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Alzheimer Disease

Updated : February 19, 2024





Background

Alzheimer disease is a neurological condition that causes a gradual decline in behavioral and cognitive abilities such as memory, interpretation, language, concentration, thinking, and decisions.

Alzheimer is the most prevalent dementia, contributing to two-thirds of dementia cases in persons 65 and older.

Early onset before age 65 is rare and occurs in less than 10% of Alzheimer patients. There is no cure for Alzheimer, although a recent development has shown progress in slowing cognitive decline.

Epidemiology

The global incidence of dementia is estimated at 24 million individuals, which is expected to double by 2050. Alzheimer disease is predicted to cost $172 billion in health care costs in the United States annually. After the age of 65, the risk of Alzheimer increases every five years.

The age-specific incidence rises significantly from less than 1% per year before age 65 to 6% per year beyond age 85. The prevalence rate rises from 10% at age 65 to 40% after age 85. Women have a slightly greater incidence rate of Alzheimer disease, especially after age 85.

Anatomy

Pathophysiology

Alzheimer disease is characterized by the buildup of aberrant neurofibrillary tangles and neuritic plaques in the brain. An increase in beta-amyloid 42 levels produce amyloid aggregation, which causes neurotoxicity. Beta-amyloid 42 promotes aggregate fibrillary amyloid protein production over normal APP breakdown.

The APP gene is found on chromosome 21, related to familial Alzheimer disease. Amyloid deposition occurs in Alzheimer disease surrounding meningeal and cerebral arteries, as well as gray matter. Gray matter deposits are multifocal and create miliary structures known as plaques.

Tau is hyperphosphorylated because of extracellular beta-amyloid aggregation, leading to tau aggregates’ production. Tau aggregates generate neurofibrillary tangles, which are tangled paired helical filaments. They begin in the hippocampus and can spread across the cerebral cortex. Tau-aggregates accumulate within neurons.

Braak and Braak created a staging approach based on the topographic staging of neurofibrillary tangles into six phases. This Braak staging is an essential aspect of the National Institute on Aging and Reagan Institute neuropathological criteria for Alzheimer diagnosis. Tangles are more strongly linked to Alzheimer disease than plaques.

Alzheimer disease is an autosomal dominant condition has complete penetrance. Mutations in three genes have been associated with the autosomal dominant type of the disease: the AAP gene on chromosome 21, Presenilin1 on chromosome 14, and Presenilin2 on chromosome 1. APP mutations may enhance beta-amyloid peptide production and aggregation.

PSEN1 & PSEN2 mutations cause beta-amyloid aggregation by interfering with gamma-secretase processing. Mutations in these three genes are responsible for 5% to 10% of all cases and early-onset Alzheimer disease predominance.

Etiology

Alzheimer is a neurological condition that causes neuronal cell loss over time. It usually begins in the hippocampus’s entorhinal cortex. Both early and late-onset Alzheimer disease has a hereditary component.

Trisomy 21 is a risk factor for developing dementia at a young age. Alzheimer disease has been linked to several risk factors. The primary risk factor for Alzheimer disease is becoming older.

Traumatic brain injury, older parental age, depression, cardiovascular and cerebrovascular illness, a family history of dementia, smoking, elevated homocysteine levels, and the presence of the APOE e4 allele have all been linked to an increased risk of Alzheimer disease.

Genetics

Prognostic Factors

Alzheimer is usually progressing. A person diagnosed with Alzheimer disease at age 65 has an average life expectancy of 4 to 8 years.

Some people with Alzheimer might live for up to 20 years after the first symptoms appear. Pneumonia is the leading cause of mortality in Alzheimer disease.

Clinical History

Age:

  • Late-Onset Alzheimer’s Disease (LOAD): Most cases of Alzheimer’s disease occur in individuals aged 65 and older. The risk of developing Alzheimer’s increases with age, and it is the most common cause of dementia in older adults.
  • Early-Onset Alzheimer’s Disease (EOAD): In some cases, Alzheimer’s disease may manifest before the age of 65, referred to as early-onset Alzheimer’s.

Associated Comorbidities:

  • Cardiovascular Conditions: Conditions such as hypertension, diabetes, and high cholesterol have an increased risk of Alzheimer’s disease.
  • Genetic Factors: In some cases, a family history of Alzheimer’s or specific genetic mutations may contribute to the development of the disease.
  • Down Syndrome: Individuals with Down syndrome may have an increased risk of developing Alzheimer’s disease at an earlier age.

Acuity of Presentation:

  • Insidious Onset: Alzheimer’s disease typically has an insidious onset, with symptoms gradually progressing over time. Early signs may include subtle memory lapses and difficulty recalling recent events.
  • Memory Impairment: Progressive memory loss is a hallmark feature, initially involving recent memories and later impacting more distant memories.
  • Cognitive Decline: Individuals may experience a decline in cognitive functions such as problem-solving, language skills, and spatial awareness.
  • Behavioral Changes: Changes in mood and behavior, including increased apathy, irritability, and social withdrawal, may be observed.
  • Functional Impairment: As the disease advances, individuals may struggle with daily activities and tasks, eventually requiring assistance with self-care.

Physical Examination

The objective of the physical examination is to evaluate different aspects of an individual’s health and neurological condition. Below are key elements of the physical examination for Alzheimer’s disease:

Neurological Examination:

  • Assessment of Mental Status: Evaluate cognitive functions, including memory, attention, language, and executive function.
  • Cranial Nerve Examination: Evaluate the function of each cranial nerve, providing insights into brain function.
  • Motor Function: Assess muscle strength, tone, coordination, and reflexes.

Vital Signs:

  • Measurement of blood pressure, heart rate, respiratory rate, and body temperature. Deviations from normal vital signs may suggest other health issues or contribute to cognitive impairment.

General Physical Examination:

  • Evaluation of overall health and well-being.
  • Examination of the cardiovascular system, respiratory system, gastrointestinal system, and other organ systems to identify potential contributing factors or coexisting conditions.

Gait and Mobility Assessment:

  • Observation of the patient’s gait, balance, and overall mobility. Changes in these areas may indicate neurological dysfunction.

Sensory Examination:

  • Assessment of sensory perception, including vision, hearing, and tactile sensation. Sensory deficits can impact the ability to interact with the environment and contribute to cognitive decline.

Functional Assessment:

  • Evaluation of the patient’s ability to perform activities of daily living (ADLs), such as dressing, grooming, and feeding. Impairments in these areas may indicate the severity of cognitive decline.

Psychiatric Assessment:

  • Examination of mood, behavior, and psychiatric symptoms. Depression and anxiety are common in individuals with Alzheimer’s disease and can significantly impact overall functioning.

Laboratory and Ancillary Tests:

  • While not part of the physical examination per se, various laboratory tests (e.g., blood tests, cerebrospinal fluid analysis) and imaging studies (e.g., MRI, CT scans) are often utilized to rule out other potential causes of cognitive impairment.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Various conditions that may be considered in the differential diagnosis of Alzheimer’s disease include:

Vascular Dementia (VaD):

Vascular dementia results from compromised blood flow to the brain, often due to strokes or other vascular issues. Symptoms can overlap with those of Alzheimer’s disease.

