Down syndrome, Alzheimer’s disease and seizures

Abstract

Neuropathologically, Alzheimer-type abnormalities are demonstrated in patients with Down syndrome (DS), both demented and nondemented and more than a half of patients with DS above 50 years develop Alzheimer's disease (AD). The apolipoprotein E epsilon4 allele, oestrogen deficiency, high levels of Abeta1-42 peptide, elevated expression of BACE2, and valine polymorphism of prion protein gene are associated with earlier onset of dementia in DS individuals. Advanced AD alone may be an important risk factor for new-onset seizures in older adults and age above 60 years is a recognized risk factor for poor outcome from convulsive and nonconvulsive status epilepticus. DS patients aged over 45 years are significantly more likely to develop Alzheimer's disease than those less than 45 years and up to 84% demented individuals with DS develop seizures. Late-onset epilepsy in DS is associated with AD, while early-onset epilepsy is associated with an absence of dementia. In AD patients with a younger age of dementia onset are particularly susceptible to seizures. DS adults with epilepsy score significantly higher overall on the adaptive behaviour profile. Language function declined significantly more rapidly in AD patients with seizures and there is a good correlation between the severity of EEG abnormalities and cognitive impairment whereas in DS slowing of the dominant occipital rhythm is related to AD and the frequency of the dominant occipital activity decreases at the onset of cognitive deterioration.