Alzheimer's Disease Overview and Epidemiology

Alzheimer's Disease Overview

• Alzheimer's Disease (AD) was first recognized in 1906 by Dr. Alois Alzheimer.
• It is an irreversible progressive neurodegenerative disease.
• Characterized by memory impairment and other cognitive disturbances.
• Symptoms gradually decline in three key areas: activities of daily living, behavior, and personality, and cognition.
• Most common cause of dementia in people aged 65 and older.

Epidemiology of AD

• AD affects an estimated 1 in 14 people aged over 65 and 1 in 6 people aged over 80.
• Globally, AD is estimated to affect at least 50 million people.
• By 2050, the prevalence of AD is expected to reach nearly 100 million globally.
• The prevalence of AD doubles every five years beyond the age of 65.
• The fifth-leading cause of death among those aged 65 and older and a leading cause of disability and poor health.
• Typical life expectancy after an AD diagnosis is four to eight years.

Pathophysiology of AD

• Hallmarks: amyloid plaques, neurofibrillary tangles (NFTs), and synaptic and neuronal cell death.
• Brain atrophy: Shrinking of the brain tissue.
• Inflammation: The brain's response to damage and injury.
• Initial sites: The hippocampus and medial temporal lobe are the initial sites affected.

Amyloid Precursor Protein (APP)

• APP is the precursor to amyloid plaques.
• APP sticks through the neuron membrane.
• Enzymes cut the APP into fragments of protein, including beta-amyloid.
• Beta-amyloid fragments clump together to form plaques.

AD Neuropathology

• Multifactorial (difficult treatment).
• Accumulation of Aß is the initial insult, leading to abnormal tau phosphorylation and formation of NFTs.
• Defect in microglial activation, leading to inefficient clearing of Aß.
• Acetylcholinesterase may promote Aß assembly.
• Hyperphosphorylated tau damages the cytoskeleton and signal transduction in neurons.
• This contributes to memory decline and neuroinflammation (neuronal damage and death).

Pathologies Associated With AD

• Amyloid deposition (plaques) increases with age.
• Microglial activation/inflammation increases with age.
• Neurofibrillary tangles (NFTs) increase with age.
• Neuronal loss/atrophy increases with age.
• Symptoms emerge with age.

Progression of AD

• The disease progresses through different stages: preclinical AD, mild cognitive impairment due to AD, mild AD, moderate AD, and severe AD.
• Each stage is characterized by increasing cognitive impairment and affecting different brain regions.

Characteristics of Alzheimer Dementia

• Cognitive symptoms, including acalculia, aphasia, apraxia, amnesia, and agnosia.
• Behavioral symptoms, including depression, apathy, anxiety, delusions, hallucinations, and psychosis.
• Extrapyramidal symptoms may present, such as gait disturbance, myoclonus, tremor, and urinary incontinence.

Types of AD

• Familial AD (Early-onset): Very rare, typically occurs before age 60, and involves gene mutations.
• Sporadic AD (Late-onset): The most common type, typically occurs after age 60, and is linked to the apo E4 gene.

Diagnosis of AD

• Thorough medical history review, physical examinations, and laboratory tests.
• Brain imaging techniques (MRI or CT scans) help detect structural changes.
• PET scans can identify abnormal protein accumulation.
• CSF analysis or genetic testing may be considered for a more accurate diagnosis.

Risk Factors of AD

• Modifiable: sedentary lifestyle, poor nutrition, depression, lack of social engagement, low education level, head injury, poor sleep, stress management, hearing loss, smoking, excessive alcohol consumption, hypertension, high cholesterol, and obesity.
• Unmodifiable: age, female sex, Black, Hispanic, or Native American race, family history of AD, and APOE ε4 carrier status.

Identifying Warning Signs of AD

• Memory loss occurs more frequently in individuals with AD and may interfere in everyday activities.
• Executive function and completing familiar tasks may be difficult.
• Confusion with time or place occurs more frequently in individuals with AD than in normal aging.
• Trouble with visual images and spatial relationships happens more frequently in individuals with AD than in normal aging.
• Difficulty with speaking or writing, and misplacing items.
• Decreased or poor judgment is more common in individuals with AD.
• Withdrawal from work or social activities and changes in mood.

Mental Status Assessment

• Folstein MMSE: A 30-point scale assessing cognitive function, heavily relying on verbal skills. Higher score indicates better function.
• St. Louis University Mental Status Examination (SLUMS): A 30-point scale assessing cognitive function, with adjustment for poor education.
• Montreal Cognitive Assessment (MOCA): A 30-point scale with multiple cognitive domains.
• Mini-Cog: A quick (2-3 minute) assessment that includes verbal recall and clock drawing; a score of < 3 or < 4 may suggest a need for further evaluation.

Treatment Goals

• Maintaining quality of life (QoL).
• Maximizing function and activities of daily living (ADLs).
• Stabilizing cognition.
• Managing behavioral problems.
• Reducing caregiver distress and burden.

Drugs to Improve AD Symptoms

• Donepezil, Rivastigmine, Galantamine, and Memantine are FDA-approved drugs used to treat AD symptoms. 
• These drugs work by various mechanisms to improve cognitive function, particularly in the earlier stages of the disease.

FDA-Approved Disease Modifiers

• Aducanumab (Aduhelm)
• Lecanemab
• Donanemab-azbt (Kisunla) 
• These drugs are being used to target the amyloid plaques and/or other proteins implicated in AD development and progression.

Aducanumab Controversy

• FDA approval, even with controversy because of contradictory trial results.
• Subsequent discontinuation for lack of Medicare funding and health concerns.

Shared Decision Making

• Patients and caregivers working with physicians to set goals collaboratively throughout the diagnosis and management of AD.
• This aims for shared understanding and decision-making to best manage the disease and the associated healthcare challenges.

Pharmacist Roles for AD

• Counsel on risk and prevention by educating patients and informing them about conditions and related medications that may increase the risk of AD.
• Enhance medication compliance, especially as dysphagia may become a problem as the disease progresses. 
• Educate on available drugs and potential therapies, emphasizing realistic expectations and the limitations of current treatments.
• Eliminate dangerous drugs that can exacerbate dementia or AD-associated symptoms.
• Recommend resources, make referrals, and take note of changes in patients that may signal a concern to a physician.
• Become a dementia-friendly pharmacy to improve patients' quality of life during the progression of AD.