What Is: Dementia

Illustration Credit: Scientific Frontline

The End of the Passive Era

The year 2025 marks a definitive inflection point in the history of neuroscience and geriatric medicine. For decades, the field of dementia care was characterized by a certain fatalism—a paradigm of "diagnose and manage" where the clinician’s role was largely to document decline and support the family. That era has officially closed. We have entered the age of precision intervention, defined by the ability to detect neurodegenerative pathology in blood plasma decades before symptoms arise, the availability of disease-modifying immunotherapies that clear toxic proteins from the brain, and a nuanced biological understanding that has shattered the monolithic concept of "senility" into a spectrum of distinct, treatable molecular events.

Our Scientific Frontline report provides an exhaustive analysis of the dementia landscape as it stands in late 2025. It synthesizes data from the latest clinical trials, including the landmark approval of subcutaneous maintenance dosing for anti-amyloid therapies, and examines the emerging economic reality where the global cost of dementia is projected to triple by mid-century. We explore the biological underpinnings of conditions ranging from classic Alzheimer’s Disease to the newly characterized Limbic-predominant Age-related TDP-43 Encephalopathy (LATE), and we evaluate the transformative potential of 14 modifiable risk factors that could prevent nearly half of all cases.

Concordia researchers identify key marker linking coronary artery disease to cognitive decline

Zacharie Potvin-Jutras, with Claudine Gauthier:
“Our goal is to examine conditions at the onset of a heart disease, before there has been any significant impact on the brain”
Photo Credit: Courtesy of Concordia University

Individuals with coronary artery disease (CAD) — a constricting or blocking of blood vessels feeding the heart — face increased risks of strokes, cognitive impairment and dementia. However, the link between CAD and cognitive function is not fully understood. 

A new study led by Concordia researchers looks at how the disease affects the brain’s white matter, the network of nerve fibers that connects different regions of the brains and is critical to transmitting information efficiently. 

The study, published in the Journal of Neuroscience, applied a novel multivariate approach using 12 separate metrics. The researchers compared test results and MRI scans of 43 patients with CAD to those of 36 healthy individuals. All participants were over the age of 50. 

Scientists uncover how the brain falls asleep

Scientists have been able to pinpoint, for the first time, the exact moment the brain transitions into sleep, and precisely map the unfolding process in real time.
Photo Credit: Zohre Nemati

In the new study, the researchers demonstrated that the human brain falls asleep abruptly, rather than gradually, with a ‘tipping point’ marking the transition from wakefulness into sleep. They were then able to predict the momentary progression into sleep with unprecedented precision. 

The findings could be used to develop new ways to diagnose and treat sleep disorders, such as insomnia, and as a marker of brain health in the context of ageing and neurodegenerative disease, and even to improve how we monitor anesthesia during surgical procedures.  

Study reveals genetic link between childhood brain disorder and Parkinson's disease in adults

Image Credit: Dmitriy Kievskiy

Errors in a gene known to cause a serious neurodevelopmental condition in infants are also linked to the development of Parkinson’s disease in adolescence and adulthood, according to new research

The study, published in the Annals of Neurology, looked at a gene called EPG5. Errors in this gene are already known to cause Vici syndrome – a rare and severe inherited neurodevelopmental condition that presents early in life and affects multiple organ systems. Now researchers at King’s College London, University College London (UCL), the University of Cologne and the Max Planck Institute for Biology of Ageing have found that errors in the same gene are linked to changes in nerve cells that lead to more common age-related conditions like Parkinson’s disease and dementia.

Cholesterol-lowering drugs could reduce the risk of dementia

Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomization — this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimizing the influence of confounding factors like weight, diet, and other lifestyle habits.

Brain inflammation treatment could be ally in fight against dementia

Samira Aghlara-Fotovat
Photo Credit: Jeff Fitlow/Rice University

Scientists from Rice University and Houston Methodist have developed a new way to reduce inflammation in the brain, a discovery that could help fight diseases such as Alzheimer’s and Parkinson’s.

