ReCent Medical News
Alzheimer's disease
Are we on the cusp of something special?
April 2025
Image: unai - stock.adobe.com
Alzheimer’s disease (Alzheimer’s) accounts for 60-80% of all dementias and is so named after Dr Alois Alzheimer - a researcher and pathologist - who in 1906 noticed tangled clumps of fibres in the brain of a lady who had died from an unusual mental illness. [1] [2] Today, we know these tangled clumps as being amyloid plaques and neurofibrillary tangles; a hallmark of Alzheimer’s that distinguishes it from other dementias.
Abstract
Alzheimer’s involves areas of the brain that control thought, memory and language; destroying connections between brain cells, eventually causing the cells to die and the brain to shrink. Alzheimer’s is a progressive neurodegenerative disease that takes a patient through a spectrum of illness from the pre-clinical stage to mild memory loss to significantly impairing one’s ability to carry out daily activities. The average life expectancy of Alzheimer’s disease is 4-8 years from diagnosis [3], with variation often explained by age at diagnosis and the presence or absence of comorbidities.
Figure 1: Stages of Alzheimer's [3]
Images derived from necozawa - stock.adobe.com
Mild cognitive impairment
Duration: 5-10 years
Area: Temporal lobe
Symptoms: short term memory loss
Mild Alzheimer’s
Duration: 2-3 years
Area: Temporal & parietal lobes
Symptoms: Mild cognitive issues (reading, writing etc) difficulty in organising or expressing thoughts
Impairment in object recognition, directions
Moderate Alzheimer’s
Duration: 2-3 years
Area: Spreads to frontal lobe
Symptoms: Greater memory loss and confusion, judgement issues, personality difficulties, impairment in activities of daily living
Severe Alzheimer’s
Duration: 3-5 years
Area: Spreads to occipital lobe
Symptoms: visual issues, near total memory loss, unable to communicate. Full time care assistance required.
Alzheimer’s disease is a diagnosis typically given to those aged over 65 and is the focus of this article. However, cases with diagnoses before age 65 are termed ‘early-onset Alzheimer’s’. Early-onset disease only accounts for around 5% of overall Alzheimer’s diagnoses and has a strong genetic component. You can read more about this here. The greatest risk factor for Alzheimer’s disease is age, with the number of people living with Alzheimer’s in many countries doubling every 5 years beyond age 65.[4] In the earlier stages of disease, care is generally given in the home, which can be made more comfortable through modifications designed to reduce the risk of confusion and accident, and to prolong independence where suitable. In the final stages, individuals often lose the ability to communicate, control movement, or respond to their surroundings, usually requiring specialist care. The most common causes of death for people with Alzheimer’s include infections (such as pneumonia; often due to aspiration), complications from falls, or other health conditions exacerbated by the disease.[5]
What causes Alzheimer’s disease?
The exact cause of Alzheimer’s disease is not fully understood, but it is believed to result from a combination of genetic, environmental, and lifestyle factors that affect the brain over time.
One thing is certain, Alzheimer’s is characterised by the accumulation of two types of proteins in the brain: amyloid plaques and tau tangles. Amyloid plaques are clumps of a protein called beta-amyloid that build up between neurons. The plaques disrupt communication between neurons, impacting normal brain function. Tau proteins help stabilise structures in neurons, but in Alzheimer’s, they become abnormally shaped and form tangles inside neurons, disrupting their internal transport system and leading to cell death. Alzheimer’s disease has such a broad range of symptoms as it can affect sensory neurons, interneurons and – at the later stages – motor neurons.
While a specific cause for Alzheimer’s isn’t known, there is a good understanding of risk factors which include age, inflammation in the brain, vascular health, lifestyle (diet and excess alcohol in particular) and environmental factors (including brain injury, social isolation, poor sleep and mental health issues).[6] There is also a link between disturbances in the gut microbiome and the onset and severity of disease. These disturbances can lead to inflammation, which may cause neuroinflammation and worsen the build-up of beta-amyloid in the brain.[7] The increasing prevalence of metabolically unhealthy lives is a growing concern owing to the impact that will have on chronic diseases such as Alzheimer’s.[8] The exact interplay between these factors may remain unclear, but we know that Alzheimer’s disease develops over many years, with changes in the brain occurring long before noticeable symptoms appear. Prevention and treatment efforts focus on mitigating risk factors related to lifestyle, managing cardiovascular health, and promoting mental engagement to reduce the likelihood of developing the disease, or at least delay its development.
