We report a case of a 77 years old patient who was admitted to our memory clinic because of progressive gait impairment and amnestic cognitive decline associated with extrapyramidal symptoms and behavioral changes. The clinical picture was consistent with a possible diagnosis of Alzheimer’s Disease associated with parkinsonian symptoms or with a Parkinson Plus syndrome. After a complete investigation, she was found to have a high plasma level of homocysteine due to homozygous methylene-tetrahydrofolate reductase (MTHFR) gene C665 T polymorphism, cognitive and motor impairment were associated with a severe cortical atrophy and mild subcortical vascular disease. PET neuroimaging excluded a significant amyloid load. Clinically, she showed improvement of the movement disorder and functional status after folate integration plus levodopa and memantine administration. We concluded for a primary degenerative dementia with movement impairment associated with persistent hyperhomocysteinemia. We hypothesized that neurodegeneration is driven by mechanisms linked to homocysteine metabolism possibly associated with tauopathy.

我们报告了一例 77 岁患者，该患者因进行性步态障碍和与锥体外系症状和行为改变相关的遗忘性认知衰退而入院。临床表现与帕金森症状或帕金森综合征相关的阿尔茨海默病的可能诊断一致。经过全面调查，她被发现由于纯合亚甲基四氢叶酸还原酶 (MTHFR) 基因 C665 T 多态性导致血浆同型半胱氨酸水平较高，认知和运动障碍与严重的皮质萎缩和轻度皮质下血管疾病有关。PET 神经影像学排除了显着的淀粉样蛋白负荷。临床上，在叶酸整合加左旋多巴和美金刚给药后，她表现出运动障碍和功能状态的改善。我们得出结论，患有与持续性高同型半胱氨酸血症相关的运动障碍的原发性退行性痴呆。我们假设神经变性是由与可能与 tau 病变相关的同型半胱氨酸代谢相关的机制驱动的。