Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease

Although neuropsychiatric symptoms are not part of diagnostic criteria for sporadic Creutzfeldt-Jakob disease (sCJD), a few retrospective studies and our clinical experience have suggested they are prominent and often occur early. The objective of our study was to assess prospectively the neuropsychiatric features in sCJD (and their impact on caregivers) and compare them with five other neurodegenerative diseases: Alzheimer's disease (AD), dementia with Lewy bodies (DLB), progressive supranuclear palsy, behavioural variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia. The Neuropsychiatric Inventory (NPI) was given at the first UCSF research visit to caregivers of 789 serial patients evaluated at the UCSF Memory and Aging Center from January 2000 through November 2016 who met the diagnostic research criteria for one of these six neurodegenerative disorders. All subjects underwent a Mini-Mental State Examination, and demographic data (age, sex, years of education) were collected. We hypothesized that sCJD has a very prominent behavioural and neuropsychiatric profile, which might help to distinguish it from other neurodegenerative diseases. Of our sCJD cohort (n = 92), 97% exhibited at least one and 50% at least six of the 12 symptoms on the NPI at the time of their first research visit. The most common behavioural symptoms, which occurred in >50% of the sCJD patient cohort, were: appetite/eating disturbances (68%), apathy/indifference (66%), night-time behaviour disturbances (53%), aberrant motor behaviour (53%) and anxiety (52%). Even the least common behaviour, disinhibition, occurred in 19%. Compared with DLB and bvFTD, two conditions with very prominent behavioural features that are included in their diagnostic criteria, sCJD had significantly higher mean NPI frequency × severity scores for night-time behaviour disturbances and delusions. Patients with sCJD scored higher for hallucinations and dysphoria than bvFTD patients and higher for appetite/eating disturbances, aberrant motor behaviour and agitation than patients with DLB. sCJD resulted in significantly worse frequency × severity scores than AD in nine of the NPI symptom domains, with our data revealing sCJD to be a highly behavioural syndrome. No neuropsychiatric symptom is pathognomonic for sCJD, but specific symptoms may enable the differentiation of sCJD from other neurodegenerative diseases. Our findings support the inclusion of behavioural symptoms in sCJD diagnostic criteria.