Alzheimer’s Disease

Causes

• Brain Abnormalities: The hallmark of Alzheimer's disease is the presence of amyloid plaques (abnormal clumps of beta-amyloid protein) and neurofibrillary tangles (twisted strands of tau protein) in the brain. These abnormal proteins are believed to disrupt cell function and lead to widespread brain cell death.
• Genetics: Genetics play a role, particularly in early-onset Alzheimer's (which is rare). Specific genes (e.g., APOE-e4 allele) increase the risk of late-onset Alzheimer's, but inheriting them does not guarantee development of the disease.
• Age: Advancing age is the greatest known risk factor. Most people with Alzheimer's are 65 and older.
• Sex: Women appear to be more likely to develop Alzheimer's than men, possibly because they live longer on average.
• Down Syndrome: Many people with Down syndrome develop Alzheimer's due to having an extra copy of chromosome 21, which carries the gene for amyloid precursor protein.
• Head Trauma: A history of moderate or severe head injury increases the risk.
• Lifestyle and Heart Health: Factors linked to heart disease and stroke, such as high blood pressure, high cholesterol, diabetes, obesity, and smoking, also increase the risk of Alzheimer's.

Symptoms

• Memory Loss: Forgetting recently learned information, important dates or events, asking for the same information repeatedly, increasing reliance on memory aids or family members.
• Challenges in Planning or Solving Problems: Difficulty following a familiar recipe, managing finances, or concentrating.
• Difficulty Completing Familiar Tasks: Trouble driving to a familiar location, managing a budget, or remembering rules of a favorite game.
• Confusion with Time or Place: Losing track of dates, seasons, and the passage of time; difficulty understanding something if it's not happening immediately.
• Trouble Understanding Visual Images and Spatial Relationships: Difficulty reading, judging distance, or determining color or contrast (beyond age-related vision changes).
• New Problems with Words in Speaking or Writing: Difficulty following or joining a conversation, stopping in the middle of a conversation with no idea how to continue, repeating themselves, or struggling to find the right word.
• Misplacing Things and Losing the Ability to Retrace Steps: Putting things in unusual places; accusing others of stealing.
• Decreased or Poor Judgment: Making poor decisions with money or personal hygiene.
• Withdrawal from Work or Social Activities: Losing interest in hobbies, sports, or social engagements.
• Changes in Mood and Personality: Becoming confused, suspicious, depressed, fearful, or anxious, especially when out of their comfort zone.

Diagnosis

• Medical History and Physical Exam: The doctor will gather detailed information from the individual and family about cognitive changes, medical history, medications, and lifestyle. A physical and neurological exam is performed.
• Cognitive and Neuropsychological Tests:
  • Screening tests: Such as the Mini-Mental State Examination (MMSE) or Montreal Cognitive Assessment (MoCA), assess memory, thinking, and reasoning.
  • More extensive neuropsychological testing: Provides a detailed profile of cognitive strengths and weaknesses.
• Brain Imaging:
  • MRI (Magnetic Resonance Imaging) or CT scan: To rule out other causes of memory impairment (e.g., stroke, tumors, hydrocephalus, bleeding). They can show brain shrinkage (atrophy) but not definitively diagnose Alzheimer's.
  • PET (Positron Emission Tomography) scans: Can detect amyloid plaques (amyloid PET) or tau tangles (tau PET) in the brain, which are characteristic of Alzheimer's. Fludeoxyglucose (FDG-PET) can show patterns of reduced brain metabolism associated with Alzheimer's.
• Cerebrospinal Fluid (CSF) Analysis: Measuring levels of amyloid-beta and tau proteins in CSF obtained via a spinal tap can support an Alzheimer's diagnosis.
• Blood Tests: To rule out other reversible causes of memory loss (e.g., thyroid problems, vitamin B12 deficiency, infections). Newer blood tests for amyloid are emerging to aid diagnosis.

