Last year, aducanumab, a high-profile new drug to treat dementia, was not approved in Japan. One problem is the drug's high price. Additionally, early detection of dementia is key, but testing can be expensive. "Money barriers" that hinder early detection of dementia, early treat

Last year, the much-anticipated new drug aducanumab, which was used to treat dementia , was not approved in Japan. One problem is the drug's high price. Additionally, early detection of dementia is key, but testing can be expensive. "Money barriers" that hinder early detection of dementia, early treatment and prevention of dementia progression are a major challenge. In this context, the results of a study showing the effectiveness of a low-cost, feasible approach have been published. The

research results show that a low-cost approach can be implemented.

New dementia drug fails to gain approval in Japan, 'monetary barrier' too high.

In June 2021, news broke that a new dementia drug had been approved in the United States for the first time in about 20 years, albeit with conditions. The name of the new drug is "adocanumab." It is a compound that targets the aggregation of amyloid beta protein (Aβ), which is thought to play a major role in the onset of Alzheimer's disease , and is said to inhibit (aggravate) cognitive decline. .

'Those expected to benefit are patients with mild cognitive impairment (MCI) and mild Alzheimer's disease. 'It delays the onset of disease by removing disease-causing factors while nerve cells are still healthy.

Alzheimer’s expert Dr. Heii Arai (director of the Tokyo Alzheimer Clinic) also had high hopes for the drug, but unfortunately perhaps it was in that the European Medicines Agency decided not to approve aducanumab, citing reasons However, Japan's approval was also delayed after its efficacy and safety were not clearly proven.

The main reason is "low cost effectiveness". The 23% preventive effect confirmed in the trial was a statistically significant number, but clinically weak.

In addition, the drug is sold for about 470,000 yen per time, which is 6.1 million yen per year. That's even more expensive than the controversial cancer drug Opdivo, whose high price has sparked debate, so perhaps the harsh assessment is justified.

Are dementia drugs still just a dream? Just when I was feeling discouraged, good news came from Japan a few days ago. This is information on a low-cost approach to early diagnosis and treatment.

There is a silver lining in early detection and prevention of the development of dementia.

The person who told us is Honorary Professor Otsuka Kunaki of Tokyo Women's Medical University . He is an internist with a wide range of knowledge, from space medicine to cancer detection using the nematode worm , and he is also a famous doctor who served as director of the Eastern Medical Center of Tokyo Women's Medical University. He has a special focus on geriatric medicine and organized the General Internal Medicine Department of Chrono Medicine and Geriatric Medicine (endowed clinical research department).

The medical community refers to the early stage of dementia as mild cognitive impairment (MCI). Early detection of mild cognitive impairment is extremely important because if left untreated, it may develop into Alzheimer's disease in a year or two, but this is actually very difficult. Early detection is also important with aducanumab, as the earlier the disease is detected, the better the treatment, but it is said that reliably detecting the disease requires an extremely expensive test, an "amyloid PET scan" "

Even so, if MCI is caught early enough, it may be possible to receive appropriate treatment. However, if testing can only slow the progression of the disease (the effect of current drugs), then the barrier is too high and early detection may lead to early despair.

Professor Otsuka and his group have brought light to this situation.

　Although no effective drug has been found, if detected early and given appropriate lifestyle treatment, it is not uncommon for patients to return to a healthy state. That's why (early detection) is a very important issue in health care. However, the only tool available so far is MoCA from Montreal .

MoCA is a diagnostic tool for mild dementia designed in 2005 by a team at the University of Montreal: It is a simple 30-question test that takes 10-20 minutes to complete and is useful for assessing dementia, with a score of 25 or The following represents MCI, the sensitivity (accuracy in detecting patients) is 80-100%, and the specificity (accuracy in distinguishing normal people from MCI) is 50-87%. (The accuracy of detecting patients) is said to be 50-87%.

However, since the test was not developed for the Japanese, Professor Otsuka and his colleagues developed ToCA (Tokyo version of MoCA) six years ago in order to achieve higher accuracy, and it has been used since 2000 It was used to examine memory loss in Urausu Town, Hokkaido (population: 1,671 at the end of May 2010), in cooperation with the town health center, as part of a field medical survey. Since 2000, this system has been incorporated into memory loss examinations conducted in the town of Urausu, Hokkaido (population 1,671 at the end of May 2010) as part of field medical surveys in collaboration with the town's health center.

It was a small initiative to detect MCI in its early stages and prevent its progression to dementia, but the results were startling.

How can MCI be diagnosed early without a medical expert?

First, let’s take a look at the filtering method. By administering ToCA-centric testing to 121 elderly residents who had been screened for memory loss, MCI was found to have a sensitivity of 88.2% and a specificity of 88.5%.

Let’s go back in time.

Since 2000, Professor Otsuka and his colleagues have been conducting geriatric examinations on a town basis in the town of Urausu, Hokkaido. The town has a large elderly population, and the primary issue is how to protect the health of the elderly. However, being a poor town, it was impossible to spend a lot of money. In pursuit of high-efficiency results, the town addresses lifestyle-related diseases ( hypertension , diabetes , dyslipidemia , etc.) and depression by providing guidance on diet, exercise and sleep. , and achieved positive results.

Additionally, screening methods to accurately diagnose MCI have not yet been fully developed. Therefore, the professors developed a clinical neuropsychological test suitable for Japanese people, the Tokyo Cognitive Assessment (ToCA)-MCI, based on the above-mentioned MoCA, to early detect MCI in elderly residents.

