Alzheimer's disease

The first symptoms of Alzheimer’s vary from person to person. Memory problems are typically one of the first signs related to this disease. The decline in non-memory aspects of cognition, such as word-finding and impaired reasoning or judgment, may also signal the very early stages of Alzheimer’s. Alzheimer’s disease progresses through several stages, explained as follows:

1. Early Symptoms

In the early stages, the main symptom of Alzheimer's disease is memory lapses. This is characterized by a cognitive decline that requires compensatory strategies to maintain independence and perform daily living activities. The early Alzheimer’s symptoms may include:

• Trouble thinking of the right word
• Misplaced items
• Poor judgment or difficulty making decisions
• Forgetting recent conversations or events
• Hesitation to try new things
• Asking about the same things repeatedly
• Mood changes, such as increased anxiety or agitation

2. Middle-Age Symptoms

In mild Alzheimer’s disease, a person may seem healthy but can be characterized by symptoms that mildly impair daily living activities, requiring supervision over complex tasks. This stage necessitates more intensive supervision and care. It is characterized by symptoms like increased memory loss, confusion, and moderately impaired daily life activities. Other symptoms may also develop, such as:

• Obsessive, repetitive, or impulsive behavior
• Disturbed sleep
• Increased confusion and disorientation
• Problems with speech or language (aphasia)
• Seeing or hearing things that are not perceived by others (hallucinations)
• Changes in mood, such as frequent mood swings
• Difficulty performing spatial tasks, such as judging distances

3. Later Symptoms

People with severe Alzheimer’s cannot communicate and depend entirely on others for their care. They rely on caregivers to handle even their most basic needs, including eating, washing, and using the bathroom. Several other symptoms may also develop as Alzheimer's disease progresses, such as:

• Gradual loss of speech
• Weight loss
• Difficulty changing position or moving around
• Unintentional passing of urine (urinary incontinence)
• Significant problems with short- and long-term memory

Alzheimer’s is a progressive brain disease characterized by changes in the brain that result in the loss of nerve cells and their connections. However, the complete understanding of the causes of this disease is not yet known. Various hypotheses have been proposed for the development of Alzheimer’s disease, with moderate or strong evidence. These are:

• Cholinergic hypothesis: The cholinergic hypothesis of Alzheimer’s disease states that deficits in acetylcholine (ACh), a chemical messenger that plays a vital role in the transmission of signals in the nervous system, and choline acetyltransferase (the enzyme responsible for the synthesis of acetylcholine) lead to memory and cognitive decline.
• Amyloid hypothesis: According to this hypothesis, Alzheimer's disease may be caused by the deposition of oligomeric or fibrillar amyloid beta (Aβ) peptide in brain tissue.
• Tau hypothesis: Tau is a protein that helps stabilize the internal framework of nerve cells (neurons) in the brain. This internal framework has a tube-like shape through which nutrients and other important substances travel to reach different parts of the neuron. In Alzheimer’s disease, an abnormal, insoluble form of tau builds up and causes this internal framework to disintegrate.

Alzheimer’s disease is thought to be a combination of age-related brain changes, genetic, environmental, and lifestyle factors. These factors are discussed as below:

