Introduction

What is precision medicine?

As suggested by its name, precision medicine aims to provide an approach as precise as possible for the prevention, diagnosis, and treatment of disease. Depending on the case and the disease in question, that approach can be applied to a specific subpopulation or in some cases can be tailored to a single individual. 

This shift from traditional medicine, also called a “one size fits all” approach has emerged as a consequence of years of studies that showed the magnitude of the impact that inter-individual differences can make on whether or not a treatment will be successful. These differences include various factors such as genetic variations, age, gender, addictions, race, ethnicity, concomitant drugs, comorbidities, environmental factors, and many others.¹

Precision medicine's principal objective is to incorporate all these factors when creating a health intervention (i.e. diagnosis or treatment). This shift towards a more personalised medicine would not have been possible without several, recently discovered tools including omics, pharmacogenomics, big data, artificial intelligence (AI) and machine learning (ML) along with an improved understanding of how environmental, social and behavioural factors impact our health.²

Overview of dementia and its impact 

Dementia can be defined as a progressive decline in cognition that is significant enough to interfere with an individual’s independent and daily functioning and is an umbrella term for a group of diseases.³

Symptoms of dementia vary a lot among individuals but what they do have in common is that they are almost always gradual, persistent and progressive. Individuals suffering from dementia experience changes in cognition, function and behaviour. These individuals can experience memory loss, communication and language impairments, agnosia (i.e. the inability to recognise objects), apraxia (i.e. the inability to perform previously learned tasks) and impaired executive function (e.g., reasoning, judgement and planning).⁴ The causes of dementia are varied and include primary neurologic, neuropsychiatric, and medical conditions.³

Significance of personalised approaches in dementia treatment 

Person-centred care could be life-changing for people with dementia. Unfortunately, there is no cure for this syndrome, but a personalised approach to managing it could have a significant impact on the patient's wellbeing. The importance of a personalised approach has been discussed and analysed to a greater extent recently. 

One study that took place in four facilities across Europe explored the impact of a patient-tailored intervention called SENSE-GARDEN used for care practices for people with dementia. The results indicated that this intervention contributed significantly to helping patients maintain a sense of self and purpose in life, but also had a positive impact on healthcare workers, giving them a sense of purpose and satisfaction in their work.⁵ 

Understanding dementia  

Types of dementia 

As mentioned before, dementia is a term used to describe a progressive decline of someone’s cognitive state.⁴ However, its subtypes are classified based on the cause of dementia. The four common types of dementia are:

• Alzheimer's disease (AD)
• Vascular dementia
• Lewy body dementia  
• Frontotemporal dementia

Alzheimer's disease (AD) is a neurodegenerative condition characterised by the build-up of harmful proteins in the brain (accumulation of beta-amyloid plaques and neurofibrillary tangles) which causes a gradual decline in memory and thinking skills, eventually leading to dementia.⁶ It is the most common subtype of dementia, accounting for about 60% to 80% of cases.⁴ AD is usually diagnosed later in life, around the age of 60, but early-onset cases, that occur between ages 30 to 60, are linked to autosomal dominant mutations in genes like PSEN1, APP, and PSEN2.⁷

Vascular dementia represents the second most common form of dementia (~20% of cases) and it develops when there is a reduced blood flow to the brain, often due to strokes. It can coexist with AD in which case it is said that the patient suffers from mixed dementia.⁴

Lewy body dementia (LBD) is accountable for approximately 5% to 15% of cases of dementia and is defined by abnormal deposits of alpha-synuclein protein (i.e. Lewy bodies) in neurons.⁴ Distinctive features include fluctuating cognitive impairment, visual hallucinations, and parkinsonism.⁸

Frontotemporal dementia (FTD) includes disorders that affect the frontal and temporal lobes, such as Pick's disease, and usually occurs between the ages 40 to 75. FTD is characterised by personality changes and behavioural disturbances, and unlike AD, the ability to perceive and understand spatial relationships, orientation, and visual information remains relatively intact.⁴

Current challenges in addressing dementia

The current challenges when treating dementia are the high economic costs, reduced societal awareness, as well as a series of clinical obstacles. The economic costs associated with treating dementia patients are significantly high. Out of these costs, the largest portion is represented by costs occurring due to informal care. It is extremely important that more initiatives are created to help raise awareness of dementia patients and their families. This is a crucial part of tackling this syndrome because it can help overcome stereotypes and stigma associated with dementia. 