Lewy Body Dementia (LBD):

LBD is characterized by the presence of Lewy bodies in the brain, leading to cognitive and motor symptoms. It shares certain features with both Alzheimer’s disease and Parkinson’s disease.

Frontotemporal Dementia (FTD):

FTD encompasses a group of disorders that predominantly affect the frontal and temporal lobes of the brain, causing changes in personality, behavior, and language. Memory loss may not be as apparent in the early stages.

Parkinson’s Disease Dementia (PDD):

Individuals with Parkinson’s disease may develop dementia as the condition progresses. Cognitive impairment may manifest as memory loss and executive dysfunction.

Normal Pressure Hydrocephalus (NPH):

NPH is characterized by an abnormal accumulation of cerebrospinal fluid in the brain, leading to gait disturbances, urinary incontinence, and cognitive decline.

Huntington’s Disease:

Huntington’s disease is a genetic disorder resulting in progressive degeneration of nerve cells in the brain, causing both motor and cognitive symptoms.

Chronic Traumatic Encephalopathy (CTE):

CTE is associated with repeated head injuries, as observed in athletes participating in contact sports, and can result in cognitive and behavioral changes.

Metabolic and Endocrine Disorders:

Conditions such as hypothyroidism, vitamin B12 deficiency, and metabolic disorders can induce cognitive impairment and should be ruled out.

Infections:

Chronic infections, such as neurosyphilis or HIV-related dementia, can induce cognitive decline.

Depression and Anxiety:

Mood disorders, especially in older adults, may occasionally present with cognitive symptoms that could be confused with dementia.

Medication Side Effects:

Some medications, particularly those with anticholinergic effects, may contribute to cognitive impairment.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Medication Management:

  • Cholinesterase Inhibitors (e.g., Donepezil, Rivastigmine, Galantamine): These drugs enhance acetylcholine levels in the brain, temporarily improving cognitive symptoms and functional abilities.
  • NMDA Receptor Antagonist (Memantine): Memantine regulates glutamate activity, providing symptomatic relief and slowing cognitive decline.

Non-Pharmacological Approaches:

  • Cognitive Stimulation Therapy: Activities and exercises to engage and stimulate cognitive functions.
  • Occupational Therapy: Helps individuals maintain independence in daily activities.
  • Physical Exercise: Regular physical activity may support overall health and potentially slow cognitive decline.

Supportive Care and Education:

  • Caregiver Education: Providing information and resources to caregivers on managing symptoms, coping strategies, and support services.
  • Support Groups: Connecting individuals with AD and their caregivers to share experiences and advice.

Healthy Lifestyle Practices:

  • Nutritious Diet: Emphasizing a well-balanced, heart-healthy diet.
  • Physical Activity: Encouraging regular exercise for overall health benefits.
  • Cognitive Engagement: Engaging in mentally stimulating activities.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Non-Pharmacological treatment of Alzheimer Disease

Lifestyle modifications:

  • Healthy Diet: Emphasize a balanced, nutrient-rich diet with a variety of fruits, whole grains, vegetables, lean proteins, and healthy fats. Consider the Mediterranean or DASH diet, associated with cognitive benefits.
  • Regular Physical Exercise: Engage in regular physical activity, such as walking, swimming, or gentle exercises. Exercise improves the cognitive function and overall well-being.
  • Cognitive Stimulation: Engage in mentally stimulating activities, such as puzzles, games, and reading. Stimulating the brain may help maintain cognitive function.
  • Social Engagement: Maintain social connections through interactions with family, friends, and community. Social engagement contributes to emotional well-being.
  • Stress Management: Practice stress-reducing techniques like deep breathing, meditation, or yoga. Stress management contributes to overall well-being.
  • Routine and Structure: Establish and maintain a daily routine to provide structure and reduce confusion. Consistency in daily activities can be beneficial.
  • Memory Aids: Use memory aids like calendars, reminders, and labelled objects to enhance daily functioning. Memory aids can compensate for cognitive challenges.
  • Safety Measures: Implement safety measures at home, such as removing tripping hazards and ensuring a secure environment. Safety measures reduce the risk of accidents.
  • Limiting Alcohol and Tobacco: Limit alcohol intake, as excessive alcohol can adversely affect cognitive function. Quit smoking, as smoking is associated with an increased risk of cognitive decline.
  • Hydration: Ensure adequate hydration by drinking an appropriate amount of water. Dehydration can negatively impact cognitive and physical function.
  • Regular Medical Check-ups: Attend routine medical check-ups to monitor overall health and address any emerging health concerns. Regular check-ups support proactive health management.
  • Caregiver Support: Caregivers should seek support from community resources and support groups. Caregiver well-being is crucial for effective care provision.

Use of Cholinesterase Inhibitors in the treatment of Alzheimer Disease

Cholinesterase inhibitors are a class of medications commonly used in the treatment of Alzheimer’s disease. They increase the levels of acetylcholine, a neurotransmitter involved in memory and cognitive function.

Donepezil (Aricept, Aricept ODT):

  • Donepezil inhibits acetylcholinesterase, an enzyme that breaks down acetylcholine, thereby increasing acetylcholine levels in the brain. It is typically taken orally as a tablet or orally disintegrating tablet (ODT). Initial low doses are often recommended, with gradual titration to higher doses as tolerated. It has been shown to modestly improve cognitive function, activities of daily living, and global function in some individuals with mild to moderate Alzheimer’s disease.

Rivastigmine (Exelon, Exelon Patch):

  • Rivastigmine inhibits both acetylcholinesterase and butyrylcholinesterase, leading to increased acetylcholine levels. It is available in oral form (capsules or liquid) and as a transdermal patch for continuous delivery. Based on the formulation, it may be administered once or twice daily for oral forms, and the patch is typically applied once daily. Similar to donepezil, rivastigmine may improve cognitive and functional outcomes in individuals with mild to moderate Alzheimer’s disease.

Galantamine (Razadyne, Razadyne ER):

  • Galantamine is a reversible acetylcholinesterase inhibitor and an allosteric modulator of nicotinic It is available in immediate-release and extended-release formulations. It is usually administered twice daily (immediate-release) or once daily (extended-release). Like other cholinesterase inhibitors, galantamine may provide modest cognitive and functional benefits in individuals with mild to moderate Alzheimer’s disease.

Donepezil transdermal (Adlarity):

  • Similar to oral donepezil, the transdermal patch inhibits acetylcholinesterase, leading to increased acetylcholine levels. It is administered through a once-daily transdermal patch. The patch is designed for continuous 24-hour drug delivery. Studies suggest that transdermal formulation may offer a convenient alternative to oral administration, with similar efficacy in improving cognitive function.

Use of Anti-amyloid beta monoclonal antibodies in the treatment of Alzheimer Disease

Anti-amyloid beta monoclonal antibodies represent a newer class of medications designed to target and remove beta-amyloid plaques, which are characteristic pathological features of Alzheimer’s disease (AD).

