Tiny fragments of plastic known as nanoplastics interact with a particular protein that is naturally found in the brain, creating changes linked to Parkinson’s disease and some types of dementia, according to a Duke University-led study.
In Science Advances, the researchers report that the findings create a foundation for a new area of investigation, fuelled by the timely impact of environmental factors on human biology.
“Parkinson’s disease has been called the fastest growing neurological disorder in the world,” said principal investigator, Andrew West, PhD, professor at Duke University School of Medicine.
“Numerous lines of data suggest environmental factors might play a prominent role in Parkinson’s disease, but such factors have for the most part not been identified.”
Improperly disposed plastics have been shown to break into very small pieces and accumulate in water and food supplies, and were found in the blood of most adults in a recent study.
“Our study suggests that the emergence of micro and nanoplastics in the environment might represent a new toxin challenge with respect to Parkinson’s disease risk and progression,” West said.
“This is especially concerning given the predicted increase in concentrations of these contaminants in our water and food supplies.”
West and colleagues in Duke’s Nicholas School of the Environment and the Department of Chemistry at Trinity College of Arts and Sciences found that nanoparticles of the plastic polystyrene — typically found in single use items such as disposable drinking cups and cutlery — attract the accumulation of the protein known as alpha-synuclein.
West said the study’s most surprising findings are the tight bonds formed between the plastic and the protein within the area of the neuron where these accumulations are congregating, the lysosome.
Researchers said the plastic-protein accumulations happened across three different models performed in the study – in test tubes, cultured neurons, and mouse models of Parkinson’s disease.
West said that questions remain about how such interactions might be happening within humans and whether the type of plastic might play a role.
“While microplastic and nanoplastic contaminants are being closely evaluated for their potential impact in cancer and autoimmune diseases, the striking nature of the interactions we could observe in our models suggest a need for evaluating increasing nanoplastic contaminants on Parkinson’s disease and dementia risk and progression,” West said.
“The technology needed to monitor nanoplastics is still at the earliest possible stages and not ready yet to answer all the questions we have,” he said.
A new form of deep brain stimulation offers hope for an alternative treatment option for dementia, without the need for surgery.
Researchers at Imperial College London are leading the development of the technique, known as temporal interference (TI). This non-invasive method works by delivering electrical fields to the brain through electrodes placed on the patient’s scalp and head. Their initial findings, which are published in the journal Nature Neuroscience, could lead to an alternative treatment for brain diseases such as Alzheimer’s, and its associated memory loss.
Temporal interference
By targeting the overlapping electrical fields researchers were able to stimulate an area deep in the brain called the hippocampus, without affecting the surrounding areas – a procedure that until now required surgery to implant electrodes into the brain.
The approach has been successfully trialled with 20 healthy volunteers for the first time by a team at the UK Dementia Research Institute (UK DRI) at Imperial and the University of Surrey.
Their initial results show that when healthy adults perform a memory task whilst receiving TI stimulation it helped to improve memory function.
The team is now conducting a clinical trial in people with early-stage Alzheimer’s disease, where they hope TI could be used to improve symptoms of memory loss.
Dr Nir Grossman, from the Department of Brain Sciences at Imperial College London, who led the work said: “Until now, if we wanted to electrically stimulate structures deep inside the brain, we needed to surgically implant electrodes which of course carries risk for the patient, and can lead to complications.
“With our new technique we have shown for the first time, that it is possible to remotely stimulate specific regions deep within the human brain without the need for surgery. This opens up an entirely new avenue of treatment for brain diseases like Alzheimer’s which affect deep brain structures.”
Reaching deep brain regions
TI was first described by the team at Imperial College London in 2017 and shown to work in principle in mice.
This latest work, funded and carried out through the UK Dementia Research Institute, shows for the first time that TI is effective at stimulating regions deep within the human brain.
According to the researchers, this could have broad applications and will enable scientists to stimulate different deep brain regions to discover more about their functional roles, accelerating the discovery of new therapeutic targets.
