Tag: dementia

Long-term Study Finds Link between Earlier Diabetes Diagnosis and Dementia Risk

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People diagnosed with type 2 diabetes at a younger age are at a higher risk for developing dementia than those diagnosed later in life, according to a study led by researchers at the NYU Rory Meyers College of Nursing. The findings, published in PLOS ONE, show that the increased risk is especially pronounced among adults with obesity.

“Our study suggests that there may be cognitive consequences to earlier onset type 2 diabetes, and it points to the need for strategies to prevent dementia that consider both diabetes and obesity,” said Xiang Qi, assistant professor at NYU Meyers and the study’s first author.

Type 2 diabetes is a known risk factor for dementia. Although the underlying mechanisms are not fully understood, scientists think that some of the hallmarks of diabetes, such as high blood sugar, insulin resistance, and inflammation, may encourage the development of dementia in the brain.

While type 2 diabetes was once a disease of older adults, it is increasingly prevalent among younger individuals: one in five people with type 2 diabetes worldwide is under 40 years old.

To understand how the timing of a type 2 diabetes diagnosis relates to dementia risk, the research team analyzed data from 2002 to 2016 in the Health and Retirement Study, a longitudinal study conducted by the University of Michigan Institute for Social Research. The PLOS ONE study included 1213 US adults aged 50 and over with type 2 diabetes confirmed by blood tests, without dementia at baseline. Following participants for up to 14 years, 216 (17.8%) developed dementia based on follow-up telephone interviews.

The researchers found that adults diagnosed with type 2 diabetes at younger ages were at increased risk for developing dementia, compared to those diagnosed at 70 years or older. Adults diagnosed with diabetes before age 50 were 1.9 times as likely to develop dementia as those diagnosed at 70 and older, while those diagnosed between 50–59 years were 1.72 times as likely and those diagnosed between 60–69 years were 1.7 times as likely.

Using linear trend tests, the researchers found a graded association between age at diagnosis and dementia risk: for each year younger a person is at the time of their type 2 diabetes diagnosis, their risk for developing dementia increases by 1.9%.

“While we do not know for sure why an earlier diabetes diagnosis would increase the risk for dementia, prior studies show that people diagnosed with type 2 diabetes in mid-life may experience more vascular complications, poor blood sugar control, and insulin resistance – all of which are known risk factors for cognitive impairment,” said Bei Wu, the Dean’s Professor in Global Health and vice dean for research at NYU Meyers and the study’s senior author.

In addition, obesity appeared to influence the relationship between type 2 diabetes and dementia. Individuals with obesity who were diagnosed with type 2 diabetes before age 50 had the highest dementia risk in the study.

The researchers note that this greater understanding of the connection between diabetes onset, obesity, and dementia may help inform targeted interventions to prevent dementia.

“Our study highlights the importance of one’s age at diabetes diagnosis and suggests that specifically targeting obesity – whether through diet and exercise or perhaps medication – may play a role in staving off dementia in younger adults with diabetes,” said Wu.

Source: New York University

Extra Year of Education does Not Protect the Brain

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Thanks to a ‘natural experiment’ involving 30 000 people, researchers at Radboud university medical centre were able to very precisely determine the effect of an extra year of education to the brain in the long term. To their surprise, they found no effect on brain structure and no protective benefit of additional education against brain ageing. Their findings appear in eLife.

It is well-known that education has many positive effects. People who spend more time in school are generally healthier, smarter, and have better jobs and higher incomes than those with less education. However, whether prolonged education actually causes changes in brain structure over the long term and protects against brain ageing, was still unknown.

It is challenging to study this, because alongside education, many other factors influence brain structure, such as the conditions under which someone grows up, DNA traits, and environmental pollution. Nonetheless, researchers Rogier Kievit (PI of the Lifespan Cognitive Dynamics lab) and Nicholas Judd from Radboudumc and the Donders Institute found a unique opportunity to very precisely examine the effects of an extra year of education.

Ageing

In 1972, a change in the law in the UK raised the number of mandatory school years from 15 to 16, while all other circumstances remained constant. This created an interesting ‘natural experiment’, an event not under the control of researchers which divides people into an exposed and unexposed group. Data from approximately 30 000 people who attended school around that time, including MRI scans taken much later (46 years after), is available. This dataset is the world’s largest collection of brain imaging data.

