Alzheimer’s Disease: Into the Depths of Cognitive Decline
In the expansive realm of neurological disorders, Alzheimer’s disease poses one of the most formidable challenges of our century. Studies indicate an anticipated 40 million individuals suffering from dementia worldwide, with projections indicating a doubling of this figure every two decades until around 2050. In the light of recent developments, we wanted to discuss Alzheimer’s disease in depth and compile the results of scientific studies. In a very informative interview with Prof. Gökhan Erkol from the Department of Neurology at Koç University Hospital, we examined where we are in the world and in Turkey regarding Alzheimer’s disease.
Since its initial identification by German psychiatrist and neuropathologist Alois Alzheimer in 1906, the disease has emerged as a predominant cause of dementia, presenting a global health concern. Alois Alzheimer made his ground-breaking discovery while examining the brain of a deceased patient who had displayed symptoms of severe memory loss, language difficulties, and erratic behaviour during her lifetime. Upon post-mortem examination, Alzheimer observed abnormal protein clumps and tangled fibres in the patient’s brain tissue. These are still considered the hallmark indicators of Alzheimer’s disease: the extracellular aggregation of amyloid-beta plaques and intracellular tau protein tangles in the brain’s nerve tissue. Another critical element involved is the reduction in the levels of acetylcholine, a neurotransmitter crucial for memory and learning in the brain. The majority of Alzheimer’s disease research focuses on these factors, particularly the efforts for early detection and therapy design.
Alzheimer’s disease is a progressive neurodegenerative disorder primarily affecting the cognitive functions of the brain. The disease disrupts communication between brain cells, resulting in the gradual deterioration of neural networks over time. Symptoms typically begin with mild memory loss and confusion, progressing to more severe impairments in thinking, reasoning, and communication. Patients commonly face language dysfunction, visual-spatial impairment, as well as alterations in personality and behaviour, all necessitating extensive caregiving.
The cause
Alzheimer’s disease is not an inevitable part of ageing, although age remains the most significant risk factor. Research points that the cause is rooted in a combination of genetic, environmental, and lifestyle factors. Ongoing studies propose that lifestyle choices, such as diet, exercise, and cognitive engagement play a role in an individual’s susceptibility to the disease.
The disease has also been linked to various health conditions, including cardiovascular disease, diabetes, and hypertension. Conditions such as diabetes, blood pressure, vascular problems that may affect the oxygen supply to the brain or sleep apnoea can accelerate the symptoms of the disease if they are not corrected. Several recent studies now focus on the connection of Alzheimer’s disease with sleep habits, coffee consumption and oral hygiene.
Get your sleep
The connection between sleep and Alzheimer’s disease is of specific interest in scientific research. A growing body of evidence suggests that disrupted sleep patterns, particularly poor sleep quality and insufficient sleep duration, may play a role in the development and progression of the disease.
Studies indicate that poor sleep might be linked to an increased production and reduced clearance of amyloid-beta, leading to its accumulation in the brain. Additionally, disrupted sleep has been associated with elevated levels of tau protein in the brain, suggesting another potential contribution to the disease.
A noteworthy 2020 study by researchers at Uppsala University revealed that even a single night of sleep deprivation could elevate tau protein levels in the blood. Tau protein and amyloid-beta are key components of Alzheimer’s disease, and sleep deprivation has been found to increase these biomarkers in cerebrospinal fluid.
On the other hand, the relationship between sleep and Alzheimer’s disease is bidirectional. The disease can impact the brain regions responsible for regulating the sleep-wake cycle, influencing sleep patterns and causing disturbances, such as difficulties in falling asleep and staying asleep. Patients often experience behavioural and psychological symptoms, which may further disrupt sleep patterns.
Experts recommend maintaining a regular sleep schedule, creating a comfortable sleep environment, and avoiding stimulants close to bedtime as potential measures with benefits for both preventing and managing Alzheimer’s disease.
Coffee is also good though…
The association between coffee consumption and Alzheimer’s disease has also been explored in several studies. Some evidence suggests that moderate coffee consumption might be linked to a reduced risk of Alzheimer’s disease, and cognitive decline in general.
This notion is supported by the fact that coffee is rich in bioactive compounds, which have a protective effect on nerve cells against degeneration. The anti-inflammatory effect of coffee also provides additional protection to nerve cells. Furthermore, caffeine, a natural stimulant present in coffee, has cognitive-enhancing effects.