• Advanced age: Patients over 65 years of age are at an increased risk for dementia compared to younger people. Older age does not cause Alzheimer’s, but it is the most important known cause of the disease.
• Family history: A family history of Alzheimer’s disease increases the patient’s chances of developing the disease by up to seven times.
• Genes: The Apolipoprotein E (ApoE) gene is implicated in Alzheimer’s disease. The E4 allele of this gene seems to be a strong risk factor for developing this condition. The higher the number of apoE4 alleles, the higher the risk of AD and the lower the age of onset. The early-onset familial AD is usually caused by mutations in the genes coding for amyloid precursor protein (APP), presenilin 1, and presenilin 2.
• Gender: Women are at a higher risk of developing this disease. They make up approximately two-thirds of all Alzheimer’s patients.
• Overweight and obesity: People with a higher BMI or obesity, particularly abdominal obesity, are at an increased risk of dementia after the age of 25 years.
• Alcohol: Middle-aged alcoholics, especially apoE4 allele carriers, are found to have a three-fold higher risk of dementia and AD later in their lives.
• High blood pressure (hypertension): Elevated blood pressure in middle age, especially if uncontrolled, is associated with a higher risk of AD development.
• Cardiovascular and cerebrovascular diseases: A significant increase in the risk of dementia and AD is associated with stroke, clinically silent cerebral infarction, and cardiovascular diseases like peripheral artery disease.
• Hypercholesterolemia: People with high total serum cholesterol levels in middle age are at risk of developing AD and other dementias later in life.
• Hormone imbalances: Imbalanced hormones can create havoc within the body in many systemic ways and increase the risk of Alzheimer’s. For example, changes in estrogen levels, in particular, seem to affect cognition, as estrogen both protects and helps the brain to grow.
• Down syndrome: Many people with Down syndrome develop Alzheimer’s disease as they age. They are born with an extra copy of chromosome 21, which carries a gene that produces a specific protein called amyloid precursor protein (APP). An excess of APP protein leads to a buildup of protein clumps called beta-amyloid plaques in the brain. The presence of beta-amyloid plaques is one of the hallmarks of Alzheimer's disease.
• Head injury: A head injury can usually be directly linked to increasing the chances of developing Alzheimer’s or other forms of dementia later in life.
• Hearing loss: People with hearing loss are more likely to have Alzheimer’s. Research suggests that the part of the brain responsible for hearing and processing auditory information may function differently when hearing diminishes, potentially altering brain structure in a manner related to Alzheimer’s disease.
• Chronic stress: Chronic stress and depression contribute to the buildup of amyloid-beta proteins in the brain, which may play a role in the pathogenesis of Alzheimer’s.
• Sleep issues: Sleep disturbances and poor sleep schedules may lead to mild cognitive impairment and trigger the onset of Alzheimer’s.
• Sedentary lifestyle: A sedentary lifestyle with a lack of mental and physical stimulation increases the risk of this disease.
• Social network and social engagement: The risk of dementia and AD is two-fold higher in elderly individuals with increased social isolation and less frequent, unsatisfactory contact with relatives and friends.

An early and accurate diagnosis is crucial for several reasons. It can inform individuals whether their symptoms are due to Alzheimer’s disease or another cause, such as:

• Stroke
• Tumor
• Parkinson’s disease
• Sleep disturbances
• Side effects of medications
• Other conditions that may be treatable and possibly reversible

Doctors can usually diagnose the disease with the help of the following:

1. Past medical history and current health status: The doctor typically asks the person experiencing symptoms, as well as a family member or friend, questions about overall health, history of Alzheimer’s disease in the family, diet, past medical problems, and ability to carry out daily activities. The history should include information from the person related to the patient.
2. Changes in behavior and personality: A psychiatric evaluation is crucial to distinguish Alzheimer’s from other conditions that can mimic it, such as depression, delirium, and mild cognitive impairment.
3. Cognitive tests involving memory: Diagnosis of Alzheimer's disease is based on tests to assess memory and thinking skills. Most cognitive assessments involve a series of pen and paper tests and questions, each of which carries a score. The tests assess various mental abilities, including attention span, concentration, vision-related abilities, communication skills, and short-term memory. These tests can assist doctors in understanding the situation, but individuals should not use them to self-diagnose this disease.
4. Medical tests: Blood, urine, and other standard medical tests can help identify other possible causes of the problem. Certain tests, such as thyroid profile total, vitamin B12, vitamin D (25-OH), complete blood count (CBC), and erythrocyte sedimentation rate, can help check for infectious conditions, autoimmune conditions, or nutritional deficiencies, as these are other potential causes of Alzheimer's disease. Depending on the test results, the doctor may recommend more detailed tests to confirm the findings.
5. Imaging studies: Neuroimaging is a promising and widely expanding area of research for detecting Alzheimer’s disease. Multiple brain imaging procedures can identify abnormalities in the brain, including CT, MRI, and PET scans. These tests are considered preliminary for disease detection.

Computed tomography (CT) scan: A CT scan of the brain provides more detailed information about its tissues and structures than standard X-rays of the head.

Magnetic resonance imaging (MRI) scan: A strong magnetic field and radio waves are used to produce detailed images of the brain to identify parts that are not functioning correctly and to help determine the cause.