The team created “AstroCapsules,” small hydrogel capsules that enclose human astrocytes ⎯ star-shaped brain cells that support healthy nervous system function. Inside the capsules, the cells were engineered to release interleukin-1 receptor antagonist, an anti-inflammatory protein. Tests in human brain organoids and mouse models showed the treatment lowered neuroinflammation and resisted immune rejection.

Rice bioengineer Omid Veiseh, whose lab studies how to design biomaterials that work with the immune system, is co-corresponding author on the paper published in Biomaterials.

“Encapsulating cells in a way that shields them from immune attack has been a central challenge in the field,” said Veiseh, professor of bioengineering at Rice, Cancer Prevention and Research Institute of Texas Scholar and director of the Rice Biotech Launch Pad. “In our lab, we have been working on biomaterials for many years, and this project was an opportunity to draw from that experience to address the uniquely complex immune environment of the brain. Our hope is that this work will help move cell therapies closer to becoming real treatment options for patients with neurodegenerative disease.”

Does isolated REM sleep behavior disorder predict Parkinson’s disease or dementia?

Image Credit: Gerd Altmann

An international research team led by Université de Montréal medical professor Shady Rahayel has made a major breakthrough in predicting neurodegenerative diseases. 

Thanks to two complementary UdeM studies, scientists are now able to determine, years in advance, which individuals with a particular sleep disorder will develop Parkinson’s disease or dementia with Lewy bodies (DLB). 

The studies focus on isolated REM sleep behavior disorder (iRBD)—a condition in which people yell, thrash, or act out their dreams, sometimes violently enough to injure a bed partner. 

“It’s not just restless sleep—it’s a neurological warning sign,” said Rahayel, a neuropsychologist and researcher at the Centre for Advanced Research in Sleep Medicine at Sacré-Cœur Hospital in Montreal. 

Roughly 90 per cent of people with this sleep disorder will go on to eventually develop Parkinson’s disease or DLB. Until now, however, it was impossible to know which disease would occur—or when. 

Study reveals reasons for misdiagnosis of frontotemporal dementia

Researchers have discovered patterns in the misdiagnosis of frontotemporal dementia
Photo Credit: Anna Shvets

University of Queensland researchers discovered that nearly 70 per cent of suspected frontotemporal dementia patients ultimately did not have the disease, in a study aimed at identifying factors that contribute to misdiagnosis of this notoriously difficult to diagnose disorder.

Psychiatrist Dr Joshua Flavell, working with cognitive neurologist Professor Peter Nestor at the Mater Hospital Memory and Cognitive Disorders clinic and UQ’s Queensland Brain Institute, analyzed data from 100 patients suspected of having frontotemporal dementia who had been referred by specialist physicians like neurologists, psychiatrists or geriatricians.

“Of the 100 patients, 34 were true-positive, and 66 were false-positive for frontotemporal dementia,” Dr Flavell said.

“We found that misinterpretation of brain scans, particularly nuclear imaging, led to 32 patients being incorrectly diagnosed.

Patients with delirium more likely to develop dementia

Professor Ruth Hubbard interacting with a patient.
Photo Credit: The University of Queensland

University of Queensland researchers have found older patients who experience delirium are three times more likely to develop dementia.

Professor Ruth Hubbard from UQ’s Centre for Health Services Research (CHSR) said the study also found that every episode of delirium increased the chance of developing dementia by 20 per cent.

“Delirium is an acute confusional state which particularly impacts older people and can have long term detrimental effects on patients,” Professor Hubbard said.

“Our study found that it is also strongly linked to dementia.”

The researchers analyzed a cohort of more than 110,000 patients from New South Wales hospitals over five years.

Lead author and CHSR research fellow, Dr Emily Gordon, said more than 55,000 patients who had experienced delirium were compared to patients who had not.