A recent study also revealed that caffeine and genistein in coffee effectively inhibit the accumulation of tau protein. Coffee extracts containing these two molecules could potentially be explored in relevant therapies.
However, moderation is crucial. Excessive caffeine intake can lead to adverse effects such as insomnia, increased heart rate, and digestive issues. Notably, a 2021 study led by researchers from the University of South Australia found that consuming more than six cups of coffee a day is associated with a 53% increased risk for dementia and smaller total brain volume.
Mind your oral health
Several studies suggest a potential link between Alzheimer’s disease and oral hygiene, particularly in the context of gum disease (periodontitis) and tooth loss.
Systemic inflammation has been proposed as a potential factor in the development and progression of Alzheimer’s disease. Inflammation of the gums and the oral cavity may release inflammatory molecules into the bloodstream, contributing to systemic inflammation.
Studies have also explored the possibility that bacteria associated with gum disease may enter the bloodstream, travel to the brain, and contribute to the development of Alzheimer’s. Porphyromonas gingivalis, a bacterium linked to gum disease, has been found in the brains of Alzheimer’s patients. Studies suggest that this bacterium may produce enzymes that can contribute to the formation of amyloid-beta plaques. Previously, amyloid-beta was thought to be produced locally in the brain, but it was later revealed that these proteins may be produced by all cells in the body in response to infection, including gum disease and root canal infection.
Another noteworthy phenomenon is the potential association between tooth loss and cognitive decline in older adults, as observed in several studies. Tooth loss, primarily caused by periodontitis in adults, is associated with decreased feeding quality (particularly in terms of vitamin and nutrient intake) and reduced masticatory capacity, contributing to reduced cerebral blood flow and, consequently, diminished oxygenation in neurons.
In summary, maintaining good oral hygiene practices, such as regular brushing, flossing, and professional dental cleanings, may have protective effects against Alzheimer’s disease and cognitive decline in general.
Early detection and therapeutic approaches
Early diagnosis and intervention are imperative in this disease as well. Established methods are already widely used for nearly accurate diagnosis. However, researchers are actively working on developing blood tests that can facilitate the process more efficiently and swiftly.
A research team led by Valerie Daggett from the University of Washington has introduced a blood test called the soluble oligomer binding assay (SOBA), designed to identify amyloid-beta deposits in the blood of Alzheimer’s patients. These deposits play a crucial role in the early stages of the disease and can develop up to ten years before symptoms manifest. The test incorporates a specialised synthetic molecule (AP193) that can efficiently bind to amyloid deposits. It is reported to outperform conventional diagnostic tests and holds the potential for application in other types of dementia and diseases such as Parkinson’s.
The Hong Kong University of Science and Technology is also in the process of developing a blood test to identify specific blood proteins associated with Alzheimer’s disease and mild cognitive impairment. Simultaneously, the NHS in the UK has initiated a study to assess the effectiveness of blood tests for the early diagnosis of Alzheimer’s disease, with the goal of transitioning these cost-effective tests from the laboratory to real-world applications.
While there is no definitive cure for Alzheimer’s disease, current approaches primarily focus on managing or delaying symptoms. Drugs like cholinesterase inhibitors provide temporary relief but do not halt or reverse the disease’s progression. Ongoing research explores various treatment approaches, including immunotherapies targeting amyloid plaques and tau proteins. Promising new drugs in clinical trials aim to enhance treatment efficacy and improve patients’ quality of life.
One noteworthy example is a study published in 2023 by researchers at the University of Queensland. The active compound derived from the lion’s mane mushroom (Hericium erinaceus) demonstrated positive effects on nerve cell growth and memory development. Traditionally used in Asian medicine for centuries, the mushroom’s impact on brain cells was scientifically evaluated through pre-clinical tests. The findings hold promise for treating neurodegenerative diseases, including Alzheimer’s disease.
Beyond drug treatments, interventions like cognitive stimulation therapy, real-life adaptation training, and reminiscence therapies strive to enhance patients’ well-being. Counselling and/or medication may be recommended for conditions such as depression and anxiety. Physical exercises, known for cognitive benefits and overall health protection, complement these practices. Occupational therapy is also employed to aid individuals in adapting to daily tasks, maintaining independence, and managing cognitive difficulties. Communication challenges that may arise as the disease progresses are addressed by speech therapy.