Aducanumab (Aduhelm):

  • Aducanumab is the monoclonal antibody that targets beta-amyloid plaques in the brain. It aims to reduce the accumulation of beta-amyloid, which is believed to contribute to the progression of Alzheimer’s disease. It is administered through intravenous (IV) infusion. It is typically given monthly under the supervision of healthcare professionals.

Lecanemab (Leqembi):

  • Lecanemab is another anti-amyloid beta monoclonal antibody targeting beta-amyloid plaques. Like Aducanumab, it aims to clear beta-amyloid from the brain. It is administered through subcutaneous injection typically given monthly.

Use of NMDA antagonist in the treatment of Alzheimer Disease

Memantine (Namenda, Namenda XR):

  • Mechanism of Action: Memantine modulates the activity of glutamate, an excitatory neurotransmitter in the brain, by blocking NMDA receptors. It helps regulate excessive glutamate activity, which is implicated in the neurodegenerative processes seen in Alzheimer’s disease.
  • Indication: Memantine is primarily indicated for the treatment of moderate to severe Alzheimer’s disease. It is used in combination with cholinesterase inhibitors, such as donepezil, for a more comprehensive approach to symptom management.
  • Administration: Available in immediate-release (Namenda) and extended-release (Namenda XR) formulations. The immediate-release form is typically administered twice daily, while the extended-release form is taken once daily.
  • Efficacy: Memantine has been shown to provide modest benefits in the cognitive function, activities of daily living, and global functioning in individuals with moderate to severe Alzheimer’s disease. It is considered particularly beneficial for individuals who may not tolerate or adequately respond to cholinesterase inhibitors alone.
  • Adverse Effects: The side effects include dizziness, headache, constipation, and confusion. Adverse effects are mild, but individuals may react differently, and close monitoring is recommended.

Use of Combination Drugs in the treatment of Alzheimer Disease

Combination drugs, such as Memantine/Donepezil (brand name: Namzaric), are formulations that combine multiple medications to treat Alzheimer’s disease. Namzaric specifically combines two active ingredients: memantine, an NMDA receptor antagonist, and donepezil, a cholinesterase inhibitor.

Memantine/Donepezil (Namzaric):

  • Dual Mechanism of Action: Memantine is an NMDA Receptor Antagonist that modulates glutamate activity by blocking NMDA receptors. Donepezil is a Cholinesterase Inhibitor that increases acetylcholine levels in brain by inhibiting its breakdown.
  • Indication: Namzaric is used for the treatment of moderate to severe Alzheimer’s disease. The combination addresses different aspects of neurotransmitter regulation to enhance overall efficacy.
  • Simplified Administration: Combining memantine and donepezil into a single medication simplifies the treatment regimen for patients, as they do not need to manage two separate medications.
  • Dosage and Administration: Available in different strengths, allowing for dose adjustment based on individual patient needs. Typically administered once daily.
  • Efficacy: Studies have shown that the combination of memantine and donepezil may provide additional benefits compared to either medication alone.
  • Adverse Effects: Adverse effects are consistent with the individual components (memantine and donepezil) and may include dizziness, headache, and gastrointestinal symptoms. Side effects should be monitored, and healthcare professionals may adjust the dosage as needed.

 

Use of Nutritional Supplement in the treatment of Alzheimer Disease

Axona, also known for its active ingredient Caprylidene, is a nutritional supplement that has been explored in the context of Alzheimer’s disease management. It is a medical food designed to provide an alternative energy source for the brain.

Caprylidene (Axona):

  • Active Ingredient: The active ingredient in Axona is caprylic triglyceride, a medium-chain triglyceride (MCT) derived from coconut oil.
  • Mechanism of Action: Caprylidene is metabolized into ketones, an alternative energy source for the brain. The idea is to provide the brain with ketones as fuel, especially in individuals with Alzheimer’s disease who may have impaired glucose metabolism.
  • Indication: Axona is classified as a medical food and is intended for the dietary management of individuals with mild to moderate Alzheimer’s disease.
  • Administration: Typically administered as a liquid supplement. The recommended dose is usually taken once daily.
  • Efficacy: Studies have explored the cognitive benefits of Caprylidene in Alzheimer’s disease. While some studies suggested potential cognitive improvements, results have been mixed, and further research is needed to establish its effectiveness.

Use of Diagnostic Imaging Agents in Alzheimer Disease

Diagnostic imaging agents are not used in treating Alzheimer’s disease; instead, they are used in diagnosing and evaluating the disease. These agents are radiopharmaceuticals designed for positron emission tomography (PET) imaging to visualize and detect the beta-amyloid plaques in brain, a hallmark of Alzheimer’s disease.

  • Florbetapir F 18 (AMYViD): Florbetapir F 18 is used for PET imaging to estimate the beta-amyloid neuritic plaque density in the brain. It is administered intravenously, and PET imaging is performed shortly afterward. It helps clinicians assess the extent of beta-amyloid deposition in the brain, aiding in the diagnosis of Alzheimer’s disease.
  • Flutemetamol F 18 (Vizamyl): Flutemetamol F 18 is another PET imaging agent used to visualize beta-amyloid plaques in the brain. It is administered intravenously, and PET imaging is conducted afterward. It assists in the evaluation of beta-amyloid plaque density and can contribute to the diagnosis of Alzheimer’s disease.
  • Florbetaben F 18 (Neuraceq): Florbetaben F 18 is used for PET imaging to detect the beta-amyloid plaques in the brain. It is administered intravenously before PET imaging. It aids in the assessment of beta-amyloid neuritic plaque density, supporting the diagnostic process for Alzheimer’s disease.

Deep Brain Stimulation in the treatment of Alzheimer Disease

Deep brain stimulation (DBS) is not widely established as a standard treatment for Alzheimer’s disease. Deep brain stimulation involves implanting electrodes into the specific areas of the brain and connecting them to a pulse generator placed under the skin. The electrodes deliver electrical impulses to modulate abnormal brain activity. The use of deep brain stimulation in Alzheimer’s disease has been explored in research and clinical trials, but the results have been mixed, and the procedure is not yet considered a routine or proven treatment. Alzheimer’s disease is a neurodegenerative disorder, and its underlying mechanisms involve widespread changes and damage in the brain. While DBS has shown promise in addressing certain symptoms in other neurological conditions, its application to Alzheimer’s disease is still under investigation. The clinical trials have explored the potential benefits of deep brain stimulation in Alzheimer’s disease. These studies often focus on targeting specific brain regions involved in memory and cognition. The results of studies have been variable, with some showing potential cognitive improvements and others showing limited or no benefits. The variability in outcomes may be influenced by factors such as patient selection, stimulation parameters, and the stage of Alzheimer’s disease.

Phases of management of Alzheimer Disease

 

Acute Phase Management:

  • Diagnosis and Assessment: Prompt and accurate diagnosis is crucial. Comprehensive cognitive assessments, imaging studies (e.g., MRI or PET scans), and laboratory tests help confirm the diagnosis.
  • Medication Management: Cholinesterase Inhibitors (e.g., donepezil, rivastigmine, galantamine) and NMDA receptor antagonist (memantine) may be prescribed to manage cognitive symptoms. Medications are adjusted based on the individual’s response and tolerance.
  • Behavioral Interventions: Addressing acute behavioral symptoms such as agitation, aggression, or hallucinations with non-pharmacological approaches. Creating a calm environment, providing structured routines, and using behavioral strategies.
  • Support for Caregivers: Education and support for family members and caregivers. Guidance on coping with behavioral changes and accessing community resources.