The researchers examined the MRI scans for the structure of various brain regions, but they found no differences between those who attended school longer and those who did not. ‘This surprised us’, says Judd. ‘We know that education is beneficial, and we had expected education to provide protection against brain aging. Aging shows up in all of our MRI measures, for instance we see a decline in total volume, surface area, cortical thickness, and worse water diffusion in the brain. However, the extra year of education appears to have no effect here.’

Brain structure

It’s possible that the brain looked different immediately after the extra year of education, but that wasn’t measured. “Maybe education temporarily increases brain size, but it returns to normal later. After all, it has to fit in your head,” explains Kievit. “It could be like sports: if you train hard for a year at sixteen, you’ll see a positive effect on your muscles, but fifty years later, that effect is gone.” It’s also possible that extra education only produces microscopic changes in the brain, which are not visible with MRI.

Both in this study and in other, smaller studies, links have been found between more education and brain benefits. For example, people who receive more education have stronger cognitive abilities, better health, and a higher likelihood of employment. However, this is not visible in brain structure via MRI. Kievit notes: “Our study shows that one should be cautious about assigning causation when only a correlation is observed. Although we also see correlations between education and the brain, we see no evidence of this in brain structure.”

Source: Radboud University Medical Centre

New Research Shows that Recombinant Shingles Vaccine Protects Against Dementia

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New research published in Nature has shown that the recombinant shingles vaccine, as with the live version, might have a protective effect against dementia.

While evidence is emerging that the live herpes zoster (shingles) vaccine might protect against dementia, it has now been replaced by recombinant vaccines in many countries. But a lack of data meant that whether the recombinant vaccines conferred the same benefit was unknown. Fortunately, since there was a rapid switch from live to recombinant vaccines, there was an opportunity for a natural experiment to compare the risk of dementia between vaccine types.

The study demonstrated that the recombinant vaccine is associated with a significantly lower risk of dementia in the 6 years post-vaccination. Specifically, receiving the recombinant vaccine is associated with a 17% increase in diagnosis-free time, translating into 164 additional days lived without a diagnosis of dementia in those subsequently affected.

The recombinant shingles vaccine was also associated with lower risks of dementia than were two other vaccines commonly used in older people: influenza and tetanus–diphtheria–pertussis vaccines. The effect was robust across multiple secondary analyses, and was present in both men and women but was greater in women. These findings should stimulate studies investigating the mechanisms underpinning the protection and could facilitate the design of a large-scale randomised control trial to confirm the possible additional benefit of the recombinant shingles vaccine.

SGLT-2 Inhibitors may Lower Risk of Dementia and Parkinson’s Disease

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A class of drugs for diabetes may be associated with a lower risk of dementia and Parkinson’s disease, according to a study published in Neurology®, the medical journal of the American Academy of Neurology. The study looked at sodium-glucose cotransporter-2 (SGLT2) inhibitors, which are also known as gliflozins. They lower blood sugar by causing the kidneys to remove sugar from the body through urine.

“We know that these neurodegenerative diseases like dementia and Parkinson’s disease are common and the number of cases is growing as the population ages, and people with diabetes are at increased risk of cognitive impairment, so it’s encouraging to see that this class of drugs may provide some protection against dementia and Parkinson’s disease,” said study author Minyoung Lee, MD, PhD, of Yonsei University College of Medicine in Seoul, South Korea.

The retrospective study looked at people with type 2 diabetes who started diabetes medication from 2014 to 2019 in South Korea. People taking SGLT2 inhibitors were matched with people taking other oral diabetes drugs, so the two groups had people with similar ages, other health conditions and complications from diabetes.

Then researchers followed the participants to see whether they developed dementia or Parkinson’s disease. Those taking the SGLT2 inhibitors were followed for an average of two years and those taking the other drugs were followed for an average of four years.

Among the 358 862 participants with an average age of 58, a total of 6837 people developed dementia or Parkinson’s disease during the study. For Alzheimer’s disease, the incidence rate for people taking SGLT2 inhibitors was 39.7 cases per 10 000 person-years, compared to 63.7 cases for those taking other diabetes drugs. Person-years represent both the number of people in the study and the amount of time each person spends in the study.