Current situation in the world and in Türkiye
Prof. Dr. Gökhan Erkol, a member of the Koç University Hospital, serves as the Chairman of the Behavioural Neurology and Dementia Working Group of the Turkish Neurological Association. With years of experience working with dementia and Alzheimer’s patients, Erkol shared insights in response to our questions.
Where are we in terms of diagnosis and evaluation?
In Türkiye, we have access to all globally accepted examinations used for these purposes. Various methods exist for dementia diagnosis; for instance, the ability of certain brain regions to utilise blood sugar can be impaired, magnetic resonance imaging (MRI) can show us if there is a loss in brain volume. However, we primarily employ two methods for a definitive diagnosis of Alzheimer’s disease. The first is amyloid PET, which, when showing brain flashes, strongly indicates the likelihood of Alzheimer’s. Similarly, FDG-PET is also helpful. In situations where these scans are not possible, the diagnosis can be achieved through cerebrospinal fluid (CSF) analysis, examining amyloid and tau ratios. These established methods boast an accuracy rate exceeding 90%, even for early Alzheimer’s diagnosis, with or without dementia.
Are there cases of Alzheimer’s without dementia?
Indeed. Not every case of dementia is linked to Alzheimer’s, and vice versa. Alzheimer’s-specific proteins may not be present in every dementia, leading to diverse clinical presentations. Some dementias manifest with behavioural disorders, daydreaming, or spatial disorientation. Likewise, the presence of Alzheimer’s in the brain doesn’t necessarily mean dementia. Cognitive reserve plays a pivotal role here. Individuals with high cognitive reserve might not experience dementia despite exhibiting Alzheimer’s symptoms.
How do you diagnose Alzheimer’s disease in your practice?
We initially assess whether the patient displays symptoms consistent with Alzheimer’s dementia. If memory impairment is prominent, accompanied by cognitive deficits and slow progression, we want to have an imaging. This helps us identify if there are any other potential causes for the memory impairment. It also enables us to see if there is any degeneration in the brain tissue, and it the degeneration aligns with the Alzheimer’s pattern. The imaging also shows us the vascular condition in the brain, which is also important as vascular impairments may affect dementia progression. Then we examine the patient’s history and other health problems. If forgetfulness dominates the complaints from the start, and the imaging aligns with that of Alzheimer’s, we may decide that this is Alzheimer’s-related dementia. Additional tests are ordered only if the patient is working or when a clear diagnosis is legally or personally required. A definitive diagnosis is also important for treatments. Especially if we are planning to start an expensive treatment, we have to make sure to have a definite diagnosis so that we avoid mistakes that may further harm the patient.
What about treatment?
Current treatments aim to slow disease progression and to manage symptoms, but they cannot reverse the loss in brain tissue. Besides cholinesterase inhibitors and Memantine, at least two more FDA-approved immunotherapy drugs are available, and another is on the way for approval. These drugs currently are able to postpone dementia onset by approximately 8 months or a bit more. We do not yet have immunotherapy in Türkiye, and it is in fact not yet widespread globally, only available in limited locations, particularly in the USA. It will possibly being in some European countries soon. And of course, drugs are becoming more effective thanks to ongoing research efforts.
Which developments do you find the most promising?
Immunotherapies, becoming successful. Of course, a real cure involves not only stopping the disease from progressing, we also have to find a way to reverse brain tissue loss.
The possibility of having blood-based tests with the ability to provide near definite diagnosis is also significant. I believe we will have blood tests with high accuracy soon. This will be an amazing progress, as the thought of lumbar punctures is scary for many patients. Blood tests will be much less invasive.
To what extent do genetic factors contribute to Alzheimer’s?
Genetic factors account for only 3 to 5% of Alzheimer’s cases, relatively low. Genetic testing may be considered if the disease persists through generations or its frequency is relatively high in the family. However, genetic forms are rare. An amyloid PET scan is often more informative than genetic testing.
Is there a sure way to avoid this disease?
Aerobic exercises or walking are good, as well as leisure activities that involve cognitive planning, such as sewing or knitting. These may all delay the onset of the disease, although they cannot provide absolute prevention. There is no singular miraculous activity or food that can definitively prevent Alzheimer’s. However, a Mediterranean-type diet is beneficial, so is moderate consumption of caffeine.
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