Chronic Phase Management:

  • Continuation of Medications: Long-term use of cognitive-enhancing medications to help manage symptoms. Regular follow-ups with healthcare professionals to assess medication effectiveness and adjust dosages as needed.
  • Cognitive Stimulation: Engagement in cognitive activities and stimulation to support brain function. Participation in activities that promote memory recall and cognitive abilities.
  • Nutritional Support: Ensuring a balanced diet that supports overall health and cognitive function. Addressing nutritional concerns and adapting meal plans as needed.
  • Physical Exercise: Encouraging regular physical activity, which has shown benefits for both physical and cognitive health. Exercise may include activities suitable for the individual’s abilities, such as walking or gentle movements.
  • Regular Monitoring and Adjustments: Ongoing assessment of the individual’s cognitive and functional status. Regular communication with healthcare professionals to adapt the care plan as the disease progresses.
  • End-of-Life Care Planning: Discussion and planning for end-of-life care preferences. Support for family members in making decisions related to care and treatment options.

Acute Phase Management:

  • Diagnosis and Assessment: Prompt and accurate diagnosis is crucial. Comprehensive cognitive assessments, imaging studies (e.g., MRI or PET scans), and laboratory tests help confirm the diagnosis.
  • Medication Management: Cholinesterase Inhibitors (e.g., donepezil, rivastigmine, galantamine) and NMDA receptor antagonist (memantine) may be prescribed to manage cognitive symptoms. Medications are adjusted based on the individual’s response and tolerance.
  • Behavioral Interventions: Addressing acute behavioral symptoms such as agitation, aggression, or hallucinations with non-pharmacological approaches. Creating a calm environment, providing structured routines, and using behavioral strategies.
  • Support for Caregivers: Education and support for family members and caregivers. Guidance on coping with behavioral changes and accessing community resources.

Chronic Phase Management:

  • Continuation of Medications: Long-term use of cognitive-enhancing medications to help manage symptoms. Regular follow-ups with healthcare professionals to assess medication effectiveness and adjust dosages as needed.
  • Cognitive Stimulation: Engagement in cognitive activities and stimulation to support brain function. Participation in activities that promote memory recall and cognitive abilities.
  • Nutritional Support: Ensuring a balanced diet that supports overall health and cognitive function. Addressing nutritional concerns and adapting meal plans as needed.
  • Physical Exercise: Encouraging regular physical activity, which has shown benefits for both physical and cognitive health. Exercise may include activities suitable for the individual’s abilities, such as walking or gentle movements.
  • Regular Monitoring and Adjustments: Ongoing assessment of the individual’s cognitive and functional status. Regular communication with healthcare professionals to adapt the care plan as the disease progresses.
  • End-of-Life Care Planning: Discussion and planning for end-of-life care preferences. Support for family members in making decisions related to care and treatment options.

Medication

 

rivastigmine

Oral- mild-to-moderate Initial dose: 1.5 mg capsule orally every 12hr; increase it up to 1.5 mg/dose every 2 weeks Do not exceed the dose up to 6 mg orally every 12 hours Maintenance dose: 3-6 mg capsule orally every 12 hours Transdermal- mild, moderate, and severe Initial dose: Apply the patch 4.6 mg every 24 hours; increase it up to 9.5 mg every 24 hours minimum 4 weeks; further after additional 4 weeks increase dose up to 13.3 mg patch Mild-to-moderate: 9.5-13.3 mg every 24 hours Moderate-to-severe: 13.3 mg every 24 hours Replace with new patch every 24 hours



galantamine

Initial Conventional: 4 mg orally 2 times a day ER: 8 mg orally once a day Maintenance Conventional: Titrate to 8-12 mg orally two times and increase up to 4 mg every 12 hours for <4 weeks ER: 16-24 mg orally once a day and increase by 8 mg a day for <4 weeks



memantine donepezil

10 mg of memantine two times a day or 28 mg of memantine ER once a day; and donepezil 10 mg once a day: 28 mg Memantine ER and donepezil 10 mg orally once a day every evening



memantine

5 mg tablet orally may be increased up to 5 mg/day each week. Maintenance dose: 20 mg/day orally twice a day 7 mg PO Capsule-ER may be increased up to 7 mg/day each week Maintenance dose: 28 mg/day orally daily



donepezil transdermal

apply a 5 mg patch once in a week; and increase up to 10 mg patch once a week after 4-6 weeks



donepezil (Rx)

Mild/moderate: 5 mg orally daily, may increase up to10 mg after 4-6 weeks Moderate/severe: 5 mg/day orally, increase up to 10 mg/day after 4-6 weeks; and after 3 months increase up to 23 mg/day Administration Take at bedtime and dissolve the drug under the tongue and follow with water



Dose Adjustments

Dose Modification Renal Impairment: Not Available Hepatic Impairment: Not Available

nadh 

Take 10-15 mg of medication orally every other day to once a day



phosphatidylserine 


Indicated for Alzheimer's Disease
100 mg orally three times a day
Senile Dementia and Memory/Cognitive Impairment
100 mg orally three times a day



piracetam 

1.6 to 9.6 grams/day orally



huperzine A 

Administer orally twice daily at a dosage range of 50-200 mcg



aducanumab 


Indicated for Alzheimer Disease
Administered every four weeks as intravenously infused nearly 21 days apart
Dosing titration regimen:
1-2 Infusions: 1 mg/kg intravenously every 4 weeks
3-4 Infusions: 3 mg/kg intravenously every 4 weeks
5-6 Infusions: 6 mg/kg intravenously every 4 weeks
7 and beyond Infusions: 10 mg/kg intravenously every 4 weeks



caprylidene 

Initial dosing involves the administration of 10 grams one time a day over a period of two days
To gradually increase the dosage, it is recommended to administer the drug in 10 grams increments every 2 days until a total of 40 grams is reached, to be taken one time daily on seventh day
It is important to consider a slower titration rate if the patient encounters any adverse events
a maintenance dosage of 40 grams one time a day is recommended to sustain therapeutic efficacy



ipidacrine 

20 mg given 2 to 3 times daily



tacrine 

Take an initial dose of 10 mg orally four times daily if possible, in between food up to 6 weeks
The maintenance dose may raise up to 20 mg orally four times daily
It may further raise up to 120 mg and 160 mg daily may be done in 6-week intervals



methanesulfonyl fluoride 

3.6 mg, 7.2 mg, 10.8 mg MSF were given orally to 27 healthy volunteers (between the ages 50 to 72 years) in a randomised, placebo-controlled phase I research. The individuals got the same dosages three times a week for two weeks after a single dose phase and a one-week wash-out period



inositol 

6

g

Orally 

once a day

1

month



taurursodiol 

off-label:

