[Feature: The Future of Preventive Medicine] Masaru Mimura: The Importance of Preventive Medicine and Mental Health—Aging with a Healthy Mind

2023/11/06

“No health without mental health.” This was the recommendation in a 2007 Lancet paper by Prince et al.*1. Among Japan's five major diseases (diabetes, mental illness, malignant tumors, cerebrovascular disease, and ischemic heart disease), the prevalence of mental illness is the second highest after diabetes. Regarding the burden of disease measured by Disability-Adjusted Life Years (DALY), depression ranked second globally in 2020, following ischemic heart disease. Mental health is truly a critical issue when considering human health.

The WHO Constitution adopted in 1947 defines "health" as "a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity." For a person to be healthy, they must not only have physical health but also be mentally fulfilled, maintain cognitive function, and have appropriate social connections. Coincidentally, October 10th was World Mental Health Day, with events held worldwide. Here, I would like to reflect once again on the importance of mental health in preventive medicine.

The Keio University Center for Preventive Medicine, which is expanding and relocating to Azabudai Hills, has the slogan "Medicine that walks with each individual's life." Its basic principles are "to play a role in extending healthy life expectancy," "to develop and practice highly personalized health management programs," and "to create new value in preventive medicine." Mental health is indispensable to all of these concepts.

People do not necessarily remain in a desirable physical, mental, and social state forever. Naturally, the core mission of the Center for Preventive Medicine is the early detection and treatment of physical diseases, but some people may feel anxious when an abnormality is found during a health checkup. Mental distress can also occur when a proper diagnosis or treatment is not reached, or when symptoms persist even after treatment. The key in such situations is resilience. In Japanese, it is translated as "resistance to disease" or "stress resistance." It is certain that even after experiencing similar adversity, stress, or trauma, some people fall into mental health problems while others do not; some have high stress resistance and others low. This is a concept born from a positive way of living (Positive Psychology/Positive Psychiatry*2). To use an analogy, stress is the dent created when you press a rubber ball with your finger, and resilience is the image of it expanding back to its original shape. The ultimate mission of mental health support at the Center for Preventive Medicine is to walk alongside each health checkup examinee and enhance the resilience of the client and their family.

The Center for Preventive Medicine will collaborate with the preceding "Hills Joint Research Laboratory for Future Preventive Medicine and Wellness" (hereafter, Future Preventive Medicine Lab) (Project Professor Taishiro Kishimoto) to promote research on preventive medicine aimed at creating a "city where people of all generations can live healthily and vibrantly." In particular, we are developing an app to predict mental health status by collecting and analyzing health data related to daily activities and mental states (perceived stress scale, life satisfaction scale, sleepiness, etc.) using healthcare devices such as wearables. Based on this information, we intend to implement new preventive medicine and wellness services in society while providing advice on lifestyle habits such as diet, exercise, and sleep.

The Center for Preventive Medicine considers support for three major generations excluding early childhood: adolescence to young adulthood, middle age, and old age. Adolescence to young adulthood generally refers to ages 15 to 39, also known as the AYA generation, but I will omit that here due to space constraints. Below, I will briefly introduce my plans for middle age and old age.

Middle Age (Business Person Generation)

These are working-age individuals generally in their 40s to 60s. They play core roles in companies and are the primary targets for health checkups and physical health management at the Center for Preventive Medicine.

On the other hand, this is an age group that often experiences mental health issues such as adjustment disorders, depression, bipolar disorder, and anxiety disorders, triggered by stress from work or family issues. While stress checks are mandatory for many companies, the current reality is that they struggle with the discovery and handling of high-stress individuals. I have served as the Director of the Keio University Keio Center for Stress Research (CSR). At the core of our activities, the Keio Employee Assistance Program (KEAP), we have developed multidisciplinary industrial mental health services under the slogan "Working is within Wellness," collaborating with certified public psychologists, industrial physicians, and health management personnel from various companies. For the business people who are clients of the Center for Preventive Medicine, we must balance job satisfaction with economic growth.

The accuracy of early diagnosis and treatment techniques for depression is improving every year. Regarding diagnosis, a project led by Project Professor Kishimoto of the aforementioned Future Preventive Medicine Lab—which uses machine learning for wearable devices, digital phenotypes, brain MRI findings, EEG, and body movements—has made it possible to diagnose depression with very high accuracy (Figure 1). Regarding treatment, we are also developing a smartphone AI support app through the "International Brain" project to provide tailor-made predictions on which of the four treatment techniques currently insurance-approved for depression will be most effective for a specific individual.

