Johnson Sterling C, Christian Bradley T, Okonkwo Ozioma C, Oh Jennifer M, Harding Sandra, Xu Guofan, Hillmer Ansel T, Wooten Dustin W, Murali Dhanabalan, Barnhart Todd E, Hall Lance T, Racine Annie M, Klunk William E, Mathis Chester A, Bendlin Barbara B, Gallagher Catherine L, Carlsson Cynthia M, Rowley Howard A, Hermann Bruce P, Dowling N Maritza, Asthana Sanjay, Sager Mark A
Geriatric Research Education and Clinical Center, Wm. S. Middleton Memorial VA Hospital, Madison, WI, USA; Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA; Wisconsin Alzheimer's Institute, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
Neurobiol Aging. 2014 Mar;35(3):576-84. doi: 10.1016/j.neurobiolaging.2013.09.028. Epub 2013 Oct 23.
To determine the relationship between amyloid burden and neural function in healthy adults at risk for Alzheimer's Disease (AD), we used multimodal imaging with [C-11]Pittsburgh compound B positron emission tomography, [F-18]fluorodeoxyglucose, positron emission tomography , and magnetic resonance imaging, together with cognitive measurement in 201 subjects (mean age, 60.1 years; range, 46-73 years) from the Wisconsin Registry for Alzheimer's Prevention. Using a qualitative rating, 18% of the samples were strongly positive Beta-amyloid (Aβ+), 41% indeterminate (Aβi), and 41% negative (Aβ-). Aβ+ was associated with older age, female sex, and showed trends for maternal family history of AD and APOE4. Relative to the Aβ- group, Aβ+ and Aβi participants had increased glucose metabolism in the bilateral thalamus; Aβ+ participants also had increased metabolism in the bilateral superior temporal gyrus. Aβ+ participants exhibited increased gray matter in the lateral parietal lobe bilaterally relative to the Aβ- group, and no areas of significant atrophy. Cognitive performance and self report cognitive and affective symptoms did not differ between groups. Amyloid burden can be identified in adults at a mean age of 60 years and is accompanied by glucometabolic increases in specific areas, but not atrophy or cognitive loss. This asymptomatic stage may be an opportune window for intervention to prevent progression to symptomatic AD.
为了确定有患阿尔茨海默病(AD)风险的健康成年人中淀粉样蛋白负荷与神经功能之间的关系,我们对来自威斯康星州阿尔茨海默病预防登记处的201名受试者(平均年龄60.1岁;范围46 - 73岁)进行了多模态成像,包括[C - 11]匹兹堡化合物B正电子发射断层扫描、[F - 18]氟脱氧葡萄糖正电子发射断层扫描以及磁共振成像,并进行了认知测量。采用定性评分,18%的样本为强阳性β淀粉样蛋白(Aβ+),41%为不确定(Aβi),41%为阴性(Aβ-)。Aβ+与年龄较大、女性性别相关,并且在AD的母系家族史和APOE4方面呈现出一定趋势。相对于Aβ-组,Aβ+和Aβi参与者双侧丘脑的葡萄糖代谢增加;Aβ+参与者双侧颞上回的代谢也增加。相对于Aβ-组,Aβ+参与者双侧外侧顶叶的灰质增加,且无明显萎缩区域。各组之间的认知表现以及自我报告的认知和情感症状没有差异。淀粉样蛋白负荷可在平均年龄60岁的成年人中被识别,并且伴有特定区域的葡萄糖代谢增加,但没有萎缩或认知丧失。这个无症状阶段可能是进行干预以预防进展为有症状AD的合适时机。