Fessel Jeffrey
Professor of Clinical Medicine, Emeritus Department of Medicine University of California, San Francisco San Francisco California USA.
Alzheimers Dement (N Y). 2021 Jul 28;7(1):e12199. doi: 10.1002/trc2.12199. eCollection 2021.
It is better to attempt stopping Alzheimer's disease (AD) before it starts than trying to cure it after it has developed. A cerebral scan showing deposition of either amyloid or tau identifies those elderly persons whose cognition is currently normal but who are at risk of subsequent cognitive loss that may develop into AD. Synaptic hypometabolism is usually present in such at-risk persons. Although inadequate adenosine triphosphate (ATP) may cause synaptic hypometabolism, that may not be the entire cause because, in fact, measurements in some of the at-risk persons have shown normal ATP levels. Thiamine deficiency is often seen in elderly, ambulatory persons in whom thiamine levels correlate with Mini-Mental State Examination scores. Thiamine deficiency has many consequences including hypometabolism, mitochondrial depression, oxidative stress, lactic acidosis and cerebral acidosis, amyloid deposition, tau deposition, synaptic dysfunction and abnormal neuro-transmission, astrocyte function, and blood brain barrier integrity, all of which are features of AD. Although the clinical benefits of administering supplementary thiamine to patients with AD or mild cognitive impairment have been mixed, it is more likely to succeed at preventing the onset of cognitive loss if administered at an earlier time, when the number of aberrant biochemical pathways is far fewer. Providing a thiamine supplement to elderly persons who still have normal cognition but who have deposition of either amyloid or tau, may prevent subsequent cognitive loss and eventual dementia. A clinical trial is needed to validate that possibility.
在阿尔茨海默病（AD）发病前尝试阻止它，要比在其发病后试图治愈它更好。脑部扫描显示淀粉样蛋白或tau蛋白沉积，可识别出那些认知目前正常但有随后发生认知丧失风险、可能发展为AD的老年人。突触代谢减退通常存在于这类有风险的人群中。虽然三磷酸腺苷（ATP）不足可能导致突触代谢减退，但这可能不是全部原因，因为事实上，对一些有风险人群的测量显示ATP水平正常。硫胺素缺乏在能走动的老年人中经常可见，硫胺素水平与简易精神状态检查表评分相关。硫胺素缺乏有许多后果，包括代谢减退、线粒体抑制、氧化应激、乳酸酸中毒和脑酸中毒、淀粉样蛋白沉积、tau蛋白沉积、突触功能障碍和神经传递异常、星形胶质细胞功能以及血脑屏障完整性，所有这些都是AD的特征。虽然给AD患者或轻度认知障碍患者补充硫胺素的临床益处不一，但如果在更早的时候给药，当异常生化途径的数量少得多时，更有可能成功预防认知丧失的发生。给认知仍正常但有淀粉样蛋白或tau蛋白沉积的老年人补充硫胺素，可能预防随后的认知丧失和最终的痴呆。需要进行一项临床试验来验证这种可能性。
