Dementia and Hereditary Testing
Dementia is an illness that changes lives. This broad term encompasses a group of symptoms that are seen in disorders affecting the brain, including impairments to cognitive abilities, such as memory and language, which impact a person’s daily activities. Dementia rates are very low among those younger than 65 but increase dramatically with age. The prevalence of dementia more than doubles every 5 years among seniors (from less than 1% in those aged 65 to 69 to about 25% in those aged 85 and older)1. There are many causes of dementia, some of which are hereditary and can be tested for.
According to clinical and research criteria, there are four primary dementia subtypes2,3:
- Alzheimer’s disease (most common)
- Vascular dementias
- Frontotemporal dementias (FTD)
- Dementia with Lewy bodies
- Most cases present after age 65 and are more strongly associated to environmental factors as opposed to genetic abnormalities
- Up to 5% of patients have disease onset before age 60-65 and a positive family history, suggestive of Early Onset Familial Alzheimer’s Disease (EOFAD)
- A genetic mutation is identified in 40-80% of families with EOFAD and in a small number of patients with early-onset disease without a family history4
- Second most common cause of dementia in individuals under age 65
- Approximately 40% of affected individuals with FTD do have a family history that includes at least one other relative diagnosed with a neurodegenerative disease5
- Some genes and mutations may give insight to severity of disease, possibility of Parkinsonism and resting tremor, and responsiveness to certain drugs
Reasons for Genetic Testing
Confirmation of a clinical diagnosis through genetic testing may be helpful.
- A specific diagnosis may help patients and their families plan for the future before dementia becomes severe
- Knowing the specific diagnosis may help predict the progression and severity of disease
- Testing may facilitate access to medications that may help alleviate symptoms and improve quality of life
- Identification of at-risk family members provides information about potential age of onset, reproductive risks, preconception/prenatal options, and appropriate referral for patient support and resources
LifeLabs Genetics offers the following Next-Generation Sequencing panels (Sequencing and Copy Number Variant analyses)
- Dementia Panel: APOE, APP, C9orf72*, CHMP2B, CSF1R, FUS, GRN, MAPT, PRNP*, PSEN1, PSEN2, SORL1, TARDBP, TREM2, UBE3A, VCP
- Alzheimer’s Dementia Panel: APOE, APP, PRNP*, PSEN1, PSEN2, SORL1, TREM2
- Frontotemporal Dementia Panel: C9orf72*, CHCHD10, CHMP2B, CSF1R, DCTN1, FUS, GRN, ITM2B, MAPT, PRNP*, PSEN1, PSEN2, SIGMAR1, TARDBP, TREM2, TUBA4A, UBQLN2, VCP
- Broad Alzheimer and Dementia Panel: A2M, ABCD1, ACE, ACSF3, APOE, APP, APTX, ATP13A2, ATP7B, BIN1, C19orf12, CHCHD10, CHMP2B, CLN3, CLN6, CP, CSF1R, CST3, CTSF, DCAF17, DCTN1, DNAJC5, DNMT1, FTL, FUS, GBA, GBE1, GCDH, GIGYF2, GM2A, GRN, HEXA, HFE, HSD17B10, HTRA1, HTT, ITM2B, MAPT, MLYCD, MMACHC, NDP, NOS3, NOTCH3, NPC1, NPC2, PANK2, POLG, PPT1, PRKCG, PSEN1, PSEN2, PTEN, SERPINI1, SIGMAR1, SNCA, SNCB, SORL1, SPAST, SPG21, SPG7, SQSTM1, TARDBP, TBK1, TIMM8A, TREM2, TTR, TUBA4A, TYROBP, UBE3A, UBQLN2, UCHL1, VAMP1, VCP, VPS35, WDR45
*These genes are analyzed by Repeat Expansion
- Canadian Institute for Health Information. Dementia in Canada. https://www.cihi.ca/en/dementia-in-canada/how-dementia-impacts-canadians#ref1
- Loy et al. Genetics of dementia. Lancet. 2014 Mar 1;383(9919):828-40.
- American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington DC: American Psychiatric Association, 1994: 133–155.
- J Geriatr Psychiatry Neurol. 2010 Dec; 23(4): 213–227. doi: 10.1177/0891988710383571
- The Association for Frontaltemporal Degeneration. Genetics of FTD. https://www.theaftd.org/what-is-ftd/genetics-of-ftd/