PRECISION MEDICINE IN GERIATRIC CARE: HARNESSING THE POWER OF GENETIC PRO ﬁ LING FOR PERSONALIZED THERAPIES IN OLDER ADULTS

: Precision medicine, an approach that tailors medical treatments to individual genetic pro ﬁ les, holds immense potential for improving geriatric care. By leveraging pharmacogenomics and genetic pro ﬁ ling, personalized therapies can optimize treatment outcomes and minimize adverse effects in elderly patients. This narrative review explores the current state of personalized medicine in geriatrics, focusing on its applications in neurodegenerative diseases, psychiatric conditions, and other age-related disorders. We discuss the role of genetic markers in guiding treatment strategies, highlight the challenges and opportunities in implementing precision medicine in clinical practice, and provide future directions for research and translational efforts. As the ﬁ eld continues to evolve, integrating genetic pro ﬁ les into geriatric care offers a promising avenue for enhancing the ef ﬁ cacy, safety, and quality of life for older adults.


INTRODUCTION
The rapidly aging global population presents a significant challenge for healthcare systems worldwide.However, with the emergence of precision medicine, which tailors medical interventions to individual genetic profiles, there is a promising strategy to address the complex healthcare needs of the geriatric population.This approach offers hope and optimism for the future, as it can optimize treatment outcomes and improve the quality of life for older adults [2]. 1 Faculdades Unidas do Norte de Minas Funorte. 2 Centro Universitário São Camilo. 3Centro Universitário de Votuporanga (UNIFEV) 4 Santa Casa de Misericórdia de Vitoria Higher School of Sciences -EMESCAM.Santa Luíza -Vitória -ES -Brazil, Molecular Dynamics and Modeling Laboratory (DynMolLab) 5 Molecular Dynamics and Modeling Laboratory (DynMolLab) Santa Luíza -Vitória -ES -Brazil.
Personalized therapies in geriatrics leverage the power of pharmacogenomics, the study of how genes influence an individual's response to drugs.By identifying genetic variants that impact disease susceptibility, progression, and treatment response, healthcare providers can develop targeted interventions that maximize therapeutic benefits while minimizing adverse effects.This emphasis on genetic profiling in guiding treatment strategies should reassure the audience about the effectiveness of personalized therapies [4].This narrative review explores the current state of personalized medicine in geriatric care, focusing on its applications in various age-related conditions.We discuss the role of genetic markers in guiding treatment strategies, highlight the challenges and opportunities in implementing precision medicine in clinical practice, and stress the importance of future research and collaborative efforts.By doing so, we aim to engage the audience and make them feel part of the solution in overcoming the challenges of precision medicine in geriatric care.

METHODOLOGY
A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, and ScienceDirect databases.The search terms included combinations of "precision medicine," "personalized therapy," "pharmacogenomics," "genetic profiling," "geriatrics," "elderly," "neurodegenerative diseases," "psychiatric conditions," and specific disease names (e.g., Alzheimer's disease, Parkinson's disease).Relevant articles published in English between 2010 and 2023 were selected for review.The reference lists of the identified articles were also manually searched for additional relevant studies.The included studies were critically appraised for their methodological quality and relevance, ensuring a comprehensive and reliable review.

Alzheimer's Disease
Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly, characterized by progressive cognitive decline and functional impairment [6].Genetic factors play a significant role in AD susceptibility and progression, with the apolipoprotein E (APOE) ε4 allele being the most potent genetic risk factor [7]. Individuals carrying the APOE ε4 allele have an increased risk of developing AD and tend to have an earlier onset and more rapid cognitive decline compared to non-carriers [8].
Genetic profiling of APOE status can inform personalized treatment strategies in AD.
For example, APOE ε4 carriers may benefit from targeted interventions that address the underlying pathological processes associated with this genetic variant, such as brain inflammation, amyloid processing, and oxidative stress [9].Several studies have investigated the potential of APOE-targeted therapies, including anti-inflammatory agents, antioxidants, and amyloid-modifying drugs [10][11][12].While some of these approaches have shown promise in preclinical and early clinical trials, further research is needed to establish their efficacy and safety in larger patient populations.
In addition to APOE, other genetic markers have been identified as potential targets for personalized therapies in AD.For instance, variations in the genes encoding for brain-derived neurotrophic factor (BDNF) and serotonin transporter (5-HTT) have been associated with differential responses to cognitive enhancers and antidepressants, respectively [13,14].By considering these genetic factors, clinicians may be able to optimize treatment selection and dosing for individual patients.

Parkinson's Disease
Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by motor symptoms such as tremor, rigidity, and bradykinesia, as well as nonmotor symptoms like cognitive impairment and mood disorders [15].While most PD cases are sporadic, genetic factors contribute to disease risk and progression in many patients [16].
Several genetic mutations have been implicated in PD pathogenesis, including those in the glucocerebrosidase (GBA) and leucine-rich repeat kinase 2 (LRRK2) genes [17].These mutations are associated with distinct disease phenotypes and progression rates, which can inform personalized treatment strategies [18].For example, patients with GBA mutations tend to have earlier onset, more rapid cognitive decline, and a higher risk of developing dementia compared to non-carriers [19].Targeted interventions for GBA-associated PD may focus on modulating the lysosomal pathway and reducing α-synuclein aggregation [20].
Similarly, LRRK2 mutations, particularly the G2019S variant, are associated with a more benign clinical course and better response to dopaminergic therapy than other genetic subtypes [21].Patients with LRRK2 mutations may benefit from personalized treatment plans that optimize dopaminergic medication dosing and consider the potential for delayed disease progression [22].
Pharmacogenetic testing can also guide the selection and dosing of antiparkinsonian medications.Genetic variations in enzymes involved in drug metabolism, such as cytochrome P450 2D6 (CYP2D6), can impact the efficacy and safety of commonly used drugs like levodopa and dopamine agonists [23].By tailoring medication regimens based on individual genetic profiles, clinicians can minimize adverse drug reactions and optimize symptom control in PD patients.

