Research
Study uncovers early warning signs for Alzheimer’s
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.
Biomarkers
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.”
Development
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.”
NICE will review whether new Alzheimer’s drugs should be offered on the NHS after an appeal found their wider impact was not fully counted.
An appeal found that the National Institute for Health and Care Excellence had failed to properly account for the wider impact of the treatments, including the heavy burden on unpaid carers, when calculating the cost effectiveness of the medicines.
Both treatments, lecanemab and donanemab, will now return to a NICE committee for further consideration.
“Today’s ruling is an opportunity for NICE to consider the real cost of Alzheimer’s on people and their families, and we welcome the decision to look again at whether new medicines could be provided on the NHS,” said David Thomas, head of policy and public affairs at Alzheimer’s Research UK.
Lecanemab and donanemab do not cure Alzheimer’s, but they slow it by targeting and clearing clumps of amyloid proteins, sticky protein build-ups in the brain linked to the disease.
While the drugs are available privately in the UK for people who can afford them, NICE ruled last year that they were too expensive to be made available on the NHS in England and Wales.
It is estimated informal dementia care costs the economy more than £20bn a year.
Alzheimer’s Research UK wants NICE to update how it assesses the value of new dementia drugs and factor in the huge additional costs this condition places on society and the wider economy.
NICE and its expert committees assess whether new drugs are good value for money for the NHS based on a wide range of evidence.
This includes how treatments perform in clinical trials, the experiences of patients and carers, and the costs of new drugs as well as any changes to NHS services needed to provide access.
When NICE weighs up whether a new Alzheimer’s drug is cost effective for the NHS, it carries out a limited assessment of the impact dementia has on the health of carers.
But the condition takes an enormous toll on families and society because caring for someone with dementia can lead people to become more isolated and give up work.
It can have a major emotional impact and put families under financial strain.
Thomas said: “Research has delivered new treatments with the potential to provide people with valuable extra months of independence, lessening the burden on carers.
“While these treatments offer modest benefits and can cause serious side effects, they provide the foundation for a future where dementia becomes a treatable condition.
“Now we need NICE to look again at how these medicines could benefit both people with early Alzheimer’s and their carers.”
Chris, whose mother Shirley is living with Alzheimer’s disease, said: “The real cost of Alzheimer’s is far greater than many people realise.
“In order to give my mum the care she needed, I moved back home to help my dad as the care was too much for him alone. After my dad passed away from Covid in 2021, I became sole carer for my mum.
“It was a very difficult period, working a full-time job, caring for Mum and dealing with the loss of my dad. Eventually I got some in-home care support to help.
“The family has borne most of the cost of Mum’s care, both in time and fees, and the family home has been sold to finance it.”
“The emotional and financial strain Alzheimer’s has taken on our family is horrendous, and I know many families across the UK are experiencing this pressure.”
He is backing Alzheimer’s Research UK’s call for NICE to change how it evaluates new dementia treatments.
The timeframe for the next NICE meetings to discuss the drugs is still to be set, and it is not certain follow-up hearings would change NICE’s guidance on access to the medicines.
But Alzheimer’s Research UK is continuing to push to make sure dementia is now a main priority for political and NHS decision-makers.
The head of the ongoing independent review into adult social care, Baroness Louise Casey, has called on the government to act, show leadership and prioritise dementia.
She has proposed appointing a dementia tsar to drive forward the prevention, treatment and care of dementia.
Baroness Casey has also argued for more funding for dementia treatment trials.
With more than 130 Alzheimer’s drugs in clinical trials worldwide, the charity says it is vital the NHS runs trials of new treatments now to understand how to deliver them to eligible patients in future.
In addition to changing how NICE assesses new medicines, the health service needs to collect real-world evidence on new dementia drugs and prepare for diagnostic tests and innovative treatments that are coming.
“Alzheimer’s Research UK is calling on the government to give dementia the same political determination that transformed cancer care,” Thomas said.
“We urgently need investment and a clear UK-wide plan so new treatments can be assessed in the NHS and reach the people who stand to benefit.”
Health and social care secretary Wes Streeting has said dementia is “one of the greatest challenges of our time” and pledged that the UK should become a world leader in dementia clinical trials.
Osteoporosis drugs may lower dementia risk, with a study suggesting one widely used treatment could help prevent Alzheimer’s and related dementias.
The research found that nitrogen-containing bisphosphonates, drugs widely used to treat osteoporosis, may significantly reduce the risk of Alzheimer’s disease and related dementias in older adults with osteoporosis or fragility fractures.
Osteoporosis and dementia often coexist in older adults and share several risk factors, including advanced age, female sex and reduced physical activity.
