Laboratory for Molecular Neuropsychiatry, Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia.
Department for Biological Psychiatry and Psychogeriatry, University Hospital Vrapce, 10000 Zagreb, Croatia.
Genes (Basel). 2023 Nov 6;14(11):2048. doi: 10.3390/genes14112048.
Dementia is a syndrome of global and progressive deterioration of cognitive skills, especially memory, learning, abstract thinking, and orientation, usually affecting the elderly. The most common forms are Alzheimer's disease, vascular dementia, and other (frontotemporal, Lewy body disease) dementias. The etiology of these multifactorial disorders involves complex interactions of various environmental and (epi)genetic factors and requires multiple forms of pharmacological intervention, including anti-dementia drugs for cognitive impairment, antidepressants, antipsychotics, anxiolytics and sedatives for behavioral and psychological symptoms of dementia, and other drugs for comorbid disorders. The pharmacotherapy of dementia patients has been characterized by a significant interindividual variability in drug response and the development of adverse drug effects. The therapeutic response to currently available drugs is partially effective in only some individuals, with side effects, drug interactions, intolerance, and non-compliance occurring in the majority of dementia patients. Therefore, understanding the genetic basis of a patient's response to pharmacotherapy might help clinicians select the most effective treatment for dementia while minimizing the likelihood of adverse reactions and drug interactions. Recent advances in pharmacogenomics may contribute to the individualization and optimization of dementia pharmacotherapy by increasing its efficacy and safety via a prediction of clinical outcomes. Thus, it can significantly improve the quality of life in dementia patients.
痴呆是一种认知功能(尤其是记忆力、学习能力、抽象思维能力和定向能力)全面且进行性恶化的综合征,通常影响老年人。最常见的形式是阿尔茨海默病、血管性痴呆和其他(额颞叶、路易体病)痴呆。这些多因素疾病的病因涉及各种环境和(表观遗传)因素的复杂相互作用,需要多种形式的药物干预,包括用于认知障碍的抗痴呆药物、抗抑郁药、抗精神病药、用于痴呆的行为和心理症状的抗焦虑药和镇静剂,以及用于合并症的其他药物。痴呆患者的药物治疗具有药物反应个体间显著变异性和不良反应发展的特点。目前可用药物的治疗反应仅对部分个体有效,大多数痴呆患者出现副作用、药物相互作用、不耐受和不依从。因此,了解患者对药物治疗的遗传反应基础可能有助于临床医生在最小化不良反应和药物相互作用的情况下,选择最有效的痴呆治疗方法。药物基因组学的最新进展可能通过预测临床结果来提高药物治疗的疗效和安全性,从而有助于实现痴呆的个体化和优化治疗。因此,它可以显著改善痴呆患者的生活质量。