Risk factors for faster aging in the brain revealed in new study

Governments have been urged to act decisively before 2035 to ensure global warming can be kept below 2°C by 2100.
Photo Credit: Nöel Puebla

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 so-called ‘modifiable’ risk factors − as they can potentially be changed throughout life to reduce the risk of dementia − into 15 broad categories: blood pressure, cholesterol, diabetes, weight, alcohol consumption, smoking, depressive mood, inflammation, pollution, hearing, sleep, socialization, diet, physical activity, and education.

Human brains are getting larger. That may be good news for dementia risk

Image Credit: Dmitriy Gutarev

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 hypothesize 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 Charles DeCarli, first author of the study. DeCarli is 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.”

The aging brain: protein mapping furnishes new insights

Stained mouse microvessels under the fluorescence microscope (green: vascular endothelium, red: cell nuclei). 
Image Credit: © Dichgans Lab

For the neurons in the brain to work smoothly and be able to process information, the central nervous system needs a strictly regulated environment. This is maintained by the blood-brain barrier, whereby specialized brain endothelial cells lining the inner walls of blood vessels regulate the exchange of molecules between the circulatory and nervous systems. Earlier studies have shown that various functions that are dependent on these cells, such as the integrity of the blood-brain barrier or the regulation of blood supply to the brain, decline over the course of a person’s life. This dysregulation leads to a dysfunction of the brain vasculature and is therefore a major contributor to medical conditions such as strokes and dementia.

However, the molecular changes that underlie this loss of function have remained largely obscure. To improve our mechanistic understanding, researchers carry out molecular profiling studies to investigate the different components of brain endothelial cells and collect their findings in large databases. “The transcriptome – that is to say, the RNA contained in endothelial cells – has since been quite comprehensively mapped,” says LMU professor Martin Dichgans, Director of the Institute for Stroke and Dementia Research at University of Munich Hospital and Principal Investigator at the SyNergy Cluster of Excellence. “What has been lacking is corresponding data on the complete set of proteins in the cells, the proteome.” A study recently published in the journal Nature Aging, which had major contributions by researchers from LMU and SyNergy, has now closed this knowledge gap.

Alzheimer’s Drug Fermented with Help from AI and Bacteria Moves Closer to Reality

Photo-Illustration Credit: Martha Morales/The University of Texas at Austin

Galantamine is a common medication used by people with Alzheimer’s disease and other forms of dementia around the world to treat their symptoms. Unfortunately, synthesizing the active compounds in a lab at the scale needed isn’t commercially viable. The active ingredient is extracted from daffodils through a time-consuming process, and unpredictable factors, such as weather and crop yields, can affect supply and price of the drug. 

Now, researchers at The University of Texas at Austin have developed tools — including an artificial intelligence system and glowing biosensors — to harness microbes one day to do all the work instead. 

In a paper in Nature Communications, researchers outline a process using genetically modified bacteria to create a chemical precursor of galantamine as a byproduct of the microbe’s normal cellular metabolism.  Essentially, the bacteria are programmed to convert food into medicinal compounds.

“The goal is to eventually ferment medicines like this in large quantities,” said Andrew Ellington, a professor of molecular biosciences and author of the study. “This method creates a reliable supply that is much less expensive to produce. It doesn’t have a growing season, and it can’t be impacted by drought or floods.” 

Risk of young-onset dementia could be reduced through targeting health and lifestyle factors

Researchers have identified a wide range of risk factors for young-onset dementia. The findings challenge the notion that genetics are the sole cause of the condition, laying the groundwork for new prevention strategies.

The largescale study identified 15 risk factors, which are similar to those for late-onset dementia. For the first time, they indicate that it may be possible to reduce the risk of young-onset dementia by targeting health and lifestyle factors.

Relatively little research has been done on young-onset dementia, though globally there are around 370,000 new cases of young-onset dementia each year.

