Performance on complex memory tests is associated with β-amyloid in individuals at risk of developing Alzheimer's disease

IF 2 4区 心理学 Q2 PSYCHOLOGY
Pernille Louise Kjeldsen, Malene Flensborg Damholdt, Lasse Stensvig Madsen, Peter Henrik Nissen, Joel Fredrik Astrup Aanerud, Peter Parbo, Rola Ismail, Malene Kaasing, Simon Fristed Eskildsen, Leif Østergaard, David James Brooks
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Abstract

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta-amyloid (Aβ) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2–3 times and is associated with earlier Aβ accumulation. Although it is difficult to identify Aβ-related cognitive impairment in early AD with standard cognitive tests, more sensitive memory tests may be able to do this. We sought to examine associations between Aβ and performance on three tests within three subdomains of memory, verbal, visual, and associative memory, to elucidate which of these tests were sensitive to Aβ-related cognitive impairment in at-risk subjects. 55 APOE ε4 carriers underwent MRI, 11C-Pittsburgh Compound B (PiB) PET, and cognitive testing. A composite cortical PiB SUVR cut-off score of 1.5 was used to categorise subjects as either APOE ε4 Aβ+ or APOE ε4 Aβ−. Correlations were carried out using cortical surface analysis. In the whole APOE ε4 group, we found significant correlations between Aβ load and performance on verbal, visual, and associative memory tests in widespread cortical areas, the strongest association being with performance on associative memory tests. In the APOE ε4 Aβ+ group, we found significant correlations between Aβ load and performance of verbal and associative, but not visual, memory in localised cortical areas. Performance on verbal and associative memory tests provides sensitive markers of early Aβ-related cognitive impairment in at-risk subjects.

Abstract Image

在阿尔茨海默氏症高危人群中,复杂记忆测试的成绩与β-淀粉样蛋白有关。
阿尔茨海默病(AD)的病理生理学发展始于临床症状出现前数年的大脑中。β-淀粉样蛋白(Aβ)的积累被认为是最先出现的大脑皮层病理变化。携带一个载脂蛋白E(APOE)ε4等位基因会使罹患AD的风险至少增加2-3倍,并且与更早的Aβ积累有关。虽然标准认知测试很难识别早期 AD 中与 Aβ 相关的认知障碍,但更灵敏的记忆测试或许可以做到这一点。我们试图研究 Aβ 与记忆的三个子领域(言语记忆、视觉记忆和联想记忆)中的三种测试表现之间的关联,以阐明这些测试中哪些对高危受试者的 Aβ 相关认知障碍敏感。55 名 APOE ε4 携带者接受了核磁共振成像、11 C 匹兹堡化合物 B(PiB)PET 和认知测试。皮质 PiB SUVR 综合临界值为 1.5,用于将受试者分为 APOE ε4 Aβ+ 或 APOE ε4 Aβ-。使用皮质表面分析法进行相关分析。在整个 APOE ε4 组中,我们发现在广泛的皮层区域中,Aβ 负荷与言语、视觉和联想记忆测试成绩之间存在显著相关性,其中与联想记忆测试成绩的相关性最强。在 APOE ε4 Aβ+ 组中,我们发现 Aβ 负荷与大脑皮层局部区域的言语记忆和联想记忆的表现有显著相关性,但与视觉记忆的表现无显著相关性。语言和联想记忆测试的表现为高危人群早期与Aβ相关的认知障碍提供了敏感的标记。
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来源期刊
Journal of Neuropsychology
Journal of Neuropsychology 医学-心理学
CiteScore
4.50
自引率
4.50%
发文量
34
审稿时长
>12 weeks
期刊介绍: The Journal of Neuropsychology publishes original contributions to scientific knowledge in neuropsychology including: • clinical and research studies with neurological, psychiatric and psychological patient populations in all age groups • behavioural or pharmacological treatment regimes • cognitive experimentation and neuroimaging • multidisciplinary approach embracing areas such as developmental psychology, neurology, psychiatry, physiology, endocrinology, pharmacology and imaging science The following types of paper are invited: • papers reporting original empirical investigations • theoretical papers; provided that these are sufficiently related to empirical data • review articles, which need not be exhaustive, but which should give an interpretation of the state of research in a given field and, where appropriate, identify its clinical implications • brief reports and comments • case reports • fast-track papers (included in the issue following acceptation) reaction and rebuttals (short reactions to publications in JNP followed by an invited rebuttal of the original authors) • special issues.
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