International Journal of Molecular Medical Science, 2024, Vol.14, No.6, 355-368 http://medscipublisher.com/index.php/ijmms 361 dementia types; for example, mutations in LRRK2, typically associated with Parkinson's disease, have been implicated in both AD and LBD, suggesting common molecular mechanisms (Wang et al., 2019). Comparative genetic analysis across dementia types reveals both unique and shared factors, offering insights into the molecular foundations of these conditions and identifying promising targets for therapeutic development. 6 Genetic Testing and Counseling 6.1 Predictive genetic testing Predictive genetic testing for dementia has progressed considerably with next-generation sequencing technologies, offering precise molecular diagnoses crucial for assessing personal risk, guiding reproductive decisions, and identifying suitable candidates for clinical trials (Koriath et al., 2020). The probability of detecting a specific genetic cause depends on clinical presentation, age of onset, and family history. For most cases, gene panel testing combined with C9orf72 expansion analysis is recommended, optimizing discovery potential while controlling costs and minimizing the identification of variants of uncertain significance. Although whole-exome and whole-genome sequencing are increasingly feasible, they present challenges such as secondary findings and uncertain variant interpretation (Koriath et al., 2020). Despite advancements, the uptake of predictive testing remains low, though it may rise as therapeutic options expand. 6.2 Ethical considerations Ethical considerations in genetic testing for dementia are complex, with key concerns surrounding the capacity of patients to make informed decisions regarding testing, treatment, and data sharing (Koriath et al., 2020). Genetic counseling plays a vital role in helping patients and families understand the implications of test results, including the psychological impact and risks associated with secondary findings (Koriath et al., 2020). Structured protocols, such as the Italian Dominantly Inherited Alzheimer’s and Frontotemporal Network (IT-DIAfN) model, demonstrate that genetic counseling and testing can be conducted safely, with follow-up showing no catastrophic psychological reactions (Mega et al., 2020). However, responses to predictive testing vary widely; while some individuals experience relief, others may struggle with feelings of guilt, anxiety, or even suicidal thoughts (Crook et al., 2021). Therefore, genetic counseling approaches must be adaptable to manage these diverse outcomes effectively and support individuals at risk. 6.3 Implications for patients and families Genetic testing has significant implications for patients with dementia and their families. A positive result can offer a definitive diagnosis, especially valuable for early-onset cases with atypical presentations (Perrone et al., 2018). Such diagnoses can clarify the familial occurrence of the disease and inform clinical management strategies. For relatives at risk, predictive testing may shape life decisions and coping mechanisms. Research indicates that individuals undergoing predictive testing often experience benefits like enhanced resilience and a proactive approach to planning, without adverse psychological effects (Galluzzi et al., 2022). Nevertheless, the decision to pursue testing is shaped by various personal, familial, and practical considerations, as well as the direct experience of the disease (Crook et al., 2021). Thus, comprehensive genetic counseling and ongoing support are essential to help patients and families navigate the complexities of these decisions and their potential consequences (Mega et al., 2020; Crook et al., 2021; Huq et al., 2021; Galluzzi et al., 2022). 7 Current and Emerging Therapeutic Strategies 7.1 Targeted gene therapy Targeted gene therapy represents a promising therapeutic approach for dementia, particularly AD, through techniques aimed at modifying or correcting disease-associated genetic mutations. A significant advancement in this field is CRISPR/Cas9 technology, which enables precise genome editing to correct mutations in genes such as presenilin (PSEN) and APP, both implicated in AD pathology (Uddin et al., 2020; Bhardwaj et al., 2021). The clinical application of CRISPR/Cas9, however, encounters challenges, notably in ensuring the safe and efficient delivery of gene-editing components. Non-viral vectors, including nanoparticles and microvesicles, are being investigated as safer alternatives to viral vectors for in vivo delivery (Hanafy et al., 2020). Insights from
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