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 Plus 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 Plus + 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; Lipoprotein glomerulopathy; Coronary artery disease, severe, susceptibility to; Hyperlipoproteinemia, type III||AD, AR||4|
|APP||104760||Alzheimer disease 1, familial; Cerebral amyloid angiopathy, Dutch, Italian, Iowa, Flemish, Arctic variants||AD||38|
|CHMP2B||609512||Dementia, familial, nonspecific; Amyotrophic lateral sclerosis 17||AD||3|
|CSF1R||164770||Leukoencephalopathy, diffuse hereditary, with spheroids||AD||29|
|FUS||137070||Amyotrophic lateral sclerosis 6, with or without frontotemporal dementia; Essential tremor, hereditary, 4||AD||26|
|GRN||138945||Aphasia, primary progressive; Frontotemporal lobar degeneration with ubiquitin-positive inclusions; Ceroid lipofuscinosis, neuronal, 11||AD, AR||18|
|MAPT||157140||Parkinson disease, susceptibility to; Pick disease; Supranuclear palsy, progressive atypical; Dementia, frontotemporal, with or without parkinsonism; Supranuclear palsy, progressive||AD, AR, Isolated cases, MF||25|
|PRNP||176640||Creutzfeldt-Jakob disease; Cerebral amyloid angiopathy, PRNP-related; 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; Alzheimer disease, type 3; Alzheimer disease, type 3, with spastic paraparesis and apraxia; Alzheimer disease, type 3, with spastic paraparesis and unusual plaques; Cardiomyopathy, dilated, 1U; ?Acne inversa, familial, 3||AD, Isolated cases||16|
|PSEN2||600759||Alzheimer disease-4; Cardiomyopathy, dilated, 1V||AD||15|
|TARDBP||605078||Amyotrophic lateral sclerosis 10, with or without FTD; Frontotemporal lobar degeneration, TARDBP-related||AD||11|
|UBE3A||601623||Angelman syndrome||Isolated cases||19|
|VCP||601023||Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1; Amyotrophic lateral sclerosis 14, with or without frontotemporal dementia; Charcot-Marie-Tooth disease, type 2Y||AD||13|