<i>APOE</i>‐ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Saeed, Usman; Mirza, Saira Saeed; MacIntosh, Bradley J.; Herrmann, Nathan; Keith, Julia; Ramirez, Joel; Nestor, Sean M.; Yu, Qinggang; Knight, Jo; Swardfager, Walter; Potkin, Steven G.; Rogaeva, Ekaterina; George-Hyslop, Peter St; Black, Sandra E.; Masellis, Mario

doi:10.1016/j.jalz.2018.04.005

Cited by 40 publications

(51 citation statements)

References 61 publications

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“…Because of the high frequency of coexisting neurodegenerative pathologies, 32,33 shared risk factors and pathologies cannot be disentangled if samples are segregated on clinical diagnoses alone. 15 Although a unified model with an interaction term is the optimum method to test effect modification, an important limitation is that more statistical power is required than for association testing, and thus false-negative results may be seen in smaller samples. The documented strong biological effects of APOE e4 28 formed the basis of our a priori hypothesis; that is, greater WMH burden relates more strongly with worse cognition in APOE e4 carriers, which is why we also tested associations separately in carriers and noncarriers irrespective of the interaction results.…”

Section: Discussionmentioning

confidence: 99%

“…All DLB cases were confirmed to have DLB, with varying degrees of neurofibrillary tangle pathology. 15 A total of 66.6% (n = 8/12) of the APOE e4 noncarriers had CAA compared to 76% (n = 16/21) of APOE e4 carriers. Sixty-four percent (n = 9/14) of heterozygous APOE e4 carriers had CAA, whereas 100% (n = 7/7) of the homozygous APOE e4 carriers had CAA.…”

Section: Exploratory Neuropathology Sample: Sdsmentioning

confidence: 93%

“…Thirty-six of the SDS cases had a postmortem neuropathologic examination to diagnose and stage neurodegenerative disease phenomena. 15 This workup included a screen for CAA using immunohistochemistry for β-amyloid (Aβ) (Dako, Glostrup, Denmark; Mach 4 detection system) in at least 2 brain sections (cerebellum and frontal cortex). For 34 of these 36 cases, the original autopsy reports were reviewed by a neuropathologist (J.K.) to determine the presence or absence of CAA.…”

Section: Neuropathology Methods In Sds (Exploratory Sample)mentioning

confidence: 99%

“…This work was embedded within the Sunnybrook Dementia Study (SDS), a prospective observational study of patients with dementia. 15 The majority of participants in the SDS are Caucasian of European descent.…”

Section: Settingmentioning

confidence: 99%

“…Details of MRI acquisition are provided elsewhere. 15 MRIs were processed using the Semi-Automated Brain Region Extraction and Lesion Explorer processing pipeline. 22 WMHs were identified as lesions that appear as punctate or diffuse regions of hyperintense signal on T2/PD MRI.…”

Section: Mri (Wmh Volume) Sds Samplementioning

confidence: 99%

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APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

et al. 2019

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ObjectiveTo determine if APOE ε4 influences the association between white matter hyperintensities (WMH) and cognitive impairment in Alzheimer disease (AD) and dementia with Lewy bodies (DLB).MethodsA total of 289 patients (AD = 239; DLB = 50) underwent volumetric MRI, neuropsychological testing, and APOE ε4 genotyping. Total WMH volumes were quantified. Neuropsychological test scores were included in a confirmatory factor analysis to identify cognitive domains encompassing attention/executive functions, learning/memory, and language, and factor scores for each domain were calculated per participant. After testing interactions between WMH and APOE ε4 in the full sample, we tested associations of WMH with factor scores using linear regression models in APOE ε4 carriers (n = 167) and noncarriers (n = 122). We hypothesized that greater WMH volume would relate to worse cognition more strongly in APOE ε4 carriers. Findings were replicated in 198 patients with AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI-I), and estimates from both samples were meta-analyzed.ResultsA significant interaction was observed between WMH and APOE ε4 for language, but not for memory or executive functions. Separate analyses in APOE ε4 carriers and noncarriers showed that greater WMH volume was associated with worse attention/executive functions, learning/memory, and language in APOE ε4 carriers only. In ADNI-I, greater WMH burden was associated with worse attention/executive functions and language in APOE ε4 carriers only. No significant associations were observed in noncarriers. Meta-analyses showed that greater WMH volume was associated with worse performance on all cognitive domains in APOE ε4 carriers only.ConclusionAPOE ε4 may influence the association between WMH and cognitive performance in AD and DLB.