For vascular dementia, which is dementia caused by vascular disease, the incidence rate for people taking the SGLT2 drugs was 10.6 cases per 10 000, compared to 18.7 for those taking the other drugs. For Parkinson’s disease, the incidence rate for those taking the SGLT2 drugs was 9.3 cases per 10 000, compared to 13.7 for those taking the other drugs.

After researchers adjusted for other factors that could affect the risk of dementia or Parkinson’s disease, such as complications from diabetes and medications, they found that SGLT2 inhibitor use was associated with a 20% reduced risk of Alzheimer’s disease and a 20% reduced risk of Parkinson’s disease. Those taking the drugs had a 30% reduced risk of developing vascular dementia.

“The results are generally consistent even after adjusting for factors like blood pressure, glucose, cholesterol and kidney function,” Lee said. “More research is needed to validate the long-term validity of these findings.” Lee said that since participants were followed for less than five years at the most, it’s possible that some participants would later develop dementia or Parkinson’s disease.

Source: American Academy of Neurology

Shingles Increases Risk of Cognitive Decline in Later Life

The risk was higher for men who were carriers of a gene linked to dementia

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A new study led by investigators from Brigham and Women’s Hospital found that an episode of shingles is associated with about a 20 percent higher long-term risk of subjective cognitive decline. The study’s findings provide additional support for getting the shingles vaccine to decrease risk of developing shingles, according to the researchers. Their results are published in Alzheimer’s Research & Therapy.

“Our findings show long-term implications of shingles and highlight the importance of public health efforts to prevent and promote uptake of the shingles vaccine,” said corresponding author Sharon Curhan, MD, of the Channing Division for Network Medicine at Brigham and Women’s Hospital. “Given the growing number of Americans at risk for this painful and often disabling disease and the availability of a very effective vaccine, shingles vaccination could provide a valuable opportunity to reduce the burden of shingles and possibly reduce the burden of subsequent cognitive decline.”

Shingles, medically known as “herpes zoster,” is a viral infection that often causes a painful rash. Shingles is caused by the varicella zoster virus (VZV), the same virus that causes chickenpox. After a person has chickenpox, the virus stays in their body for the rest of their life. Most of the time, our immune system keeps the virus at bay. Years and even decades later, the virus may reactivate as shingles.

Almost all individuals in the US age 50 years and older have been infected with VZV and are therefore at risk for shingles. There’s a growing body of evidence that herpes viruses, including VZV, can influence cognitive decline. Subjective cognitive decline is an individual’s self-perceived experience of worsening or more frequent confusion or memory loss. It is a form of cognitive impairment and is one of the earliest noticeable symptoms of Alzheimer’s disease and related dementias.

Previous studies of shingles and dementia have been conflicting. Some research indicates that shingles increases the risk of dementia, while others indicate there’s no association or a negative association. In recent studies, the shingles vaccine was associated with a reduced risk of dementia.

To learn more about the link between shingles and cognitive decline, Curhan and her team used data from three large, well-characterized studies of men and women over long periods: The Nurses’ Health Study, the Nurses’ Health Study 2, and the Health Professionals Follow-Up Study. The study included 149,327 participants who completed health status surveys every two years, including questions about shingles episodes and cognitive decline. They compared those who had shingles with those who didn’t.

Curhan designed the study with first author Tian-Shin Yeh, formerly of the Harvard TH Chan School of Public Health. The researchers found that a history of shingles was significantly and independently associated with a higher risk – approximately 20% higher – of subjective cognitive decline in both women and men. That risk was higher among men who were carriers of the gene APOE4, which is linked to cognitive impairment and dementia. That same association wasn’t present in the women.

Researchers don’t know the mechanisms that link the virus to cognitive health, but there are several possible ways it may contribute to cognitive decline. There is growing evidence linking VZV to vascular disease, called VZV vasculopathy, in which the virus causes damage to blood vessels in the brain or body. Curhan’s group previously found that shingles was associated with higher long-term risk of stroke or heart disease.

Other mechanisms that may explain how the virus may lead to cognitive decline include causing inflammation in the brain, directly damaging the nerve and brain cells, and the activation of other herpesviruses.