A study published in The Lancet Healthy Longevity shows that brain metabolism, detected with advanced imaging techniques, declines more sharply in middle-aged people with a sustained high cardiovascular risk over 5 years
Cardiovascular disease and dementia frequently occur together in elderly people. Nevertheless, few longitudinal studies have examined how atherosclerosis and its associated risk factors affect brain health from middle age. Now, a new study by scientists at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid provides new data on this relationship; the results confirm the importance of controlling traditional cardiovascular risk factors, such as hypertension, cholesterol, diabetes, smoking, and a sedentary lifestyle, not only to preserve cardiovascular health, but also to prevent Alzheimer’s disease and other dementias.
The CNIC study shows that atherosclerosis (accumulation of fatty deposits in the arteries) and its associated risk factors, in addition to being the main cause of cardiovascular disease, are also implicated in the cerebral alterations typically found in Alzheimer’s disease, the most frequent cause of dementia.
According to study author Dr Valentín Fuster, CNIC General Director, the new findings are important because they open up the possibility of treating a modifiable disorder, ie cardiovascular disease, to prevent the development a presently untreatable disease – dementia. “The sooner we act to control cardiovascular risk factors, the better it is for our brain health,” said Dr. Fuster.
“Everybody knows that a healthy lifestyle and controlling cardiovascular risk factors are important for preventing a heart attack,” continued Dr Fuster. “Nevertheless, the additional information linking the same risk factors to a decline in brain health could further increase awareness of the need to acquire healthy habits from the earliest life stages.”
In 2021, CNIC scientists discovered that the presence of cardiovascular risk factors and subclinical (presymptomatic) atherosclerosis in the carotid arteries (the arteries that supply the brain) was associated with lower glucose metabolism in the brains of apparently healthy 50-year-old participants in the PESA-CNIC-Santander study. Glucose metabolism in the brain is considered an indicator of brain health.
The PESA-CNIC-Santander study directed by Dr Fuster is a prospective study that includes more than 4000 asymptomatic middle-aged participants who have been exhaustively assessed for the presence and progression of subclinical atherosclerosis since 2010.
Dr Fuster’s team, led by Drs Marta Cortés Canteli and Juan Domingo Gispert, have continued to monitor the cerebral health of these participants over 5 years. Their research shows that individuals who maintained a high cardiovascular risk throughout this period had a more pronounced reduction in cerebral glucose metabolism, detected using imaging techniques such as positron emission tomography (PET).
“In participants with a sustained high cardiovascular risk, the decline in cerebral metabolism was three times greater than in participants who maintained a low cardiovascular risk,” commented Catarina Tristão-Pereira, first author on the study and INPhINIT fellow.
Glucose is the main energy source for neurons and other brain cells. “If there is a sustained decline in cerebral glucose consumption over several years, this may limit the brain ability to withstand neurodegenerative or cerebrovascular diseases in the future,” explained Dr Gispert, an expert in neuroimaging at the CNIC and Barcelonaβeta Research Center.
Through a collaboration with Drs Henrik Zetterberg and Kaj Blennow, world experts in the identification of new blood biomarkers at the University of Gothenburg in Sweden, the CNIC team discovered that the individuals showing this metabolic decline already show signs of neuronal injury. “This is a particularly important finding because neuronal death is irreversible”, said Dr. Cortés Canteli, a neuroscientist at the CNIC and a Miguel Servet fellow at the Fundación Jiménez Díaz Health Research Institute.
The CNIC team also discovered that the progression of subclinical atherosclerosis in the carotid arteries over five years is linked to a metabolic decline in brain regions vulnerable to Alzheimer’s disease, in addition to the effect of cardiovascular risk factors. “These results provide yet another demonstration that the detection of subclinical atherosclerosis with imaging techniques provides highly relevant information,” said Dr Fuster, who is the principal investigator on the PESA study. “The interaction between the brain and the heart is a fascinating topic, and with this study we have seen that this relationship begins much earlier than was thought.”
The scientists conclude that, “carotid screening has great potential to identify individuals at risk of cerebral alterations and cognitive decline in the future.” In the published article they write, “this work could have important implications for clinical practice since it supports the implementation of primary cardiovascular prevention strategies early in life as a valuable approach for a healthy cerebral longevity.”
“Although we still don’t know what impact this decline in cerebral metabolism has on cognitive function, the detection of neuronal injury in these individuals shows that the earlier we start to control cardiovascular risk factors, the better it will be for our brain,” concluded Dr Cortés Canteli.
