Dementia describes a set of clinical symptoms that include impairment of memory, communication, and ability to perform daily tasks. The lifetime risk of dementia in the general population is 10%. Approximately 25% of all people aged 55 years and older have a positive family history of dementia 1.
According to clinical and research criteria there are four primary dementia subtypes 1, 2:
1) Alzheimer’s disease (most common)
2) Vascular dementias
3) Frontotemporal dementias
4) Dementia with Lewy bodies.
5-10% of adults >60 years of age have dementia3
Major clinical symptoms 4:
- Memory failure and memory loss, subtle and poorly recognized, progressive.
- Language disturbance.
- Confusion and poor judgment.
- Progressive behavioral changes, agitation, withdrawal, and hallucinations.
Less common clinical symptoms 4:
- Seizures and myoclonus
- Parkinsonian features
- Increased muscle tone
- General malnutrition, pneumonia.
- Presence of the specific clinical features for progressive dementia.
- Neuropathologic findings of β-amyloid plaques and intraneuronal neurofibrillary tangles are the gold standard for diagnosis (however, performed only on the brain tissue).
- Positive family history of dementia.
- Identification of a heterozygous pathogenic variant in one of the following genes (Table 1): APOE, APP, CHMP2B, CSF1R, FUS, GRN, MAPT, PRNP, PSEN1, PSEN2, SORL1, TARDBP, TREM2, UBE3A, VCP.
- There are no specific treatments or cures to slow or stop the progression of dementia.
- There are medications that can reduce agitation and other behavioral problems and/or depression which can improve quality of life4.
- Parkinson disease
- Amyotrophic lateral sclerosis
- Picks disease
- Creutzfeldt-Jakob disease
- Chronic drug intoxication
- Chronic CNS infection
- Thyroid disease
- Vitamin B12 and thiamine deficiencies
To confirm/establish the diagnosis, CENTOGENE offers the following tests:
- Dementia NGS Panel which includes sequencing of the genes APOE, APP, CHMP2B, CSF1R, FUS, GRN, MAPT, PRNP, PSEN1, PSEN2, SORL1, TARDBP, TREM2, UBE3A, VCP and repeat expansion analysis of the genes C9orf72 and PRNP
- Dementia NGS Panel + CNV which includes sequencing and additionally detection of large deletions and duplications from the NGS data
- Individuals with a positive family history of dementia
- Individuals with most common symptoms of dementia (regardless of family history)
Confirmation of a clinical diagnosis through genetic testing of dementia can allow for genetic counseling and may direct medical management.
Table 1: Overview of genes included in Dementia panel
|Gene||OMIM (Gene)||Associated diseases (OMIM)||Inheritance||CentoMD® exclusive variant numbers (++)|
|APOE||107741||Alzheimer Disease 2; Sea-blue histiocyte disease; Macular Degeneration, Age-Related, 1; Lipoprotein glomerulopathy||AD, AR||8|
|APP||104760||Alzheimer Disease; Cerebral Amyloid Angiopathy, App-Related||AD||37|
|CHMP2B||609512||Dementia, familial, nonspecific; amyotrophic lateral sclerosis 17||AD||3|
|CSF1R||164770||hereditary diffuse leukoencephalopathy with axonal spheroids and pigmented glia||AD, AR||28|
|DCTN1||601143||amyotrophic lateral sclerosis 1; Perry syndrome; Neuronopathy, Distal Hereditary Motor, Type Viib||AD, AR||12|
|FUS||137070||amyotrophic lateral sclerosis 6; Tremor, hereditary essential, 4||AD||26|
|GRN||138945||frontotemporal lobar degeneration with ubiquitin-positive inclusions; neuronal ceroid lipofuscinosis type 11||AD, AR||16|
|MAPT||157140||susceptibility to late-onset Parkinson disease; Pick disease; Dementia, frontotemporal||AD, AR||25|
|NOTCH3||600276||CADASIL; Lateral meningocele syndrome||AD||62|
|PRNP||176640||Creutzfeldt-Jakob disease; Gerstmann-Straussler disease; Kuru, susceptibility to; Insomnia, fatal familial; Huntington disease-like 1; Prion disease with protracted course||AD||7|
|PSEN1||104311||Pick disease; Dementia, frontotemporal; early-onset familial Alzheimer disease-3; dilated cardiomyopathy-1U; Acne inversa, familial, 3||AD||15|
|PSEN2||600759||Alzheimer disease, type 4; dilated cardiomyopathy-1V||AD||17|
|SNCA||163890||Lewy body dementia; Parkinson disease 1||AD||27|
|SQSTM1||601530||Frontotemporal dementia and/or amyotrophic lateral sclerosis 3; Neurodegeneration with ataxia, dystonia, and gaze palsy, childhood-onset||AD, AR||4|
|TARDBP||605078||amyotrophic lateral sclerosis 10||AD||11|
|UBQLN2||300264||amyotrophic lateral sclerosis 15||XLD||1|
|VCP||601023||inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 1; amyotrophic lateral sclerosis 14; Charcot-Marie-Tooth disease type 2Y||AD||15|