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Study uncovers early warning signs for Alzheimer’s



The Alzheimer's study included examinations of the brain (Photo: DZNE/Frommann)

When people feel that their memory or other mental abilities are declining, but objective tests do not reveal any deterioration, this is referred to in medicine as subjective cognitive impairment, or SCD for short.

The phenomenon has been a topic of research for several years.

“The affected individuals report cognitive problems that cause them serious concern, but which are not measurable with current techniques,” explained Proffessor Frank Jessen, a DZNE scientist and director of the Department of Psychiatry at University of Cologne.

By now it has turned out: SCD is a risk factor, but not a conclusive warning sign for upcoming dementia.

“In many individuals with SCD, there is no progressive loss of cognitive performance. To assess the individual risk more accurately, other factors have to be taken into account”, the dementia researcher said.

“We have now been able to specify these. If, in addition to SCD, there is also evidence that certain proteins accumulate in the brain, then taken together that’s a strong sign for a developing Alzheimer’s disease.”

The team reported the findings of a nationwide study into dementia in the scientific journal ‘Alzheimer’s & Dementia‘.

The study

This assessment is based on a long-term DZNE study called DELCODE, which comprises ten study centres across Germany and involves several university hospitals.

Within this framework, cognitive performance of almost 1,000 older women and men has been recorded annually since several years.

This is done by means of established neuropsychological test procedures.

In addition, the cerebrospinal fluid of many study participants is analysed and brain volume determined by means of magnetic resonance imaging (MRI).

Jessen and his colleagues have now evaluated measurement series of the individual subjects, each data set covered a period of up to five years.

Mean age of the study participants was around 70 years, they were originally recruited through memory clinics at the participating university hospitals and through newspaper advertisements.

The cohort included more than 400 people with SCD at baseline and around 300 individuals who had measurable cognitive impairments – up to symptoms of dementia due to Alzheimer’s disease.

In addition, the cohort comprised more than 200 adults whose cognitive performance was within the normal range and who did not exhibit SCD at baseline: These ‘healthy’ people served as a control group.

All in all, this represents one of the most comprehensive studies on SCD to date.


The protein beta-amyloid, which accumulates in the brain in the course of Alzheimer’s disease, played an important role in the investigations.

Accumulation in the brain can be assessed indirectly – on the basis of the level of the protein in the cerebrospinal fluid: if the reading is beyond a threshold value, this is regarded as evidence that beta-amyloid is concentrating in the brain.

These individuals are then considered ‘amyloid-positive’. Eighty-three study participants with SCD and 25 volunteers from the control group had this status.

“Deposition of beta-amyloid, like SCD, is a risk factor for Alzheimer’s disease. On their own, however, neither phenomenon is a clear indicator of disease,” Jessen said.

“But the picture sharpens, as evidenced by our study, when these phenomena are considered together and over a longer time period.”


During the study period, some subjects from the SCD group and also some from the control group evolved measurable cognitive deficits.

This was particularly evident in amyloid-positive subjects with SCD at baseline.

In comparison, cognitive decline was much on average much lower in amyloid-positive individuals of the control group.

MRI data of the brain also showed differences: The hippocampus, a brain area divided over both brain hemispheres and considered the control centre of memory, tended to be smaller in amyloid-positive subjects with SCD than in amyloid-positive individuals of the control group: an indication of atrophy, ie. loss of brain mass.

Stage two

“When you add up all the findings, including the data from those subjects who already had measurable cognitive deficits at baseline, we see the combination of SCD and amyloid-positive status as a strong indicator of early-stage Alzheimer’s disease,” Jessen said.

“If you classify Alzheimer’s into six stages according to common practice, with stage six representing severe dementia, then, in our view, the combination of SCD and amyloid-positive status corresponds to stage two.

“This occurs before the stage where measurable symptoms first appear and which is also referred to as mild cognitive impairment.”

Early detection

To date, there is no effective treatment for Alzheimer’s disease. However, it is generally believed that therapy should begin as early as possible.

“If there are measurable clinical symptoms, then the brain has already been significantly damaged. From today’s perspective, treatment then has little chance of lasting success,” said Jessen.

“The question, therefore, is how to identify apparently healthy individuals who actually have Alzheimer’s disease and are very likely to develop dementia.