The prevalence of microplastics in the environment is well known, along with their harm to marine organisms, but few studies have examined the potential health impacts on mammals. Now, a new study published in the International Journal of Molecular Sciences has found that in mice, the infiltration of microplastics was as widespread in the body as it is in the environment, leading to behavioural changes, especially in older test subjects.
Study leader University of Rhode Island Professor Jaime Ross and her team focused on neurobehavioural effects and inflammatory response to exposure to microplastics, as well as the accumulation of microplastics in tissues, including the brain.
“Current research suggests that these microplastics are transported throughout the environment and can accumulate in human tissues; however, research on the health effects of microplastics, especially in mammals, is still very limited,” said Ross, an assistant professor of biomedical and pharmaceutical sciences at the Ryan Institute for Neuroscience and the College of Pharmacy. “This has led our group to explore the biological and cognitive consequences of exposure to microplastics.”
Behavioural changes detected
Ross’ team exposed young and old mice to varying levels of microplastics in drinking water over the course of three weeks. They found that microplastic exposure induces both behavioural changes and alterations in immune markers in liver and brain tissues. The study mice began to exhibit behaviours akin to dementia in humans. The results were even more profound in older animals.
“To us, this was striking. These were not high doses of microplastics, but in only a short period of time, we saw these changes,” Ross said. “Nobody really understands the life cycle of these microplastics in the body, so part of what we want to address is the question of what happens as you get older. Are you more susceptible to systemic inflammation from these microplastics as you age? Can your body get rid of them as easily? Do your cells respond differently to these toxins?”
To understand the physiological systems that may be contributing to these changes in behaviour, Ross’ team investigated how widespread the microplastic exposure was in the body, dissecting several major tissues including the brain, liver, kidney, gastrointestinal tract, heart, spleen and lungs. The researchers found that the particles had begun to bioaccumulate in every organ, including the brain, as well as in bodily waste.
“Given that in this study the microplastics were delivered orally via drinking water, detection in tissues such as the gastrointestinal tract, which is a major part of the digestive system, or in the liver and kidneys was always probable,” Ross said. “The detection of microplastics in tissues such as the heart and lungs, however, suggests that the microplastics are going beyond the digestive system and likely undergoing systemic circulation. The brain blood barrier is supposed to be very difficult to permeate. It is a protective mechanism against viruses and bacteria, yet these particles were able to get in there. It was actually deep in the brain tissue.”
Possible mechanism
That brain infiltration also may cause a decrease in glial fibrillary acidic protein (called “GFAP”), a protein that supports many cell processes in the brain, results have shown. “A decrease in GFAP has been associated with early stages of some neurodegenerative diseases, including mouse models of Alzheimer’s disease, as well as depression,” Ross said. “We were very surprised to see that the microplastics could induce altered GFAP signalling.”
She intends to investigate this finding further in future work. “We want to understand how plastics may change the ability for the brain to maintain its homeostasis or how exposure may lead to neurological disorders and diseases, such as Alzheimer’s disease,” she said.
A study of nearly 9000 older people in Japan found that those who have little social contact with others may be more likely to have reduction of overall brain volume, and in areas of the brain affected by dementia, compared with those who have more frequent social contact. The study results were published in Neurology.
“Social isolation is a growing problem for older adults,” said study author Toshiharu Ninomiya, MD, PhD, of Kyushu University in Fukuoka, Japan. “These results suggest that providing support for people to help them start and maintain their connections to others may be beneficial for preventing brain atrophy and the development of dementia.”
The study involved 8896 people without dementia, average age 73. They had MRI brain scans and health exams, and were asked how often they were in contact with friends or relatives that did not live with them.
The people with the lowest amount of social contact had overall brain volume that was significantly lower than those with the most social contact. The total brain volume, or the sum of white and grey matter, as a percentage of the total intracranial volume, or the volume within the cranium, including the brain, meninges, and cerebrospinal fluid, was 67.3% in the lowest contact group compared to 67.8% in the highest contact group. They also had lower volumes in areas of the brain such as the hippocampus and amygdala that play a role in memory and are affected by dementia.
The researchers took into account other factors that could affect brain volume, such as age, diabetes, smoking and exercise.
