Development of novel clinical examination scales for the measurement of disease severity in Creutzfeldt-Jakob disease

ObjectiveTo use a robust statistical methodology to develop and validate clinical rating scales quantifying longitudinal motor and cognitive dysfunction in sporadic Creutzfeldt-Jakob disease (sCJD) at the bedside.MethodsRasch analysis was used to iteratively construct interval scales measuring composite cognitive and motor dysfunction from pooled bedside neurocognitive examinations collected as part of the prospective National Prion Monitoring Cohort study, October 2008–December 2016.A longitudinal clinical examination dataset constructed from 528 patients with sCJD, comprising 1030 Motor Scale and 757 Cognitive Scale scores over 130 patient-years of study, was used to demonstrate scale utility.ResultsThe Rasch-derived Motor Scale consists of 8 items, including assessments reliant on pyramidal, extrapyramidal and cerebellar systems. The Cognitive Scale comprises 6 items, and includes measures of executive function, language, visual perception and memory. Both scales are unidimensional, perform independently of age or gender and have excellent inter-rater reliability. They can be completed in minutes at the bedside, as part of a normal neurocognitive examination. A composite Examination Scale can be derived by averaging both scores. Several scale uses, in measuring longitudinal change, prognosis and phenotypic heterogeneity are illustrated.ConclusionsThese two novel sCJD Motor and Cognitive Scales and the composite Examination Scale should prove useful to objectively measure phenotypic and clinical change in future clinical trials and for patient stratification. This statistical approach can help to overcome obstacles to assessing clinical change in rapidly progressive, multisystem conditions with limited longitudinal follow-up.

The expansion and severity of chronic MS lesions follows a periventricular gradient

Background and Objectives: Expansion of chronic lesions in MS patients and recently described CSF-related gradient of tissue damage are linked to microglial activation. The aim of the current study was to investigate whether lesion expansion is associated with proximity to ventricular CSF spaces. Methods: Pre- and post-gadolinium 3D-T1, 3D FLAIR and diffusion tensor images were acquired from 36 RRMS patients. Lesional activity was analysed between baseline and 48 months at different distances from the CSF using successive 1-mm thick concentric rings radiating from the ventricles. Results: Voxel-based analysis of the rate of lesion expansion demonstrated a clear periventricular gradient decreasing away from the ventricles. This was particularly apparent when lesions of equal diameter were analysed. Periventricular lesional tissue showed higher degree of tissue distraction at baseline that significantly increased during follow-up in rings close to CSF. This longitudinal change was proportional to degree of lesion expansion. Lesion-wise analysis revealed a gradual, centrifugal decrease in the proportion of expanding lesions from the immediate periventricular zone. Discussion: Our data suggest that chronic white matter lesions in close proximity to the ventricles are more destructive, show a higher degree of expansion at the lesion border and accelerated tissue loss in the lesion core.

Association of APOE ɛ4 and Plasma p-tau181 with Preclinical Alzheimer’s Disease and Longitudinal Change in Hippocampus Function

Background: The Apolipoprotein E (APOE) ɛ4 allele has been linked to increased tau phosphorylation and tangle formation. APOE ɛ4 carriers with elevated tau might be at the higher risk for AD progression. Previous studies showed that tau pathology begins early in areas of the medial temporal lobe. Similarly, APOE ɛ4 carriers showed altered hippocampal functional integrity. However, it remains unknown whether elevated tau accumulation on hippocampal functional changes would be more pronounced for APOE ɛ4 carriers. Objective: We related ɛ4 carriage to levels of plasma phosphorylated tau (p-tau181) up to 15 years prior to AD onset. Furthermore, elevated p-tau181 was explored in relation to longitudinal changes in hippocampal function and connectivity. Methods: Longitudinal population-based study. Plasma p-tau181 was analyzed in 142 clinically defined Alzheimer’s disease (AD) cases and 126 controls. The longitudinal analysis involved 87 non-demented individuals with two waves of plasma samples and three waves of functional magnetic resonance imaging during rest and memory encoding. Results: Increased p-tau181 was observed for both ɛ4 carriers and non-carriers close to AD, but exclusively for ɛ4 carriers in the early preclinical groups (7- and 13-years pre-AD). In ɛ4 carriers, longitudinal p-tau181 increase was paralleled by elevated local hippocampal connectivity at rest and subsequent reduction of hippocampus encoding-related activity. Conclusion: Our findings support an association of APOE ɛ4 and p-tau181 with preclinical AD and hippocampus functioning.

