This week, the world’s largest dementia forum has taken place – the annual 2015 Alzheimer’s Association International Conference in Washington, DC. The conference provides the opportunity for dementia researchers around the globe to come together and share their study results, with the aim of stepping closer to prevention and treatment strategies for Alzheimer’s and other dementias. And this year’s conference has reported some of the most promising results to date.
Worldwide, around 36 million people are living with Alzheimer’s disease – a condition that accounts for around 60-80% of dementia cases. In the US alone, around 5.3 million people are living with the disease – of whom 5.1 million are aged 65 and older.
Over the next 10 years, the number of seniors with the condition is expected to rise to 7.1 million. By 2050, around 13.8 million older adults will be living with Alzheimer’s.
This year, it is estimated that around 700,000 people in the US aged 65 and older will die from Alzheimer’s, making it the 6th leading cause of death in the country – the only cause of death in the top 10 for which their is no way to prevent, slow or cure it.
In August last year, a Spotlight feature from Medical News Today investigated how close researchers are to finding a cure for Alzheimer’s.
The feature highlighted many barriers to prevention and treatment strategies for Alzheimer’s. Prominent among these was lack of techniques to diagnose Alzheimer’s in its early stages, and many researchers believe early intervention is key to combatting the disease.
Helen Snyder, PhD, director of medical and scientific operations at the Alzheimer’s Association told MNT:
“Evidence suggests that the process of Alzheimer’s disease begins more than a decade before clinical symptoms appear, suggesting we may need to intervene earlier to have a major impact on the course of the disease, particularly when using therapies designed to prevent the development of abnormal protein structures – plaques and tangles – that are abundant in the brains of people with Alzheimer’s.”
Gaining a better understanding of the risk factors for Alzheimer’s is also important for prevention of the disease; if we are aware of what triggers the condition, more can be done to reduce the risk of developing it.
These points were the focus of a number of studies presented at this year’s Alzheimer’s Association International Conference (AAIC). And yesterday, the results of one study were labeled by many as a “potential breakthrough” in Alzheimer’s research – the discovery of a drug that could delay Alzheimer’s decline if administered in the early stages of the disease.
In this Spotlight, we take a look at some of the studies presented at the AAIC that are advancing our knowledge of dementia and Alzheimer’s, bringing researchers closer to finding ways to stop the condition in its tracks.
Age is the most well-established risk factor for Alzheimer’s; the vast majority of individuals with the disease are aged 65 and older.
According to the Alzheimer’s Association, the risk for Alzheimer’s doubles every 5 years after the age of 65, while after the age of 85, the risk rises to almost 50%.
A family history of Alzheimer’s and the presence of certain genes – such as apolipoprotein E-e4 (APOE-e4) – are also considered to be risk factors for the disease, but increasingly, researchers are uncovering other elements that may contribute to increased likelihood for Alzheimer’s.
Sedentary behavior and lack of exercise
At the AAIC, Tina Hoang, of the Northern California Institute of Research and Education (NCIRE) in San Francisco, and colleagues presented a study suggesting lack of physical activity and high TV viewing between the ages of 18 and 30 may lead to poorer cognitive function later in life, potentially increasing the risk for Alzheimer’s and other dementias.
The study, involving more than 3,200 adults aged 18-30 who were followed-up for 25 years, revealed that subjects who watched at least 4 hours of TV daily or who had low physical activity levels – defined as activity below 300 Kcal per 50-minute session, three times weekly – had poorer memory, executive function and processing speed in cognitive tests taken in mid-life.
Based on these findings, Hoang and colleagues believe physical activity in early and mid-adulthood may be an important factor for healthy cognitive aging.
“Sedentary behaviors, like TV viewing, could be especially relevant for future generations of adults due to the growing use of screen-based technologies,” says Hoang. “Because research indicates that Alzheimer’s and other dementias develop over several decades, increasing physical activity and reducing sedentary behavior beginning in early adulthood may have a significant public health impact.”
Type 1 diabetes
Previous research has indicated that individuals with type 2 diabetes may be at greater risk for Alzheimer’s and other dementias. But according to Rachel Whitmer, PhD, of Kaiser Permanente Division of Research in Oakland, CA, and colleagues, it has been unclear how type 1 diabetes impacts Alzheimer’s risk.
At the AAIC, Whitmer and colleagues presented the first study of dementia among elderly adults with type 1 diabetes.
To reach their findings, the team analyzed the health history of 490,344 individuals aged 60 and older who had no history of dementia. Of these participants, 334 had type 1 diabetes.
The incidence of dementia among the elderly adults with type 1 diabetes was assessed over 12 years of follow-up and was compared with dementia incidence among participants with type 2 diabetes and those without diabetes.
Compared with participants without type 1 diabetes, adults with this condition were found to be at 83% higher risk for dementia. After adjusting for stroke, hypertension and peripheral arterial disease, the increased risk stood at 61%.
