Inheritance of Dementia: Genetic Perspective
Dementia, a condition that affects a person's memory, thinking, and communication, is a concern that affects millions worldwide. One of the most common causes of dementia is Alzheimer's disease.
Alzheimer's is the most prevalent form of dementia, and some genes can increase a person's risk of developing it. The APOE gene, particularly the APOE4 allele, is a significant genetic risk factor for sporadic Alzheimer's disease. Carrying one copy of APOE4 increases the risk 2 to 4 times, while two copies raise the risk more than 10 times compared to the common APOE3 variant.
For early-onset familial Alzheimer's disease, which typically occurs before age 65, rare but highly penetrant mutations in the APP (amyloid precursor protein), PSEN1 (presenilin 1), and PSEN2 (presenilin 2) genes are causative.
Genetic links are not limited to Alzheimer's. Mutations in the GRN (progranulin) gene, specifically the p.R493X variant, have been linked to several types of dementia, including frontotemporal dementia (FTD), frontotemporal lobar degeneration (FTLD), Alzheimer's disease, dementia with Lewy bodies (DLB), and corticobasal degeneration.
In summary, key genes associated with an increased risk of Alzheimer's and related dementias include APOE4, APP, PSEN1, PSEN2, and GRN. Environmental and lifestyle factors also play a role in whether these genetic risks manifest as disease.
It's essential to note that while genetic testing can identify these variants, it does not guarantee disease outcome given the complexity of genetic risks across dementia types.
People can have combinations of two or more types of dementia conditions, which doctors call mixed dementia. Frontotemporal dementia is another uncommon but genetically linked type of dementia.
While there is no way to avoid dementia completely, avoiding triggers and following certain lifestyle habits can help reduce a family's dementia risk. Lifestyle changes that may help include controlling high blood pressure, keeping blood sugar within certain levels, eating a nutritious diet, staying physically and mentally active, preventing social isolation and loneliness, treating hearing problems and hearing loss, preventing or avoiding head injuries, drinking less or no alcohol, quitting or avoiding smoking, and managing depression.
References:
- Alzheimer's Research UK
- Alzheimer's Association
- Mayo Clinic
- National Institute on Aging
- Genetics Home Reference
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