Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study
Clinical and cognitive trajectories in cognitively healthy elderly individuals with suspected non-Alzheimer's disease pathophysiology (SNAP) or Alzheimer's disease pathology: a longitudinal study
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DOI：
10.1016/s1474-4422(16)30125-9
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发表时间：
2016-09-01
期刊：
影响因子：
48
通讯作者：
Villemagne, Victor L.
中科院分区：
文献类型：
--
作者：
Burnham, Samantha C.;Bourgeat, Pierrick;Villemagne, Victor L.
研究背景：脑淀粉样蛋白β（A β）沉积和神经退行性变在大约50-60%的认知健康的老年人（60岁或以上）中有记录。阿尔茨海默病病理学和神经退行性变的长期认知后果，以及它们对认知是否有独立或协同作用，尚不清楚。我们的目的是使用两个标记来描述健康老年人的长期临床和认知轨迹。方法在2006年11月3日至2014年11月25日期间，在澳大利亚墨尔本和珀斯的573名认知健康个体，（平均年龄73.1岁[SD 6.2]; 58%为女性）入组澳大利亚成像、生物标志物和生活方式（Aibl）研究。通过PET测量A β沉积来确定阿尔茨海默病病理学（A），并通过使用MRI测量海马体积来建立神经变性（N）。个体被分类为A（-）N（-）、A（+）N（-）、A（+）N（+）或疑似非阿尔茨海默病病理生理学（A（-）N（+），SNAP）。在6年的随访中评估了临床进展、海马体积、标准神经心理学测试以及特定领域和整体认知综合评分。采用线性混合效应模型和生存率的考克斯比例风险模型来评估、比较和对比四种AN类别患者的临床、认知和体积轨迹。SNAP 126例（22%）。A（+）N（+）（27; 54%）和A（+）N（-）（42; 48%）组的受试者中APOE β 4的频率高于A（-）N（-）（66; 21%）和SNAP组（23; 18%）。A（+）N（-）和A（+）N（+）组的认知功能下降明显快于A（-）N（-）组（AIBL-临床前AD认知复合量表[PACC]为0.08 SD/年; p
Background Brain amyloid beta (A beta) deposition and neurodegeneration have been documented in about 50-60% of cognitively healthy elderly individuals (aged 60 years or older). The long-term cognitive consequences of the presence of Alzheimer's disease pathology and neurodegeneration, and whether they have an independent or synergistic effect on cognition, are unclear. We aimed to characterise the long-term clinical and cognitive trajectories of healthy elderly individuals using a two-marker (Alzheimer's disease pathology and neurodegeneration) imaging construct.Methods Between Nov 3, 2006, and Nov 25, 2014, 573 cognitively healthy individuals in Melbourne and Perth, Australia, (mean age 73.1 years [SD 6.2]; 58% women) were enrolled in the Australian Imaging, Biomarker and Lifestyle (AIBL) study. Alzheimer's disease pathology (A) was determined by measuring A beta deposition by PET, and neurodegeneration (N) was established by measuring hippocampal volume using MRI. Individuals were categorised as A(-)N(-) , A(+)N(-), A(+)N(+), or suspected non-Alzheimer's disease pathophysiology (A(-)N(+), SNAP). Clinical progression, hippocampal volume, standard neuropsychological tests, and domain-specific and global cognitive composite scores were assessed over 6 years of follow-up. Linear mixed effect models and a Cox proportional hazards model of survival were used to evaluate, compare, and contrast the clinical, cognitive, and volumetric trajectories of patients in the four AN categories.Findings 50 (9%) healthy individuals were classified as A(+)N(+), 87 (15%) as A(+)N(-), 310 (54%) as A(-)N(-), and 126 (22%) as SNAP. APOE epsilon 4 was more frequent in participants in the A(+)N(+) (27; 54%) and A(+)N(-) (42; 48%) groups than in the A(-)N(-) ( 66; 21%) and SNAP groups (23; 18%). The A(+)N(-) and A(+)N(+) groups had significantly faster cognitive decline than the A(-)N(-) group (0.08 SD per year for AIBL-Preclinical AD Cognitive Composite [PACC]; p