

Sex: A Significant Risk Factor for Neurodevelopmental and Neurodegenerative Disorders

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