“I consider the combination of SCD and amyloid-positive status to be a promising criterion that should be further investigated and tested in future studies.”


Early Alzheimer’s prediction platform secures €21 million investment



PREDICTOM Dag Aarsland. Photo: Frida Moberg.
PREDICTOM's Dag Aarsland. Photo: Frida Moberg.

The project aims to identify people at risk of dementia before symptoms appear.

More than 7 million people are living with dementia in the EU. This number is projected to double, reaching 14 million by 2050.

There is currently no cure for Alzheimer’s disease. Although the search for potential treatments is showing promise, it is anticipated that these medications will be most effective in the early stages of the disease.

The recently launched AI screening platform, PREDICTOM aims to identify individuals at risk of developing dementia, even before symptoms manifest.

The cognitive and biomarker screening platform has this week announced it will be backed by €21 million in funding, with €8 million from the EU, €9 million from industry and €4 million from UKRI.

A consortium of 30 partners from academia, business, civil society and hospitals is steering the project. The Consortium includes partners from 15 countries across Europe, Asia and America and is led by Stavanger University Hospital.

Dag Aarsland, Professor of Old Age Psychiatry at King’s College London and research lead at Stavanger University Hospital, is the leading the project.

“Detecting early signs of dementia is key to slowing its progression. Unfortunately, a majority of those at risk are not identified in time. Our platform seeks to change this by enabling early discovery, allowing timely intervention and preventative treatment,” Aarsland said.

A crucial aspect of PREDICTOM is that much of the screening can be performed by the patients themselves in the comfort of their homes.

By initiating the process at home, the project aims to reduce strain on healthcare services and associated costs. Biomarkers, including saliva, stool, digital markers and blood via prick-tests, will be collected at participants’ homes or GP offices, streamlining a process traditionally carried out in hospitals or specialised clinics.

More than 4000 participants will partake in PREDICTOM’s trial project. The samples will be based on a pool of people from previous initiatives like PROTECT UK, PROTECT Norway and Radar-AD, as well as people from the catchment area of other participating centres in Germany, France, Switzerland, Belgium and Spain.

“If our project succeeds, there will be significant savings in both cost and time,” Aarsland said

After the home collection, samples will be sent to PREDICTOM, where their platform will process the participant data, integrating blood, cerebrospinal fluid, imaging, electrophysiological and digital biomarkers.

AI algorithms will generate risk assessments, early diagnoses and prognoses, laying the foundation for early intervention and treatment.

This project is part of the Innovative Health Initiative (IHI), a public-private partnership (PPP) between the European Union and the European life science industries.

“We are very pleased to have such a robust team with top notch expertise spanning diverse fields, including IT, AI, medicine, ageing research and professionals from both small and large businesses,” Aarsland added.

The project runs from 1st November 2023 to 31st October 2027.

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New partnership to bring dementia-specific programmes to Washington State



Washington state dementia

The partnership will bring non-pharmacological interventions for dementia and alternatives to high-cost drugs to patients across Washington State.

A new partnership between brain health company, Together Senior Health and accountable care organisation, Rainier Health Network,

The partnership will introduce Together’s suite of dementia-specific programs, including in-home virtual interventions, to patients across Rainier Health Network in Washington state where the organisation oversees the healthcare of over 60,000 Medicare patients.

Alzheimer’s and related dementias affect more than 6.7 million Americans with 14 million projected cases by 2060. The associated healthcare costs for individuals with dementia are among the highest of any condition. Payers and providers face significant challenges in managing this expanding population.

According to a recent survey conducted by Sage Growth Partners, 77 per cent of health plans and value-based care organizations agree the need to address the growing cost of ADRD is urgent or very urgent; however, only 4 per cent have a fully-developed solution in place to support this population.

Approximately half of those surveyed also indicated a concern with the costs of Leqembi and other high-cost pharmaceuticals.

Together’s Moving Together programme offers a non-pharmacological intervention for dementia and a safe alternative to high-cost drugs that are not clinically appropriate for many dementia patients and have potential side effects.

The programme allows payers and risk-bearing healthcare organisations to more effectively manage patients. Together Senior Health says the programme results in improved engagement, reduced costs and improved health outcomes.