The limitations of this research include that it was an observational study, information was based on self-report, and included a mostly white, highly educated population. In future studies, the researchers hope to learn more about preventing shingles and its complications.

“We’re evaluating to see if we can identify risk factors that could be modified to help reduce people’s risk of developing shingles,” Curhan said. “We also want to study whether the shingles vaccine can help reduce the risk of adverse health outcomes from shingles, such as cardiovascular disease and cognitive decline.” 

Source: Brigham and Women’s Hospital

New Pulsatility Metric in Brain Blood Vessels for Studying Dementia

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Researchers from the Mātai Institute and the Auckland Bioengineering Institute have developed a new metric from measured blood circulation in the brain. The new metric opens up new research avenues for brain conditions, including Alzheimer’s disease and other forms of dementia. The research has been published in the leading research journal Scientific Reports Nature.

Each time the heart beats, it pumps blood through the brain vessels, causing them to expand slightly and then relax. This pulsation in the brain helps distribute blood evenly across different areas of the brain, ensuring that all parts receive the oxygen and nutrients they need to function properly.

In healthy vessels, the pulse wave is dampened before it reaches the smallest vessels, where high pulsatility could be harmful. The new metric provides a comprehensive measure of the small vessel pulsatility risk.

The new metric is based on 4D flow MRI technology, and is particularly crucial because increased vascular pulsatility is linked to several brain conditions, including Alzheimer’s disease and other forms of dementia.

By accurately measuring how pulsatility is transmitted in the brain, researchers can better understand the underlying mechanisms of these diseases and potentially guide the development of new treatments.

Current MRI methods face limitations due to anatomical variations and measurement constraints. The new technique removes this issue by integrating thousands of measurements across all brain vessels, rather than the traditional method of looking at one spot. This provides a richer metric representative of the entire brain.

“The ability to measure how pulsatility is transmitted through the brain’s arteries could revolutionise our approach to neurological diseases, and support research in vascular damage hypotheses,” says first author Sergio Dempsey.

“Our method allows for a detailed assessment of the brain’s vascular health, which is often compromised in neurodegenerative disorders.”

The study also highlighted the potential to enhance clinical assessments and research on brain health. By integrating this new metric into routine diagnostic procedures, healthcare providers can offer more precise and personalised care plans for individuals at risk of or suffering from cognitive impairments.

To make the most of the new metric’s implications for patient care, the researchers have made their tools publicly available, integrating them into pre-existing open-source software. This enables scientists and clinicians worldwide to adopt the advanced methodology, fostering further research and collaboration in the field of neurology.

Results from the initial study of the metric also identified important sex differences in vascular dynamics which has initiated a new study focusing on sex-related dynamics.

The research team is planning further studies to explore the applications of this technique in larger and more diverse populations.

Source: University of Auckland

Risk Factors for Faster Aging in the Brain Revealed in New Study

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Researchers from the Nuffield Department of Clinical Neurosciences at the University of Oxford have used data from UK Biobank participants to reveal that diabetes, traffic-related air pollution and alcohol intake are the most harmful out of 15 modifiable risk factors for dementia.

The researchers had previously identified a ‘weak spot’ in the brain, which is a specific network of higher-order regions that not only develop later during adolescence, but also show earlier degeneration in old age.

They showed that this brain network is also particularly vulnerable to schizophrenia and Alzheimer’s disease.

In this new study, published in Nature Communications, they investigated the genetic and modifiable influences on these fragile brain regions by looking at the brain scans of 40 000 UK Biobank participants aged over 45.

The researchers examined 161 risk factors for dementia, and ranked their impact on this vulnerable brain network, over and above the natural effects of age.

They classified these modifiable risk factors into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialisation, diet, physical activity, and education.

Prof Gwenaëlle Douaud, who led this study, said: “We know that a constellation of brain regions degenerates earlier in aging, and in this new study we have shown that these specific parts of the brain are most vulnerable to diabetes, traffic-related air pollution – increasingly a major player in dementia – and alcohol, of all the common risk factors for dementia.”

“We have found that several variations in the genome influence this brain network, and they are implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s diseases, as well as with the two antigens of a little-known blood group, the elusive XG antigen system, which was an entirely new and unexpected finding.”

