Government health officials have approved the first new drug for Alzheimer’s disease in nearly 20 years. The Food and Drug Administration said it granted approval to the drug from Biogen based on results that seemed “reasonably likely” to benefit Alzheimer’s patients.

It’s the only drug that U.S. regulators have said can likely treat the underlying disease, rather than manage symptoms like anxiety and insomnia.

This is in spite of independent advisers feeling that it hasn’t been shown to help slow the brain-destroying disease.

The decision is certain to have disagreements among physicians, medical researchers and even patient groups.

The new drug, which Biogen developed with Japan’s Eisai Co., did not reverse mental decline, only slowing it in one study. The medication, aducanumab, will be marketed as Aduhelm and is to be given every four weeks.

Dr. Caleb Alexander, an FDA adviser who recommended against the drug’s approval, said he was “surprised and disappointed” by the decision.

“The FDA gets the respect that it does because it has regulatory standards that are based on firm evidence. In this case, I think they gave the product a pass,” said Alexander, a researcher at Johns Hopkins University.

Since the FDA’s approval researchers and pharma watchers have called the agency’s decision “disgraceful,” “a grave error” and a “dangerous precedent” that will end up “eroding confidence in the agency as a whole.”

The FDA’s top drug regulator acknowledged in a statement that “residual uncertainties” surround the drug, but said Aduhelm’s ability to reduce harmful clumps of plaque in the brain “is expected” to help slow dementia.

The FDA is requiring the drugmaker to conduct a follow-up study to confirm benefits for patients. If the study fails to show effectiveness, the FDA could pull the drug from the market.

Nearly 6 million people in the U.S. have Alzheimer’s.

Aducanumab (pronounced “addyoo- CAN-yoo-mab”) helps clear a protein linked to Alzheimer’s, called betaamyloid, from the brain.

People with dementia may experience increased levels of pain 16 years before their diagnosis, according to new research. The study, funded in part by NIA and published in Pain, is the first to examine the link between pain and dementia over an extended period.

Dementia and chronic pain both cause changes to the brain and can affect a person’s brain health. Although many people who have dementia also have chronic pain, it is unclear whether chronic pain causes or accelerates the onset of dementia, is a symptom of dementia, or is simply associated with dementia because both are caused by some other factor. The new study, led by researchers at Université de Paris, examined the timeline of the association between dementia and self-reported pain by analyzing data from a study that has been gathering data on participants for as many as 27 years.

The researchers used data from the Whitehall II study, a long-term study of health in British government employees. Participants were between the ages of 35 and 55 when they enrolled in the study. Using surveys conducted multiple times over the course of the study, the researchers measured two aspects of participant-reported pain: pain intensity, which is how much bodily pain a participant experiences, and pain interference, which is how much a participant’s pain affects his or her daily activities. They used electronic health records to determine whether (and when) participants were diagnosed with dementia.

Out of 9,046 participants, 567 developed dementia during the period of observation. People who were diagnosed with dementia reported slightly more pain as early as 16 years before their diagnosis, driven mostly by differences in pain interference. These participants reported steadily increasing pain levels relative to those who were never diagnosed with dementia. At the time of diagnosis, people with dementia reported significantly more pain than people without dementia.

The researchers note that, because the brain changes associated with dementia start decades before diagnosis, it is unlikely that pain causes or increases the risk of dementia. Instead, they suggest that chronic pain might be an early symptom of dementia or simply correlated with dementia. Future studies that include data on the cause, type, location, and characteristics of pain and the type and seriousness of a patient’s dementia could help define in more detail the link between dementia and pain.

This research was supported in part by NIA grants R01AG056477 and RF1AG062553.

People with mental disorders in youth tend to have signs of accelerated aging in midlife and a higher risk of developing other diseases and of dying earlier, according to a pair of related studies supported in part by NIA. The findings, which appeared in JAMA Network Open and in JAMA Psychiatry, suggest that improving individuals’ mental health could enhance their overall health and extend their lives. The respective studies were led by researchers at Duke University and the University of Michigan.