When participants with type 2 diabetes were excluded – leaving only participants without any form of diabetes – the team found the dementia risk for those with type 1 diabetes increased to 93% – 73% after adjusting for stroke, hypertension and peripheral arterial disease.
Whitmer notes that managing type 1 diabetes is tricky, requiring “vigilance and constant self-care.” As such, she says cognitive impairment poses a significant threat to this vulnerable population.
“More research is needed to identify risk and protective factors for Alzheimer’s and other dementias in this group that is newly entering the aging population,” she adds.
Cognitive ability in childhood and job complexity in adulthood
In April, Medical News Today reported on a study published in Neurology that associated more challenging jobs with longer survival from frontotemporal dementia – a form of dementia that, unlike Alzheimer’s, does not affect memory.
Such studies have raised questions about whether an individual’s cognitive ability – in both childhood and adulthood – may affect the risk of dementia development. This was the focus of a new study presented at the AAIC.
In one study, Serhiy Dekhtyar, PhD, of the Karolinska Institutet in Sweden, and colleagues gathered data on the childhood cognitive ability – as determined by school grades at the age of 10 – of 7,574 adults aged 65 and older who were part of Sweden’s Uppsala Birth Cohort Study.
The incidence of dementia among the participants was assessed via 20 years of follow-up, and data on their educational attainment and occupational complexity was also gathered. During follow-up, 950 cases of dementia occurred.
The results of the analysis revealed that participants who fell into the lowest 20% of childhood school grades were at 21% greater dementia risk, compared with those who had higher school grades, regardless of their occupational complexity in adulthood.
However, higher childhood school grades alongside greater job complexity – as determined by high complexity with data and numbers – were found to be at 39% reduced risk for dementia, while a 23% lower risk was found among individuals with higher job complexity alone.
These findings, the team says, suggest that cognitive performance in childhood and early adulthood is important for “cognitive reserve” – the ability for the brain to recover quickly from any damage sustained, preserving memory and thinking later in life.
“Our findings highlight the importance of early-life cognitive performance for the late-life risk of dementia,” says Dekhtyar. “It appears that baseline cognitive ability – even at age 10 – may provide the foundation for successful cognitive aging much later in life. Formation of cognitive reserve is a process that apparently begins early in life.”
Loneliness and depression
Loneliness in older age is a well-known risk factor for depression, but could it also be a risk factor for Alzheimer’s? Dr. Nancy J. Donovan, of Brigham and Women’s Hospital and Harvard Medical School in Boston, MA, and colleagues suggest so.
The team presented a study at the AAIC in which they assessed data from more than 8,300 adults aged 65 and older who were part of the US Health and Retirement Study from 1998-2010.
Every 2 years, the researchers collected data on participants’ loneliness, depression, health status, cognitive function and memory and social network. At study baseline, 17% of participants reported loneliness, with around half reporting depression.
Over a 12-year follow-up period, the team found that the loneliest subjects experienced cognitive decline around 20% faster than participants who did not report loneliness. In addition, participants who reported depression at study baseline also experienced faster cognitive decline.
Commenting on the findings, Dr. Donovan says:
“We found that lonely people decline cognitively at a faster rate than people who report more satisfying social networks and connections. Although loneliness and depression appear closely linked, loneliness may, by itself, have effects on cognitive decline. This is important to know as we develop treatments to enhance cognitive health and quality of life for older adults.”
Dementia researchers believe early detection of Alzheimer’s and other dementias is key for successful treatment of symptoms. But at present, there is no single test to diagnose the condition.
Doctors currently rely on medical evaluation, including mental status testing and physical and neurological examinations, in order to make a dementia diagnosis.
However, new research presented at the AAIC has offered new insight into potential ways to predict the risk for dementia, bringing us closer to early diagnostic techniques.
Saliva testing
A small study led by Shraddha Sapkota, PhD, a neuroscience graduate of the University of Alberta in Canada, suggests an individual’s risk of Alzheimer’s could be detected through a simple saliva test.
Sapkota and colleagues used liquid chromatography-mass spectrometry (LCMS) to assess the saliva samples of 35 participants with normal cognitive functioning, 22 participants with Alzheimer’s and 25 participants with mild cognitive impairment (MCI) – a risk factor for Alzheimer’s.
Compared with participants with normal cognitive functioning, those with MCI and Alzheimer’s had compounds present in their saliva that the researchers linked to poorer cognitive functioning.
Sapkota says their results hold promise for a cheap, noninvasive saliva test for identifying a person’s risk for Alzheimer’s.
“Saliva is easily obtained, safe and affordable, and has promising potential for predicting and tracking cognitive decline, but we’re in the very early stages of this work and much more research is needed,” says Sapkota.
Cerebrospinal fluid
Dr. Maartje Kester, of the VU University Medical Center in Amsterdam, and colleagues presented a study suggesting a protein found in cerebrospinal fluid (CSF) may be effective for predicting the decline to Alzheimer’s among people with MCI.
