Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders.
Genetic risk for Alzheimer's disease alters the five-year trajectory of semantic memory activation in cognitively intact elders.
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DOI：
10.1016/j.neuroimage.2015.02.011
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发表时间：
2015-05-01
期刊：
影响因子：
5.7
通讯作者：
Durgerian S
中科院分区：
文献类型：
--
作者：
Rao SM;Bonner-Jackson A;Nielson KA;Seidenberg M;Smith JC;Woodard JL;Durgerian S
与年轻人相比，健康衰老与认知能力下降有关，通常伴随着与任务相关的大脑活动增加。衰老与认知的支架理论（STAC）认为，代偿性脑过程负责维持老年人正常的认知表现，尽管积累了与衰老相关的神经损伤。横断面研究表明，与低风险老年人相比，具有阿尔茨海默病遗传风险的认知完整老年人的大脑活动模式增加，这表明代偿代表了对阿尔茨海默病相关病理的早期反应。这种代偿反应是否随着认知障碍的发生而持续或减弱，只能通过纵向设计来解决。目前的前瞻性，5年的纵向研究检查了APOE ε4携带者（N=24）和非携带者（N=21）的大脑激活情况。所有年龄在65-85岁、在研究开始时认知完整的参与者在基线、18和57个月时接受了任务激活功能磁共振成像（fMRI）、结构磁共振成像（MRI）和神经心理学评估。在语义记忆任务要求参与者区分名人和非名人时，测量了fMRI的激活情况。结果表明，APOE ε4携带者和非携带者在执行语义记忆任务时的脑激活变化轨迹存在差异。APOE ε4组在基线时比低风险组表现出更大的激活，但在随后的随访期间，APOE ε4组的激活逐渐下降，并出现相应的情景记忆丧失和海马萎缩。相比之下，非携带者在5年的时间里表现出逐渐增加的激活。我们的结果与STAC模型一致，表明代偿随潜在神经损伤的严重程度而变化，并可能随着认知症状的发作和脑结构病理的增加而耗尽。我们的fMRI结果不能归因于任务表现的变化、脑灌注的组间差异或区域皮质萎缩。
Healthy aging is associated with cognitive declines typically accompanied by increased task-related brain activity in comparison to younger counterparts. The Scaffolding Theory of Aging and Cognition (STAC) posits that compensatory brain processes are responsible for maintaining normal cognitive performance in older adults, despite accumulation of aging-related neural damage. Cross-sectional studies indicate that cognitively intact elders at genetic risk for Alzheimer’s disease (AD) demonstrate patterns of increased brain activity compared to low risk elders, suggesting that compensation represents an early response to AD-associated pathology. Whether this compensatory response persists or declines with the onset of cognitive impairment can only be addressed using a longitudinal design. The current prospective, 5-year longitudinal study examined brain activation in APOE ε4 carriers (N=24) and non-carriers (N=21). All participants, ages 65–85 and cognitively intact at study entry, underwent task-activated fMRI, structural MRI, and neuropsychological assessments at baseline, 18, and 57 months. fMRI activation was measured in response to a semantic memory task requiring participants to discriminate famous from non-famous names. Results indicated that the trajectory of change in brain activation while performing this semantic memory task differed between APOE ε4 carriers and non-carriers. The APOE ε4 group exhibited greater activation than the Low Risk group at baseline, but they subsequently showed a progressive decline in activation during the follow-up periods with corresponding emergence of episodic memory loss and hippocampal atrophy. In contrast, the non-carriers demonstrated a gradual increase in activation over the 5-year period. Our results are consistent with the STAC model by demonstrating that compensation varies with the severity of underlying neural damage and can be exhausted with the onset of cognitive symptoms and increased structural brain pathology. Our fMRI results could not be attributed to changes in task performance, group differences in cerebral perfusion, or regional cortical atrophy.
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DOI：
10.1017/s1355617712000951
发表时间：
2013-01
影响因子：
2.6
作者：
Hantke, Nathan;Nielson, Kristy A.;Woodard, John L.;Breting, Leslie M. Guidotti;Butts, Alissa;Seidenberg, Michael;Smith, J. Carson;Durgerian, Sally;Lancaster, Melissa;Matthews, Monica;Sugarman, Michael A.;Rao, Stephen M.
通讯作者：
Rao, Stephen M.
DOI：
10.1093/brain/awq277
发表时间：
2010-11
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Jack CR Jr;Wiste HJ;Vemuri P;Weigand SD;Senjem ML;Zeng G;Bernstein MA;Gunter JL;Pankratz VS;Aisen PS;Weiner MW;Petersen RC;Shaw LM;Trojanowski JQ;Knopman DS;Alzheimer's Disease Neuroimaging Initiative
通讯作者：
Alzheimer's Disease Neuroimaging Initiative
影响因子：
4.8
作者：
FOLSTEIN, MF;FOLSTEIN, SE;MCHUGH, PR
通讯作者：
MCHUGH, PR
DOI：
10.1017/s1355617712000197
发表时间：
2012-05
影响因子：
2.6
作者：
Bangen, Katherine J.;Kaup, Allison R.;Mirzakhanian, Heline;Wierenga, Christina E.;Jeste, Dilip V.;Eyler, Lisa T.
通讯作者：
Eyler, Lisa T.
影响因子：
2.6
作者：
Douville, K;Woodard, JL;Rao, SA
通讯作者：
Rao, SA