Researchers at the University of Hong Kong’s department of pharmacology and pharmacy carried out a large study using the city’s electronic medical records, covering more than 120,000 patients aged 60 and above with osteoporosis or fragility fractures between 2005 and 2020.
The team found that NBP users had a 16 per cent lower risk of developing Alzheimer’s disease and related dementias than untreated patients, and a 24 per cent lower risk than those who received other osteoporosis medicines.
The association was especially marked in women and patients with hip fractures.
The researchers estimated that treating 48 patients with NBPs for five years could potentially prevent one case of dementia, underlining the possible public health value of NBPs in high-risk groups.
Professor Cheung Ching-lung, associate professor in the department of pharmacology and pharmacy at the University of Hong Kong, said: “Our study provides evidence that NBPs may offer dual benefits in strengthening bones and reducing fracture risk, as well as potentially preventing ADRD.
“Their potential neuroprotective role provides an empirical basis and supports future research on the actual effectiveness of this medication in preventing or delaying cognitive decline associated with ADRD.
“These findings are significant as they demonstrate a potential approach for reducing dementia risk in a vulnerable population using safe and widely available NBPs.
“In our rapidly ageing society, these findings suggest that while waiting for the novel therapies, existing medications can also provide additional protection for high-risk populations.”
The same research team has previously found that osteoporosis and fractures are independent risk factors for dementia, and that patients with dementia are at higher risk of falls and fractures.
This suggests treating osteoporosis may also help reduce the burden of dementia.
NBPs, including alendronate and zoledronate, are well established and commonly prescribed osteoporosis drugs.
Emerging biological research suggests the pathways affected by NBPs may also play a role in the development of Alzheimer’s disease and related dementias, raising the possibility that they could be repurposed for prevention.
A prebiotic fibre supplement may ease arthritis pain and improve grip strength in people with knee osteoarthritis, a study suggests.
The daily supplement, made from inulin, a dietary fibre found in chicory root, Jerusalem artichokes and other vegetables, also lowered pain sensitivity and saw fewer people drop out than a digital physiotherapy programme tested alongside it.
Dr Afroditi Kouraki, lead author of the study from the University of Nottingham, said: ‘Our findings suggest that targeting gut health with a prebiotic supplement is a safe, well-tolerated, and effective way to reduce pain in people with knee osteoarthritis.
“The very low dropout rate compared to the exercise group is also encouraging from a public health perspective, people were able to fit this supplement easily into their daily lives.’
Osteoarthritis of the knee, a wear-and-tear joint condition, affects hundreds of millions of people worldwide and is a leading cause of pain and disability, particularly in older adults.
Current treatments rely heavily on pain medication, which can cause side effects, or exercise programmes, which many patients find hard to maintain.
The INSPIRE trial, led by researchers at the University of Nottingham, involved 117 adults with knee osteoarthritis and tested four groups: inulin alone, digital physiotherapy-supported exercise alone, a combination of both, and a placebo. Both inulin and physiotherapy independently reduced knee pain.
However, inulin alone improved grip strength and reduced pain sensitivity, measures linked to how the nervous system processes pain, while physiotherapy did not.
The dropout rate for those taking the supplement was just 3.6 per cent, compared with 21 per cent for the physiotherapy group, suggesting a daily supplement may be easier for people to stick with than an exercise programme.
Inulin works as a prebiotic, meaning it feeds beneficial bacteria in the gut.
This leads to the production of compounds called short-chain fatty acids, particularly butyrate, which can affect inflammation and pain pathways throughout the body.
Participants taking inulin also showed increased levels of both butyrate and GLP-1, a gut hormone linked to pain regulation and muscle health.
Higher GLP-1 levels were associated with improved grip strength, pointing to a possible gut-muscle connection.
Senior author Professor Ana Valdes added: ‘The link we observed between GLP-1 and grip strength is particularly intriguing and points to a broader gut-muscle-pain axis that warrants further investigation. This could have implications not just for osteoarthritis, but for understanding how gut health influences ageing and physical resilience more broadly.’
Professor Lucy Donaldson, director of research at Arthritis UK, said: “The pain of arthritis can severely impact quality of life. Our recent lived experience survey showed that six in ten people are living in pain most or all of the time due to their arthritis.
“Researchers are starting to explore the role of the gut microbiome in our experience of pain.
“This exciting preliminary research highlights how diet and physiotherapy can act in different ways to have benefits for people with arthritis.
“We know a variety and balance of healthy foods, including fibre, and regular physical activity matter, and we’re glad to be supporting research that explores how they work to help people with arthritis.”
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