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      The role of APOE-ɛ4 and beta amyloid in the differential rate of recovery from ECT: a review

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          Abstract

          Individual biological differences may contribute to the variability of outcomes, including cognitive effects, observed following electroconvulsive treatment (ECT). A narrative review of the research literature on carriage of the apolipoprotein E ɛ4 allele ( APOE-ɛ4) and the protein biomarker beta amyloid (Aβ) with ECT cognitive outcome was undertaken. ECT induces repeated brain seizures and there is debate as to whether this causes brain injury and long-term cognitive disruption. The majority of ECT is administered to the elderly (over age 65 years) with drug-resistant depression. Depression in the elderly may be a symptom of the prodromal stage of Alzheimer's disease (AD). Carriage of the APOE-ɛ4 allele and raised cerebral Aβ are consistently implicated in AD, but inconsistently implicated in brain injury (and related syndromes) recovery rates. A paucity of brain-related recovery, genetic and biomarker research in ECT responses in the elderly was found: three studies have examined the effect of APOE-ɛ4 allele carriage on cognition in the depressed elderly receiving ECT, and two have examined Aβ changes after ECT, with contradictory findings. Cognitive changes in all studies of ECT effects were measured by a variety of psychological tests, making comparisons of such changes between studies problematic. Further, psychological test data-validity measures were not routinely administered, counter to current testing recommendations. The methodological issues of the currently available literature as well as the need for well-designed, hypothesis driven, longitudinal studies are discussed.

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          Most cited references58

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          Episodic memory: from mind to brain.

          Episodic memory is a neurocognitive (brain/mind) system, uniquely different from other memory systems, that enables human beings to remember past experiences. The notion of episodic memory was first proposed some 30 years ago. At that time it was defined in terms of materials and tasks. It was subsequently refined and elaborated in terms of ideas such as self, subjective time, and autonoetic consciousness. This chapter provides a brief history of the concept of episodic memory, describes how it has changed (indeed greatly changed) since its inception, considers criticisms of it, and then discusses supporting evidence provided by (a) neuropsychological studies of patterns of memory impairment caused by brain damage, and (b) functional neuroimaging studies of patterns of brain activity of normal subjects engaged in various memory tasks. I also suggest that episodic memory is a true, even if as yet generally unappreciated, marvel of nature.
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            Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease.

            Apolipoprotein E is immunochemically localized to the senile plaques, vascular amyloid, and neurofibrillary tangles of Alzheimer disease. In vitro, apolipoprotein E in cerebrospinal fluid binds to synthetic beta A4 peptide (the primary constituent of the senile plaque) with high avidity. Amino acids 12-28 of the beta A4 peptide are required. The gene for apolipoprotein E is located on chromosome 19q13.2, within the region previously associated with linkage of late-onset familial Alzheimer disease. Analysis of apolipoprotein E alleles in Alzheimer disease and controls demonstrated that there was a highly significant association of apolipoprotein E type 4 allele (APOE-epsilon 4) and late-onset familial Alzheimer disease. The allele frequency of the APOE-epsilon 4 in 30 random affected patients, each from a different Alzheimer disease family, was 0.50 +/- 0.06; the allele frequency of APOE-epsilon 4 in 91 age-matched unrelated controls was 0.16 +/- 0.03 (Z = 2.44, P = 0.014). A functional role of the apolipoprotein E-E4 isoform in the pathogenesis of late-onset familial Alzheimer disease is suggested.
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              Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease.

              Apolipoprotein E, type epsilon 4 allele (APOE epsilon 4), is associated with late-onset familial Alzheimer's disease (AD). There is high avidity and specific binding of amyloid beta-peptide with the protein ApoE. To test the hypothesis that late-onset familial AD may represent the clustering of sporadic AD in families large enough to be studied, we extended the analyses of APOE alleles to several series of sporadic AD patients. APOE epsilon 4 is significantly associated with a series of probable sporadic AD patients (0.36 +/- 0.042, AD, versus 0.16 +/- 0.027, controls [allele frequency estimate +/- standard error], p = 0.00031). Spouse controls did not differ from CEPH grandparent controls from the Centre d'Etude du Polymorphisme Humain (CEPH) or from literature controls. A large combined series of autopsy-documented sporadic AD patients also demonstrated highly significant association with the APOE epsilon 4 allele (0.40 +/- 0.026, p < or = 0.00001). These data support the involvement of ApoE epsilon 4 in the pathogenesis of late-onset familial and sporadic AD. ApoE isoforms may play an important role in the metabolism of beta-peptide, and APOE epsilon 4 may operate as a susceptibility gene (risk factor) for the clinical expression of AD.
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                Author and article information

                Journal
                Transl Psychiatry
                Transl Psychiatry
                Translational Psychiatry
                Nature Publishing Group
                2158-3188
                March 2015
                31 March 2015
                1 March 2015
                : 5
                : 3
                : e539
                Affiliations
                [1 ]School of Psychiatry and Clinical Neurosciences, University of Western Australia , Crawley, WA, Australia
                [2 ]Centre of Excellence for Alzheimer's Disease Research and Care, School of Medical Sciences, Edith Cowan University , Joondalup, WA, Australia
                [3 ]Sir James McCusker Alzheimer's Disease Research Unit, Hollywood Private Centre , Nedlands, WA, Australia
                [4 ]School of Psychology, University of Western Australia, Hollywood Private Hospital , Nedlands, WA, Australia
                Author notes
                [* ]Sir James McCusker Alzheimer's Disease Research Unit, Suite 22, Hollywood Medical Centre, 85 Monash Avenue , Nedlands, WA 6009, Australia. E-mail: ralph.n.martins@ 123456gmail.com
                Article
                tp201539
                10.1038/tp.2015.39
                4429172
                25826114
                0815c6eb-e68d-4e59-8d12-354a11a3290d
                Copyright © 2015 Macmillan Publishers Limited

                This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

                History
                : 16 December 2014
                : 27 January 2015
                : 23 February 2015
                Categories
                Review

                Clinical Psychology & Psychiatry
                Clinical Psychology & Psychiatry

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