Neuropsychiatric symptoms in sporadic Creutzfeldt-Jakob disease

Abstract Although neuropsychiatric symptoms are not part of diagnostic criteria for sporadic Creutzfeldt-Jakob disease 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 (PSP), behavioral variant frontotemporal dementia (bvFTD) and semantic variant primary progressive aphasia (svPPA). 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 diagnostic research criteria for one of the six neurodegenerative disorders. All subjects also had to have a Mini-Mental Status Evaluation (MMSE) and demographic data (age, sex, years of education). We hypothesized that sCJD has a very prominent behavioral and neuropsychiatric profile, which might help distinguish it from other neurodegenerative diseases. Of our sCJD cohort (n=92), 97% had at least one NPI neuropsychiatric symptom, and half had at least six of the 12 NPI symptom categories, by their first research visit. The most common behavioral symptoms, occurring in more than half of sCJD patients, were: Appetite/Eating Disorders (68%), Apathy/Indifference (66%), Night-time Behaviors (53%), Aberrant Motor Behavior (53%) and Anxiety (52%). Even the least common behavior, Disinhibition, occurred in 19%. Compared to both DLB and bvFTD ­– two conditions with very prominent behavioral features and which include behavior in their diagnostic criteria – ­sCJD had significantly higher mean NPI FrequencyxSeverity product scores for Night-time Behaviors and Delusions; sCJD also had significantly higher scores for Hallucinations and Depression/Dysphoria than bvFTD and for Appetite/Eating Disorder, Aberrant Motor behavior and Agitation than DLB. sCJD had significantly worse FrequencyxSeverity scores than AD in three-quarters of NPI categories. Our data show that sCJD is a highly behavioral syndrome. Although no neuropsychiatric symptom is pathognomonic for sCJD, certain symptoms might help differentiate sCJD from some other neurodegenerative diseases. Our findings support the inclusion of behavioral symptoms in sCJD diagnostic criteria.