In-vivo data suggests intraperitoneal administration of 500 mg/kg for every third day



phenserine 

It is indicated for mild to moderate Alzheimer’s disease
In-vivo studies suggests that administer dose of 5 mg orally every 12 hours for the starting 4 weeks of the investigation and then dose of 10 mg orally every 12 hours for the remaining 4 weeks



epothilone D 

Phase II studies were conducted on colorectal, metastatic breast, and non-small-cell lung malignancies. However, there was an end of development in favor of a second-generation analog that had a higher safety rating. Alzheimer's disease therapy was also investigated with this medication. Following the conclusion of the trial, epothilone D's examination of Alzheimer's disease was discontinued



lecanemab 

Indicated for the treatment of mild cognitive impairment or mild dementia in Alzheimer disease patients:


10 mg/kg IV infused over approximately 1 hour, given once every two weeks

Note:
This drug has received accelerated approval due to observed reductions in amyloid beta plaques in treated patients
Sustained approval for this indication may hinge upon confirmation of clinical benefits in a subsequent confirmatory trial
It is crucial to confirm the presence of amyloid beta pathology before initiating this treatment



metrifonate 

2.5

mg/kg

Tablets

Orally 

once a day

2

weeks

Off-label/br Loading dose: 2.5mg/kg orally for two weeks
Maintenance dose: 1mg/kg orally for two weeks



posiphen 

Posiphen is under Phase 2/3 clinical trial



 
 

Media Gallary

Alzheimer Disease

Updated : February 19, 2024




Alzheimer disease is a neurological condition that causes a gradual decline in behavioral and cognitive abilities such as memory, interpretation, language, concentration, thinking, and decisions.

Alzheimer is the most prevalent dementia, contributing to two-thirds of dementia cases in persons 65 and older.

Early onset before age 65 is rare and occurs in less than 10% of Alzheimer patients. There is no cure for Alzheimer, although a recent development has shown progress in slowing cognitive decline.

The global incidence of dementia is estimated at 24 million individuals, which is expected to double by 2050. Alzheimer disease is predicted to cost $172 billion in health care costs in the United States annually. After the age of 65, the risk of Alzheimer increases every five years.

The age-specific incidence rises significantly from less than 1% per year before age 65 to 6% per year beyond age 85. The prevalence rate rises from 10% at age 65 to 40% after age 85. Women have a slightly greater incidence rate of Alzheimer disease, especially after age 85.

Alzheimer disease is characterized by the buildup of aberrant neurofibrillary tangles and neuritic plaques in the brain. An increase in beta-amyloid 42 levels produce amyloid aggregation, which causes neurotoxicity. Beta-amyloid 42 promotes aggregate fibrillary amyloid protein production over normal APP breakdown.

The APP gene is found on chromosome 21, related to familial Alzheimer disease. Amyloid deposition occurs in Alzheimer disease surrounding meningeal and cerebral arteries, as well as gray matter. Gray matter deposits are multifocal and create miliary structures known as plaques.

Tau is hyperphosphorylated because of extracellular beta-amyloid aggregation, leading to tau aggregates’ production. Tau aggregates generate neurofibrillary tangles, which are tangled paired helical filaments. They begin in the hippocampus and can spread across the cerebral cortex. Tau-aggregates accumulate within neurons.

Braak and Braak created a staging approach based on the topographic staging of neurofibrillary tangles into six phases. This Braak staging is an essential aspect of the National Institute on Aging and Reagan Institute neuropathological criteria for Alzheimer diagnosis. Tangles are more strongly linked to Alzheimer disease than plaques.

Alzheimer disease is an autosomal dominant condition has complete penetrance. Mutations in three genes have been associated with the autosomal dominant type of the disease: the AAP gene on chromosome 21, Presenilin1 on chromosome 14, and Presenilin2 on chromosome 1. APP mutations may enhance beta-amyloid peptide production and aggregation.

PSEN1 & PSEN2 mutations cause beta-amyloid aggregation by interfering with gamma-secretase processing. Mutations in these three genes are responsible for 5% to 10% of all cases and early-onset Alzheimer disease predominance.

Alzheimer is a neurological condition that causes neuronal cell loss over time. It usually begins in the hippocampus’s entorhinal cortex. Both early and late-onset Alzheimer disease has a hereditary component.

Trisomy 21 is a risk factor for developing dementia at a young age. Alzheimer disease has been linked to several risk factors. The primary risk factor for Alzheimer disease is becoming older.

Traumatic brain injury, older parental age, depression, cardiovascular and cerebrovascular illness, a family history of dementia, smoking, elevated homocysteine levels, and the presence of the APOE e4 allele have all been linked to an increased risk of Alzheimer disease.

Alzheimer is usually progressing. A person diagnosed with Alzheimer disease at age 65 has an average life expectancy of 4 to 8 years.

Some people with Alzheimer might live for up to 20 years after the first symptoms appear. Pneumonia is the leading cause of mortality in Alzheimer disease.

Age:

  • Late-Onset Alzheimer’s Disease (LOAD): Most cases of Alzheimer’s disease occur in individuals aged 65 and older. The risk of developing Alzheimer’s increases with age, and it is the most common cause of dementia in older adults.
  • Early-Onset Alzheimer’s Disease (EOAD): In some cases, Alzheimer’s disease may manifest before the age of 65, referred to as early-onset Alzheimer’s.

Associated Comorbidities:

  • Cardiovascular Conditions: Conditions such as hypertension, diabetes, and high cholesterol have an increased risk of Alzheimer’s disease.
  • Genetic Factors: In some cases, a family history of Alzheimer’s or specific genetic mutations may contribute to the development of the disease.
  • Down Syndrome: Individuals with Down syndrome may have an increased risk of developing Alzheimer’s disease at an earlier age.

Acuity of Presentation:

  • Insidious Onset: Alzheimer’s disease typically has an insidious onset, with symptoms gradually progressing over time. Early signs may include subtle memory lapses and difficulty recalling recent events.
  • Memory Impairment: Progressive memory loss is a hallmark feature, initially involving recent memories and later impacting more distant memories.
  • Cognitive Decline: Individuals may experience a decline in cognitive functions such as problem-solving, language skills, and spatial awareness.
  • Behavioral Changes: Changes in mood and behavior, including increased apathy, irritability, and social withdrawal, may be observed.
  • Functional Impairment: As the disease advances, individuals may struggle with daily activities and tasks, eventually requiring assistance with self-care.

The objective of the physical examination is to evaluate different aspects of an individual’s health and neurological condition. Below are key elements of the physical examination for Alzheimer’s disease:

Neurological Examination:

  • Assessment of Mental Status: Evaluate cognitive functions, including memory, attention, language, and executive function.
  • Cranial Nerve Examination: Evaluate the function of each cranial nerve, providing insights into brain function.
  • Motor Function: Assess muscle strength, tone, coordination, and reflexes.

Vital Signs:

  • Measurement of blood pressure, heart rate, respiratory rate, and body temperature. Deviations from normal vital signs may suggest other health issues or contribute to cognitive impairment.

General Physical Examination:

  • Evaluation of overall health and well-being.
  • Examination of the cardiovascular system, respiratory system, gastrointestinal system, and other organ systems to identify potential contributing factors or coexisting conditions.