Image: anastasii25 - stock.adobe.com
Figure 2: Neuronal damage in Alzheimer's
The genetics of Alzheimer’s disease
Certain genes increase the risk of developing Alzheimer’s disease, the most well-known associated gene allele being apolipoprotein e4 (APOE-e4). Individuals with one or two copies of this gene are at a two-to-three and eight-to-twelve-fold higher risk of developing Alzheimer’s respectively.[9] Conversely, the presence of the APOE-e2 allele roughly halves the risk of developing Alzheimer’s disease. [10] Since genetic testing has become commonplace there has been an acceleration in the discovery of new genes associated with Alzheimer’s. In 2010 only 10 genetic areas were known to be associated with Alzheimer’s disease versus at least 80 genetic areas known to be associated with the disease today. [11]
Around 5% of Alzheimer’s is diagnosed before age 65.[12] Early-onset Alzheimer’s has a strong familial component, but only around 10-15% of it is inherited through known ‘deterministic genes’.[13] Examples of these rare deterministic variants include amyloid precursor protein (APP), presenilin 1 (PSEN1) and presenilin 2 (PSEN2); inheriting only one copy of these altered genes is sufficient to cause the disease as they are both autosomal dominant and near fully penetrant. [12]
At this point, it’s key to stress that, with the exception of APP, PSEN1 and PSEN2, any genetic predisposition towards Alzheimer’s – even if you have two copies of the APOE-e4 allele – does not predestine you to develop the disease, in the same way that having copies of the APOE-e2 allele does not mean you cannot develop it.
In the UK, approximately 982,000 people are living with dementia.
Prevalence, healthcare and society
Globally, around 55 million people are living with Alzheimer’s disease or other forms of dementia, according to estimates from the World Health Organization (WHO) in 2023. Alarmingly, this number is expected to rise to 139 million by 2050, largely due to ageing populations. Dementia rates are expected to rise particularly quickly in low- and middle-income countries, where about two-thirds of people with dementia currently live and where there’s greater scope for population-level increases in life expectancy at birth. [14]
In the United Kingdom, approximately 982,000 people are living with dementia. With Alzheimer's disease making up around 60-80% of all dementias, there are around 590,000 to 785,000 sufferers in the UK. In 2024, the Alzheimer's Society estimated that dementia costs the UK GBP 42 billion per year, and this is expected to rise to GBP 90 billion by 2040.[15]
However, there is more than just the financial cost of professional care and family members directing resources towards being devoted caregivers. In the absence of meaningful pharmaceutical treatments, symptoms of the disease are essentially managed through carers, environmental modifications plus psychological support. Some medications such as cholinesterase inhibitors and memantine hydrochloride have had some success in dampening symptoms of memory loss and certain anti-depressants/anti-psychotics have assisted in the management of some of the inevitable psychological impacts Alzheimer’s can have. The impact on sufferers and family members cannot be overstated. A significant proportion of carers are unpaid family members unable to detach from the deterioration in function and relationship that they’re witnessing in their loved ones.
Expected people with Alzheimer's worldwide in 2050
These numbers highlight the growing challenge posed by Alzheimer’s disease as global populations age, making it a significant public health concern. There is a clear growing need for improved care, research, treatment and support services worldwide. Does this create opportunities for insurers to further their long-established role as providers of societal good?
What’s new?
Improved detection
Geriatricians and neurologists employing neuropsychological testing can through expert judgement diagnose established dementia with a fairly high degree of accuracy based on clinical symptoms, but historically the only way to truly diagnose Alzheimer’s was through autopsy, looking for those hallmark brain changes.[16] Modern scanning technology, such as positron emission technology (PET), provide greater confidence in diagnosing Alzheimer’s disease. Amyloid PET scans allow doctors to see the accumulation of amyloid years before symptoms develop overtly. While PET scans are highly accurate, they are expensive and not widely accessible, limiting their widespread use. Another recent development is the use of PET imaging to visualise tau tangles in the brain, which contribute to cognitive decline. Tau imaging is becoming a valuable tool for detecting Alzheimer’s in its early stages, but again, availability of the technology is a major limiting factor. More recent developments in the blood testing space have been extremely exciting as they help overcome availability barriers. Tests have been developed to detect blood-based biomarkers such as amyloid and tau proteins, again before symptoms appear. One of the first commercially available blood tests for the disease, receiving breakthrough device designation by the FDA, is detecting amyloid proteins – with phosphorylated tau (p-tau) tests measuring p-tau proteins in the blood, also strongly associated with Alzheimer’s. These tests are highly promising for early detection and are being refined for clinical use.[17]
Drug discovery
There is an inherent moral quandary in identifying asymptomatic people as having pre-clinical disease or a high probability of disease in the absence of a cure for it, but newly discovered Alzheimer’s disease modifying drugs are at their most effective if prescribed when the disease is very mild.
While results need to be replicated in broader study bases, let’s look at this probable breakthrough in detecting pre-clinical Alzheimer's disease.[18] As a standalone test, plasma p-tau217 identified amyloid beta PET-positive cognitively normal adults with a positive predictive value of 80% or greater. What does this mean (if study results are replicated)? It means reduced costs and logistical barriers to identifying asymptomatic people as having pre-clinical Alzheimer’s disease. This increases the number of people identified for clinical trials, likely accelerating drug discovery and the ultimate approval process.