Treatment

• Medications:
  • Cholinesterase Inhibitors: (e.g., donepezil, rivastigmine, galantamine) increase levels of acetylcholine, a neurotransmitter important for memory. They can help with memory, thinking, and behavior for a limited time.
  • Memantine: (Namenda) Works differently to improve memory, reasoning, language, and the ability to perform daily activities. Often used in moderate to severe Alzheimer's, sometimes in combination with a cholinesterase inhibitor.
  • Lecanemab: (Leqembi) A newer monoclonal antibody approved for early Alzheimer's that targets amyloid plaques, aiming to slow cognitive decline. Requires careful patient selection and monitoring for side effects.
  • Medications for Associated Symptoms: Antidepressants for depression, anxiolytics for anxiety, or antipsychotics (used cautiously due to risks) for severe behavioral issues or psychosis.
• Non-Pharmacological Approaches:
  • Cognitive Stimulation Therapy (CST): Engaging in activities to stimulate thinking and memory.
  • Behavioral Interventions: Strategies to manage behavioral symptoms (e.g., agitation, wandering) by addressing triggers and creating a supportive environment.
  • Supportive Environment: Establishing consistent routines, simplifying tasks, ensuring safety, and providing appropriate supervision.
• Lifestyle Management:
  • Healthy Diet: A Mediterranean-style diet may support brain health.
  • Regular Physical Activity: Can help maintain cognitive function and overall health.
  • Cognitive Engagement: Keeping the brain active with puzzles, reading, and learning new skills.
  • Social Engagement: Maintaining social connections.
  • Sleep Hygiene: Addressing sleep disturbances.
• Caregiver Support: Education, resources, and support groups for family caregivers are vital, as Alzheimer's significantly impacts caregivers.

Living With Alzheimer's Disease

An Alzheimer's diagnosis starts a long stretch of decisions about medication, safety, and support that unfold over years.

What the medications do, and do not do

Donepezil modestly improves memory and daily function for many people and delays decline by months rather than years; nausea, vivid dreams, and a slowed pulse are the common reasons to adjust it, and it is taken in the morning if dreams are a problem. Memantine is added in the moderate stage. The anti-amyloid infusions lecanemab and donanemab are for the earliest stage only, require a confirmed amyloid scan or spinal fluid test and APOE gene testing, and carry a risk of brain swelling that needs repeated MRI monitoring, and are arranged through neurology. Treating hearing loss, depression, and sleep apnea often improves function more than any pill.

Agitation: the environment before the prescription

Pain, constipation, infection, hunger, noise, and unfamiliar surroundings drive most agitation, and fixing those comes first. When medication is still needed, brexpiprazole is the one antipsychotic approved for Alzheimer's agitation, used at low dose with the stroke and mortality warning that applies to the whole class. Benzodiazepines such as lorazepam and sleep aids such as zolpidem worsen confusion and falls, and bladder drugs such as oxybutynin and over-the-counter sleep aids containing diphenhydramine erode memory directly; our polypharmacy article covers the medication review.

A sudden change is not the disease

Alzheimer's worsens over months; a person who is markedly more confused over a day or two has delirium from a urinary infection, dehydration, a new medication, or pain until proven otherwise, and it is usually reversible. Florida heat causes a share of these episodes in people who no longer notice thirst; our heat safety guide applies.

Safety decisions that come earlier than expected

Driving is reassessed at diagnosis and revisited every six months; our driving safety for older adults guide covers Florida's process. Finances, scam calls, firearms, the stove, and wandering each need a plan. A health-care surrogate and durable power of attorney must be signed while the person can still understand them, which our advance directives article explains. Hurricane evacuation with a person who has dementia is planned in May, not in the storm.

The caregiver is the second patient

Caregivers of people with Alzheimer's have higher rates of depression, illness, and neglected medical care of their own, and respite is a medical necessity rather than a luxury; our caregiver stress article lists local supports. Our neurologic team coordinates care with neurology and memory clinics. The National Institute on Aging and the Alzheimer's Association publish guidance for patients and families.

If a family member's memory has changed, or you are caring for someone with Alzheimer's and have not had a visit of your own this year, schedule a visit.