Gait and Mobility Assessment:

  • Observation of the patient’s gait, balance, and overall mobility. Changes in these areas may indicate neurological dysfunction.

Sensory Examination:

  • Assessment of sensory perception, including vision, hearing, and tactile sensation. Sensory deficits can impact the ability to interact with the environment and contribute to cognitive decline.

Functional Assessment:

  • Evaluation of the patient’s ability to perform activities of daily living (ADLs), such as dressing, grooming, and feeding. Impairments in these areas may indicate the severity of cognitive decline.

Psychiatric Assessment:

  • Examination of mood, behavior, and psychiatric symptoms. Depression and anxiety are common in individuals with Alzheimer’s disease and can significantly impact overall functioning.

Laboratory and Ancillary Tests:

  • While not part of the physical examination per se, various laboratory tests (e.g., blood tests, cerebrospinal fluid analysis) and imaging studies (e.g., MRI, CT scans) are often utilized to rule out other potential causes of cognitive impairment.

Various conditions that may be considered in the differential diagnosis of Alzheimer’s disease include:

Vascular Dementia (VaD):

Vascular dementia results from compromised blood flow to the brain, often due to strokes or other vascular issues. Symptoms can overlap with those of Alzheimer’s disease.

Lewy Body Dementia (LBD):

LBD is characterized by the presence of Lewy bodies in the brain, leading to cognitive and motor symptoms. It shares certain features with both Alzheimer’s disease and Parkinson’s disease.

Frontotemporal Dementia (FTD):

FTD encompasses a group of disorders that predominantly affect the frontal and temporal lobes of the brain, causing changes in personality, behavior, and language. Memory loss may not be as apparent in the early stages.

Parkinson’s Disease Dementia (PDD):

Individuals with Parkinson’s disease may develop dementia as the condition progresses. Cognitive impairment may manifest as memory loss and executive dysfunction.

Normal Pressure Hydrocephalus (NPH):

NPH is characterized by an abnormal accumulation of cerebrospinal fluid in the brain, leading to gait disturbances, urinary incontinence, and cognitive decline.

Huntington’s Disease:

Huntington’s disease is a genetic disorder resulting in progressive degeneration of nerve cells in the brain, causing both motor and cognitive symptoms.

Chronic Traumatic Encephalopathy (CTE):

CTE is associated with repeated head injuries, as observed in athletes participating in contact sports, and can result in cognitive and behavioral changes.

Metabolic and Endocrine Disorders:

Conditions such as hypothyroidism, vitamin B12 deficiency, and metabolic disorders can induce cognitive impairment and should be ruled out.

Infections:

Chronic infections, such as neurosyphilis or HIV-related dementia, can induce cognitive decline.

Depression and Anxiety:

Mood disorders, especially in older adults, may occasionally present with cognitive symptoms that could be confused with dementia.

Medication Side Effects:

Some medications, particularly those with anticholinergic effects, may contribute to cognitive impairment.

Medication Management:

  • Cholinesterase Inhibitors (e.g., Donepezil, Rivastigmine, Galantamine): These drugs enhance acetylcholine levels in the brain, temporarily improving cognitive symptoms and functional abilities.
  • NMDA Receptor Antagonist (Memantine): Memantine regulates glutamate activity, providing symptomatic relief and slowing cognitive decline.

Non-Pharmacological Approaches:

  • Cognitive Stimulation Therapy: Activities and exercises to engage and stimulate cognitive functions.
  • Occupational Therapy: Helps individuals maintain independence in daily activities.
  • Physical Exercise: Regular physical activity may support overall health and potentially slow cognitive decline.

Supportive Care and Education:

  • Caregiver Education: Providing information and resources to caregivers on managing symptoms, coping strategies, and support services.
  • Support Groups: Connecting individuals with AD and their caregivers to share experiences and advice.

Healthy Lifestyle Practices:

  • Nutritious Diet: Emphasizing a well-balanced, heart-healthy diet.
  • Physical Activity: Encouraging regular exercise for overall health benefits.
  • Cognitive Engagement: Engaging in mentally stimulating activities.

Lifestyle modifications:

  • Healthy Diet: Emphasize a balanced, nutrient-rich diet with a variety of fruits, whole grains, vegetables, lean proteins, and healthy fats. Consider the Mediterranean or DASH diet, associated with cognitive benefits.
  • Regular Physical Exercise: Engage in regular physical activity, such as walking, swimming, or gentle exercises. Exercise improves the cognitive function and overall well-being.
  • Cognitive Stimulation: Engage in mentally stimulating activities, such as puzzles, games, and reading. Stimulating the brain may help maintain cognitive function.
  • Social Engagement: Maintain social connections through interactions with family, friends, and community. Social engagement contributes to emotional well-being.
  • Stress Management: Practice stress-reducing techniques like deep breathing, meditation, or yoga. Stress management contributes to overall well-being.
  • Routine and Structure: Establish and maintain a daily routine to provide structure and reduce confusion. Consistency in daily activities can be beneficial.
  • Memory Aids: Use memory aids like calendars, reminders, and labelled objects to enhance daily functioning. Memory aids can compensate for cognitive challenges.
  • Safety Measures: Implement safety measures at home, such as removing tripping hazards and ensuring a secure environment. Safety measures reduce the risk of accidents.
  • Limiting Alcohol and Tobacco: Limit alcohol intake, as excessive alcohol can adversely affect cognitive function. Quit smoking, as smoking is associated with an increased risk of cognitive decline.
  • Hydration: Ensure adequate hydration by drinking an appropriate amount of water. Dehydration can negatively impact cognitive and physical function.
  • Regular Medical Check-ups: Attend routine medical check-ups to monitor overall health and address any emerging health concerns. Regular check-ups support proactive health management.
  • Caregiver Support: Caregivers should seek support from community resources and support groups. Caregiver well-being is crucial for effective care provision.

Cholinesterase inhibitors are a class of medications commonly used in the treatment of Alzheimer’s disease. They increase the levels of acetylcholine, a neurotransmitter involved in memory and cognitive function.

Donepezil (Aricept, Aricept ODT):

  • Donepezil inhibits acetylcholinesterase, an enzyme that breaks down acetylcholine, thereby increasing acetylcholine levels in the brain. It is typically taken orally as a tablet or orally disintegrating tablet (ODT). Initial low doses are often recommended, with gradual titration to higher doses as tolerated. It has been shown to modestly improve cognitive function, activities of daily living, and global function in some individuals with mild to moderate Alzheimer’s disease.

Rivastigmine (Exelon, Exelon Patch):

  • Rivastigmine inhibits both acetylcholinesterase and butyrylcholinesterase, leading to increased acetylcholine levels. It is available in oral form (capsules or liquid) and as a transdermal patch for continuous delivery. Based on the formulation, it may be administered once or twice daily for oral forms, and the patch is typically applied once daily. Similar to donepezil, rivastigmine may improve cognitive and functional outcomes in individuals with mild to moderate Alzheimer’s disease.