Positron emission tomography (PET) scan: A PET scan can detect changes in metabolism, blood flow, cellular communication processes, and other brain activities. The most commonly used PET scan is a fluorodeoxyglucose (FDG) PET scan, which identifies brain regions with reduced glucose metabolism. The pattern of metabolism change can aid in diagnosing various degenerative brain diseases. Recently developed PET scans can detect clusters of amyloid proteins (plaques) or tau (neurofibrillary tangles) associated with Alzheimer's disease; however, these types of PET scans are typically used for research purposes.

The exact cause of Alzheimer's disease is still unknown. Although there's no certain way to prevent the condition, a healthy lifestyle can help reduce its risk.

Reduce the risk of cardiovascular disease: By reducing the risk of cardiovascular disease, a person reduces the risk of Alzheimer’s disease, stroke, and heart attack by following a few steps:

• Quit smoking
• Eat a healthy and balanced diet by including fruits and vegetables every day
• Include regular moderate exercise in the schedule
• Appropriate treatment to manage hypertension, obesity, increased glucose levels, and diabetes mellitus

Stay mentally and socially active: Evidence suggests that the rate of dementia is lower in people who remain mentally and socially active throughout their lives. Maintain an active and socially integrated lifestyle by ensuring an extensive social network and frequent participation in social, physical, and intellectually stimulating activities like:

• Learning foreign languages
• Playing musical instruments
• Joining book clubs
• Engaging in gardening or crafts

Currently, there is no cure for Alzheimer's disease, though symptomatic relief can be provided. Current treatments are discussed as follows:

1. Medications to Improve Symptoms

Medicines may be prescribed for Alzheimer's disease to help temporarily improve some symptoms. These may include:

• Cholinesterase (AChE) Inhibitors: Alzheimer’s disease can be caused by low levels of a chemical called acetylcholine in the brain. Acetylcholine performs the function of sending messages between nerve cells. Cholinesterase inhibitors (CI) aim to increase the availability of acetylcholine in neurotransmission to treat memory disturbances. Various medications to treat Alzheimer's include donepezil, rivastigmine, and galantamine.
• N–methyl–D–aspartate (NMDA) Receptor Blocker: Memory loss in Alzheimer’s disease is due to excessive production of glutamate (a chemical messenger) in the brain, which is mediated by NMDA receptors. These medications work by preventing the action of NMDA receptors and regulating the production of glutamate involved in the transmission of nerve signals. An example of this type of drug is memantine, which is used for moderate or severe Alzheimer's disease. It is suitable for those who cannot take or are unable to tolerate AChE inhibitors. This drug is also prescribed for severe Alzheimer's disease in patients who have already been taking an AChE inhibitor.
• Medicines to Treat Challenging Behavior: In the later stages of dementia, a significant number of people will develop what's known as behavioral and psychological symptoms of dementia (BPSD). These symptoms include anxiety, depression, wandering, and aggression. A consultant psychiatrist can prescribe anti-anxiety drugs to manage anxiety and agitation. Antidepressant drugs can be prescribed to treat restlessness, aggression, and depression. Anticonvulsants are sometimes used to manage aggression, while antipsychotics can also be used to treat paranoia and hallucinations.
• Disease-Modifying Treatments: While symptomatic treatments have proven to be helpful, finding a cure is most vital. Since the amyloid hypothesis indicates that Aß generation and deposition is the basis of Alzheimer’s disease, interest centers on amyloid therapies. These therapies aim to decrease the production of Aß, increase clearance of Aß, and prevent Aß aggregation into amyloid plaques. An example is aducanumab, a newly approved agent identified as an amyloid beta-directed monoclonal antibody.

2. Psychosocial Interventions

These interventions are used as an adjunct to medicinal treatment:

• Cognitive Stimulation Therapies: These involve participating in group activities and exercises designed to improve memory and problem-solving skills.
• Cognitive Rehabilitation: Cognitive rehabilitation helps individuals use the working parts of their brain to assist the parts that are not functioning well. A patient practices on a computer program for memory training.
• Recollections and Past Stories: Life story work involves compiling photos, notes, and keepsakes from childhood to the present day. These approaches can sometimes help improve mood and well-being.

