Correction: APOE ε4 Is Associated with Disproportionate Progressive Hippocampal Atrophy in AD
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PROVIDER: S-EPMC4114877 | biostudies-literature | 2014 Jan
REPOSITORIES: biostudies-literature
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Project description:ObjectivesTo investigate whether APOE ε4 carriers have higher hippocampal atrophy rates than non-carriers in Alzheimer's disease (AD), mild cognitive impairment (MCI) and controls, and if so, whether higher hippocampal atrophy rates are still observed after adjusting for concurrent whole-brain atrophy rates.MethodsMRI scans from all available visits in ADNI (148 AD, 307 MCI, 167 controls) were used. MCI subjects were divided into "progressors" (MCI-P) if diagnosed with AD within 36 months or "stable" (MCI-S) if a diagnosis of MCI was maintained. A joint multi-level mixed-effect linear regression model was used to analyse the effect of ε4 carrier-status on hippocampal and whole-brain atrophy rates, adjusting for age, gender, MMSE and brain-to-intracranial volume ratio. The difference in hippocampal rates between ε4 carriers and non-carriers after adjustment for concurrent whole-brain atrophy rate was then calculated.ResultsMean adjusted hippocampal atrophy rates in ε4 carriers were significantly higher in AD, MCI-P and MCI-S (p≤0.011, all tests) compared with ε4 non-carriers. After adjustment for whole-brain atrophy rate, the difference in mean adjusted hippocampal atrophy rate between ε4 carriers and non-carriers was reduced but remained statistically significant in AD and MCI-P.ConclusionsThese results suggest that the APOE ε4 allele drives atrophy to the medial-temporal lobe region in AD.
| S-EPMC4039513 | biostudies-literature
Project description:This study investigates relationships between white matter hyperintensity (WMH) volume, cerebrospinal fluid (CSF) Alzheimer's disease (AD) pathology markers, and brain and hippocampal volume loss. Subjects included 198 controls, 345 mild cognitive impairment (MCI), and 154 AD subjects with serial volumetric 1.5-T MRI. CSF Aβ42 and total tau were measured (n = 353). Brain and hippocampal loss were quantified from serial MRI using the boundary shift integral (BSI). Multiple linear regression models assessed the relationships between WMHs and hippocampal and brain atrophy rates. Models were refitted adjusting for (a) concurrent brain/hippocampal atrophy rates and (b) CSF Aβ42 and tau in subjects with CSF data. WMH burden was positively associated with hippocampal atrophy rate in controls (P = 0.002) and MCI subjects (P = 0.03), and with brain atrophy rate in controls (P = 0.03). The associations with hippocampal atrophy rate remained following adjustment for concurrent brain atrophy rate in controls and MCIs, and for CSF biomarkers in controls (P = 0.007). These novel results suggest that vascular damage alongside AD pathology is associated with disproportionately greater hippocampal atrophy in nondemented older adults. © 2016 The Authors Hippocampus Published by Wiley Periodicals, Inc.
| S-EPMC5324634 | biostudies-literature
Project description:IntroductionPresence of apolipoprotein E (APOE) ε4 has shown greater predisposition to medial temporal involvement in posterior cortical atrophy (PCA) and logopenic progressive aphasia (LPA). Little is known about its influence on memory network connectivity, a network comprised of medial temporal structures.MethodsFifty-eight PCA and 82 LPA patients underwent structural and resting state functional magnetic resonance imaging (MRI). Bayesian hierarchical linear models assessed the influence of APOE ε4 on within and between-network connectivity for five networks.ResultsAPOE ε4 carriers showed reduced memory and language within-network connectivity in LPA and increased salience within-network connectivity in PCA compared to non-carriers. Between-network analysis showed evidence of reduced DMN connectivity in APOE ε4 carriers, with reduced DMN-to-salience and DMN-to-language network connectivity in PCA, and reduced DMN-to-visual network connectivity in LPA.DiscussionThe APOE genotype influences brain connectivity, both within and between-networks, in atypical Alzheimer's disease. However, there was evidence that the modulatory effects of APOE differ across phenotype.HighlightsAPOE genotype is associated with reductions in within-network connectivity for the memory and language networks in LPA APOE genotype is associated with reductions in language-to-visual connectivity in LPA and PCA APOE genotype has no effect on the memory network in PCA.
