Did You Know: 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 subtypes^2,3:

1. Alzheimer’s disease (most common)
2. Vascular dementias
3. Frontotemporal dementias (FTD)
4. Dementia with Lewy bodies

Alzheimer’s disease

• 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

Frontotemporal Dementia

• 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

References

1. Canadian Institute for Health Information. Dementia in Canada. https://www.cihi.ca/en/dementia-in-canada/how-dementia-impacts-canadians#ref1
2. Loy et al. Genetics of dementia. Lancet. 2014 Mar 1;383(9919):828-40.
3. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington DC: American Psychiatric Association, 1994: 133–155.
4. J Geriatr Psychiatry Neurol. 2010 Dec; 23(4): 213–227. doi: 10.1177/0891988710383571
5. The Association for Frontaltemporal Degeneration. Genetics of FTD. https://www.theaftd.org/what-is-ftd/genetics-of-ftd/