Sporadic Creutzfeldt-Jakob Disease in the young (50 and below): 10-year review of United Kingdom surveillance.

INTRODUCTION: Sporadic Creutzfeldt-Jakob Disease (sCJD) is the commonest human prion disease, with a median age of onset of 68 years. We characterise the clinical, investigation, and neuropathological features in young individuals with sCJD using data from UK national CJD surveillance. METHODS: Referrals between 2011 and 2021 were examined, with definite (post-mortem confirmed) or probable sCJD cases included. Clinical features, MRI, EEG, CSF RT-QuIC, 14-3-3, PRNP sequencing and neuropathological findings were examined. We compared younger (≤ 50 years age of onset) with older individuals. Records of Non-sCJD referrals were also reviewed. RESULTS: 46 (4%) young individuals were identified (age at onset 25-50) from 1178 cases. 15 (33%) were autopsy confirmed. Psychiatric disturbance (37% vs 22%, p = 0.02) and headache (11% vs 3%, p = 0.01) at presentation, and longer disease duration (by 1.45 months, 95% CI 0.43-2.79, logrank p = 0.007) were commoner. CSF RT-QuIC showed lower sensitivity (82% vs 93%, p = 0.02). There was no difference in sensitivity of MR brain or CSF 14-3-3. There were no significant co-pathologies in autopsy-confirmed cases. For non-sCJD referrals, 41 cases were of other CJD subtypes, and 7 non-prion diagnoses. CONCLUSIONS: Young-onset sCJD is more likely to present with neuropsychiatric symptoms and headache, longer disease duration, and lower sensitivity of RT-QuIC. These findings may be driven by the underlying molecular subtypes. Our results guide the evaluation of younger individuals presenting with rapidly progressive cognitive, neuropsychiatric, and motor decline, and emphasise the need for additional vigilance for atypical features by clinicians and CJD surveillance programmes worldwide.

Impact of the COVID-19 pandemic on Creutzfeldt-Jakob disease surveillance and patient care in the United Kingdom.

BACKGROUND AND PURPOSE: Creutzfeldt-Jakob disease (CJD) is lethal and transmissible. We assessed the impact of the COVID-19 pandemic on UK CJD surveillance. We hypothesized that (i) disruptions prolonged diagnostic latency; (ii) autopsy rates declined; and (iii) COVID-19 infection negatively affected diagnosis, care, and survival. METHODS: We retrospectively investigated the first year of the pandemic, using the preceding year as a comparator, quantifying numbers of individuals assessed by the UK National CJD Research & Surveillance Unit for suspected CJD, time to diagnosis, disease duration, and autopsy rates. We evaluated the impact of COVID-19 status on diagnosis, care, and survival in CJD. RESULTS: A total of 148 individuals were diagnosed with CJD in the pandemic (from a total of 166 individuals assessed) compared to 141 in the comparator (from 145 assessed). No differences were identified in disease duration or time to diagnosis. Autopsy rates were unchanged. Twenty individuals had COVID-19; 60% were symptomatic, and 10% had severe disease. Disruptions in diagnosis and care were frequently identified. Forty percent of COVID-19-positive individuals died; however, COVID-19 status did not significantly alter survival duration in CJD. CONCLUSIONS: The COVID-19 pandemic has not impacted UK CJD case ascertainment or survival, but diagnostic evaluation and clinical care of individuals have been affected.

Different subtypes of impulsivity differentiate uncontrolled eating and dietary restraint.

The current study explored the relationship between three subtypes of impulsivity (Reflection Impulsivity, Impulsive Choice, and Impulsive Action) and measures of uncontrolled eating (TFEQ-D) and restraint (TFEQ-R). Eighty women classified as scoring higher or lower on TFEQ-D and TFEQ-R completed the Matching Familiar Figures Test (MFFT20), Delay Discounting Task (DDT), a Go No Go task, Balloon Analogue Risk Task (BART), and the Barrett Impulsivity Scale-11 (BIS-11). To test whether these relationships were affected by enforced controls overeating, half of the participants fasted the night before and ate breakfast in the laboratory before testing and half had no such control. Women scoring higher on the TFEQ-D were significantly more impulsive on the MFFT20 and BIS-11 overall but not on DDT, Go No Go or BART. Women scoring higher on TFEQ-R were significantly less impulsive on the Go No Go task but did not differ on other measures. The eating manipulation modulated responses on the BART and BIS-11 non-planning scale depending on TFEQ-D classification. These results confirm recent data that high scores on TFEQ-D are related to impulsivity, but imply this relates more to Reflection Impulsivity rather than Impulsive Choice or Action. In contrast restrained eating was associated with better inhibitory control. Taken together, these results suggest that subtypes of impulsivity further differentiate uncontrolled eating and restraint, and suggest that a poor ability to reflect on decisions may underlie some aspects of overeating.

Saccharomyces cerevisiae deletion strains with complex DNA content profiles.