| S-EPMC10523970 | biostudies-literature
Project description:A single nucleotide polymorphism, rs17070145, in the KIdney and BRAin expressed protein (KIBRA) gene has been associated with cognition and hippocampal volume in cognitively normal (CN) individuals. However, the impact of rs17070145 on longitudinal cognitive decline and hippocampal atrophy in CN adults at greatest risk of developing Alzheimer's disease is unknown. We investigated the impact rs17070145 has on the rate of cognitive decline and hippocampal atrophy over six years in 602 CN adults, with known brain Aβ-amyloid levels and whether there is an interactive effect with APOE genotype. We reveal that whilst limited independent effects of KIBRA genotype were observed, there was an interaction with APOE in CN adults who presented with high Aβ-amyloid levels across study duration. In comparison to APOE ε4-ve individuals carrying the rs17070145-T allele, significantly faster rates of cognitive decline (global, p = 0.006; verbal episodic memory, p = 0.004), and hippocampal atrophy (p = 0.04) were observed in individuals who were APOE ε4 + ve and did not carry the rs17070145-T allele. The observation of APOE effects in only non-carriers of the rs17070145-T allele, in the presence of high Aβ-amyloid suggest that carriers of the rs17070145-T allele are conferred a level of resilience to the detrimental effects of high Aβ-amyloid and APOE ε4.
| S-EPMC5794989 | biostudies-literature
Project description:IntroductionWe investigated hippocampal synaptic density using synaptic vesicle 2A positron emission tomography (PET), and its association with amyloid beta (Aβ) and cognitive performance in healthy apolipoprotein E (APOE) ε4 carriers.MethodsSynaptic density was assessed in 46 individuals (APOE ε4/ε4 n = 14; APOE ε3/ε4 n = 16; APOE ε3/ε3 n = 16) with [11C]UCB-J-PET standardized uptake value ratios (SUVRs), by using the centrum semiovale as a reference region. Differences in hippocampal [11C]UCB-J SUVRs were analyzed with analysis of variance (ANOVA) and linear models. Associations among [11C]UCB-J SUVR, Aβ, hippocampal volume, and cognitive variables were analyzed with Spearman correlation.ResultsHippocampal synaptic density was different among the APOE groups (PANOVA = 0.016): APOE ε4/ε4 carriers had lower [11C]UCB-J SUVRs compared to APOE ε3/ε3 (p = 0.013). Hippocampal synaptic density did not correlate with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) total score (rho = -0.052, p = 0.74), Alzheimer's Prevention Initiative Preclinical Cognitive Composite (APCC) score (rho = 0.17, p = 0.28), or [11C]PiB uptake (rho = -0.10, p = 0.50).DiscussionHippocampal synaptic loss emerges early in the AD continuum and is measurable in vivo in cognitively unimpaired high-risk individuals.HighlightsSynaptic density was studied in vivo in healthy older adults using [11C]UCB-J positron emission tomography. Apolipoprotein E (APOE) ε4/ε4 carriers had lower hippocampal synaptic density compared to APOE ε3/ε3. Synaptic density was not associated with cognitive performance in this population. Hippocampal synaptic alterations occur before clinical symptoms in APOE ε4/ε4 carriers.
| S-EPMC11667521 | biostudies-literature
Project description:BackgroundThere are contradicting reports on the associations between Apolipoprotein E4 (ApoE ε4) and brain outcomes in HIV with some evidence that relationships may be greatest in older age groups.MethodsWe assessed cognition in 76 clinically stable HIV-infected participants over age 60 and genotyped ApoE. Sixty-one of these subjects underwent structural brain magnetic resonance imaging and diffusion tensor imaging.ResultsThe median age of the participants was 64 years (range: 60-84) and the median estimated duration of HIV infection was 22 years. Apo ε4 carriers (n = 19) were similar to noncarriers (n = 57) in sex (95% vs. 96% male), and education (16.0 vs. 16.2 years) ApoE ε4 carriers demonstrated greater deficits in cognitive performance in the executive domain (P = 0.045) and had reduced fractional anisotropy and increased mean diffusivity throughout large white matter tracts within the brain compared with noncarriers. Tensor-based morphometry analyses revealed ventricular expansion and atrophy in the posterior corpus callosum, thalamus, and brainstem among HIV-infected ApoE ε4 carriers compared with ε4 noncarriers.ConclusionsIn this sample of older HIV-infected individuals, having at least 1 ApoE ε4 allele was associated with decreased cognitive performance in the executive functioning domain, reduced brain white matter integrity, and brain atrophy. Brain atrophy was most prominent in the posterior corpus callosum, thalamus, and brainstem. This pattern of cognitive deficit, atrophy, and damage to white matter integrity was similar to that described in HIV, suggesting an exacerbation of HIV-related pathology; although emergence of other age-associated neurodegenerative disorders cannot be excluded.
