fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer's disease

Trivedi, Mehul A.; Schmitz, Taylor W.; Ries, Michele L.; Hess, Timothy; Fitzgerald, Michele E.; Atwood, Craig S.; Rowley, Howard A.; Asthana, Sanjay; Sager, Mark A.; Johnson, Sterling C.

doi:10.1016/j.neuropsychologia.2007.11.035

Cited by 55 publications

(48 citation statements)

References 38 publications

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“…Elevated hippocampal activation observed on fMRI has also been reported in a number of other conditions that confer risk for AD including cognitively normal carriers of the ApoE-4 allelic variation (Bookheimer et al, 2000, Trivedi et al, 2008, Filippini et al, 2009, Dennis et al, 2010). ApoE-4 is the largest known genetic risk factor for sporadic AD (Corder et al, 1993) and increased hippocampal activation has been observed in ApoE-4 carriers decades before any cognitive symptoms would be expected to appear (Bookheimer et al, 2000, Burggren et al, 2002).…”

Section: Introductionmentioning

confidence: 71%

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment

Tran

Speck

Pisupati

et al. 2017

NeuroImage: Clinical

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Increased fMRI activation in the hippocampus is recognized as a signature characteristic of the amnestic mild cognitive impairment (aMCI) stage of Alzheimer's disease (AD). Previous work has localized this increased activation to the dentate gyrus/CA3 subregion of the hippocampus and showed a correlation with memory impairments in those patients. Increased hippocampal activation has also been reported in carriers of the ApoE-4 allelic variation independently of mild cognitive impairment although these findings were not localized to a hippocampal subregion. To assess the ApoE-4 contribution to increased hippocampal fMRI activation, patients with aMCI genotyped for ApoE-4 status and healthy age-matched control participants completed a high-resolution fMRI scan while performing a memory task designed to tax hippocampal subregion specific functions. Consistent with previous reports, patients with aMCI showed increased hippocampal activation in the left dentate gyrus/CA3 region of the hippocampus as well as memory task errors attributable to this subregion. However, this increased fMRI activation in the hippocampus did not differ between ApoE-4 carriers and ApoE-4 non-carriers and the proportion of memory errors attributable to dentate gyrus/CA3 function did not differ between ApoE-4 carriers and ApoE-4 non-carriers. These results indicate that increased fMRI activation of the hippocampus observed in patients with aMCI is independent of ApoE-4 status and that ApoE-4 does not contribute to the dysfunctional hippocampal activation or the memory errors attributable to this subregion in these patients.

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Section: Introductionmentioning

confidence: 71%

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment

Tran

Speck

Pisupati

et al. 2017

NeuroImage: Clinical

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“…Several studies from our group and others have suggested that family history of AD is associated with preclinical brain changes (Bassett et al, 2006; Fleisher et al, 2009; Johnson et al, 2006, 2007; Schmitz et al, 2004; Trivedi et al, 2007; Xiong et al, 2011; Xu et al, 2009a). Based on prior findings with regard to risk, and patterns observed in AD and mild cognitive impairment, we expected that parental family history of AD would be associated with lower FA, and higher diffusivities.…”

