From the Guidelines
Genetically inherited dementia can manifest in several forms, including familial Alzheimer's disease, Huntington's disease, frontotemporal dementia, CADASIL, and familial prion diseases, which are caused by specific gene mutations and can be passed down through families with a 50% chance of inheritance if one parent carries the mutation. These forms of dementia are typically characterized by distinct clinical features and ages of onset. For instance, familial Alzheimer's disease is often caused by mutations in genes like APP, PSEN1, and PSEN2, leading to early-onset symptoms before age 65 1. Huntington's disease, on the other hand, is caused by a specific mutation in the HTT gene and is characterized by movement disorders alongside cognitive decline. Frontotemporal dementia has genetic forms linked to mutations in genes such as MAPT, GRN, and C9ORF72, affecting personality, behavior, and language skills. CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy) is caused by NOTCH3 gene mutations, leading to stroke-like episodes and dementia. Familial prion diseases like Creutzfeldt-Jakob disease can be inherited through PRNP gene mutations. It's worth noting that while these genetic forms of dementia are significant, they represent a smaller proportion of all dementia cases, with the majority being attributed to other factors such as lifestyle behaviors, associated illnesses, and less education in early life, as highlighted in a recent overview of dementia types, risk factors, and prevalence 1. Given the complexity and variability of dementia, genetic testing and counseling are crucial for at-risk individuals to understand their risk and make informed decisions, although current management focuses on symptom control and supportive care due to the lack of specific treatments to prevent these conditions. Key points to consider include:
- The importance of genetic counseling for individuals with a family history of dementia
- The role of genetic testing in identifying specific mutations associated with inherited dementia
- The need for a comprehensive approach to dementia management, incorporating symptom control, supportive care, and lifestyle modifications
- The significance of recent research in understanding the epidemiology and risk factors of dementia, as discussed in a 2023 literature overview 1.
From the Research
Types of Genetically Inherited Dementia
- Alzheimer's disease (AD) is a type of dementia that can be caused by mutations in the APP, PSEN1, and PSEN2 genes 2, 3, 4, 5.
- Frontotemporal dementia (FTD) is another type of dementia that can be caused by mutations in the MAPT, GRN, C9ORF72, and other genes 2, 3, 4, 5.
- Early-onset Alzheimer's disease (EOAD) and frontotemporal lobar dementia (FTLD) account for the majority of early-onset dementia, and have a high frequency of genetic forms 3.
- Monogenic forms of EOAD are often caused by mutations in the PSEN1, APP, and PSEN2 genes, while monogenic forms of FTLD are often caused by mutations in the GRN, MAPT, and C9ORF72 genes 3.
- Other types of genetically inherited dementia include those caused by mutations in the APOE, TARDBP, CHMP2B, TREM2, VCP, and FUS genes 4, 5.
Genetic Testing and Counseling
- Genetic testing can be used to identify disease-causing mutations in patients with dementia, and can provide important information for clinical investigation and family counseling 2, 4, 5, 6.
- Genetic counseling is important for patients and asymptomatic at-risk family members, and can help navigate the complexities of genetic testing and results 2, 5, 6.
- Next-generation sequencing technologies have improved genetic diagnostics, but also require careful interpretation of results and consideration of the benefits and limitations of different genetic tests 6.