A Longitudinal Change Patterns of Depression and Its Relationship with Socioeconomic Deprivation among Middle-Aged Adults in South Korea

This study aimed to identify the longitudinal pattern changes of South Koreans’ midlife depression and determine the impact of socioeconomic deprivation on the observed change in patterns. In total, 3975 middle-aged individuals were examined by conducting a latent class growth analysis and multinomial logistic regression analysis on seven years of Korea Welfare Panel data (2012–2018) using STATA 16.0 (StataCorp LLC, College Station, TX, USA). The change patterns of midlife depression were classified into normal depression reduction group, mild depression maintenance group, and serious depression increase group. The impact of the experience of socioeconomic deprivation on the classified change patterns was examined using the normal depression reduction group as the reference group. It was found that the higher an individual’s nutritional, housing, occupational/economic, and healthcare deprivation, the higher their risk of mild depression maintenance or serious depression increase. The serious depression increase group showed higher relative risk ratios in all domains. Comprehensive and integrated social welfare services, such as stable income, housing welfare, and healthcare services, should be provided along with appropriate clinical interventions for depression alleviation that account for the pattern changes in midlife depression.

Development of a Longitudinal Diagnosis and Prognosis in Patients with Chronic Kidney Disease: Intelligent Clinical Decision-Making Scheme

Previous studies on CKD patients have mostly been retrospective, cross-sectional studies. Few studies have assessed the longitudinal assessment of patients over an extended period. In consideration of the heterogeneity of CKD progression. It’s critical to develop a longitudinal diagnosis and prognosis for CKD patients. We proposed an auto Machine Learning (ML) scheme in this study. It consists of four main parts: classification pipeline, cross-validation (CV), Taguchi method and improve strategies. This study includes datasets from 50,174 patients, data were collected from 32 chain clinics and three special physical examination centers, between 2015 and 2019. The proposed auto-ML scheme can auto-select the level of each strategy to associate with a classifier which finally shows an acceptable testing accuracy of 86.17%, balanced accuracy of 84.08%, sensitivity of 90.90% and specificity of 77.26%, precision of 88.27%, and F1 score of 89.57%. In addition, the experimental results showed that age, creatinine, high blood pressure, smoking are important risk factors, and has been proven in previous studies. Our auto-ML scheme light on the possibility of evaluation for the effectiveness of one or a combination of those risk factors. This methodology may provide essential information and longitudinal change for personalized treatment in the future.

Pet Ownership and Longitudinal Change in Physical Function: Evidence From the BLSA

Successful aging depends on avoiding disease and disability, maintaining high physical and cognitive function, and psychological adaptation. Research examining the relationship of pet ownership (PO) or human-animal interaction (HAI) to human health supports contributions to these successful ag-ing-related outcomes at some point in the life-cycle, mostly in populations with diseases or disabili-ties. We examine the contributions of PO to maintaining physical capacity among generally healthy community-dwelling older participants in the Baltimore Longitudinal Study of Aging (BLSA). Partici-pants’ [N=637, mean age=68.3 years (SD=9.6), pet owners N=149] completed a standardized physi-cal function test battery (among other measures) every 1-4 years and a ten-year PO history. Linear mixed, or generalized linear mixed, models with time varying PO were used to examine change in successful aging-related outcomes over up to 13 years [mean=7.5, (SD=3.6)] according to PO. Physi-cal function declined across all domains examined, but was observed to be less severe with PO in overall physical performance (p<0.001), rapid gait speed (p=0.041), 400-meter walk time (p<0.001), and reported physical wellbeing (p=0.032). No differences were observed for grip strength (p=0.56), usual gait speed (p=0.07), and leisure time physical activity (p=0.26) after con-trolling for age. This study provides the first longitudinal evidence that PO may promote successful aging among community-dwelling healthy older adults by moderating age-related declines in physical functional status in late-life.