It is important to ensure safety and quality of life for patients suffering from Alzheimer's disease. Caring for a relative or loved one who is suffering from this disease can be challenging. Here are a few points that can help:

1. Always keep the atmosphere at home pleasant, positive, and caring. Never make the patient feel that they are a burden.
2. Encourage the person to maintain a diary or calendar to note down important things or days which will help them remember.
3. Ensure that the patient has access to important data, such as identity documents, home address, important telephone numbers, etc., at all times. This can help in situations where the patient loses their way home or is unable to remember their identity or whereabouts.
4. People with dementia are often at an increased risk of falls due to concurrent motor issues. Hence, take care and ensure that their surroundings are well-lit, spacious, and free of obstacles. A few things you or your caregiver can do to make your living space safer include the following:

• Install a sturdy handrail on staircases.
• Remove unnecessary furniture to allow for free movement.
• Install carpet on stairs or mark the edges of each step with bright colored tape.
• Ensure all electrical cords are tucked out of the way.
• Keep sharp objects stored safely away.

Alzheimer's is a progressive condition that can worsen with time. The treatments currently available are known to slow the progression of the disease but cannot entirely stop it. Alzheimer's can cause the following complications as it worsens gradually:

• Safety issues: Patients with Alzheimer's disease are at an increased risk of injuries even while performing activities like walking, cooking, cleaning, etc.
• Personal hygiene: In the later stages, Alzheimer's patients struggle with basic human hygiene, such as brushing, bathing, grooming, and using the bathroom.
• Nutritional challenges: With advanced Alzheimer's, a person may forget to eat and may lose interest in eating. This can lead to a variety of malnutrition-related problems.
• Aspiration or choking: Trouble swallowing food can lead to aspiration or choking and cause pneumonia in the lungs.
• Death: Severe forms of Alzheimer's result in death, often due to infections like pneumonia and conditions like dehydration and malnutrition.

1. Exercise and yoga: Performing light exercises can help enhance mood, manage anxiety, and maintain physical activity status in patients with Alzheimer's. These light exercises can include home-based aerobic routines, dancing, lifting light weights, and yoga, such as Pranayama.

2. Physiotherapy and occupational therapy: Certain modifications suggested by physiotherapists or occupational therapists may need to be implemented in a patient’s home or work environment to make it safer and prevent injuries due to falls.

3. Massage therapy and aromatherapy: Massage therapy and aromatherapy induce relaxation and may be helpful for patients with Alzheimer's.

4. Ayurveda: Alzheimer's is known as “Smruthi Nasha” in Ayurveda. Panchkarma and medicinal herbs, such as Shankhpushpi, Guduchi (Giloy), Brahmi, Ashwagandha, and Shatavari, may be useful in treating Alzheimer's disease.

Receiving a diagnosis of Alzheimer's can be a life-altering and challenging situation for patients and their caregivers. Coming to terms with the diagnosis can invoke feelings of anxiety, depression, anger, rage, and guilt. However, it is important to remember that even with a diagnosis, it is possible to live a happy life. Some key points to remember are:

• Take care of oneself: These steps can help protect health, foster feelings of control and self-worth, and find meaningful ways to engage with others.
• Care for physical health by exercising and eating a healthy diet.
• Care for mental health by participating in mentally stimulating activities such as playing games, reading books, and engaging in calming activities like yoga.
• Care for emotional health by experiencing a range of emotions without labeling them as good or bad. Join a support group to connect with others in similar situations and maintain close relationships.

Stay active and engaged: Patients should try to keep up with activities they enjoy and spend time with family and friends. If someone can no longer do certain things safely, they should consider taking on new activities at times of the day when they feel best.

Minimize stress from life: Stress can be an inevitable part of life with Alzheimer’s. Taking steps to prevent or manage it can improve daily life. To stay calm, engage in relaxing activities such as listening to music, gardening, or keeping a journal.

Add a few routines that can make life easier: Alzheimer’s-related memory loss can be frustrating and hazardous. A few helpful strategies include:

• Always keep keys, cellphones, and other essentials in the same place at home.
• Arrange for automatic payment of bills.
• Schedule regular appointments on the same day at the same time.
• Use a calendar or whiteboard at home for your daily schedule, and make a list of tasks as you complete them.

Care for caregivers: Caring for someone with Alzheimer’s can be uniquely challenging as the person becomes increasingly dependent and unable to express their wants and needs. This situation can take a toll on caregivers' mental health. Here are a few tips:

• Keep the mood positive. Convey feelings of affection through facial expressions and touch.
• If the person becomes agitated or upset, acknowledge those feelings, change the topic, or suggest a distraction like going for a walk.
• Maintain a sense of humor, and find activities that both you and the person you care for can enjoy and laugh about.