Depression
Late-life depression is a common and debilitating condition that affects a significant proportion of older adults [24].While multiple factors contribute to the development of depression in the elderly, genetic variations play a role in treatment response and adverse effects [25].
Pharmacogenetic testing can guide the selection and dosing of antidepressant medications in older adults.Genetic polymorphisms in cytochrome P450 enzymes, particularly CYP2D6 and CYP2C19, can influence the metabolism of commonly prescribed antidepressants such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs) [26].Patients with specific genetic variants may require dose adjustments or alternative medications to achieve optimal therapeutic outcomes and minimize side effects [27].
In addition to pharmacogenetics, genetic markers related to neurotransmitter systems and stress response pathways have been investigated as potential targets for personalized depression treatment.For example, variations in the serotonin transporter gene (SLC6A4) and the brain-derived neurotrophic factor gene (BDNF) have been associated with differential responses to SSRIs and cognitive-behavioral therapy, respectively [28,29].By considering these genetic factors, clinicians may be able to tailor treatment plans to individual patient characteristics and improve outcomes in late-life depression.

Anxiety Disorders
Anxiety disorders, including generalized anxiety disorder (GAD) and panic disorder, are prevalent in older adults and can significantly impact quality of life [30].Genetic factors play a role in the development and treatment response of anxiety disorders, providing opportunities for personalized interventions [31].
Like depression, pharmacogenetic testing can guide the selection and dosing of anxiolytic medications in the elderly.Genetic variations in CYP enzymes can influence the metabolism of benzodiazepines and other commonly prescribed anti-anxiety drugs [32].By tailoring medication regimens based on individual genetic profiles, clinicians can optimize symptom control and minimize adverse effects in older adults with anxiety disorders.
Genetic markers related to neurotransmitter systems, such as the serotonin transporter gene (SLC6A4) and the catechol-O-methyltransferase gene (COMT), have also been investigated as potential targets for personalized anxiety treatment [33,34].Variations in these genes have been associated with differential responses to pharmacological and psychological interventions, suggesting that genotype-guided treatment strategies may improve outcomes in elderly patients with anxiety disorders.

Complexity of Age-Related Diseases
One of the significant challenges in implementing precision medicine in geriatric care is the complex nature of age-related diseases.Many geriatric conditions, such as neurodegenerative disorders and chronic diseases, involve multiple genetic, environmental, and lifestyle factors that interact in complex ways [35].This complexity makes it difficult to identify single genetic markers that can reliably predict disease risk, progression, or treatment response [36].
To address this challenge, researchers are developing more sophisticated approaches to integrate genetic data with other types of information, such as epigenetic, transcriptomic, and proteomic data [37].These multi-omics approaches can provide a more comprehensive understanding of the molecular mechanisms underlying age-related diseases and help identify novel targets for personalized interventions [38].

Limited Evidence Base
Another challenge in implementing precision medicine in geriatric care is the limited evidence base for personalized therapies in older adults.Many clinical trials and research studies have focused on younger populations, leaving a gap in knowledge regarding the efficacy and safety of customized interventions in the elderly [39].
To address this challenge, there is a need for more research specifically designed to evaluate personalized therapies in older adults.This includes conducting clinical trials with adequate representation of geriatric populations and developing age-specific guidelines for the use of pharmacogenetic testing and other precision medicine tools [40].

Ethical and Social Considerations
Implementing precision medicine in geriatric care also raises important ethical and social considerations.Genetic testing and personalized therapies may have implications for privacy, confidentiality, and informed consent, particularly in age-related cognitive impairment [41].
There are also concerns about potential disparities in access to precision medicine technologies and treatments and the potential for genetic information to be used for discriminatory purposes [42].Addressing these ethical and social issues will require ongoing dialogue among healthcare providers, researchers, policymakers, and patient advocates to ensure that the benefits of precision medicine are distributed equitably and that the rights and well-being of older adults are protected [43].In the realm of psychiatric conditions, pharmacogenetic testing can guide the selection and dosing of psychotropic medications, minimizing adverse drug reactions and improving therapeutic efficacy in older adults with depression and anxiety disorders.Genetic markers related to neurotransmitter systems and stress response pathways also hold promise as potential targets for personalized interventions in these conditions.However, implementing precision medicine in geriatric care faces several challenges, including the complexity of age-related diseases, the limited evidence base for personalized therapies in older adults, and various ethical and social considerations.Addressing these challenges will require ongoing research, clinical trials specifically designed for geriatric populations, and collaborative efforts among healthcare providers, researchers, policymakers, and patient advocates.
As the field of precision medicine continues to evolve, it is crucial to prioritize the needs and well-being of older adults in developing and implementing personalized therapies.This includes ensuring equitable access to precision medicine technologies, protecting patient privacy and confidentiality, and promoting shared decision-making between healthcare providers and older adults regarding the use of genetic information in clinical care.

DISCUSSION
Precision medicine holds immense potential for improving the care of older adults by tailoring medical interventions to individual genetic profiles.By leveraging pharmacogenomics and genetic profiling, personalized therapies can optimize treatment outcomes, minimize adverse effects, and enhance the quality of life for elderly patients with various age-related conditions.The applications of precision medicine in geriatric care are particularly relevant in the context of neurodegenerative diseases, such as Alzheimer's and Parkinson's, where genetic factors play a significant role in disease susceptibility, progression, and treatment response.Genetic profiling of markers such as APOE, GBA, and LRRK2 can inform targeted interventions that address the underlying pathological processes associated with these variants and optimize symptom management.