Prof Lloyd Elliott, a co-author from Simon Fraser University in Canada, concurs: ‘In fact, two of our seven genetic findings are located in this particular region containing the genes of the XG blood group, and that region is highly atypical because it is shared by both X and Y sex chromosomes.

This is really quite intriguing as we do not know much about these parts of the genome; our work shows there is benefit in exploring further this genetic terra incognita.’

Importantly, as Prof Anderson Winkler, a co-author from the National Institutes of Health and The University of Texas Rio Grande Valley in the US, points out: “What makes this study special is that we examined the unique contribution of each modifiable risk factor by looking at all of them together to assess the resulting degeneration of this particular brain ‘weak spot’. It is with this kind of comprehensive, holistic approach – and once we had taken into account the effects of age and sex – that three emerged as the most harmful: diabetes, air pollution, and alcohol.”

This research sheds light on some of the most critical risk factors for dementia, and provides novel information that can contribute to prevention and future strategies for targeted intervention.

Source: University of Oxford

Human Brains are Getting Larger, which may Protect against Dementia

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A new study by researchers at UC Davis Health found human brains are getting larger. Study participants born in the 1970s had 6.6% larger brain volumes and almost 15% larger brain surface area than those born in the 1930s. The researchers hypothesise that the increased brain size may lead to an increased brain reserve, potentially reducing the overall risk of age-related dementias.

The findings were published in JAMA Neurology.

“The decade someone is born appears to impact brain size and potentially long-term brain health,” said first author Charles DeCarli, a distinguished professor of neurology and director of the UC Davis Alzheimer’s Disease Research Center.

“Genetics plays a major role in determining brain size, but our findings indicate external influences – such as health, social, cultural and educational factors – may also play a role.”

75-year study reveals brain changes between generations

The researchers used brain magnetic resonance imaging (MRIs) from participants in the Framingham Heart Study (FHS). The community-based study was launched in 1948 in Framingham, Massachusetts, to analyse patterns of cardiovascular and other diseases.

The original cohort consisted of 5209 men and women between the ages of 30 and 62. The research has continued for 75 years and now includes second and third generations of participants.

The MRIs were conducted between 1999 and 2019 with FHS participants born during the 1930s through the 1970s.

The brain study consisted of 3226 participants (53% female, 47% male) with an average age of about 57 at the time of the MRI.

The research led by UC Davis compared the MRIs of people born in the 1930s to those born in the 1970s.

It found gradual but consistent increases in several brain structures.

For example, a measure that looked at brain volume (intracranial volume) showed steady increases decade by decade.

For participants born in the 1930s, the average volume was 1234mL, but for those born in the 1970s, the volume was 1321 mL, or about 6.6% greater volume.

Cortical surface area showed an even greater increase over the decades.

Participants born in the 1970s had an average surface area of 2104cm2 compared to 2056cm2 for participants born in the 1930s — almost a 15% increase in volume.

The researchers found brain structures such as white matter, gray matter and hippocampus (a brain region involved in learning and memory) also increased in size when comparing participants born in the 1930s to those born in the 1970s.

Larger brains may mean lower incidence of dementia

Although the numbers are rising with America’s aging population, the incidence of Alzheimer’s – the percentage of the population affected by the disease – is decreasing.

A previous study found a 20% reduction in the incidence of dementia per decade since the 1970s.

Improved brain health and size may be one reason why.

“Larger brain structures like those observed in our study may reflect improved brain development and improved brain health,” DeCarli said.

“A larger brain structure represents a larger brain reserve and may buffer the late-life effects of age-related brain diseases like Alzheimer’s and related dementias.”

One of the study’s strengths is the design of the FHS study, which allows the researchers to examine brain imaging of three generations of participants with birthdates spanning almost 80 years.

A limitation is that non-Hispanic white participants make up the majority of the FHS cohort, which is not representative of the U.S. population.

Source: University of California – Davis Health

Visions of Nonphysical World are Common Among Cognitively Healthy American Indians

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Visual hallucinations are common among people with Lewy body dementia and other types of dementia. Identifying visual hallucinations is an important component of a wide variety of medical and psychiatric diagnoses and treatments, but without cultural context, some patients’ symptoms can be misinterpreted or misdiagnosed.