Section: Discussionmentioning

confidence: 87%

White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

Adluru¹,

Destiche²,

Lu³

et al. 2014

NeuroImage: Clinical

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IntroductionLittle is still known about the effects of risk factors for Alzheimer's disease (AD) on white matter microstructure in cognitively healthy adults. The purpose of this cross-sectional study was to assess the effect of two well-known risk factors for AD, parental family history and APOE4 genotype.MethodsThis study included 343 participants from the Wisconsin Registry for Alzheimer's Prevention, who underwent diffusion tensor imaging (DTI). A region of interest analysis was performed on fractional anisotropy maps, in addition to mean, radial, and axial diffusivity maps, aligned to a common template space using a diffeomorphic, tensor-based registration method. The analysis focused on brain regions known to be affected in AD including the corpus callosum, superior longitudinal fasciculus, fornix, cingulum, and uncinate fasciculus. Analyses assessed the impact of APOE4, parental family history of AD, age, and sex on white matter microstructure in late middle-aged participants (aged 47–76 years).ResultsBoth APOE4 and parental family history were associated with microstructural white matter differences. Participants with parental family history of AD had higher FA in the genu of the corpus callosum and the superior longitudinal fasciculus. We observed an interaction between family history and APOE4, where participants who were family history positive but APOE4 negative had lower axial diffusivity in the uncinate fasciculus, and participants who were both family history positive and APOE4 positive had higher axial diffusivity in this region. We also observed an interaction between APOE4 and age, whereby older participants (=65 years of age) who were APOE4 carriers, had higher MD in the superior longitudinal fasciculus and in the portion of the cingulum bundle running adjacent to the cingulate cortex, compared to non-carriers. Older participants who were APOE4 carriers also showed higher radial diffusivity in the genu compared to non-carriers. Across all participants, age had an effect on FA, MD, and axial and radial diffusivities. Sex differences were observed in FA and radial diffusivity.ConclusionAPOE4 genotype, parental family history of AD, age, and sex are all associated with microstructural white matter differences in late middle-aged adults. In participants at risk for AD, alterations in diffusion characteristics—both expected and unexpected—may represent cellular changes occurring at the earliest disease stages, but further work is needed. Higher mean, radial, and axial diffusivities were observed in participants who are more likely to be experiencing later stage preclinical pathology, including participants who were both older and carried APOE4, or who were positive for both APOE4 and parental family history of AD.

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“…Since electrical networks are prominently involved in memory formation, it is proposed that soluble Ab-induced perturbation of neuronal network activity, which induces dysfunction and memory deficits, may be a major and early contributor to AD pathogenesis. Consistent with this view, evidence from high-resolution fMRI in humans indicates, elevated hippocampal activation is observed in conditions that confer risk for Alzheimer's disease, including amnestic mild cognitive impairment [9]. On converse, reduction of hippocampal hyperactivity improves cognition in amnestic mild cognitive impairment [10].…”

Section: Introductionmentioning

confidence: 83%

Rhynchophylline Protects Against the Amyloid β-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats

Shao

et al. 2015

Neurochem Res

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Accumulated soluble amyloid β (Aβ)-induced aberrant neuronal network activity has been recognized as a key causative factor leading to cognitive deficits which are the most outstanding characteristic of Alzheimer's disease (AD). As an important structure associated with learning and memory, the hippocampus is one of the brain regions that are impaired very early in AD, and the hippocampal CA1 region is selectively vulnerable to soluble Aβ oligomers. Our recent study showed that soluble Aβ1-42 oligomers induced hyperactivity and perturbed the firing patterns in hippocampal neurons. Rhynchophylline (RIN) is an important active tetracyclic oxindole alkaloid isolated from Uncaria rhynchophylla which is a traditional Chinese medicine and often used to treat central nervous system illnesses such as hypertension, convulsions, tremor, stroke etc. Previous evidence showed that RIN possessed neuroprotective effects of improving the cognitive function of mice with Alzheimer-like symptoms. In the present study, we aimed to investigate the protective effect of RIN against soluble Aβ1-42 oligomers-induced hippocampal hyperactivity. The results showed that (1) the mean frequency of spontaneous discharge was increased by the local application of 3 μM soluble Aβ1-42 oligomers; (2) 30 μM RIN did not exert any obvious effects on basal physiological discharges; and (3) treatment with RIN effectively inhibited the soluble Aβ1-42 oligomers-induced enhancement of spontaneous discharge, in a concentration-dependent manner with an IC50 = 9.0 μM. These in vivo electrophysiological results indicate that RIN can remold the spontaneous discharges disturbed by Aβ and counteract the deleterious effect of Aβ1-42 on neural circuit. The experimental findings provide further evidence to affirm the potential of RIN as a worthy candidate for further development into a therapeutic agent for AD.

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fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: Risk factors for Alzheimer's disease

Cited by 55 publications

References 38 publications

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment

Increased hippocampal activation in ApoE-4 carriers and non-carriers with amnestic mild cognitive impairment

White matter microstructure in late middle-age: Effects of apolipoprotein E4 and parental family history of Alzheimer's disease

Rhynchophylline Protects Against the Amyloid β-Induced Increase of Spontaneous Discharges in the Hippocampal CA1 Region of Rats

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