Published in JAMA Neurology, the new research by the University of Exeter and Maastricht University followed more than 350,000 participants younger than 65 across the United Kingdom from the UK Biobank study. The team evaluated a broad array of risk factors ranging from genetic predispositions to lifestyle and environmental influences. The study revealed that lower formal education, lower socioeconomic status, genetic variation, lifestyle factors such as alcohol use disorder and social isolation, and health issues including vitamin D deficiency, depression, stroke, hearing impairment and heart disease significantly elevate risk of young-onset dementia

Enlarged Spaces in Infant Brains Linked to Higher Risk of Autism, Sleep Problems

Dea Garic, PhD, and Mark Shen, PhD, both in the UNC School of Medicine’s Department of Psychiatry, have found that enlarged perivascular spaces in the brains of babies, caused by an accumulation of excess cerebrospinal fluid, have a 2.2 times greater chance of developing autism later in life.
Photo Credit: Courtesy of University of North Carolina at Chapel Hill

Throughout the day and night, cerebrospinal fluid (CSF) pulses through small fluid-filled channels surrounding blood vessels in the brain, called perivascular spaces, to flush out neuroinflammation and other neurological waste. A disruption to this vital process can lead to neurological dysfunction, cognitive decline, or developmental delays.

For the first time, researchers Dea Garic, PhD, and Mark Shen, PhD, both at the UNC School of Medicine’s Department of Psychiatry, discovered that infants with abnormally enlarged perivascular spaces have a 2.2 times greater chance of developing autism compared to infants with the same genetic risk. Their research also indicated that enlarged perivascular spaces in infancy are associated with sleep problems seven to 10 years after diagnosis.

“These results suggest that perivascular spaces could serve as an early marker for autism,” said Garic, assistant professor of psychiatry and a member of the Carolina Institute for Developmental Disabilities (CIDD).

The researchers studied infants at increased likelihood for developing autism, because they had an older sibling with autism. They followed these infants from 6-24 months of age, before the age of autism diagnosis. Their study, published in JAMA Network Open, found that thirty percent of infants who later developed autism had enlarged perivascular spaces by 12 months. By 24 months of age, nearly half of the infants diagnosed with autism had enlarged perivascular spaces.

Clues to preventing Alzheimer’s come from patient who, despite genetics, evaded disease

A woman who never developed Alzheimer's despite a strong genetic predisposition may hold the key to stopping the disease in its tracks. Studying the woman's unique complement of genetic mutations, researchers at Washington University School of Medicine in St. Louis have found clues that could help cut the link between the early, asymptomatic stage and the late stage, when cognitive decline sets in.
Image Credit: AartlistDesign

Alzheimer’s disease has plagued one large Colombian family for generations, striking down half of its members in the prime of life. But one member of that family evaded what had seemed would be fate: Despite inheriting the genetic defect that caused her relatives to develop dementia in their 40s, she stayed cognitively healthy into her 70s.

Researchers at Washington University School of Medicine in St. Louis now think they know why. A previous study had reported that, unlike her relatives, the woman carried two copies of a rare variant of the APOE gene known as the Christchurch mutation. In this study, researchers used genetically modified mice to show that the Christchurch mutation severs the link between the early phase of Alzheimer’s disease, when a protein called amyloid beta builds up in the brain, and the late phase, when another protein called tau accumulates and cognitive decline sets in. So the woman stayed mentally sharp for decades, even as her brain filled with massive amounts of amyloid. The findings, published in the journal Cell, suggest a new approach to preventing Alzheimer’s dementia.

Ural Scientists Have Synthesized a New Substance for the Treatment of Alzheimer’s Disease

Scientists from the Ural Federal University, the Institute of Organic Synthesis of the Ural Branch of the Russian Academy of Sciences, together with colleagues from India have developed a method for creating safe and non-toxic substances that could become the basis for drugs for Alzheimer's disease. Using the new technology, they synthesized and tested several compounds of tacrine analogues, which toxicity is estimated to be from two to five times lower than that of the known drug. The description of the new method and the compounds obtained was published in the Journal of Heterocyclic Chemistry. 

