What is Alzheimer’s?
Alzheimer’s disease (also known as Alzheimer’s) is one of the most common forms of neurodegenerative dementia and is characterised by a progressive deterioration of cognitive functions, memory and reasoning capacity, which interferes with the individual’s socio-occupational activities without alterations in consciousness or attention.
Although the exact cause of Alzheimer’s disease has not been fully understood, it is known that the disease is multifactorial, that is, it is influenced by a combination of factors: genetic, environmental and lifestyle.
What is the role of the APOE gene?
One of the most significant genetic factors associated with Alzheimer’s disease is the APOE gene, located on chromosome 19, which codes for a protein (Apolipoprotein E) involved in cholesterol transport.
There are three main variants of this gene: APOE ε2, APOE ε3 and APOE ε4.
– APOE ε2: this is the least common variant and appears to have a protective role against Alzheimer’s disease. People carrying this variant have a lower risk of developing it than those with other variants.
– APOE ε3: is the most common variant and is considered neutral: it does not significantly influence the risk.
– APOE ε4: this is the variant associated with the highest risk of developing Alzheimer’s disease. People with one copy of APOE ε4 have a higher risk, with two copies (one inherited from the mother and the other from the father) the risk is even higher. The presence of the APOE ε4 allele affects the age of onset of the disease: carriers of this gene variant tend to manifest symptoms earlier than non-carriers.
Despite this, the APOE gene is not a determining cause of the disease, but rather represents a predisposing factor. In fact, many people with APOE ε4 never develop this disease, while others without this variant can still develop the disease.
What are the symptoms?
Symptoms may vary depending on the stage of Alzheimer’s disease.
Initial symptoms
In the early stages, the disease manifests itself with mild symptoms and, for this reason, is often overlooked both by the patient and his or her family, and by the doctor.
– Short-term memory loss: people may forget recent events, names or newly-learnt information.
– Difficulty in finding the right words: increased language difficulties, with problems following or participating in conversations.
– Spatial disorientation: difficulty remembering familiar routes or finding one’s way around familiar places.
– Behavioural and personality alterations: apathy, depression or anxiety
Final symptoms
As the disease progresses, the symptoms become more severe and disabling.
– Complete memory loss: even the most distant memories are erased, and patients are no longer able to recognise family and friends.
– Difficulties in movement: inability to perform everyday actions, such as dressing, eating or walking.
– Inability to communicate: the loss of language becomes complete, with an inability to express oneself and understand.
– Aggressive behaviour or agitation: episodes of agitation, hallucinations and paranoia may occur.
– Complete dependence on others: in the terminal phases, the patient is completely dependent on assistance for all activities of daily living.
What causes Alzheimer’s disease?
There are two pathological mechanisms underlying the development of Alzheimer’s disease: structural brain damage and loss of neurons. These events result from the progressive loss of the ability to dispose of certain proteins, with their consequent accumulation.
The following characteristic alterations are therefore found in the brain:
– Deposits of beta-amyloid plaques: amyloid plaques (formed by the beta-amyloid protein) accumulate between nerve cells in the brain, hindering neuronal communication and causing cell death.
– Neurofibrillary tangles: these are abnormal accumulations of the tau protein within neurons, which impair their functioning and lead to their degeneration.
– Inflammation and oxidative stress: chronic inflammation of brain tissue and oxidative damage contribute to cognitive decline.
In addition to ageing, genetic predisposition (as seen, the presence of the APOE ε4 gene is an important risk factor), environmental and lifestyle factors (e.g., diet, physical activity, alcohol consumption and smoking contribute to the onset of the disease).
Difference between Alzheimer’s disease and age-related dementia
Alzheimer’s disease and age-related dementia are often confused, but have significant differences. Age-related dementia is an umbrella term referring to cognitive decline associated with ageing, and can be caused by a number of diseases, including Alzheimer’s.
In particular:
– Alzheimer’s disease: it is a progressive neurodegenerative disease that represents the most common cause of dementia and has specific characteristics, such as the presence of amyloid plaques and neurofibrillary tangles;
– age-related dementia: this term describes a cognitive decline associated with age that can be linked to various other diseases, such as stroke, Parkinson’s or vascular dementia, it is not always progressive like Alzheimer’s disease and can arise from a variety of causes.
Prevention
Although there is no definitive cure for Alzheimer’s disease, several studies suggest that certain lifestyle changes may reduce the risk or delay the onset:
– physical activity: regular exercise helps maintain cardiovascular health, improve blood flow to the brain and reduce risk;
– diet: following a balanced diet, such as the Mediterranean diet rich in fruit, vegetables, whole grains, fish and olive oil, can reduce the risk;
– treating hypertension and dyslipidaemia effectively: not only exercise and diet, but also appropriate drug therapies can reduce the risk of cardiovascular disorders, which are believed to be associated with the risk of dementia;
– cognitive stimulation: keeping the brain active with activities that stimulate thinking, memory and problem-solving, such as reading, playing games or learning, can help protect cognitive functions.