To identify Saccharomyces cerevisiae genes required for the proper timing of cell cycle transitions, we previously reported a systematic examination of the DNA content of homozygous diploid deletion strains. However, deletion strains with complex DNA content profiles were not examined in that study. Here, we report S. cerevisiae genes that when deleted give rise to DNA content profiles consistent with roles of the corresponding gene products during DNA replication. We also identified a set of genes whose deletion leads to increased DNA content, consistent with defects in mitosis, cytokinesis, or cell separation. Finally, we examined known interactions between the gene products of each group, placing these gene products in functional networks. Taken together, the data we present further validate the roles of the corresponding gene products in these processes, facilitating efforts to delineate gene function critical for genome replication, maintenance, and segregation.

Effects of energy density and portion size on development of acquired flavour liking and learned satiety.

The concept of learned satiety (LS) suggests that associations between the sensory quality and post-ingestive effects of foods may lead to acquired control of meal-size. Although a recent study appeared to support LS since participants learned to eat more of a flavoured cereal with lower energy density (ED) after repeated experience, suggesting that they adjusted voluntary intake to ensure adequate energy was consumed, the large serving portion used in training may have lead to over-satiation. To investigate this further, groups of 12 men were assigned to one of four conditions based on the trained serving portion (150 or 300 g) and presence or absence of cues to differentiate high and low ED versions. In the absence of sensory cues, neither mass consumed nor rated pleasantness differed between high and low ED conditions either before or after training, resulting in greater energy intake in the high ED condition. When sensory cues differentiated ED, intake increased significantly post-training in both the high ED condition trained with the small portion and low ED condition trained with the large portion, and flavour pleasantness changed similarly. Moreover hunger increased significantly after the food was tasted in both conditions where intake increased. These data provide further evidence that learning can moderate meal-size dependent on energy content, but suggest that these changes are driven by changes in flavour liking rather than LS.

Differential hedonic, sensory and behavioral changes associated with flavor-nutrient and flavor-flavor learning.

Flavor-flavor and flavor-nutrient associations can modify liking for a flavor CS, while flavor-flavor associations can also modify the sensory experience of the trained flavor. Less is known about how these associations modify behavioral responses to the trained CS. To test this, 60 participants classified as sweet likers were divided into five training conditions with a novel flavor CS. In the flavor-flavor only condition, participants consumed the target CS in a sweetened, low-energy form, with energy (maltodextrin) but no sweetness added in the flavor-nutrient only condition and both energy and sweetness (sucrose) in the combined flavor-flavor, flavor-nutrient condition. Comparison groups controlled for exposure to the CS, and repeat testing. Training was conducted in a hungry state on four non-consecutive days. To test for acquired changes in evaluation and intake, the flavor CS was processed into a low-energy sorbet, which was evaluated and consumed ad libitum on test days before and after training. Liking for the flavor CS increased only in the sucrose-sweetened condition, but intake increased significantly in both high-energy conditions. In contrast, rated sweetness of the sorbet increased in both sucrose-sweetened and aspartame-sweetened conditions. These findings suggest that liking changes were maximal when flavor-flavor and flavor-nutrient associations co-occurred, but that behavioral changes were specific to flavor-nutrient associations.

Impulsivity is associated with the disinhibition but not restraint factor from the Three Factor Eating Questionnaire.

Recent data implicate impulsivity as a personality trait associated with obesity, binge eating and restrained eating. However, impulsivity is recognised as having multiple dimensions, and it remains unclear which aspects of impulsive behaviour best predict disordered eating. To try and elucidate further the relationship between impulsivity and eating behaviour, 147 women completed a behavioural measure and two self-report measures of impulsivity along with the Three Factor Eating Questionnaire (TFEQ). Overall scores on the Barratt Impulsiveness Scale (BIS-II), along with scores on the Non-planning and Motor Subscales of the BIS-II, were higher in women scoring high on the TFEQ disinhibition (TFEQ-D) scale. Likewise, women scoring high on the TFEQ-D showed more impulsive choice when discounting hypothetical monetary awards. However, responses to measures of functional relative to dysfunctional impulsivity did not differ depending on TFEQ-D score. No measure of impulsivity was related to scores on the TFEQ restraint scale. These data suggest that a tendency to act impulsively is associated with a tendency to overeat, and may be a factor which predicts the likelihood of the development of binge eating and the breakdown of dieting.

Risk factors for variant Creutzfeldt-Jakob disease: a case-control study.

OBJECTIVE: To investigate the potential risk factors for variant Creutzfeldt-Jakob disease (VCJD) in the United Kingdom. METHODS: Definite and probable vCJD cases (n = 136) were residing in Great Britain at disease onset, and were referred between May 1995 and November 2003. Control subjects (n = 922) were recruited between 2002 and 2003, from 100 randomly selected geographical clusters sampled to represent the geographical distribution of vCJD. RESULTS: Reported frequent consumption of beef and beef products thought likely to contain mechanically recovered or head meat, or both, including burgers and meat pies, was associated with increased risk for vCJD, as was reported frequent chicken consumption. Surgical operations were generally similarly reported for cases and control subjects, with the exception of a small group of minor operations, possibly attributable to underreporting in control subjects. Cases and control subjects had similar reported occupational histories and exposure to animals. INTERPRETATION: These findings are consistent with dietary exposure to contaminated beef products being the main route of infection of vCJD, but recall bias cannot be excluded. There was no convincing evidence of increased risk through medical, surgical, or occupational exposure or exposure to animals.