International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 355-368 http://medscipublisher.com/index.php/ijmms 363 Clinical decision support tools that incorporate genomic data are being developed to guide personalized interventions, including targeted diet and lifestyle modifications, as well as the use of supplements with a "generally regarded as safe" (GRAS) rating (Hausman-Cohen et al., 2022). These approaches aim to address the specific genetic and environmental factors contributing to each patient's condition, thereby optimizing treatment efficacy. 8.3 Challenges in translating genetic research to clinical practice Despite the promising potential of genetic research in informing therapeutic strategies for dementia, several challenges remain in translating these findings into clinical practice. One major challenge is the complexity of the genetic architecture of dementia, which involves numerous genetic variants with varying degrees of impact on disease risk (Licher et al., 2019; Bellenguez et al., 2020). Additionally, the interaction between genetic and environmental factors further complicates the development of effective interventions (Eid et al., 2019; Licher et al., 2019). Another challenge is the ethical and practical considerations of disclosing genetic risk information to individuals, particularly in the absence of definitive preventive or curative treatments (Galluzzi et al., 2022). Moreover, while preclinical models have shown success in targeting specific genetic pathways, translating these findings to human clinical trials has proven difficult (Serrano‐Pozo et al., 2021). The need for large-scale, longitudinal studies to validate the efficacy of personalized medicine approaches and to identify additional rare genetic variants remains a significant hurdle (Heart et al., 2019; Kunkle et al., 2019; Bellenguez et al., 2020). Addressing these challenges will require continued research, collaboration, and the development of robust clinical guidelines to ensure the safe and effective implementation of genetic findings in dementia care. 9 Concluding Remarks The role of genetic factors in dementia has been extensively studied, revealing significant insights into the pathogenesis and risk factors associated with various forms of dementia, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). Key genetic contributors such as the apolipoprotein E (APOE) gene, particularly the APOE ε4 allele, have been identified as major risk factors for AD, influencing both the risk and age of onset. Genome-wide association studies (GWAS) have further expanded our understanding by identifying new risk loci and implicating pathways related to amyloid precursor protein (APP) metabolism, tau protein binding, immunity, and lipid metabolism. Additionally, the interaction between genetic predispositions and modifiable lifestyle factors has been shown to influence dementia risk, although the protective effects of favorable lifestyle choices appear limited in individuals with high genetic risk. Genetic research is crucial in unraveling the complex etiology of dementia. It not only helps in identifying individuals at higher risk but also provides insights into the underlying biological mechanisms driving the disease. Understanding genetic factors allows for the development of targeted therapeutic strategies and personalized medicine approaches. For instance, the identification of specific genetic variants can lead to the development of drugs that target these pathways, potentially modifying the disease course. Moreover, genetic research highlights the importance of considering gene-environment interactions, which can inform public health strategies aimed at reducing the overall burden of dementia through lifestyle modifications. The future of dementia research lies in the integration of genetic, environmental, and lifestyle data to develop comprehensive risk profiles and personalized intervention strategies. Advances in next-generation sequencing and other genomic technologies will continue to uncover rare genetic variants and novel risk loci, further enhancing our understanding of dementia's genetic architecture. Additionally, there is a critical need to expand genetic research to diverse populations, as most studies have predominantly focused on individuals of European ancestry. This inclusivity will ensure that findings are applicable to a broader demographic, ultimately leading to more equitable healthcare outcomes. Continued efforts in genetic research, combined with advancements in precision medicine, hold the promise of transforming dementia diagnosis, treatment, and prevention in the coming years.
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