| S-EPMC5085854 | biostudies-literature
Project description:IntroductionWe evaluated how the apolipoprotein E (APOE) ε4 allele modulated the spatial patterns of longitudinal atrophy in the Alzheimer's disease-vulnerable brain areas of patients with mild traumatic brain injury (mTBI) from the acute to chronic phase post injury.MethodsFifty-nine adult patients with acute mTBI and 48 healthy controls with APOE ε4 allele testing underwent T1-weighted magnetic resonance imaging and neuropsychological assessments with 6 to 12 months of follow-up. Progressive brain volume loss was compared voxel-wise in the temporal lobes.ResultsPatients with the APOE ε4 allele presented significant longitudinal atrophy in the left superior and middle temporal gyri, where the progressive gray matter volume loss predicted longitudinal impairment in language fluency, whereas mTBI APOE ε4 allele noncarriers showed mainly significant longitudinal atrophy in the medial temporal lobes, without significant neuropsychological relevance.DiscussionThe atrophy progression observed in mTBI patients with the APOE ε4 allele may increase the possibility of developing a specific phenotype of Alzheimer's disease with language dysfunction.HighlightsThe apolipoprotein E (APOE) ε4 allele and mild traumatic brain injury (mTBI) are risk factors for Alzheimer's disease (AD) progression.It is unclear how the interaction of mTBI with the APOE ε4 allele impacts the progressive atrophy topography in AD-vulnerable brain regions.In this study, patients with the APOE ε4 allele showed progressive atrophy patterns similar to the early stage of logopenic variant of primary progressive aphasia (lvPPA) phenotype of AD. APOE ε4 allele carriers with mTBI history may be at the risk of developing a given AD phenotype with language dysfunction.
| S-EPMC10870335 | biostudies-literature
Project description:IntroductionApolipoprotein E (APOE) ε4 is an important genetic risk factor for typical Alzheimer's disease (AD), influencing brain volume and tau burden. Little is known about its influence in atypical presentations of AD.MethodsAn atypical AD cohort of 140 patients diagnosed with either posterior cortical atrophy or logopenic progressive aphasia underwent magnetic resonance imaging and positron emission tomography. Linear mixed effects models were fit to assess the influence of APOE ε4 on cross-sectional and longitudinal regional metrics.ResultsAt baseline, APOE ε4 carriers had smaller hippocampal and amygdala volumes and greater tau standardized uptake volume ratio in the hippocampus and entorhinal cortex compared to non-carriers while longitudinally, APOE ε4 non-carriers showed faster rates of atrophy and tau accumulation in the entorhinal cortex, with faster tau accumulation in the hippocampus.DiscussionAPOE ε4 influences patterns of neurodegeneration and tau deposition and was associated with more medial temporal involvement, although there is evidence that non-carriers may be catching up over time.
| S-EPMC9742387 | biostudies-literature
Project description:African Americans are 1.4 times more likely than European Americans to carry the apolipoprotein E (APOE) ε4 allele, a risk factor for Alzheimer's disease (AD). However, little is known about the neural correlates of cognitive function in older African Americans and how they relate to genetic risk for AD. In particular, no past study on African Americans has examined the effect of APOE ε4 status on pattern separation-mnemonic discrimination performance and its corresponding neural computations in the hippocampus. Previous work using the mnemonic discrimination paradigm has localized increased activation in the DG/CA3 hippocampal subregions as being correlated with discrimination deficits. In a case-control high-resolution functional magnetic resonance imaging study of 30 healthy African Americans, aged 60 years and older, we observed APOE ε4-related impairments in mnemonic discrimination, coincident with dysfunctional hyperactivation in the DG/CA3, and CA1 regions, despite no evidence of structural differences in the hippocampus between carriers and noncarriers. Our results add to the growing body of evidence that deficits in pattern separation may be an early marker for AD-related neuronal dysfunction.
| S-EPMC6392014 | biostudies-literature
Project description:ObjectiveSmall Vessel Disease (SVD) is known to be associated with higher AD risk, but its relationship to amyloidosis in the progression of AD is unclear. In this cross-sectional study of cognitively normal older adults, we explored the interactive effects of SVD and amyloid-beta (Aβ) pathology on hippocampal functional connectivity during an associative encoding task and on hippocampal volume.MethodsThis study included 61 cognitively normal older adults (age range: 65-93 years, age mean ± standard deviation: 75.8 ± 6.4, 41 [67.2%] female). PiB PET, T2-weighted FLAIR, T1-weighted and face-name fMRI images were acquired on each participant to evaluate brain Aβ, white matter hyperintensities (WMH+/- status), gray matter density, and hippocampal functional connectivity.ResultsWe found that, in WMH (+) older adults greater Aβ burden was associated with greater hippocampal local connectivity (i.e., hippocampal-parahippocampal connectivity) and lower gray matter density in medial temporal lobe (MTL), whereas in WMH (-) older adults greater Aβ burden was associated with greater hippocampal distal connectivity (i.e., hippocampal-prefrontal connectivity) and no changes in MTL gray matter density. Moreover, greater hippocampal local connectivity was associated with MTL atrophy.ConclusionThese observations support a hippocampal excitotoxicity model linking SVD to neurodegeneration in preclinical AD. This may explain how SVD may accelerate the progression from Aβ positivity to neurodegeneration, and subsequent AD.
| S-EPMC10768933 | biostudies-literature