Neuropathology and cognitive performance in self-reported cognitively healthy centenarians.
Neuropathology and cognitive performance in self-reported cognitively healthy centenarians.
复制标题
DOI：
10.1186/s40478-018-0558-5
复制
发表时间：
2018-07-23
影响因子：
7.1
通讯作者：
Holstege H
中科院分区：
文献类型：
--
作者：
Ganz AB;Beker N;Hulsman M;Sikkes S;Netherlands Brain Bank;Scheltens P;Smit AB;Rozemuller AJM;Hoozemans JJM;Holstege H
随着年龄的增长，认知健康个体的大脑中神经退行性疾病的神经病理学特征的发生率会增加。目前尚不清楚这些特征在多大程度上与极端年龄的疾病症状有关。来自100多名研究队列的40名百岁老人捐赠了他们的大脑。百岁老人自我报告在基线时认知健康，这一点得到了代理人的证实。生前认知功能的客观测量与年龄和AD相关神经病理学标志的患病率、分布和数量相关。尽管自我报告的认知健康，客观的神经心理学测试表明不同水平的生前认知功能。尸检发现，与年龄和神经退行性疾病相关的神经病理学标志，如Aβ和Tau病理学，以及动脉粥样硬化，在大多数或所有百岁老人中大量存在，而Lewy小体和pTDP-43病理学很少。我们观察到病理负荷增加与病理亚型相关，并且总体趋势是较高的病理负荷与较低的认知测试表现相关。这种趋势尤其表现为存在神经纤维缠结（NFT）和颗粒空泡变性（GVD），以及在较小程度上表现为Aβ相关病理。脑淀粉样血管病（CAA）与百岁老人执行功能低下有关。总之，我们发现，虽然这个队列中的百岁老人逃脱或延迟认知障碍，直到极端的年龄，他们的大脑揭示了不同程度的疾病相关的神经病理学标志，其中一些与认知表现有关。本文的在线版本（10.1186/s40478-018-0558-5）包含补充材料，可供授权用户使用。
With aging, the incidence of neuropathological hallmarks of neurodegenerative diseases increases in the brains of cognitively healthy individuals. It is currently unclear to what extent these hallmarks associate with symptoms of disease at extreme ages. Forty centenarians from the 100-plus Study cohort donated their brain. Centenarians self-reported to be cognitively healthy at baseline, which was confirmed by a proxy. Objective ante-mortem measurements of cognitive performance were associated with the prevalence, distribution and quantity of age- and AD-related neuropathological hallmarks. Despite self-reported cognitive health, objective neuropsychological testing suggested varying levels of ante-mortem cognitive functioning. Post-mortem, we found that neuropathological hallmarks related to age and neurodegenerative diseases, such as Aβ and Tau pathology, as well as atherosclerosis, were abundantly present in most or all centenarians, whereas Lewy body and pTDP-43 pathology were scarce. We observed that increased pathology loads correlated across pathology subtypes, and an overall trend of higher pathology loads to associate with a lower cognitive test performance. This trend was carried especially by the presence of neurofibrillary tangles (NFTs) and granulovacuolar degeneration (GVD) and to a lesser extent by Aβ-associated pathologies. Cerebral Amyloid Angiopathy (CAA) specifically associated with lower executive functioning in the centenarians. In conclusion, we find that while the centenarians in this cohort escaped or delayed cognitive impairment until extreme ages, their brains reveal varying levels of disease-associated neuropathological hallmarks, some of which associate with cognitive performance. The online version of this article (10.1186/s40478-018-0558-5) contains supplementary material, which is available to authorized users.
登录
查看更多内容
影响因子：
12.7
作者：
Kovacs GG;Ferrer I;Grinberg LT;Alafuzoff I;Attems J;Budka H;Cairns NJ;Crary JF;Duyckaerts C;Ghetti B;Halliday GM;Ironside JW;Love S;Mackenzie IR;Munoz DG;Murray ME;Nelson PT;Takahashi H;Trojanowski JQ;Ansorge O;Arzberger T;Baborie A;Beach TG;Bieniek KF;Bigio EH;Bodi I;Dugger BN;Feany M;Gelpi E;Gentleman SM;Giaccone G;Hatanpaa KJ;Heale R;Hof PR;Hofer M;Hortobágyi T;Jellinger K;Jicha GA;Ince P;Kofler J;Kövari E;Kril JJ;Mann DM;Matej R;McKee AC;McLean C;Milenkovic I;Montine TJ;Murayama S;Lee EB;Rahimi J;Rodriguez RD;Rozemüller A;Schneider JA;Schultz C;Seeley W;Seilhean D;Smith C;Tagliavini F;Takao M;Thal DR;Toledo JB;Tolnay M;Troncoso JC;Vinters HV;Weis S;Wharton SB;White CL 3rd;Wisniewski T;Woulfe JM;Yamada M;Dickson DW
通讯作者：
Dickson DW
影响因子：
4.2
作者：
den Dunnen, Wilfred F. A.;Brouwer, Wiebo H.;Holstege, Gert
通讯作者：
Holstege, Gert
影响因子：
11
作者：
Lindeboom, J;Schmand, B;Jonker, C
通讯作者：
Jonker, C
影响因子：
3.9
作者：
Alafuzoff, Irina;Gelpi, Ellen;Kretzschmar, Hans
通讯作者：
Kretzschmar, Hans
DOI：
10.1186/alzrt181
发表时间：
2013
期刊：
Alzheimer's research & therapy
影响因子：
--
作者：
Gardner RC;Valcour V;Yaffe K
通讯作者：
Yaffe K