Additionally, there are also a lot of obstacles that need to be overcome in terms of treatment. There are very few effective disease-modifying drugs; and while new therapies are starting to be developed, these are surrounded by many controversies regarding their effectiveness. Significant progress in the available therapies for dementia is needed to substantially improve the way the syndrome is managed at the moment.⁹

The concept of precision medicine 

As mentioned previously, the main principles of precision medicine are to adopt a patient-centred approach. Although various steps need to be taken to achieve this goal, it seems more and more achievable with the improvement of genomic sequencing, the constant development of biotechnology techniques and the rise of AI and machine learning.

Application in various medical fields 

In the past few years, applications of personalised medicine have been developed across various medical fields. Some of the most important ones are defined below:¹⁰

• Oncology: Tailored cancer treatments which include CAR-T cell therapy, medications targeting specific genetic mutations in tumours, and overall improving efficacy and reducing side effects that are usually associated with oncologic therapies.
• Genetics and Genomics: The main application that improved healthcare and continues to do so is the introduction of genetic testing that aids the identification of individuals at risk for hereditary diseases, enabling early intervention and personalised treatment plans.
• Pharmacogenomics: A huge breakthrough is represented by the discoveries about genetic variations and how they impact drug metabolism and response. This can help guide medication selection and dosage for optimal therapeutic outcomes.
• Cardiology: Genetic profiling is another important discovery that has a significant impact in the cardiology field.  This technique changed the way cardiovascular disease risk is assessed and helps in guiding the selection of medications and interventions tailored to individual genetic makeup.
• Neurology: Discovering in the neurology field led to the development of personalised approaches in diagnosing and treating neurological disorders like Alzheimer's and Parkinson's disease based on genetic factors and biomarkers.
• Endocrinology: In the case of endocrinology, a discovery worth noting brought up by the ability to create a personalised approach is the improved management of diabetes. Currently, it is possible to carry out genetic testing to guide treatment decisions and predict responses to insulin therapy and other interventions.
• Immunology: The development of individualised immunotherapies targeting specific immune system components made it possible to offer precise treatments for autoimmune diseases and allergies.

Tools and technologies in precision medicine for dementia 

• Biomarker identification and diagnostic tools: Biomarkers play a crucial role in early detection and monitoring of dementia progression.¹¹ Advanced technologies like proteomics and metabolomics enable the identification of novel biomarkers for accurate diagnosis and prognosis.
• Genomic profiling and genetic testing: Genetic testing enables personalised risk assessment and targeted interventions.¹² Next-generation sequencing technologies facilitate comprehensive genomic profiling, uncovering genetic variants associated with dementia susceptibility and progression.
• Imaging techniques: High-resolution imaging modalities such as MRI and PET scans provide insights into structural and functional changes in the brain, aiding in early detection and disease monitoring.¹³
• Big data analytics and machine learning: Leveraging big data analytics and machine learning algorithms enables the integration of multi-omics data for predictive modelling and precision medicine approaches in dementia.¹⁴

Challenges and ethical considerations

• Accessibility and affordability: Limited access to advanced diagnostics and treatments exacerbates healthcare disparities, underscoring the need for affordable and accessible precision medicine solutions.¹⁵
• Privacy concerns: The collection and sharing of sensitive genetic and health data raise privacy concerns, necessitating robust data protection measures and informed consent protocols.¹⁶
• Ensuring equity and inclusivity: Addressing biases in data collection and algorithm development is essential to ensure equitable access to precision medicine benefits across diverse populations.¹⁷

Future directions and possibilities

• Emerging trends: Integration of multi-omics data with artificial intelligence holds promise for uncovering novel therapeutic targets and biomarkers for precision medicine in dementia.¹⁸
• Potential breakthroughs: Advancements in nanotechnology and drug delivery systems may enable targeted interventions and disease-modifying treatments for dementia.¹⁹
• Collaborative efforts: Collaborative initiatives involving academia, industry, and regulatory bodies are vital for accelerating the translation of precision medicine technologies from bench to bedside.²⁰

Summary

Precision medicine for dementia presents unprecedented opportunities for early diagnosis, targeted treatment, and personalised care. Stakeholders must collaborate and invest in accessible and equitable solutions to address the growing burden of dementia worldwide. Despite challenges, an optimistic outlook prevails, with the potential to transform dementia care, improving outcomes and quality of life for patients and families alike.