Recently, the company has been gaining industry traction. In addition to its partnership with Rainer Health Network, the firm is affiliated with the likes of VNS Health, VillageMD and the Alzheimer’s Association.

“Supporting our members with Alzheimer’s disease and related dementias is critical,” said Dr Francis Mercado chief medical officer and board chair at Rainier Health Network.It’s a vulnerable population and Together Senior Health’s Moving Together™ solution is a proven, natural way to improve their lives and control costs.”

Together’s Moving Together™ programme is based on over ten years of clinical research in neuroscience with the University of California, San Francisco (UCSF) and the National Institutes of Health (NIH).

Results from Together’s randomised control trial show statistically significant improvements in quality of life for individuals with cognitive decline and in caregiver ability to manage stress. The data also shows a reduction in falls and proven annual cost savings of up to $4,300 per participant per year.

Caregivers in the programme have also benefited, reporting enhanced caregiving skills.

Together is in the process of commercialising RADAR, its proprietary dementia identification and stratification algorithm. The algorithm helps payors and risk-bearing healthcare organisations identify people at highest risk for Alzheimer’s disease, dementia and cognitive decline using claims data, electronic health record information and other relevant data.

“We are proud of the positive impact Together is making on the lives of those affected by dementia and are excited to partner with one of the nation’s premier ACOs to extend dementia-specific programs to its patients,” said Alissa Meade, CEO of Together Senior Health.

“Rainier Health Network, Virginia Mason Franciscan Health and Together share a deep commitment to providing holistic dementia solutions that enrich the lives of participants while empowering forward-thinking, risk-bearing organizations to engage and manage this rapidly growing patient population effectively.”

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One in 25 carry genotype associated with shortened lifespan



Genotype associated with shortened lifespan found in 1 in 25.
Kari Stefansson, Patrick Sulem and Brynjar Örn Jensson scientists at deCODE genetics and authors on the paper

The study used genomic data from 58,000 Icelanders and discovered the presence of a life-shortening genotype across 4 per cent of the population.

Scientists at deCODE Genetics, a subsidiary of Amgen, have published a study on actionable genotypes detected in the Icelandic population and their association with lifespan.

The researchers determined that 1 in 25 individuals carried an actionable genotype and have, on average, a shortened lifespan.

“The identification and disclosure of actionable genotypes to participants can guide clinical decision-making, which may result in improved patient outcomes,” said Kari Stefansson, author of the paper and CEO of deCODE Genetics. “This knowledge therefore has significant potential to mitigate disease burden for individuals and society as a whole.”

The study, published today in the New England Journal of Medicine, focuses on genotypes that increase the risk of a disease for which preventive or therapeutic measures have been established. These genotypes are termed actionable genotypes.

The scientists used a population-based data set, consisting of 58,000 whole-genome sequenced Icelanders, to assess the fraction of individuals carrying actionable genotypes.

Using a list of 73 actionable genes from the guidelines from the American College of Medical Genetics and Genomics (ACMG), the scientists found that 4 per cent of Icelanders carry an actionable genotype in one or more of these genes. The diseases caused by these genotypes include cardiovascular, cancer and metabolic diseases.

The study assessed the relationship between actionable genotypes and the lifespan of their carriers. The largest effect was observed among carriers of cancer-predisposing genotypes, which had three years shorter median survival than non-carriers.

A pathogenic variant in BRCA2, predisposing to breast, ovarian and pancreatic cancer, shortened lifespan by seven years and a variant in LDLR, which causes high levels of cholesterol and cardiovascular disease, shortened lifespan by six years.

“Our results suggest that the actionable genotypes identified in our study, which are all predicted to cause serious disease, may have a drastic effect on lifespan,” said Patrick Sulem author of the paper and scientist at deCODE Genetics.

The results showed that carriers of particular actionable genotypes were more likely to have died from the disease caused by these genotypes. Individuals with a pathogenic variant in BRCA2, have a seven-fold risk of dying from breast, ovarian or pancreatic cancer.

They are also 3.5 times more likely to develop prostate cancer and seven times more likely to die from prostate cancer than those who do not carry the variant.

The results of this study are among the factors that have motivated the government of Iceland to announce a nationwide effort in precision medicine.

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