The risk of early onset Alzheimer's disease in Prader-Willi syndrome

Alzheimer's disease (AD) is well-known as a condition of old age, prevalence rising with age from about 70 years. However, some groups appear to be at risk from a much earlier age, for example people with Down's syndrome. Recently, in pathological studies of people with Prader-Willi syndrome (PWS) who died aged over 40 years, signs of AD have been found in three brains, the severity of pathology increasing with age. We propose to interview parents and carers of people with PWS aged over 40 years to ask about any signs of developing AD. This involves asking about changes in behaviour, personality, cognition, and competence in self-care. Our aim is to assess the risk of early-onset AD in people with PWS. This is relevant because life expectancy in PWS is rising as a result of early diagnosis and interventions to prevent obesity and its health threatening complications. Early diagnosis of AD has the potential to prolong the non-dependent life of people with the condition by use of suitable medication.

Research Outcomes: Project Summary

Recruitment of this age group was problematic and the evidence in inconclusive. However, we found that only those with a history of psychosis were at risk of decline and in all four cases carers described deterioration in functioning over and above that seen during acute psychotic episodes. This is in line with a case study from Curfs' group which described a women with PWS and AD who had a UPD with a history of psychosis. However, for people with psychosis in the general population any dementia usually develops much later in life. The genetic status of Professor Swaab's cases is unknown. How likely is it that their PWS was due to UPD and hence they would have had a high risk for psychosis? Our population study of PWS in the UK showed that up to age 20 the ratio of del to UPD was 3.1:1; aged 21 to 30 it was 2.5:1; aged 31 to 40 it was 2.7:1; and aged 41-50 it was 1:1. Thus, the probability increase with age that the cause of a person's PWS will be mUPD of chromosome 15. 

Research Outcomes: Publications

Ageing in people with Prader-Willi syndrome: mortality in the UK population cohort and morbidity in an older sample of adults. Whittington JE,Holland AJ, Webb T.  Psychological Medicine. 2015 Feb;45(3):615-21.