Personalized medicine is a rapidly advancing field in which an individual’s personal information (such as variations in their genetic, blood, phenotypic or psychosocial profiles) is utilized to identify the most efficacious path for disease prevention or treatment for that individual or a group of individuals with shared traits. Classic examples of personalized medicine include phenylketonuria, a genetic anomaly in which individuals lack the ability to break down phenylalanine in the body, and blood typing. The failure to detect and treat phenylketonuria early in life results in profound mental deficits. However, individuals present with this anomaly can maintain a relatively normal life with personalized dietary alterations that lower phenylalanine intake and, in some instances, medications. A more common form of personalized medicine is blood typing in which an individual’s blood type is determined to ensure an appropriate match for transfusion, i.e. the blood type given is tailored to the individual.
Lifestyle intervention has been the talk of late in terms of Alzheimer’s disease (AD) and dementia prevention. That said, until now, there wasn’t any empirical clinical evidence that personalizing risk management played a part in preventing the onset of dementia. Dr. Richard Isaacson coined the term “clinical precision medicine” to describe this prevention method. Clinical precision method is defined as “an emerging approach for disease treatment and prevention that takes into account individual variability in genes, environment, and lifestyle for each person.” In terms of AD and dementia, this entails management of modifiable risk factors, such as nutrition and physical activity, based on clinical history, anthropometrics, blood biomarkers, genotyping, and cognitive assessments [1].
A clinical study performed by Dr. Richard Isaacson and his staff at Weill Cornell studied the effects of a personalized nutrition approach on AD risk in a population of 174 individuals with little-to-no cognitive impairment. These effects were measured by tracking their risk factors for dementia and compliance with personalized recommendations over a follow-up period of 18 months [1]. The population was enriched for individuals at high risk of developing AD (family history of AD), but not currently experiencing AD or dementia symptoms. Individuals with AD were excluded from the study. Dr. Isaacson and colleagues assessed individual risk of AD by combining the results from a detailed clinical history, physical examination, anthropometrics, blood biomarkers, genotyping, and cognitive assessments. Amyloid plaques were visualized with positron emission tomography (PET) scans of the brain. Cerebrospinal fluid was also removed to test for biomarkers of AD. Both techniques were used to further assess symptomatic patients.
Based on their personalized risk (of cognitive decline) assessments, the patients were classified into two groups, prevention and early treatment. Prevention patients included those with normal cognition, subjective cognitive decline and preclinical AD. Early Treatment patients were those that demonstrated Mild Cognitive Impairment (MCI) due to AD or were diagnosed with mild AD during the course of the study. Each individual received an average of 21 recommendations from their neurologist or family practitioner. These recommendations included patient education, genetic counseling, pharmacological approaches (vitamins, supplements, and medication), and nonpharmacological approaches (nutrition, exercise, sleep, cognitive engagement, and stress), depending on the patient’s risk. Follow-up and reassessment of individual risk occurred every 6 months and allowed for patients and clinicians to track their improvement [1]. Investigators looked at the amount of cognitive decline in these groups relative to expected change in a normal population. Moreover, as previous studies have shown that compliance may vary among groups, due to the tolerability of lifestyle changes to the individual, the investigators also looked at the data with respect to compliance.
All prevention group patients showed cognitive improvement with varying levels of lifestyle intervention, while the early treatment group showed improvement in the patients with strict compliance (greater than 60%). By analyzing cognitive assessments in these groups over time, the study was able to demonstrate that cognitive decline may be able to be delayed by up to 3 years in prevention patients and 2 years in early treatment patients with high compliance [1].
This type of treatment is reliant on not only how well the guidelines are tailored to the patient, but how compliant the patient is in adhering to the lifestyle recommendations. Furthermore, despite the fact that the study design only incorporated 18 months of lifestyle intervention the data indicated a large improvement on cognitive decline, which demonstrates promise for nutritional intervention in AD. Further research and refinement is necessary to single out specific AD and dementia risk factors. This includes implementing clinical precision medicine longitudinally in clinical settings across the globe, focusing on specific modifiable risk factors and observing their association with cognitive decline, as well as developing a framework that makes AD and dementia risk management more accessible to all healthcare patients.
While it is not known exactly what can be done to prevent cognitive decline, it is clear that dedicating oneself to a healthy lifestyle greatly impacts one’s brain health. There is no disease-modifying or completely preventative treatment available, but managing our individual risk by making the necessary changes to our lifestyles could significantly delay impaired cognition [1,2].
References
[1] Isaacson, R. S.,et al. (2019). Individualized clinical management of patients at risk for Alzheimer’s dementia. Alzheimer’s & Dementia, 15(12), 1588-1602. doi:10.1016/j.jalz.2019.08.198
[2] Ngandu, T.,et al. (2015). A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): A randomised controlled trial. The Lancet, 385(9984), 2255-2263. doi:10.1016/s0140-6736(15)60461-5