Increasing evidence suggests that biological aging is best understood as a network of interacting genetic and environmental factors. As we age, our body’s repair mechanisms decline, contributing to multi-system impairment and diseases that are more common in late life, such as cancer, diabetes, cardiovascular disease, and brain diseases, such as dementia. But less is known about how early life experiences influence disease onset many years later.

In the two new studies, the researchers followed up on the observation that people with poor mental health when they are young are more likely to have age-related diseases when they are older. To better characterize the nature of this connection, they analyzed health and mortality data from large numbers of individuals in New Zealand collected over the course of decades.

For the JAMA Network Open study, the researchers examined data from more than 2 million New Zealanders aged 10 to 60 years old across the subsequent 30 years, or until death. Their analysis showed that people who had been admitted to hospitals for mental health problems — including substance use, psychotic, mood, and behavioral disorders — tended to have other diseases such as cancer, diabetes, and cardiovascular disease at a younger age, and to die earlier — than those who did not have mental health problems early in life. People with a history of mental illnesses were also more likely to develop more chronic health conditions and to be hospitalized more often and for longer periods. These patterns were seen in both men and women, and across the lifespan.

In the study published in JAMA Psychiatry, the researchers explored the idea that accelerated biological aging might drive the early onset of other health conditions in people who had previously experienced mental health problems. They used data from the Dunedin Study, which monitored the health of about 1,000 people in New Zealand from age 3 to 45.

The results showed that at middle age, people with a history of mental health problems were aging at a faster pace, as measured by a panel of biomarkers and assessments of sensory, motor, and cognitive function. The connection was significant even after the researchers controlled for other factors that could potentially speed the aging process such as smoking, being overweight, low socioeconomic status, having a preexisting health condition, or a history of poor childhood health or maltreatment.

Together, the findings suggest that treating mental disorders in young people not only improves their well-being but may also forestall the onset of health problems later on. The results also offer the possibility that further research on how adverse psychological states hasten the aging process could lead to strategies to slow its progression, possibly enabling people to stay healthy for longer.

by Erin Bryant From NIH Research Matters

Changes in sleep patterns are common in people with Alzheimer’s disease and other dementias. They may wake up often during the night and find it hard to get back to sleep. These sleep problems are thought to result from brain changes caused by the disease that affect the sleep-wake cycle.

Studies have suggested that sleep patterns earlier in life may contribute to later dementia risk. Both insufficient sleep and sleeping longer than average have been linked to a greater likelihood of developing dementia. However, it has been hard to determine whether these sleep changes contribute to the disease or simply reflect early symptoms.

Many of the studies on sleep and dementia risk have followed participants for less than a decade and focused on people over the age of 65. A study led by Dr. Séverine Sabia of Inserm and University College London examined how sleep patterns earlier in life may affect the onset of dementia decades later.

The study was supported in part by NIH’s National Institute on Aging (NIA). Findings appeared in Nature Communications on April 20, 2021.

The researchers examined data from nearly 8,000 people in Britain starting at age 50. Participants were assessed on a wide variety of measures, including being asked on six occasions between 1985 and 2016 how many hours they slept a night. To assess the accuracy of this self-reporting, some of the participants wore accelerometers to objectively measure sleep time. Over the course of the study, 521 participants were diagnosed with dementia, at an average age of 77.

Analysis of the data showed that people in their 50s and 60s getting six hours of sleep or less were at greater risk of developing dementia later. Compared to those getting normal sleep (defined as 7 hours), people getting less rest each night were 30% more likely to be diagnosed with dementia.

The researchers adjusted their model to account for other factors known to influence sleep patterns or dementia risk, including smoking, physical activity, body mass index, and medical conditions like diabetes and heart disease. They also separated out people with mental illnesses like depression, which are strongly linked to sleep disturbances.

The findings suggest that short sleep duration during midlife could increase the risk of developing dementia later in life. More research is needed to confirm this connection and understand the underlying reasons.

“While we cannot confirm that not sleeping enough actually increases the risk of dementia, there are plenty of reasons why a good night’s sleep might be good for brain health,” Sabia says.

This research was supported in part by NIA grants R01AG056477 and RF1AG062553.

Reference: Association of sleep duration in middle and old age with incidence of dementia.