Reassuringly, there are a number of new and emerging drugs for Alzheimer’s disease illustrating progress is being made. Significant resource continues to be directed towards more effective drugs, with more than 160 trials underway testing over 125 experimental treatments for Alzheimer’s across the globe, including 30 in late-stage trials. Alzheimer’s Research UK believe it “really is a matter of when, not if, new treatments become available”.[19]
Examples of some new/emerging drugs include aducanumab, a monoclonal antibody which was approved by the FDA in 2021 and is designed to reduce/remove beta-amyloid plaques in the brain. This drug, that has been discontinued by its manufacturer[20], represented a shift toward targeting the underlying disease process versus symptom management, although it’s worth noting that its approval was somewhat controversial owing to clinical trials showing mixed results. Lecanemab, approved in 2023, also targets amyloid plaques and may slow cognitive decline in early-stage Alzheimer's. Results from a large clinical trial demonstrated that lecanemab significantly slowed cognitive and functional decline in patients with early-stage Alzheimer's by about 27% over 18 months. [21] Both of these drugs are prescribed to patients with early-stage Alzheimer’s disease. One interesting outcome of these trials is that they are indeed efficient in terms of clearing amyloid deposits, yet progression of symptomology is only modestly altered. This suggests that while amyloid plaques play a role, they are not the sole cause in AD.[22]
Other trials are ongoing for treatments targeting tau protein, inflammation/neuroinflammation, and new forms of immunotherapy. More cutting edge are trials investigating the potential for vaccines, gene therapy and BACE inhibitor therapy. In addition, whether it was expected or serendipitous, there are signs from GLP-1 agonist therapies – the so-called ‘weight loss drugs’ – to suggest a material reduction in Alzheimer’s in those using the drugs.[23]
Another promising approach involves using smartphone data for early detection of dementia risk in older adults. Beyond using a smart phone for health and calories tracking, smart phone data can analyse a number of behavioural metrics including movement and communication, allowing for timely intervention and better management of Alzheimer’s.[24]
While the use of technology is interesting, most efforts remain focused on earlier detection and prompt commencement of disease-modifying drugs with a cure still an ambition for the longer-term future.
Future outlook
There have been significant breakthroughs in detecting Alzheimer’s disease earlier, thanks to advancements with blood-based biomarkers, imaging technologies and other technological innovation. Early detection is crucial for treatment, as the newest therapies are most effective in the early stages of disease. The advent of disease modifying therapies and a broader range of tools to detect dementia have the potential to make population-level differences. While there is no guaranteed way to prevent Alzheimer’s disease, research suggests that certain lifestyle choices and health measures, particularly in middle age can significantly reduce the risk of developing it.
The Lancet Commission reports that nearly 50% of dementia cases worldwide could be prevented or delayed by addressing 14 modifiable risk factors throughout an individual's life. These include preventing and treating hearing and vision loss, depression, staying cognitively active, using head protection in contact sports, reducing vascular risk factors (like high cholesterol, diabetes, obesity, hypertension), improving air quality, and fostering supportive community environments to increase social contact.[25]
This perspective shifts the risk of dementia from being seen as an inevitable part of ageing to a condition that can be actively prevented. The potential benefit from recently developed weight-loss drugs alone is significant.
Opportunities for insurance as a social good?
What role can life and health insurers play here? Our roles are plentiful, but one can perhaps split into three main areas: Influencing behaviours, product relevance and paying eligible claims. With as much as 50% of Alzheimer’s disease thought to be preventable or delayed through healthier lifestyle choices, insurers have a unique opportunity beyond that of our traditional role as risk carrier, but as a partner in improving health outcomes. The right products can influence the right health choices achieving mutually agreeable outcomes. Product design isn’t limited to increasing customer engagement or encouraging preventative healthcare. Many products are designed to support the insured or their beneficiaries in the event of an Alzheimer’s diagnosis, provided the specified policy terms are met. These include, but aren’t limited to, life and terminal illness cover, critical illness cover, income protection and long-term care products as well as enhanced annuities. Long-term care products arguably offer the most tangibility and assurance to the insured but can often be unaffordable, raising the question over whether there are other product structures that might help close that affordability and insurance gap. Finally, claims. Paying the right claims is why our industry exists and that is no different with Alzheimer’s disease. Proceeds from any Alzheimer’s claim might be more likely to go towards the cost of the patient’s care relative to other causes of claims, however, hence a potential growing need for products to complement existing product suites.
Conclusion
In summary, Alzheimer’s disease is a progressive, incurable neurological disease with a very high degree of morbidity and a life expectancy around 4 to 8 years from diagnosis. Alzheimer’s and other dementias pose a significant challenge to society; a risk that is expected to increase as populations age and poor lifestyle choices translate to increased incidence and prevalence of the disease. As our understanding of Alzheimer’s grows and drug options improve, there is scope to arrest the trend with insurers playing an important supporting role in product design, encouraging positive lifestyle choices and paying the right claims.
Author
Gareth Matthews
Chief Underwriter
Hannover Re UK Life Branch
References
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