Alzheimer’s disease

What it is

Dementia is the general term for a decline in memory, thinking and daily functioning, and Alzheimer’s disease is its most common cause¹. In most people, the symptoms of Alzheimer’s disease first appear later in life and eventually affect even the simplest tasks³.

In 2021, 57 million people were living with dementia worldwide, with nearly 10 million new cases each year, and dementia is currently the seventh leading cause of death¹. The risk rises steeply with age, and around 1 in 20 people with Alzheimer’s disease are under 65, known as young-onset Alzheimer’s disease⁵.

Brain changes begin many years, often a decade or more, before symptoms appear^3,5. For this reason, experts increasingly describe Alzheimer’s disease as a biological process that starts while people are still well and progresses through clinical stages⁸.

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Stages I–IIStages III–IVStages V–VI

Tau tangles first appear in the transentorhinal and entorhinal cortex on the inner surface of the temporal lobe¹⁹.

They then extend into limbic areas of the medial and inferior temporal lobe, including the hippocampus, and to the posterior cingulate cortex^19,20. Damage here affects the forming of new memories³.

In the late stages almost all association areas of the cortex are affected¹⁹. Primary areas for movement, touch, hearing and vision are usually reached last²⁰.

Signs and symptoms

Symptoms develop slowly over several years, and the pace differs between individuals⁴. Some people first have mild cognitive impairment, in which memory problems are greater than expected for age but do not disrupt everyday life; not everyone with mild cognitive impairment goes on to develop dementia³.

• Early stage: forgetting recent conversations or events, misplacing items, word-finding difficulty, repeating questions and poorer judgement⁴.
• In less common forms, the first problems may be with vision or language rather than memory⁵.
• Middle stage: increasing confusion and disorientation, difficulty recognising people, problems with speech and language, disturbed sleep and mood changes⁴.
• Delusions, hallucinations, agitation or aggression can occur, especially in later stages⁴.
• Later stage: difficulty eating and swallowing, moving, and controlling bladder and bowel, with a need for full-time care⁴.

Causes and risk factors

The exact trigger of Alzheimer’s disease is unknown. It is thought to result from a combination of age-related brain changes with genetic, environmental and lifestyle factors³. A 2024 Lancet Commission estimated that about 45% of dementia cases worldwide, of all types, are associated with 14 potentially modifiable risk factors, although this assumes the factors are causal⁹.

• Age, the single most important risk factor; risk roughly doubles every five years after 65⁵.
• Family history and specific genes⁵.
• Down’s syndrome, because the extra copy of chromosome 21 carries the APP gene, leading to amyloid build-up^3,5.
• Cardiovascular risk factors such as high blood pressure, diabetes, obesity, smoking and high cholesterol^1,5.
• Hearing loss, untreated depression, social isolation, physical inactivity, low educational attainment, harmful alcohol use and air pollution^1,5.
• Severe head injury may increase risk, although more research is needed⁵.

Genetics

Heritable factors are estimated to account for 60-80% of the risk of Alzheimer’s disease². In most cases there is no single genetic cause; instead, many gene variants combine with other factors³. A large genome-wide association study of more than 111,000 cases found 75 risk regions, confirming the involvement of amyloid and tau pathways and highlighting microglia, the brain’s immune cells¹⁰.

The strongest common genetic influence is the APOE gene: the APOE e4 form increases risk, whereas the e2 form may be protective³. Carrying APOE e4 does not mean a person will develop the disease, and in the United Kingdom NICE advises against using APOE testing to diagnose it⁷.

Rarely, an altered copy of one of three genes, APP, PSEN1 or PSEN2, causes the disease directly, usually with onset before 65³. Families with several affected relatives, particularly at young ages, may be offered genetic counselling⁵.

What happens in the brain

The two defining features are amyloid plaques, clumps of a protein fragment called amyloid beta that collect between nerve cells, and neurofibrillary tangles, twisted fibres of a protein called tau inside nerve cells³. The current view is that accumulating amyloid beta drives the spread of tau pathology².

As the disease progresses, nerve cells stop working, lose their connections (synapses) with each other and die. Damage usually starts in the hippocampus and entorhinal cortex, regions essential for forming memories, and later spreads across the brain, which shrinks markedly³.

Levels of acetylcholine, a chemical messenger important for memory, fall⁵. Inflammation involving microglia, blood vessel damage and other age-related changes are also thought to contribute^3,10.

How it is diagnosed

There is no single simple test. Diagnosis usually begins with a family doctor, who asks about symptoms, checks other aspects of health and the medicines being taken to rule out other causes, and may refer to a memory clinic for specialist assessment⁶.

• Memory and thinking tests, together with what the person and their family have noticed⁶.
• Blood tests to rule out other causes of symptoms⁶.
• Structural brain imaging (CT or MRI) to exclude other causes and help identify the type of dementia⁷.
• If the diagnosis remains uncertain, FDG-PET (a scan that shows how the brain uses glucose) or analysis of cerebrospinal fluid, the fluid around the brain and spinal cord, for amyloid and tau⁷.
• Amyloid PET scans and, increasingly, blood tests for phosphorylated tau (especially p-tau217) can detect Alzheimer’s disease brain changes⁸.

How scientists study it

Current treatments

Research frontiers

Living with the condition and seeking help

Anyone worried about their memory, or about someone else’s, should see a doctor; memory problems have many causes, including depression, stress and medicines, and some are treatable⁴. An early diagnosis allows time to plan, to access support and treatment, and to consider joining research studies^3,4.

If symptoms get worse suddenly, a doctor should be seen promptly, because infections, delirium or stroke may be responsible and can be treated⁴. In India, the national emergency number is 112 and the ambulance number is 108^17,18. Charities, memory services and carer support groups offer information and help, and carers should look after their own health as well.