More recent studies also demonstrate that actions such as effectively treating depression, hearing or vision loss and promoting senior housing also play a significant role in preventing Alzheimer’s disease, that is, independent dwellings or shared housing for elderly people who can then live together. These measures can serve to break down the feeling of loneliness and reduce social and functional isolation that predisposes to the development of dementia.
Alzheimer’s: diagnosis and which tests to perform
The diagnosis of Alzheimer’s is complex and requires a combination of clinical assessments, cognitive tests and advanced diagnostic tools.
An initial medical examination includes an evaluation of the medical history, the clinical history also collected with the help of family members, and a neurological physical examination. The specialist then performs neuropsychological tests, i.e., specific tests that assess various cognitive areas, such as memory, language, visual-spatial ability and attention.
Complementary imaging tests such as magnetic resonance imaging (MRI) and positron emission tomography (PET) can also be performed. These brain imaging examinations can detect structural changes in the brain, such as brain atrophy or the accumulation of amyloid proteins typical of Alzheimer’s.
Genetic testing
Finally, genetic tests can be carried out to look for associated mutations, such as those in the APOE gene. These tests are all the more indicated when family history is particularly important, for example, when both parents have Alzheimer’s disease. Genetic testing alone does not diagnose the disease, but it does identify the risk of developing it in the future. Anyone who undergoes the test and receives a positive result can take action by changing their lifestyle to try to delay or avoid the eventual development of the disease: in the event of a positive test result, it is a good idea to rely on one’s trusted doctor and specialist to identify the best prevention pathway and to obtain the correct and necessary support to understand one’s clinical situation. It is important to reiterate that an individual being a carrier of a mutation does not necessarily imply that they will develop the disease.
Although there is no cure, understanding the mechanisms underlying the disease and identifying genetic risk factors such as APOE ε4 can help in the early diagnosis and management of its manifestations with pharmacological and non-pharmacological treatments. Research in the area of prevention and treatment is ongoing and could lead to new hope for reducing the overall impact of Alzheimer’s disease.
BIBLIOGRAPHY
1. Selkoe, D. J. (2019). “Alzheimer’s Disease: Genes, Proteins, and Therapy.” Physiological Reviews, 81(2), 741-766. doi:10.1152/physrev.2001.81.2.741.
• This study examines the main genetic and molecular aspects of Alzheimer’s disease, with a focus on the role of beta-amyloid and tau proteins.
2. Liu, C. C., Kanekiyo, T., Xu, H., & Bu, G. (2013). “Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy.” Nature Reviews Neurology, 9(2), 106-118. doi:10.1038/nrneurol.2012.263.
• A comprehensive review of the role of the APOE gene in Alzheimer’s disease and its implications in genetic risk and therapeutic strategies.
3. Dubois, B., Feldman, H. H., Jacova, C., et al. (2014). “Advancing research diagnostic criteria for Alzheimer’s disease: the IWG-2 criteria.” The Lancet Neurology, 13(6), 614-629. doi:10.1016/S1474-4422(14)70090-0.
• The article explores up-to-date diagnostic criteria for Alzheimer’s, including biomarkers and clinical and neuropsychological tests used for early diagnosis.
4. Livingston, G., Huntley, J., Sommerlad, A., et al. (2020). “Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.” The Lancet, 396(10248), 413-446. doi:10.1016/S0140-6736(20)30367-6.
• An in-depth review of prevention strategies for dementia and neurodegenerative diseases, with an emphasis on Alzheimer’s disease.
5. Jack, C. R., Bennett, D. A., Blennow, K., et al. (2018). “NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease.” Alzheimer’s & Dementia, 14(4), 535-562. doi:10.1016/j.jalz.2018.02.018.
• The article proposes a new framework for defining Alzheimer’s on the basis of biological biomarkers, with particular emphasis on beta-amyloid, tau and neurodegeneration.
6. Alzheimer’s Association. (2022). “2022 Alzheimer’s Disease Facts and Figures.” Alzheimer’s & Dementia, 18(4), 700-789. doi:10.1002/alz.12638.
• A statistical and descriptive analysis of the global impact of Alzheimer’s, including the most recent estimates of the prevalence and incidence of the disease.
7. Scheltens, P., Blennow, K., Breteler, M. M. B., et al. (2016). “Alzheimer’s disease.” The Lancet, 388(10043), 505-517. doi:10.1016/S0140-6736(15)01124-1.
• A comprehensive review of current knowledge on Alzheimer’s disease, including the neuropathological and genetic basis, clinical symptoms and therapeutic strategies.
8. Qiu, C., Kivipelto, M., & von Strauss, E. (2009). “Epidemiology of Alzheimer’s disease: occurrence, determinants, and strategies toward intervention.” Dialogues in Clinical Neuroscience, 11(2), 111-128. doi:10.31887/DCNS.2009.11.2/cqiu.
• The study discusses environmental and genetic risk factors associated with Alzheimer’s and preventive intervention strategies.