Galantamine (Razadyne, Razadyne ER):

  • Galantamine is a reversible acetylcholinesterase inhibitor and an allosteric modulator of nicotinic It is available in immediate-release and extended-release formulations. It is usually administered twice daily (immediate-release) or once daily (extended-release). Like other cholinesterase inhibitors, galantamine may provide modest cognitive and functional benefits in individuals with mild to moderate Alzheimer’s disease.

Donepezil transdermal (Adlarity):

  • Similar to oral donepezil, the transdermal patch inhibits acetylcholinesterase, leading to increased acetylcholine levels. It is administered through a once-daily transdermal patch. The patch is designed for continuous 24-hour drug delivery. Studies suggest that transdermal formulation may offer a convenient alternative to oral administration, with similar efficacy in improving cognitive function.

Anti-amyloid beta monoclonal antibodies represent a newer class of medications designed to target and remove beta-amyloid plaques, which are characteristic pathological features of Alzheimer’s disease (AD).

Aducanumab (Aduhelm):

  • Aducanumab is the monoclonal antibody that targets beta-amyloid plaques in the brain. It aims to reduce the accumulation of beta-amyloid, which is believed to contribute to the progression of Alzheimer’s disease. It is administered through intravenous (IV) infusion. It is typically given monthly under the supervision of healthcare professionals.

Lecanemab (Leqembi):

  • Lecanemab is another anti-amyloid beta monoclonal antibody targeting beta-amyloid plaques. Like Aducanumab, it aims to clear beta-amyloid from the brain. It is administered through subcutaneous injection typically given monthly.

Memantine (Namenda, Namenda XR):

  • Mechanism of Action: Memantine modulates the activity of glutamate, an excitatory neurotransmitter in the brain, by blocking NMDA receptors. It helps regulate excessive glutamate activity, which is implicated in the neurodegenerative processes seen in Alzheimer’s disease.
  • Indication: Memantine is primarily indicated for the treatment of moderate to severe Alzheimer’s disease. It is used in combination with cholinesterase inhibitors, such as donepezil, for a more comprehensive approach to symptom management.
  • Administration: Available in immediate-release (Namenda) and extended-release (Namenda XR) formulations. The immediate-release form is typically administered twice daily, while the extended-release form is taken once daily.
  • Efficacy: Memantine has been shown to provide modest benefits in the cognitive function, activities of daily living, and global functioning in individuals with moderate to severe Alzheimer’s disease. It is considered particularly beneficial for individuals who may not tolerate or adequately respond to cholinesterase inhibitors alone.
  • Adverse Effects: The side effects include dizziness, headache, constipation, and confusion. Adverse effects are mild, but individuals may react differently, and close monitoring is recommended.

Combination drugs, such as Memantine/Donepezil (brand name: Namzaric), are formulations that combine multiple medications to treat Alzheimer’s disease. Namzaric specifically combines two active ingredients: memantine, an NMDA receptor antagonist, and donepezil, a cholinesterase inhibitor.

Memantine/Donepezil (Namzaric):

  • Dual Mechanism of Action: Memantine is an NMDA Receptor Antagonist that modulates glutamate activity by blocking NMDA receptors. Donepezil is a Cholinesterase Inhibitor that increases acetylcholine levels in brain by inhibiting its breakdown.
  • Indication: Namzaric is used for the treatment of moderate to severe Alzheimer’s disease. The combination addresses different aspects of neurotransmitter regulation to enhance overall efficacy.
  • Simplified Administration: Combining memantine and donepezil into a single medication simplifies the treatment regimen for patients, as they do not need to manage two separate medications.
  • Dosage and Administration: Available in different strengths, allowing for dose adjustment based on individual patient needs. Typically administered once daily.
  • Efficacy: Studies have shown that the combination of memantine and donepezil may provide additional benefits compared to either medication alone.
  • Adverse Effects: Adverse effects are consistent with the individual components (memantine and donepezil) and may include dizziness, headache, and gastrointestinal symptoms. Side effects should be monitored, and healthcare professionals may adjust the dosage as needed.

 

Axona, also known for its active ingredient Caprylidene, is a nutritional supplement that has been explored in the context of Alzheimer’s disease management. It is a medical food designed to provide an alternative energy source for the brain.

Caprylidene (Axona):

  • Active Ingredient: The active ingredient in Axona is caprylic triglyceride, a medium-chain triglyceride (MCT) derived from coconut oil.
  • Mechanism of Action: Caprylidene is metabolized into ketones, an alternative energy source for the brain. The idea is to provide the brain with ketones as fuel, especially in individuals with Alzheimer’s disease who may have impaired glucose metabolism.
  • Indication: Axona is classified as a medical food and is intended for the dietary management of individuals with mild to moderate Alzheimer’s disease.
  • Administration: Typically administered as a liquid supplement. The recommended dose is usually taken once daily.
  • Efficacy: Studies have explored the cognitive benefits of Caprylidene in Alzheimer’s disease. While some studies suggested potential cognitive improvements, results have been mixed, and further research is needed to establish its effectiveness.

Diagnostic imaging agents are not used in treating Alzheimer’s disease; instead, they are used in diagnosing and evaluating the disease. These agents are radiopharmaceuticals designed for positron emission tomography (PET) imaging to visualize and detect the beta-amyloid plaques in brain, a hallmark of Alzheimer’s disease.

  • Florbetapir F 18 (AMYViD): Florbetapir F 18 is used for PET imaging to estimate the beta-amyloid neuritic plaque density in the brain. It is administered intravenously, and PET imaging is performed shortly afterward. It helps clinicians assess the extent of beta-amyloid deposition in the brain, aiding in the diagnosis of Alzheimer’s disease.
  • Flutemetamol F 18 (Vizamyl): Flutemetamol F 18 is another PET imaging agent used to visualize beta-amyloid plaques in the brain. It is administered intravenously, and PET imaging is conducted afterward. It assists in the evaluation of beta-amyloid plaque density and can contribute to the diagnosis of Alzheimer’s disease.
  • Florbetaben F 18 (Neuraceq): Florbetaben F 18 is used for PET imaging to detect the beta-amyloid plaques in the brain. It is administered intravenously before PET imaging. It aids in the assessment of beta-amyloid neuritic plaque density, supporting the diagnostic process for Alzheimer’s disease.

Deep brain stimulation (DBS) is not widely established as a standard treatment for Alzheimer’s disease. Deep brain stimulation involves implanting electrodes into the specific areas of the brain and connecting them to a pulse generator placed under the skin. The electrodes deliver electrical impulses to modulate abnormal brain activity. The use of deep brain stimulation in Alzheimer’s disease has been explored in research and clinical trials, but the results have been mixed, and the procedure is not yet considered a routine or proven treatment. Alzheimer’s disease is a neurodegenerative disorder, and its underlying mechanisms involve widespread changes and damage in the brain. While DBS has shown promise in addressing certain symptoms in other neurological conditions, its application to Alzheimer’s disease is still under investigation. The clinical trials have explored the potential benefits of deep brain stimulation in Alzheimer’s disease. These studies often focus on targeting specific brain regions involved in memory and cognition. The results of studies have been variable, with some showing potential cognitive improvements and others showing limited or no benefits. The variability in outcomes may be influenced by factors such as patient selection, stimulation parameters, and the stage of Alzheimer’s disease.

