Luzzi Simona, Cherubini Veronica, Falsetti Lorenzo, Viticchi Giovanna, Silvestrini Mauro, Toraldo Alessio
Neurology Unit, Department of Experimental and Clinical Medicine, Polytechnic University of Marche, 60126 Ancona, Italy.
Internal and Subintensive Medicine Department, Azienda Ospedaliero-Universitaria "Ospedali Riuniti" di Ancona, 60126 Ancona, Italy.
Biomedicines. 2022 Oct 28;10(11):2741. doi: 10.3390/biomedicines10112741.
There is strong evidence that homocysteine is a risk factor not only for cerebrovascular diseases but also for degenerative dementias. A recent consensus statement renewed the importance and the role of high levels of homocysteine in cognitive decline in several forms of degenerative dementia, such as Alzheimer's disease. Although the molecular mechanisms by which homocysteine causes cell dysfunction are known, both the impact of homocysteine on specific cognitive functions and the relationship between homocysteine level and non-Alzheimer dementias have been poorly investigated. Most of the studies addressing the impact of hyperhomocysteinemia on dementias have not examined the profile of performance across different cognitive domains, and have only relied on screening tests, which provide a very general and coarse-grained picture of the cognitive status of the patients. Yet, trying to understand whether hyperhomocysteinemia is associated with the impairment of specific cognitive functions would be crucial, as it would be, in parallel, learning whether some brain circuits are particularly susceptible to the damage caused by hyperhomocysteinemia. These steps would allow one to (i) understand the actual role of homocysteine in the pathogenesis of cognitive decline and (ii) improve the diagnostic accuracy, differential diagnosis and prognostic implications. This review is aimed at exploring and revising the state of the art of these two strictly related domains. Suggestions for future research are provided.
有充分证据表明，同型半胱氨酸不仅是脑血管疾病的危险因素，也是退行性痴呆的危险因素。最近的一份共识声明再次强调了高同型半胱氨酸水平在几种形式的退行性痴呆（如阿尔茨海默病）认知衰退中的重要性和作用。尽管已知同型半胱氨酸导致细胞功能障碍的分子机制，但同型半胱氨酸对特定认知功能的影响以及同型半胱氨酸水平与非阿尔茨海默病痴呆之间的关系尚未得到充分研究。大多数研究高同型半胱氨酸血症对痴呆影响的研究并未考察不同认知领域的表现概况，仅依赖筛查测试，而这些测试只能提供患者认知状态非常笼统和粗略的情况。然而，了解高同型半胱氨酸血症是否与特定认知功能受损相关至关重要，因为与此同时，这也有助于了解某些脑回路是否特别容易受到高同型半胱氨酸血症造成的损害。这些步骤将使人们能够：（i）了解同型半胱氨酸在认知衰退发病机制中的实际作用；（ii）提高诊断准确性、鉴别诊断和预后意义。本综述旨在探讨和审视这两个密切相关领域的现有研究状况，并提供未来研究的建议。
