Clinical Research, Telemedicine and Telepharmacy Centre, University of Camerino, Camerino, Italy.
Neurology Unit, National Hospital "A. Cardarelli", Naples, Italy.
J Alzheimers Dis. 2020;76(1):317-329. doi: 10.3233/JAD-190623.
Cerebral atrophy is a common feature of several neurodegenerative disorders, including Alzheimer's disease (AD). In AD, brain atrophy is associated with loss of gyri and sulci in the temporal and parietal lobes, and in parts of the frontal cortex and cingulate gyrus.
The ASCOMALVA trial has assessed, in addition to neuropsychological analysis, whether the addition of the cholinergic precursor choline alphoscerate to treatment with donepezil has an effect on brain volume loss in patients affected by AD associated with cerebrovascular injury.
56 participants to the randomized, placebo-controlled, double-blind ASCOMALVA trial were assigned to donepezil + placebo (D + P) or donepezil + choline alphoscerate (D + CA) treatments and underwent brain magnetic resonance imaging and neuropsychological tests every year for 4 years. An interim analysis of 3-year MRI data was performed by voxel morphometry techniques.
The D + P group (n = 27) developed atrophy of the gray and white matter with concomitant increase in ventricular space volume. In the D + CA group (n = 29) the gray matter atrophy was less pronounced compared to the D + P group in frontal and temporal lobes, hippocampus, and amygdala. These morphological data are consistent with the results of the neuropsychological tests.
Our findings indicate that the addition of choline alphoscerate to standard treatment with the cholinesterase inhibitor donepezil counters to some extent the loss in volume occurring in some brain areas of AD patients. The observation of parallel less pronounced decrease in cognitive and functional tests in patients with the same treatment suggests that the morphological changes observed may have functional relevance.
脑萎缩是几种神经退行性疾病的共同特征，包括阿尔茨海默病（AD）。在 AD 中，脑萎缩与颞叶和顶叶的脑回和脑沟以及额叶皮质和扣带回的部分区域的丧失有关。
ASCOMALVA 试验除了神经心理学分析外，还评估了在 AD 患者中，在使用多奈哌齐治疗的基础上添加胆碱前体氯化胆碱是否对与脑血管损伤相关的脑容量损失有影响。
56 名随机、安慰剂对照、双盲 ASCOMALVA 试验的参与者被分配到多奈哌齐+安慰剂（D+P）或多奈哌齐+氯化胆碱（D+CA）治疗组，并在 4 年内每年接受脑磁共振成像和神经心理学测试。通过体素形态计量技术对 3 年 MRI 数据进行了中期分析。
D+P 组（n=27）出现灰质和白质萎缩，同时脑室空间体积增加。在 D+CA 组（n=29）中，与 D+P 组相比，额叶和颞叶、海马体和杏仁核的灰质萎缩程度较轻。这些形态学数据与神经心理学测试的结果一致。
我们的发现表明，在标准的胆碱酯酶抑制剂多奈哌齐治疗基础上添加氯化胆碱在一定程度上抵消了 AD 患者某些脑区的体积损失。对接受相同治疗的患者进行认知和功能测试平行且程度较轻的下降的观察表明，观察到的形态变化可能具有功能相关性。
