淀粉样蛋白和tau 阳性对认知正常个体纵向脑萎缩的影响。
Impact of amyloid and tau positivity on longitudinal brain atrophy in cognitively normal individuals.
机构信息
Department of Radiology, Kumagaya General Hospital, 4-5-1 Nakanishi, Kumagaya, 360-8567, Japan.
Department of Biostatistics, Graduate School of Medicine, Saitama Medical University, 38 Morohongo, Moroyama, 350-0495, Japan.
出版信息
Alzheimers Res Ther. 2024 Apr 10;16(1):77. doi: 10.1186/s13195-024-01450-7.
BACKGROUND
Individuals on the preclinical Alzheimer's continuum, particularly those with both amyloid and tau positivity (A + T +), display a rapid cognitive decline and elevated disease progression risk. However, limited studies exist on brain atrophy trajectories within this continuum over extended periods.
METHODS
This study involved 367 ADNI participants grouped based on combinations of amyloid and tau statuses determined through cerebrospinal fluid tests. Using longitudinal MRI scans, brain atrophy was determined according to the whole brain, lateral ventricle, and hippocampal volumes and cortical thickness in AD-signature regions. Cognitive performance was evaluated with the Preclinical Alzheimer's Cognitive Composite (PACC). A generalized linear mixed-effects model was used to examine group × time interactions for these measures. In addition, progression risks to mild cognitive impairment (MCI) or dementia were compared among the groups using Cox proportional hazards models.
RESULTS
A total of 367 participants (48 A + T + , 86 A + T - , 63 A - T + , and 170 A - T - ; mean age 73.8 years, mean follow-up 5.1 years, and 47.4% men) were included. For the lateral ventricle and PACC score, the A + T - and A + T + groups demonstrated statistically significantly greater volume expansion and cognitive decline over time than the A - T - group (lateral ventricle: β = 0.757 cm/year [95% confidence interval 0.463 to 1.050], P < .001 for A + T - , and β = 0.889 cm/year [0.523 to 1.255], P < .001 for A + T + ; PACC: β = - 0.19 /year [- 0.36 to - 0.02], P = .029 for A + T - , and β = - 0.59 /year [- 0.80 to - 0.37], P < .001 for A + T +). Notably, the A + T + group exhibited additional brain atrophy including the whole brain (β = - 2.782 cm/year [- 4.060 to - 1.504], P < .001), hippocampus (β = - 0.057 cm/year [- 0.085 to - 0.029], P < .001), and AD-signature regions (β = - 0.02 mm/year [- 0.03 to - 0.01], P < .001). Cox proportional hazards models suggested an increased risk of progressing to MCI or dementia in the A + T + group versus the A - T - group (adjusted hazard ratio = 3.35 [1.76 to 6.39]).
CONCLUSIONS
In cognitively normal individuals, A + T + compounds brain atrophy and cognitive deterioration, amplifying the likelihood of disease progression. Therapeutic interventions targeting A + T + individuals could be pivotal in curbing brain atrophy, cognitive decline, and disease progression.
背景
处于临床前阿尔茨海默病连续体的个体，特别是那些同时具有淀粉样蛋白和 tau 阳性（A+T+）的个体，表现出快速的认知衰退和更高的疾病进展风险。然而，在这个连续体中，关于在较长时间内脑萎缩轨迹的研究有限。
方法
本研究纳入了 367 名 ADNI 参与者，根据通过脑脊液测试确定的淀粉样蛋白和 tau 状态组合进行分组。使用纵向 MRI 扫描，根据全脑、侧脑室和海马体积以及 AD 特征区域的皮质厚度来确定脑萎缩。使用 Preclinical Alzheimer's Cognitive Composite（PACC）评估认知表现。使用广义线性混合效应模型来检查这些指标的组×时间交互作用。此外，使用 Cox 比例风险模型比较了各组向轻度认知障碍（MCI）或痴呆的进展风险。
结果
共纳入 367 名参与者（48 名 A+T+、86 名 A+T-、63 名 A-T+和 170 名 A-T-；平均年龄 73.8 岁，平均随访 5.1 年，47.4%为男性）。对于侧脑室和 PACC 评分，A+T-和 A+T+组的体积扩张和认知下降速度明显快于 A-T-组（侧脑室：β=0.757 cm/年[95%置信区间 0.463 至 1.050]，P<0.001 用于 A+T-，β=0.889 cm/年[0.523 至 1.255]，P<0.001 用于 A+T+；PACC：β=-0.19/年[-0.36 至 0.02]，P=0.029 用于 A+T-，β=-0.59/年[-0.80 至-0.37]，P<0.001 用于 A+T+）。值得注意的是，A+T+组还表现出包括全脑（β=-2.782 cm/年[-4.060 至-1.504]，P<0.001）、海马（β=-0.057 cm/年[-0.085 至-0.029]，P<0.001）和 AD 特征区域（β=-0.02mm/年[-0.03 至-0.01]，P<0.001）在内的额外脑萎缩。Cox 比例风险模型表明，与 A-T-组相比，A+T+组向 MCI 或痴呆进展的风险增加（调整后的危险比=3.35[1.76 至 6.39]）。
结论
在认知正常的个体中，A+T+会加剧脑萎缩和认知恶化，增加疾病进展的可能性。针对 A+T+个体的治疗干预可能是抑制脑萎缩、认知衰退和疾病进展的关键。
Zotero 插件