Over a 2-year period, 162 participants with either normal cognitive functioning, MCI or Alzheimer’s had two CSF samples taken.
At study baseline, the researchers found that CSF samples from participants with Alzheimer’s had higher levels of a protein called neurogranin, which is expressed in the brain, than participants with MCI or normal cognitive function.
In addition, baseline neurogranin levels were found to be higher among subjects with MCI that had progressed to Alzheimer’s. The team says this indicates neurogranin could be a predictor of cognitive decline among people with MCI.
“We found that neurogranin is a potentially useful marker for the diagnosis, prognosis and monitoring of Alzheimer’s,” says Dr. Kester.
The long-term goal for all dementia researchers is to find ways to prevent, slow and treat the condition, but this has proved to be very challenging.
One of the difficulties faced in uncovering such strategies has been the inability to determine exactly what causes dementia.
When it comes to Alzheimer’s, two abnormal brain structures are believed to be key players in development of the condition – plaques and tangles. Plaques are pieces of a protein called beta-amyloid that accumulate in the spaces between nerve cells, and tangles are twisted fibers of a protein called tau, which build up inside brain cells.
While the specific role of plaques and tangles in Alzheimer’s development is unclear, researchers believe they block communication between nerve cells, killing them and leading to the loss of brain tissue.
Early results suggest solanezumab may slow Alzheimer’s progression
In perhaps the most highly anticipated study presented at the AAIC, researchers suggest a drug called solanezumab, if administered early enough, could slow Alzheimer’s disease by stopping the formation of plaques in the brain.
In a clinical trial of solanezumab – a genetically engineered antibody developed by Eli Lilly and Company – Hong Liu-Seifert, PhD, research advisor for the Alzheimer’s Disease Global Development Team at Eli Lilly, and colleagues adopted a “delayed-start” approach.
This involved individuals with mild Alzheimer’s disease being randomized to one of two groups. One group was treated with solanezumab for 18 months, while the other group was given a placebo. The placebo group then began taking solanezumab after 18 months. Both groups were then monitored for a further 2 years.
“This new analytical method enabled us to assess if solanezumab had an effect that is consistent with slowing progression of disease by modifying the underlying disease progression, which, up until now, has not been studied,” says Liu-Seifert.
The results of the trial showed that both groups of patients benefitted from the drug, with both showing reductions in the rate of cognitive decline. However, the group who began taking the drug later – allowing more time for disease progression – were unable to “catch up” with the reduction in cognitive decline seen in the group who began taking solanezumab earlier.
The team says their results indicate solanezumab slows disease progression, otherwise the group who started taking the drug later would have been able to catch up with the early-start group. The findings also suggest solanezumab may be most beneficial when taken in the early stages of Alzheimer’s.
Maria Carillo, PhD, chief science officer of the Alzheimer’s Association, says the study results emphasize the importance of detecting Alzheimer’s early. “If it proves to be true, it is the strongest argument to date for early Alzheimer’s diagnosis, because getting the drug earlier makes a significant difference in the outcome,” she adds.
Dr. Eric Karran, director of Alzheimer’s research at Alzheimer’s Research UK told BBC News that if these results are replicated, we may be on the verge of a “real breakthrough in Alzheimer’s research.”
As the results stand, many researchers believe they should be approached with “cautious optimism.”
Claire Walton, research manager at the Alzheimer’s Society, told BBC News:
“The data hints that the antibodies are having an effect, it is promising and it’s better than no effect, but it’s inconclusive.
After a decade of no treatments and many drug failures, it’s exciting to get promising news, but it doesn’t really tell us either way, and we need to wait for the phase-three study, and that is in 18 months.”
There is no doubt that the studies presented at this year’s AAIC demonstrate how far the dementia research community has come in advancing knowledge of the condition, bringing us a step closer to discovering prevention and treatment strategies.
But there are still a number of factors hindering ongoing research in this field.
Funding is a major factor. Last year, Alzheimer’s disease received $562 million in funding from the National Institutes of Health (NIH). While this was an increase from the $504 million allocated to the field in 2013, it is still far less than the funding other conditions receive.
For example, cancer received almost $5.4 billion in funding from the NIH last year, while breast cancer alone received more funding than Alzheimer’s – at $682 million.
“Dementia is the biggest health and social care challenge of our generation, but research into the condition has been hugely underfunded,” James Pickett, head of research at the Alzheimer’s Society told MNT. “This lack of funding has hampered progress and also restricted the number of scientists and clinicians working in the dementia field.”
“Other diseases have demonstrated that sustained investment in research can improve lives, reduce death rates and ultimately produce effective treatments and preventions,” added Heather Snyder of the Alzheimer’s Association. “We have the tools and the talent to achieve breakthroughs in Alzheimer’s disease, but we need the resources to make this a reality.”
Despite lack of funding, scientists around the globe continue to make great strides in dementia research, as demonstrated by the studies presented at the AAIC this week. Given the optimism emitted by this year’s conference, there are high hopes for even better results next year.