ToCA-MCI is unique in that it assesses short-term memory for relatively long (25 words) stories compared to MoCA. We installed this software on the computer, told the residents about the tasks from the computer, and asked them to respond in turn.

In addition to the ToCA-MCI, the system incorporates a range of other tests, including measures of sleep disorders and depression, physical mobility (5m walking speed, grip strength) and aging syndromes (movement syndrome, sarcopenia and is weaker than ).

Mobility disorders are defined as "a condition in which balance and mobility are reduced in the aging population, with an increased risk of confinement and falls."

in this study.

　(1) Cannot stand on one leg and wear socks

(2) Trip or slip indoors

(3) Need a handrail when going up stairs

(4) Cannot cross a crosswalk when the light is green

(5) Cannot walk continuously 15 minutes.

(6) Having difficulty carrying 2kg of shopping home.

(7) Cannot use vacuum cleaner , nor can I lift and put down the bedding.

The number of items applied to the question "What is your locomo score?" is evaluated as the locomo score. Movement syndrome was defined as a movement score of 1 or higher and a decrease in walking speed to 0.8 m/s or less.

Sarcopenia is defined in this study as "age-related loss of muscle strength or age-related loss of muscle mass."

　(1) Weight loss (weight loss of at least 3 kg within two years)

(2) Decreased grip strength (20 kg for women, 30 kg for men)

(3) Decreased walking speed (0.8 m/s).

The definition of weak is when two or more of the following three criteria apply.

Frailty is defined as "a state of increased vulnerability to a variety of health problems based on age-related functional decline (loss of reserve capacity)."

　(1) Weight loss (more than 2-3 kg within 6 months)

(2) Feeling tired for no reason for two weeks

(3) Decreased grip strength (18 kg for women, 26 kg for men)

(4) Normal walking Speed ​​decreases (1.0 m/s).

(5) investigates a decrease in activity level (neither light movement/exercise nor regular movement/sport), the number of items corresponding to 0 is assessed as healthy, 1-2 as pre-frail, and 3 or more as frail .

A 20-30 minute interview with a doctor was then conducted to rate the severity of dementia on a five-point scale and the presence of depression on six items: memory, disorientation, judgment and problem solving, social adjustment, and family situation. and hobbies, as well as care situations.

The results show that ToCA-MCI can be used for early detection of pre-dementia with an accuracy of about 90%, without the use of expensive detection equipment, in the absence of professional doctors, for example, if ToCA-MCI is mainly performed by public health nurses.

I also have a new understanding of the treatment of MCI.

Professor Otsuka and colleagues conducted a study of residents diagnosed with MCI via ToCA-MCI to determine (1) whether MCI follow-up could predict progression to dementia and (2) whether comprehensive lifestyle guidance could To improve slow walking speed and reduced cognitive function (hereafter referred to as lifestyle therapy), we observed whether implementation of the program inhibited the development of dementia for at least one year.

Specifically, they were invited to participate in a lifestyle therapy class organized by the town of Urausu, which included a two-hour muscle-strengthening class focused on walking training and comprehensive lifestyle guidance, including head exercises and nutritional guidance.

This preventive lifestyle approach is performed at regular intervals throughout the week.

First, after a health check by a public health nurse/nurse, participants performed 25 minutes of group exercises (ankles, toes, knees, hips, abdomen, waist and ribs, elbows, wrists, fingers, shoulders and neck exercises, deep breathing), 5 minutes rest, 10 minutes head exercise 1 (finger exercises using rubber bands), 15 minutes head exercise 2, change weekly (one or two staff per person apply walking, in balance Mats for stamping feet, etc.), and 10 minutes for refreshments. Participation is based on a minimum of 45 treatment sessions, i.e. one year, after which continued use at home is allowed; continued use after one year is also allowed.

A subsequent 2,380-day follow-up study observed that these initiatives resulted in prevention of dementia progression.

'At 2380 days of follow-up, in the group that had participated in lifestyle coaching classes for more than a year (45 or more sessions per week), only 1 in 14 residents (7.1%) developed dementia, compared with 26 residents in the control group The top 10 (38.5%) are 0.19 times less.

Furthermore, the study confirmed that the group that participated in the lifestyle coaching class walked faster and had fewer motor syndromes, sarcopenia and frailty than the control group.

'It has been reported that the reduced walking speed seen in MCI and the very elderly is associated with abnormalities in brain functional networks that, for example, can be ameliorated by improving motor function through an intervention that lasts about 8 weeks, thereby improving cognitive decline.

Professor Yohei Otaka of Fujita Medical University is a famous rehabilitation medicine doctor. He once said the following about the rehabilitation of patients with consciousness disorders caused by road traffic accidents.

The strongest stimulus for [recovery] is to stand up. The important thing is to get them to stand up against gravity. Even in healthy people, your arousal will decrease if you sleep. Conversely, if you stand up, it will rise. The depth of consciousness is infinite. Some are very profound, some not so much. The thrill that gets you to your feet gradually raises the awareness of sinking to the bottom. "

This is a nod to the fact that walking is a more intense stimulus than standing, and it may have a better effect on cognitive recovery than drugs or mental gymnastics.

Current research suggests that therapeutic interventions for walking may act on different areas of functional brain networks to ameliorate cognitive decline and prevent progression to dementia. At the same time, it is inferred that long-term life therapy for more than one year is more effective than short-term life therapy for two to three months.

There are also reports that the older a person is, the worse the recovery of brain functional networks, so Professor Otsuka suggested, "It is best to start life therapy as young as possible.