The socially isolated people also had more small areas of damage in the brain, called white matter lesions, than the people with frequent social contact. The percentage of intracranial volume made up of white matter lesions was 0.30 for the socially isolated group, compared to 0.26 for the most socially connected group.
The researchers found that symptoms of depression partly explained the relationship between social isolation and brain volumes. However, symptoms of depression accounted for only 15% to 29% of the association.
“While this study is a snapshot in time and does not determine that social isolation causes brain atrophy, some studies have shown that exposing older people to socially stimulating groups stopped or even reversed declines in brain volume and improved thinking and memory skills, so it’s possible that interventions to improve people’s social isolation could prevent brain volume loss and the dementia that often follows,” Ninomiya said.
Since the study involved only older Japanese people, a limitation is that the findings may not be generalisable to people of other ethnicities and younger people.
People who take proton pump inhibitors for acid reflux four-and-a-half years or more may have a higher risk of dementia compared to people who do not take these medications, according to new research published in Neurology.
Acid reflux is when stomach acid flows into the oesophagus, usually after a meal or when lying down, resulting in heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GERD, which can lead to cancer of the oesophagus. Proton pump inhibitors reduce stomach acid by targeting the enzymes in the stomach lining that produce that acid.
“Proton pump inhibitors are a useful tool to help control acid reflux, however long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis, and a member of the American Academy of Neurology. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”
The study included 5712 people, aged 45 and up, without dementia at the start of the study. They had an average age of 75.
Researchers determined if participants took acid reflux drugs by reviewing their medications during study visits and during yearly phone calls. Of the participants, 1490 people, or 26%, had taken the drugs. Participants were then divided into four groups based on whether they had taken the drugs and for how long, as follows: people who did not take the drugs; those who took the drugs for up to 2.8 years; those who took them for 2.8 to 4.4 years; and people who took them for more than 4.4 years.
Participants were then followed for a median duration of 5.5 years. During this time, 585 people, or 10%, developed dementia.
Of the 4222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1000 person-years.
After adjusting for factors such as age, sex and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.
Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.
“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” said Lakshminarayan. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”
A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over the counter acid reflux drugs.
Older people who have fluctuating levels of total cholesterol and triglycerides may have a higher risk of Alzheimer’s disease and related dementias compared to people who have steady levels, according to new research published online in Neurology. Since the study is observational, it cannot establish a causative link.
“Prevention strategies for Alzheimer’s and related dementias are urgently needed,” said study author Suzette J. Bielinski, PhD, of the Mayo Clinic in Rochester, Minnesota. “Routine screenings for cholesterol and triglyceride levels are commonly done as part of standard medical care. Fluctuations in these results over time could potentially help us identify who is at greater risk for dementia, help us understand mechanisms for the development of dementia and ultimately determine whether levelling out these fluctuations could play a role in reducing dementia risk.”
Researchers used health care data to identify 11 571 people age 60 or older without a prior diagnosis of Alzheimer’s disease or dementia. They assessed total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL) and high-density lipoprotein cholesterol (HDL) for the participants on at least three different days in the five years before the start of the study. Then participants were assigned into five equal groups based on the degree of measurement fluctuation, from lowest to highest.
Participants were followed for an average of 13 years. During that time, 2473 of them developed Alzheimer’s disease or another form of dementia. After adjusting for confounding variables, researchers found for total cholesterol, participants in the highest fluctuation group had a 19% increased risk of dementia compared to those in the lowest group. Of the 2311 people in the highest group, 515 developed dementia compared to 483 of the 2311 people in the lowest group. For triglycerides, those in highest group had a 23% increased risk.
No link was found between dementia and variations in LDL and HDL, however.
“It remains unclear why and how fluctuating levels of cholesterol and triglycerides are related to the risk of Alzheimer’s disease,” said Bielinski. “Further studies looking at the changes over time for this relationship are needed in order to confirm our results and potentially consider preventative strategies.”
One study limitation was that researchers looked at Alzheimer’s disease and related dementias as a whole and did not differentiate between the types of dementia.