"We believe that our technology will help to create safe substances that will become the basis for future drugs for Alzheimer's disease. Our studies have shown that the toxicity of the resulting substances is two to five times lower than that of tacrine. At the same time, they are effective as they help to increase the level of acetylcholine in the cerebral cortex, which slows down the destruction of neuronal connections. This allows patients to maintain their cognitive functions and lead an active and fulfilling life for as long as possible," explains Nibin Joy Muthipeedika, Senior Researcher at the UrFU Organic Synthesis Laboratory.

Brain health in over 50s deteriorated more rapidly during the pandemic

Photo Credit: Gabriel Porras

Brain health in over 50s deteriorated more rapidly during the pandemic, even if they didn’t have COVID-19, according to major new research linking the pandemic to sustained cognitive decline.

Researchers looked at results from computerized brain function tests from more than 3,000 participants of the online PROTECT study, who were aged between 50 and 90 and based in the UK. The remote study, led by teams at the University of Exeter and the Institute of Psychiatry, Psychology & Neuroscience (IoPPN) at King’s College London, and part-funded by NIHR Maudsley BRC, tested participants’ short-term memory and ability to complete complex tasks.

Through analyzing the results from this big dataset, researchers found that cognitive decline quickened significantly in the first year of the pandemic, when they found a 50 per cent change to the rate of decline across the study group. This figure was higher in those who already had mild cognitive decline before the pandemic, according to the research published in The Lancet Healthy Longevity.

High metabolism is an early sign of Alzheimer’s disease

Illustration Credit: geralt

An early phase in the process of developing Alzheimer’s disease is a metabolic increase in a part of the brain called the hippocampus, report researchers from Karolinska Institutet in a study published in Molecular Psychiatry. The discovery opens up new potential methods of early intervention.

Alzheimer’s disease is the most common form of dementia and strikes about 20,000 people in Sweden every year. Researchers now show that a metabolic increase in the mitochondria, the cellular power plants, is an early indicator of the disease. 

The teams behind the study used mice that developed Alzheimer’s disease pathology in a similar way to humans. The increase in metabolism in young mice was followed by synaptic changes caused by disruption to the cellular recycling system (a process known as autophagy), a finding that was awarded the Nobel Prize in Physiology or Medicine in 2016. 

After a time, metabolism in the Alzheimer brain usually declines, which contributes to the degradation of synapses. This the researchers could also see in the older mice, which had had the disease for a longer time. 

Study Suggests Epigenetic Age May Predict Memory Function Better Than Actual Age

The Stony Brook research team investigating epigenetic age acceleration hope to understand more about the biological and environmental factors related to it. From left: Daisy V. Zavala, Stacey Scott and Krishna Veeramah.
Photo Credit: John Griffin, Stony Brook University

A study led by researchers at Stony Brook University shows that age acceleration, when one’s so-called biological clock runs quicker than one’s actual age, is linked to poorer memory and slower rates of processing information. The team measured biological “clocks” derived from the DNA of 142 adults aged 25-65 years old and had the participants complete daily cognitive tests on smartphones. Their findings, which imply that epigenetic age acceleration could be a better indicator of how well a person remembers information and how quickly they work with information, are detailed in the Journal of Gerontology: Biological Sciences.

There are well-known chronological age differences in cognitive performance — on average, younger adults tend to remember more information and respond more quickly than older adults. One presumed explanation is biological wear-and-tear across life, but until recently, there was not a way to test biological aging to explain these differences between younger and older people.

Aging researchers currently have significant interest in examining epigenetic patterns that change how the DNA in our cells fold and how genes behave. Unlike our DNA genome, which stays the same throughout our lifetime in every cell of our body, our epigenome can change through time and can be influenced by our behavior and environment. These epigenetic changes can thus indicate a person’s biological age, which may differ from chronological age.