There is little in medical literature about normal spiritual experiences in American Indian participants in the context of a neurocognitive evaluation. University of Minnesota Medical School researchers sought to understand how the culture and spirituality of the American Indian Ojibwe tribe affect a doctor’s assessment of normal aging.

Publishing in JAMA Network Open, the research team found that visions of the nonphysical world are common among cognitively healthy Ojibwe individuals and can represent normal spiritual experiences. 

“Consideration of a patient’s cultural background and belief system can help avert erroneous disqualification for disease-modifying therapy, exclusion from clinical trials and all the negative ramifications associated with a misdiagnosis of psychiatric disease,” said William Mantyh, MD, an assistant professor at the University of Minnesota Medical School and  behavioural neurologist with M Health Fairview.

In partnership with an Ojibwe Tribal Nation in Minnesota, the study recruited 33 cognitively healthy tribal elders aged 55 years or older. The research found 48% of participants reported frequent transient visions of the nonphysical world that generally were benevolent and involved spiritual beings and/or ancestors. 

According to the research team, clinicians would benefit from careful consideration of cultural or spiritual context to avoid misdiagnosis of neuropsychiatric disease. 

“Today’s environment of infrequent or insufficiently short cognitive evaluations – an average 16-minute face-to-face visit with a physician and increasing use of pre-visit symptom checklists increase the risk of falsely attributing a spiritual experience to a hallucination,” said Dr Mantyh. 

Dr Mantyh and his research team’s overarching goal is to ensure accurate diagnosis of neurodegenerative disease in American Indian communities. To reach this goal, the research team is including American Indian participants in the development of a new Alzheimer’s disease blood test. So far, more than 250 participants have been included. These new Alzheimer’s disease blood tests, up to 95% accurate, directly detect the proteins related to Alzheimer’s disease in the blood, but they also look at a patient’s APOE ε4 gene. APOE ε4 is the most significant genetic risk factor for Alzheimer’s disease, but its effect on Alzheimer’s disease depends on a patient’s ancestry. 

Source: University of Minnesota

Abnormally High Levels of HDL-C Linked to Dementia in Older Adults

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Abnormally high levels of high density lipoprotein cholesterol (HDL-C), are associated with an increased risk of dementia in older adults, according to study led by Monash University. Researchers said very high levels of the ‘good cholesterol’ HDL-C linked to dementia risk in this study were uncommon and not diet related, but more likely to reflect a metabolic disorder. The findings may help doctors to recognise a group of older patients potentially at risk of dementia, particularly in those aged 75 and older.

Published in The Lancet Regional Health – Western Pacific, this is one of the largest studies of elevated HDL-C levels and dementia in initially healthy older people aged mostly over 70, enrolled in the ASPREE* study.

Over an average 6.3 years, participants with very high HDL-C (> 80mg/dL or > 2.07mmol/L) at study entry were observed to have a 27% higher risk of dementia compared to participants with optimal HDL-C levels, while those aged 75 years and older also showed a 42% increased risk compared to those with optimal levels.

Very high HDL-C levels were categorised as 80mg/dL (> 2.07mmol/L) or above.

The optimal level of HDL-C of 40 to 60mg/dL (1.03–1.55mmol/L) for men and 50 to 60mg/dL (1.55–2.07mmol/L) for women was generally beneficial for heart health.

Among 18 668 participants included in this analysis, 2709 had very high HDL-C at study entry, with 38 incidents of dementia in those aged less than 75 years with very high levels, and 101 in those aged 75 and more with very high levels.

First author and Monash University School of Public Health and Preventive Medicine senior research fellow Dr Monira Hussain said that further research was needed to explain why a very high HDL cholesterol level appeared to affect the risk of dementia.

Dr Hussain said these study findings could help improve our understanding of the mechanisms behind dementia, but more research was required.

“While we know HDL cholesterol is important for cardiovascular health, this study suggests that we need further research to understand the role of very high HDL cholesterol in the context of brain health,” she said.

“It may be beneficial to consider very high HDL cholesterol levels in prediction algorithms for dementia risk.”

*The Aspirin in Reducing Events in the Elderly (ASPREE) trial is a double-blind, randomised, placebo-controlled trial of daily aspirin in healthy older people. 

Source: Monash University