Older people with ischaemic heart disease have an increased long-term risk of dementia and accelerated cognitive decline. Recent research in Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association suggests that the heart, the brain, and cognitive function are all connected in the ageing process. Appropriate prevention and treatment of ischaemic heart disease in older people might reduce the burden of dementia, the researchers suggest.
The researchers regularly followed a cohort of 2568 older people aged 60 years or older, without dementia at baseline and living in Stockholm, from 2001–2004 through 2013–2016. Heart diseases at the study entry were ascertained via clinical examination and linkage to the Swedish National Inpatient Register. Dementia status and cognitive function during the follow-up period were diagnosed and assessed regularly following the standard approaches.
“We used statistical methods to link ischemic heart disease at the study entry to an increased risk of dementia and a faster decline in cognitive function during the follow-up period”, says Chengxuan Qiu, at the Department of Neurobiology, Care Sciences and Society, Division of Aging Research Center (ARC) and one of the authors of the study.
Explore cognitive trajectories
Future works should explore cognitive trajectory following the onset of ischemic heart disease and further investigate to what extent medical treatments of ischemic heart disease may affect cognitive decline and dementia onset.
The SNAC-K project on which this study is based is supported by the Swedish Ministry of Health and Social Affairs. This study is supported by additional grants from the Swedish Research Council (VR), FORTE and STINT.
The Bacillus Calmette-Guérin (BCG) for tuberculosis vaccine has a number additional beneficial effects, and is currently a recommended therapy for non–muscle-invasive bladder cancer. In a new study published in JAMA Network Open, treatment with the BCG vaccine was associated with a reduced risk of Alzheimer’s disease and related dementias.
Although previous research has suggested a link between the BCG vaccine and a lower risk of dementia, studies were limited by size, study design, or analytical methods. To conduct a more robust study, researchers followed 6467 individuals for up to 15 years after they were diagnosed with non–muscle-invasive bladder cancer.
The group included 3388 patients who underwent BCG vaccine treatment and 3079 who served as controls, matched by factors such as age, sex, and medical co-morbidities.
During follow-up, 202 patients in the BCG vaccine group and 262 in the control group developed Alzheimer’s disease and related dementias. The incidence was 8.8 per 1000 person-years and 12.1 per 1000 person-years in the respective groups.
Analyses revealed that treatment with the BCG vaccine was associated with a 20% lower risk of Alzheimer’s disease and related dementias. The protective association was greater in patients aged 70 years or older. Additionally, during follow-up, 751 patients in the BCG vaccine group and 973 in the control group died. Thus, treatment with BCG vaccine was associated with a 25% lower risk of death.
Study leader Marc Weinberg, MD, Ph.D., an Instructor in Psychiatry at MGH, said: “A vaccine like BCG, if proven effective, is a perfect example of a cost-effective, population-health–based solution to a devastating illness like Alzheimer’s disease. We are shifting our focus towards studying the potential benefits of BCG vaccination of older adults in Alzheimer’s disease–related clinical trials.”
If a causal link is found, it will be important to understand the mechanisms involved. Weinberg and his colleagues note that the BCG vaccine’s effects on the immune system may play a role.
A large representative study found that individuals with newly diagnosed atrial fibrillation had a modestly elevated risk of developing dementia. The Journal of the American Heart Associationstudy found that this risk was higher in younger adults and those without chronic kidney disease, but did not substantially vary across sex, race, or ethnicity.
In this study of nearly 200 000 adults, incidence rates for dementia over a median follow-up of 3.3 years were 2.79 versus 2.04 per 100 person-years in individuals with versus without atrial fibrillation, respectively. (This means that over one year, there would be an average of 2.79 dementia diagnoses among 100 people with atrial fibrillation and 2.04 diagnoses among 100 people without atrial fibrillation. This translates to 279 per 10 000 and 204 per 10 000.)
After adjustments, atrial fibrillation was associated with a 13% higher risk of dementia. Adults aged <65 years had a 65% higher risk compared with older adults, those without chronic kidney disease had a 14% higher risk than those with chronic kidney disease.
“These data highlight a possible link between atrial fibrillation and risk of subsequent dementia in certain populations. Further studies are needed to understand the mechanisms to explain this association, which may inform the use of treatments for atrial fibrillation,” said corresponding author Nisha Bansal, MD, MAS, of the University of Washington School of Medicine.
