Influence of age on case ascertainment in CJD

Ageing is the greatest risk factor for most forms of dementia. Variant Creutzfeldt-Jakob Disease (vCJD) however is predominantly a disease of younger adults and sporadic CJD (sCJD), although a disease of the older population, mainly affects those under 80 years of age. The very low age-specific incidence of both vCJD and sCJD in the oldest age group may, in part, be due to case under ascertainment, perhaps due to a lack of familiarity with CJD, or atypical clinical presentation of CJD In the UK, suspect cases of CJD are referred by clinicians to the National CJD Research & Surveillance Unit (NCJDRSU) for clinical assessment and epidemiological review. Case ascertainment in CJD is important not only for appropriate clinical care but also, due to the potential for person-to-person transmission of the CJD agent through medical procedures, to help protect public health. In this thesis: 1) I describe the clinical and referral characteristics of CJD patients diagnosed later in their disease progression and determine if these characteristics differ in those diagnosed earlier. A retrospective review of CJD cases referred to the NCJDRSU, for vCJD between 1995 and 2015 (n = 177) and for sCJD between 2010 and 2015 (n = 584) was undertaken. Age was significantly associated with timing of diagnosis, with later diagnoses occurring in older patients, and differences in clinical and referral characteristics between these and younger patients. 2) I also pilot a study of enhanced CJD surveillance in the older population. Since January 2016, patients aged ≥65 years seen in NHS Lothian with a diagnosis of non-CJD dementia but with atypical features (e.g. rapid speed of progression or focal neurology) have been invited to participate in a study to investigate whether atypical CJD might underlie the diagnosis of some patients with dementia. For each participant, a clinical examination was undertaken, with consent, including Addenbrooke’s Cognitive Examination–III, the frontal assessment battery, the hospital anxiety and depression scale, Barthel’s Index, and the Edinburgh Motor Assessment Scale. In addition, MRI was undertaken (including DWI and FLAIR sequences), a blood sample was taken for codon-129 subtyping and patients were consented for donation of brain tissue in the event of their death. Ten patients were recruited during the initial 6 months of study. Although patients had individual features of CJD there was no evidence of CJD clinically. No patients however reached postmortem during this initial study period. Barriers to referral, including clinician time pressures, likely impacted study referral