While the diagnosis and treatment of depression have made rapid progress in recent years, challenges remain in terms of improving subjective satisfaction, such as the quality of life (QOL) and well-being of those affected. We need services that monitor various factors leading to a decline in QOL and well-being and provide feedback on lifestyle behaviors such as diet, exercise, and sleep as solutions to prevent them. We expect that this initiative will make it possible to enhance individual resilience. Furthermore, under the guidance of Professor Mitsuhiro Sado of the Health Center and Senior Lecturer Toshiaki Kikuchi of the Department of Neuropsychiatry, we are striving to widely disseminate and promote Cognitive Behavioral Therapy. We believe that Mindfulness-Based Cognitive Therapy for healthy individuals can increase life satisfaction, fulfillment, and positive emotions, contributing to the improvement of well-being for clients of the Center for Preventive Medicine*3 (Figure 2).

Old Age (Silver Generation)

This is intended for those generally aged 70 and older. In this age group, depression and depressive states are not uncommon, but even more problematic are dementia and Mild Cognitive Impairment (MCI), which can be considered a precursor. MCI refers to a stage where a person is independent in daily life and has no trouble managing personal affairs alone, but memory impairment (amnesia) is observed in cognitive function tests.

Alzheimer's disease, which accounts for more than half of dementia cases, is a disease hallmarked by the accumulation of abnormal proteins called amyloid in the brain. Surprisingly, today, one in six to seven "healthy" people (those without memory impairment) aged 65 and older already has amyloid accumulated in their brain (called preclinical Alzheimer's disease), and those individuals are extremely likely to develop Alzheimer's disease 10 to 20 years later. In Japan, where the super-aging society is progressing, the total number of people with dementia and MCI combined is at least 10 million, and we must deal with this "era of 10 million people with dementia" that will progress further in the future.

In Japan, the anti-amyloid antibody drug Lecanemab was approved this year, and I believe various other disease-modifying drugs for Alzheimer's disease will be launched in the future. The current target for anti-amyloid antibody drugs is MCI to mild Alzheimer's disease, but there is a possibility that this will expand to preclinical Alzheimer's disease in the future. In other words, an era is approaching where we can predict future dementia risk at an ultra-early stage before memory loss occurs, intervene with treatment from that stage, and suppress the progression to dementia. The Center for Preventive Medicine plans to open a Forgetfulness Consultation Clinic (tentative), assess the presence of amyloid accumulation through blood biomarkers and brain MRI, and if positive results are suspected, connect patients to Positron Emission Tomography (PET) scans at Keio University Hospital to label amyloid and tau (Figure 3).

On the other hand, guidance on lifestyle habits to prevent dementia or MCI (prevention) or to reduce risk is modest but has solid evidence. We have recently been selected by the Japan Agency for Medical Research and Development (AMED) for a project to "develop a tailor-made behavior change program based on future cognitive function prediction" to be deployed at the Center for Preventive Medicine. Here, we will incorporate a cognitive function simulation app into smartphones to increase adherence to behavior changes regarding diet and exercise habits based on predictions of cognitive reserve several years later. Additionally, sleep is important for dementia prevention, and we plan to provide guidance on sleep depth, sleep quality, and lifestyle rhythms using wearable devices such as the Apple Watch and Insomnograf from S’UIMIN Inc., founded by Professor Masashi Yanagisawa of the University of Tsukuba.

In all lifestyle habits, "aging" and "frailty" are key important concepts. It is possible to predict brain age to some extent through simple cognitive function tests on smartphones and machine learning analysis of brain MRI. In recent years, the idea that aging itself is a disease has also emerged*4, and I would like to consider the theme of how to face aging together with Project Professor Hiroshi Itoh. Regarding frailty, we will collaborate with Professor Kazuki Sato of Sports Medicine to address physical frailty, while reducing the risk of cognitive frailty and social frailty (social isolation) is also important. It is well known that MCI is likely to coexist with physical frailty, and it is required to find common factors such as lifestyle-related diseases, nutritional disorders, hormonal abnormalities, and depression early and intervene appropriately with prevention. Even as disease-modifying drugs for dementia come into clinical use, I am convinced that we should aim for a society where dementia risk can be reduced by combining these preventive factors in a multifaceted and multi-domain manner.

Above, I have described my own vision of the importance of mental health in preventive medicine as the Keio University Center for Preventive Medicine relocates to Azabudai Hills. Keeping "No health without mental health" in mind once again, I hope to contribute even a little to improving the resilience of the clients of the Center for Preventive Medicine, their families, those in related companies, and the faculty and staff of Keio University.