Is dementia inherited? Types, causes, genes and prevention

Summary — 'Dementia' is not the name of one disease but a state in which cognitive function declines from various causes enough to interfere with daily life. The most common cause is Alzheimer's disease, followed by vascular dementia, dementia with Lewy bodies and frontotemporal dementia. The influence of genes differs by type, and most Alzheimer's disease results from many genes acting together with environment. Carrying APOE ε4, the main risk gene, does not mean dementia is certain, and international reports hold that prevention such as managing vascular health is worthwhile regardless of genetic risk.

Main types and causes of dementia

• Alzheimer's dementia — over half of dementia. It is marked by plaques of amyloid-beta protein and tangles of tau protein inside neurons, and damage often starts in the hippocampus, which supports memory.
• Vascular dementia — caused by stroke or damage to small brain vessels. It may worsen stepwise or begin with reduced attention and judgement. Managing blood pressure, diabetes and smoking is especially important for prevention.
• Dementia with Lewy bodies — dementia in which protein clumps called Lewy bodies form inside neurons, characterised by vivid visual hallucinations, large fluctuations in cognition and movement symptoms resembling Parkinson's disease. The concept is known to have been established through research by the Japanese psychiatrist Professor Kenji Kosaka in the 1970s and 1980s.
• Frontotemporal dementia — mainly affecting the front and side of the brain, often beginning with personality change, behavioural problems or language difficulty rather than memory loss, and sometimes starting at a relatively young age.

There are also treatable causes, such as hypothyroidism, vitamin deficiency and normal-pressure hydrocephalus, so an accurate investigation of the cause is important when cognitive decline is suspected.

Alzheimer's disease and genes: two situations

① Rare familial Alzheimer's disease — a variant in one of the APP, PSEN1 or PSEN2 genes, which are involved in amyloid production, usually causes onset before 60, sometimes in the 30s or 40s. If one parent carries the variant, each child has a 50% chance of inheriting it. Such familial disease accounts for only a very small share of Alzheimer's disease.

② Common late-onset Alzheimer's disease and APOE — most Alzheimer's disease begins after 65 and results from many genes, lifestyle and environment acting together. The single most influential gene is apolipoprotein E (APOE). In 1993 a Duke University team reported that the more copies of the APOE ε4 form a person carries, the higher the risk of Alzheimer's disease and the earlier the age of onset; two copies carry higher risk than one. But many ε4 carriers never develop dementia and many without ε4 do, so the gene is understood as a risk factor, not destiny.

Should I have a genetic test?

Because APOE testing cannot predict whether an individual will develop the disease, several professional societies do not recommend it as routine screening for people without symptoms. Recently, however, testing is sometimes done when antibody drugs that remove amyloid are being considered, because people with two copies of ε4 face a higher risk of side effects such as brain swelling and microbleeds. If a family history suggests familial Alzheimer's disease, genetic counselling to understand the meaning and implications of testing before deciding is important.

Prevention that matters even with genetic risk

The 2024 report of the Lancet Commission on dementia set out 14 modifiable risk factors, including hearing loss, hypertension, diabetes, high LDL cholesterol, smoking, physical inactivity and social isolation. Several studies have reported that managing such lifestyle factors is worthwhile even for people at high genetic risk. WHO guidelines also recommend physical activity, stopping smoking, a balanced diet and management of vascular risk factors.

Relation to stem cell research

iPS cells made from skin or blood cells of patients with genetic causes are widely used to reproduce in the laboratory how Alzheimer's disease develops and to search for new drugs. In Japan, Kyoto University's Center for iPS Cell Research and Application and others have carried out such disease-modelling research. This is a use of stem cells as a research tool, different from treatments that put cells into the body.

Frequently asked questions

Q. If a parent had dementia, is my risk higher?
Risk is known to be somewhat higher when a parent or sibling has Alzheimer's disease, but most cases involve many genes and lifestyle factors acting together, so it is not certain. If several family members developed it before 60, it is worth consulting a specialist about possible familial Alzheimer's disease.

Q. What does carrying two copies of APOE ε4 mean?
Risk is higher and onset tends to be earlier, but it is not certain. It is relevant to assessing side-effect risk when antibody treatment is considered.

Q. When should prevention start?
International reports describe managing blood pressure, hearing and cholesterol, exercise and not smoking in midlife as especially important, and see social activity and vision care as meaningful in later life too. The shared message is that it is never too late to start.

How to look up clinical trial information

Ongoing and completed clinical trials can be checked on public registries. ClinicalTrials.gov, run by the U.S. National Library of Medicine, and jRCT, run by Japan's Ministry of Health, Labour and Welfare, publish each study's purpose, eligibility criteria, intervention, outcomes, institutions and status. Results are later published as journal papers, and the reference links below this article lead to the original information. It is also worth knowing that interventions not publicly registered are difficult to verify from outside, in both design and results.

The above summarises published papers and public-agency materials. University and institute names are given to identify research sources, not to introduce or recommend any medical institution. Please discuss genetic testing and diagnosis with your medical team and a genetic counsellor.

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