Alzheimer's Disease

What happens in the brain

Alzheimer's disease begins 15 to 20 years before symptoms appear. Two abnormal proteins build up:

• Amyloid plaques: clumps of beta-amyloid protein between nerve cells.
• Tau tangles: twisted fibers of tau protein inside nerve cells.

Together they disrupt communication between neurons, trigger inflammation and eventually kill brain cells. Damage usually starts in the hippocampus, the memory center, which is why recent memory fails first. It then spreads to areas controlling language, reasoning, orientation and behavior. The brain shrinks markedly as the disease advances.

Alzheimer's vs dementia

Dementia is an umbrella term for a decline in thinking skills severe enough to interfere with daily life. Alzheimer's disease is one cause, the most common. Others include vascular dementia, Lewy body dementia and frontotemporal dementia. Many older people have mixed causes, often Alzheimer's plus vascular changes.

Early signs of Alzheimer's

Normal aging vs Alzheimer's

Occasionally forgetting a name and remembering it later, or misplacing glasses, is normal. Forgetting recent events entirely, getting lost in familiar places, or being unable to retrace steps to find things is not. Mild cognitive impairment is an in-between stage: noticeable memory or thinking problems while daily activities remain largely independent. Some people with MCI go on to develop Alzheimer's.

Stages of Alzheimer's disease

Causes and risk factors

• Age: risk doubles about every 5 years after 65. About 1 in 3 people over 85 has Alzheimer's.
• Genetics: the APOE e4 gene variant increases risk; one copy raises it about 3-fold, two copies much more. It does not guarantee the disease. Rare inherited mutations (APP, PSEN1, PSEN2) cause early-onset familial Alzheimer's, often in the 30s to 50s.
• Down syndrome: an extra copy of chromosome 21, which carries the amyloid gene, leads to Alzheimer's changes by middle age.
• Heart and blood vessel risk factors: high blood pressure in midlife, diabetes, obesity, smoking and physical inactivity.
• Other modifiable factors: hearing loss, low education, depression, social isolation, head injury, excess alcohol and air pollution. International experts estimate a substantial share of dementia cases is linked to modifiable factors.
• Sex: women make up nearly two thirds of Americans with Alzheimer's, partly because they live longer.

Diagnosis

A primary care doctor, geriatrician or neurologist will:

1. Take a history from the person and someone who knows them well.
2. Do cognitive tests such as the MoCA or Mini-Cog.
3. Examine for neurological signs, depression and hearing or vision problems.
4. Order blood tests to rule out reversible causes: vitamin B12, thyroid function, blood count, kidney and liver function, calcium, blood sugar, and sometimes syphilis and HIV.
5. Arrange brain imaging: MRI or CT to look for strokes, tumors, normal pressure hydrocephalus and patterns of shrinkage.
6. Confirm Alzheimer's biology when it would affect treatment: amyloid PET scan, spinal fluid tests for amyloid and tau, or newer FDA-cleared blood tests for Alzheimer's proteins.

Neuropsychological testing gives a detailed profile of strengths and weaknesses. Depression, medicine side effects and sleep apnea can mimic dementia and are treatable.

Treatment

Medicines for symptoms

• Cholinesterase inhibitors (donepezil, rivastigmine, galantamine) for mild to severe disease. They boost a memory chemical and can modestly improve or stabilize memory and daily function for a time. Side effects include nausea, diarrhea, vivid dreams and a slow heart rate.
• Memantine for moderate to severe disease, alone or combined with donepezil.

Disease-modifying treatments

Anti-amyloid monoclonal antibodies, lecanemab and donanemab, remove amyloid from the brain and modestly slow decline in people with mild cognitive impairment or mild dementia due to Alzheimer's with confirmed amyloid. They are given by IV infusion and need regular MRI monitoring because of a risk of brain swelling or small bleeds (ARIA), which is higher in people with two copies of APOE e4. They are not suitable for everyone, and eligibility is assessed by specialists.

Managing behavior and mood

Agitation, aggression, sleep problems and hallucinations are first managed by looking for triggers: pain, infection, constipation, hunger, noise, unfamiliar surroundings or over-stimulation. Routine, calm communication, daytime activity and good lighting help. Medicines such as antidepressants or, sparingly, antipsychotics are used only when needed, because antipsychotics raise the risk of stroke and death in people with dementia.

Non-drug approaches

• cognitive stimulation therapy and meaningful activities
• regular physical exercise and social contact
• hearing aids and vision correction
• treating heart risk factors

Living with Alzheimer's

• Plan early: while the person can take part, make decisions about health care proxy, power of attorney, finances and wishes for future care.
• Safety: remove trip hazards, use stove shut-off devices, consider medical ID and GPS devices for wandering, and review driving regularly.
• Medicines: use pill organizers or blister packs and supervision.
• Caregiver support: caregivers have high rates of stress and depression. Respite care, support groups, adult day programs and education programs help. The Alzheimer's Association runs a 24/7 helpline.
• Late stage: focus on comfort, nutrition, preventing pressure sores and infections, and hospice care when appropriate.

Prevention

There is no guaranteed prevention, but these steps lower risk and are good for overall health:

• control blood pressure, diabetes and cholesterol
• exercise regularly: at least 150 minutes of moderate activity a week
• do not smoke, and limit alcohol
• treat hearing loss
• stay socially and mentally active
• protect your head from injury
• sleep well and treat sleep apnea

Frequently asked questions

What are the first signs of Alzheimer's disease?

The earliest sign is usually difficulty remembering recently learned information, such as conversations or appointments, and asking the same questions repeatedly. Trouble planning, word-finding problems, getting lost in familiar places and changes in mood or personality often follow.

What is the difference between Alzheimer's and dementia?

Dementia is a general term for a decline in memory and thinking that interferes with daily life. Alzheimer's disease is a specific brain disease and the most common cause of dementia. Other causes include vascular dementia, Lewy body dementia and frontotemporal dementia.

How long do people live with Alzheimer's?

On average, people live 4 to 8 years after diagnosis, but some live 20 years. Survival depends on age at diagnosis, other health conditions and the speed of progression. Pneumonia and complications of immobility are common causes of death in late stages.

Is Alzheimer's hereditary?

Most cases are not directly inherited, though having a parent or sibling with Alzheimer's raises your risk, and the APOE e4 gene increases risk. Rare inherited mutations cause early-onset familial Alzheimer's, typically before 65. Genetic testing is discussed with a genetic counselor.

Can Alzheimer's disease be cured?

No cure exists yet. Medicines can ease symptoms for a time, and anti-amyloid antibodies modestly slow decline in early-stage disease. Good care, treating other health problems and support for families make a large difference to quality of life.

Can you prevent Alzheimer's?

There is no certain way, but reducing risk factors helps: controlling blood pressure and diabetes, exercising, not smoking, limiting alcohol, treating hearing loss, staying socially and mentally active, and protecting against head injury.