 

Acute Phase Management:

  • Diagnosis and Assessment: Prompt and accurate diagnosis is crucial. Comprehensive cognitive assessments, imaging studies (e.g., MRI or PET scans), and laboratory tests help confirm the diagnosis.
  • Medication Management: Cholinesterase Inhibitors (e.g., donepezil, rivastigmine, galantamine) and NMDA receptor antagonist (memantine) may be prescribed to manage cognitive symptoms. Medications are adjusted based on the individual’s response and tolerance.
  • Behavioral Interventions: Addressing acute behavioral symptoms such as agitation, aggression, or hallucinations with non-pharmacological approaches. Creating a calm environment, providing structured routines, and using behavioral strategies.
  • Support for Caregivers: Education and support for family members and caregivers. Guidance on coping with behavioral changes and accessing community resources.

Chronic Phase Management:

  • Continuation of Medications: Long-term use of cognitive-enhancing medications to help manage symptoms. Regular follow-ups with healthcare professionals to assess medication effectiveness and adjust dosages as needed.
  • Cognitive Stimulation: Engagement in cognitive activities and stimulation to support brain function. Participation in activities that promote memory recall and cognitive abilities.
  • Nutritional Support: Ensuring a balanced diet that supports overall health and cognitive function. Addressing nutritional concerns and adapting meal plans as needed.
  • Physical Exercise: Encouraging regular physical activity, which has shown benefits for both physical and cognitive health. Exercise may include activities suitable for the individual’s abilities, such as walking or gentle movements.
  • Regular Monitoring and Adjustments: Ongoing assessment of the individual’s cognitive and functional status. Regular communication with healthcare professionals to adapt the care plan as the disease progresses.
  • End-of-Life Care Planning: Discussion and planning for end-of-life care preferences. Support for family members in making decisions related to care and treatment options.

Acute Phase Management:

  • Diagnosis and Assessment: Prompt and accurate diagnosis is crucial. Comprehensive cognitive assessments, imaging studies (e.g., MRI or PET scans), and laboratory tests help confirm the diagnosis.
  • Medication Management: Cholinesterase Inhibitors (e.g., donepezil, rivastigmine, galantamine) and NMDA receptor antagonist (memantine) may be prescribed to manage cognitive symptoms. Medications are adjusted based on the individual’s response and tolerance.
  • Behavioral Interventions: Addressing acute behavioral symptoms such as agitation, aggression, or hallucinations with non-pharmacological approaches. Creating a calm environment, providing structured routines, and using behavioral strategies.
  • Support for Caregivers: Education and support for family members and caregivers. Guidance on coping with behavioral changes and accessing community resources.

Chronic Phase Management:

  • Continuation of Medications: Long-term use of cognitive-enhancing medications to help manage symptoms. Regular follow-ups with healthcare professionals to assess medication effectiveness and adjust dosages as needed.
  • Cognitive Stimulation: Engagement in cognitive activities and stimulation to support brain function. Participation in activities that promote memory recall and cognitive abilities.
  • Nutritional Support: Ensuring a balanced diet that supports overall health and cognitive function. Addressing nutritional concerns and adapting meal plans as needed.
  • Physical Exercise: Encouraging regular physical activity, which has shown benefits for both physical and cognitive health. Exercise may include activities suitable for the individual’s abilities, such as walking or gentle movements.
  • Regular Monitoring and Adjustments: Ongoing assessment of the individual’s cognitive and functional status. Regular communication with healthcare professionals to adapt the care plan as the disease progresses.
  • End-of-Life Care Planning: Discussion and planning for end-of-life care preferences. Support for family members in making decisions related to care and treatment options.

rivastigmine

Oral- mild-to-moderate Initial dose: 1.5 mg capsule orally every 12hr; increase it up to 1.5 mg/dose every 2 weeks Do not exceed the dose up to 6 mg orally every 12 hours Maintenance dose: 3-6 mg capsule orally every 12 hours Transdermal- mild, moderate, and severe Initial dose: Apply the patch 4.6 mg every 24 hours; increase it up to 9.5 mg every 24 hours minimum 4 weeks; further after additional 4 weeks increase dose up to 13.3 mg patch Mild-to-moderate: 9.5-13.3 mg every 24 hours Moderate-to-severe: 13.3 mg every 24 hours Replace with new patch every 24 hours



galantamine

Initial Conventional: 4 mg orally 2 times a day ER: 8 mg orally once a day Maintenance Conventional: Titrate to 8-12 mg orally two times and increase up to 4 mg every 12 hours for <4 weeks ER: 16-24 mg orally once a day and increase by 8 mg a day for <4 weeks



memantine donepezil

10 mg of memantine two times a day or 28 mg of memantine ER once a day; and donepezil 10 mg once a day: 28 mg Memantine ER and donepezil 10 mg orally once a day every evening



memantine

5 mg tablet orally may be increased up to 5 mg/day each week. Maintenance dose: 20 mg/day orally twice a day 7 mg PO Capsule-ER may be increased up to 7 mg/day each week Maintenance dose: 28 mg/day orally daily



donepezil transdermal

apply a 5 mg patch once in a week; and increase up to 10 mg patch once a week after 4-6 weeks



donepezil (Rx)

Mild/moderate: 5 mg orally daily, may increase up to10 mg after 4-6 weeks Moderate/severe: 5 mg/day orally, increase up to 10 mg/day after 4-6 weeks; and after 3 months increase up to 23 mg/day Administration Take at bedtime and dissolve the drug under the tongue and follow with water



Dose Adjustments

Dose Modification Renal Impairment: Not Available Hepatic Impairment: Not Available

nadh 

Take 10-15 mg of medication orally every other day to once a day



phosphatidylserine 


Indicated for Alzheimer's Disease
100 mg orally three times a day
Senile Dementia and Memory/Cognitive Impairment
100 mg orally three times a day



piracetam 

1.6 to 9.6 grams/day orally



huperzine A 

Administer orally twice daily at a dosage range of 50-200 mcg



aducanumab 


Indicated for Alzheimer Disease
Administered every four weeks as intravenously infused nearly 21 days apart
Dosing titration regimen:
1-2 Infusions: 1 mg/kg intravenously every 4 weeks
3-4 Infusions: 3 mg/kg intravenously every 4 weeks
5-6 Infusions: 6 mg/kg intravenously every 4 weeks
7 and beyond Infusions: 10 mg/kg intravenously every 4 weeks



caprylidene 

Initial dosing involves the administration of 10 grams one time a day over a period of two days
To gradually increase the dosage, it is recommended to administer the drug in 10 grams increments every 2 days until a total of 40 grams is reached, to be taken one time daily on seventh day
It is important to consider a slower titration rate if the patient encounters any adverse events
a maintenance dosage of 40 grams one time a day is recommended to sustain therapeutic efficacy



ipidacrine 

20 mg given 2 to 3 times daily



tacrine 

Take an initial dose of 10 mg orally four times daily if possible, in between food up to 6 weeks
The maintenance dose may raise up to 20 mg orally four t