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Section: Discussionmentioning

confidence: 99%

Section: Exploratory Neuropathology Sample: Sdsmentioning

confidence: 93%

Section: Neuropathology Methods In Sds (Exploratory Sample)mentioning

confidence: 99%

Section: Settingmentioning

confidence: 99%

Section: Mri (Wmh Volume) Sds Samplementioning

confidence: 99%

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APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

et al. 2019

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Application Challenges in Fiber and Textile Electronics

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The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/adma.201901971. (2 of 25)www.advmat.de www.advancedsciencenews.com energy and then deliver it to power other electronic devices whenever we want. The existing fiber-shaped energy storage devices include the supercapacitor, [15] the lithium (Li)-ion battery, [16] the lithium-sulfur battery, [17] the lithium-air battery, [18] the zinc-air battery, [19] the aluminum-air battery, [20] the sodiumion battery, [21] the zinc-ion battery, [22] and the silver-zinc battery. [23] Among them, the supercapacitor has been reported mostly due to the easy fabrication, and lithium-ion battery has laid the foundation for the development of other fiber-shaped batteries, which are thus discussed mainly in this review. 3) Light-emitting devices have been developed for various applications such as display, illumination, and photo therapy. According to the working mechanisms, there are electroluminescence, [24] mechanoluminescence, [25] photoluminescence, [26] thermoluminescence, [27] sonoluminescence, [28] and chemiluminescence. [29] Among these, fiber-shaped electroluminescent devices have been developed extensively due to their good controllability, driven by direct current (DC) [30] or alternating current (AC) [31] electrical method, which are expounded mainly later. 4) Fibershaped sensors have found great potentials in the field of wearable medical devices for fitness monitoring and medical diagnostics especially as aging populations grow. By virtue of the 1D structure, fiber-shaped sensors can be implanted into the body with little injure or they can detect multiple signals simultaneously after integration into a tiny unit. [32] Fiber-shaped sensors generally work via physical processes on the basis of conducting fiber [33] and optical fiber, [34] and chemical processes based on chemical ligand. [35] Thereinto, fiber optic sensors have already been used in petrochemical, electric power, medical, civil engineering, etc. The detailed discussions about the above three fiber-shaped sensors are presented in the later section.Despite the great progress made in fiber and textile electronics, we have to realize that most of the research results are far from practical applications due to several existing obstacles. The performances of fiber-shaped electronic devices are not good enough to attract investors. For instance, although fiber-shaped solar cells have achieved a record power conversion efficiency (PCE) of 10%, [36] this value falls far below the certified efficiency of 24.2% for planar solar cells. [37] Besides, fiber-shaped electronic devices often decay in performance further as their lengths increase. Apart from low performances, scalable fabrication is another hard nut to crack if fiber-shaped electronic devices are to be commercialized. For one thing, researchers usually can only realize fiber-shaped electronic devices with the lengths from several to hundreds of millimeters at present owing to the absence of appropr...

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Longitudinal association between hippocampus atrophy and episodic‐memory decline in non‐demented APOE ε4 carriers

Gorbach

Pudas

Bartrés‐Faz

et al. 2020

Alzheimer's & Dementia: Diagnosis, Assessment &

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Introduction The apolipoprotein E ( APOE ) ε4 allele is the main genetic risk factor for Alzheimer's disease (AD), accelerated cognitive aging, and hippocampal atrophy, but its influence on the association between hippocampus atrophy and episodic‐memory decline in non‐demented individuals remains unclear. Methods We analyzed longitudinal (two to six observations) magnetic resonance imaging (MRI)–derived hippocampal volumes and episodic memory from 748 individuals (55 to 90 years at baseline, 50% female) from the European Lifebrain consortium. Results The change‐change association for hippocampal volume and memory was significant only in ε4 carriers (N = 173, r = 0.21, P = .007; non‐carriers: N = 467, r = 0.073, P = .117). The linear relationship was significantly steeper for the carriers [t(629) = 2.4, P = .013]. A similar trend toward a stronger change‐change relation for carriers was seen in a subsample with more than two assessments. Discussion These findings provide evidence for a difference in hippocampus‐memory association between ε4 carriers and non‐carriers, thus highlighting how genetic factors modulate the translation of the AD‐related pathophysiological cascade into cognitive deficits.

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APOE‐ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies

Abstract: These findings provide evidence that APOE-ε4 is linked to hippocampal atrophy and learning/memory phenotypes across the AD/DLB spectrum, which could be useful as biomarkers of disease progression in therapeutic trials of mixed disease.

Cited by 40 publications

References 61 publications

APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia

Application Challenges in Fiber and Textile Electronics

Longitudinal association between hippocampus atrophy and episodic‐memory decline in non‐demented APOE ε4 carriers

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