From the Guidelines
Hereditary causes account for approximately 5-10% of all dementia cases. Most cases of dementia are not directly inherited but result from a complex interaction between genetic and environmental factors. Among the hereditary forms, early-onset familial Alzheimer's disease is the most well-documented, typically caused by mutations in genes like APP, PSEN1, and PSEN2 1. Other inherited forms include certain types of frontotemporal dementia and Huntington's disease, which has a 50% inheritance risk for children of affected individuals. The APOE gene, particularly the e4 variant, increases risk but doesn't guarantee development of Alzheimer's disease 1.
Some key points to consider:
- The majority of dementia cases (90-95%) are sporadic, meaning they occur without a clear family pattern of inheritance 1.
- Family history can still be a risk factor through shared genetic susceptibility and environmental exposures.
- Genetic counseling and testing for Alzheimer's disease can be valuable and safe in certain contexts, such as in families with a history of early-onset autosomal dominant AD 1.
- The risk of inheriting a mutation from a parent affected with autosomal dominant AD is 50% 1.
In terms of morbidity, mortality, and quality of life, it is essential to consider the potential benefits and limitations of genetic testing and counseling for individuals with a family history of dementia. Genetic testing should be offered in situations where there is a strong family history of dementia or in cases of early-onset autosomal dominant AD 1. However, it is crucial to discuss the likelihood of identifying a mutation and the potential implications of test results with individuals and their families.
From the Research
Hereditary Cause of Dementia
- The exact percentage of hereditary cause of dementia is not explicitly stated in the provided studies, but it is estimated that 25% of all people aged 55 years and older have a family history of dementia 2.
- For most people with a family history of dementia, the risk is due to genetically complex disease, where many genetic variations of small effect interact to increase the risk of dementia, with a lifetime risk of about 20% compared to 10% in the general population 2.
- A small proportion of families have an autosomal dominant family history of early-onset dementia, which is often due to mendelian disease, caused by a mutation in one of the dementia genes, with a lifetime dementia risk of over 95% 2.
- Rare variants in APP, PSEN1, and PSEN2 genes increase the risk for late-onset Alzheimer's disease, with 13.7% of sequenced individuals carrying a novel or pathogenic mutation 3.
- Genetic factors are recognized to play an important role in most age-related dementias, with specific disease-causing genes and genetic factors contributing to the development of dementia 4.