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Introduction We examined the ability of plasma hyperphosphorylated tau (p-tau)181 to detect cognitive impairment due to Alzheimer's disease (AD) independently and in combination with plasma total tau (t-tau) and neurofilament light (NfL). Methods Plasma samples were analyzed using the Simoa platform for 235 participants with normal cognition (NC), 181 with mild cognitive impairment due to AD (MCI), and 153 with AD dementia. Statistical approaches included multinomial regression and Gaussian graphical models (GGMs) to assess a network of plasma biomarkers, neuropsychological tests, and demographic variables. Results Plasma p-tau181 discriminated AD dementia from NC, but not MCI, and correlated with dementia severity and worse neuropsychological test performance. Plasma NfL similarly discriminated diagnostic groups. Unlike plasma NfL or t-tau, p-tau181 had a direct association with cognitive diagnosis in a bootstrapped GGM. Discussion These results support plasma p-tau181 for the detection of AD dementia and the use of blood-based biomarkers for optimal disease detection.

Introduction: Misophonia is marked by abnormal negative reactions to specific and idiosyncratic sounds. Despite unclear etiology and diagnostic conceptualization, neuropsychology may be abl...

Background: A companion paper (Crowley et al., 2020) reports on the neuroimaging and neuropsychological profiles of statistically determined idiopathic non-dementia Parkinson’s disease (PD). Objective: The current investigation sought to further examine subtle behavioral clock drawing differences within the same PD cohort by comparing 1) PD to non-PD peers on digitally acquired clock drawing latency and graphomotor metrics, and 2) PD memory, executive, and cognitively well phenotypes on the same variables. Methods: 230 matched participants (115 PD, 115 non-PD) completed neuropsychological tests and dCDT. Statistically-derived PD cognitive phenotypes characterized PD participants as PD low executive (PDExe; n = 25), PD low memory (PDMem; n = 34), PD cognitively well (PDWell; n = 56). Using a Bayesian framework and based on apriori hypotheses, we compared groups on: total completion time (TCT), pre-first hand latency (PFHL), post-clock face latency (PCFL), total clock face area (TCFA), and total number of pen strokes. Results: Fewer strokes and slower performance to command were associated with higher odds of PD diagnosis, while a larger clock face in the copy condition was associated with lower odds of PD diagnosis. Within PD cognitive phenotypes, slower performance (TCT, PCFL) and smaller clock face to command were associated with higher odds of being PDExe than PDWell, whereas larger clock faces associated with higher odds of being PDMem than PDWell. Longer disease duration, more pen strokes (command) and smaller clocks (command) associated with higher odds of being PDExe than PDWell. Conclusion: Digitally-acquired clock drawing profiles differ between PD and non-PD peers, and distinguish PD cognitive phenotypes.

Objective In situations in which randomized experiments are impossible or unethical, propensity score matching offers a method to reduce bias on causal effect estimates (Thoemmes & Kim, 2011). In this study, we examined differences on the digital clock drawing test (dCDT; Souillard-Mandar et al., 2016) between individuals with idiopathic non-dementia Parkinson’s disease (PD) and matched controls. Method This study involved a retrospective analysis of two federally funded investigations (NSF-13-543; R01-NS082386). The sample included 261 participants (110 PD, 151 non-PD). Participants were matched according to demographic covariates, as well as measures of mood, comorbidity, and premorbid functioning. The PD group and matched controls were compared using logistic regression in a Bayesian framework, with projection predictive variable selection implemented to obtain a parsimonious model (Piironen, Paasiniemi, & Vehtari, 2018). All effects were standardized. Results Of 261 participants, 212 were matched using nearest neighbor matching (Figure 1). The final, parsimonious model included four variables from the dCDT: total strokes (command condition), total time (command condition), and area (command and copy conditions). While all effects were retained, positive to strong evidence was found for dCDT total time (βMedian = 0.91, βSD = 0.25, 95% CI [0.44, 1.42], Bayes factor [BF] = 97.80) and dCDT area (copy condition; βMedian = −0.52, βSD = 0.19, 95% CI [−0.90, −0.17], BF = 4.78). Conclusions Propensity scores can be employed in causal comparative studies to match control participants and reduce bias from nuisance covariates. Four aspects of dCDT performance were optimal in distinguishing individuals with PD from matched controls.

Several studies have shown that basic emotions are responsible for a significant enhancement of early visual processes and increased activation in visual processing brain regions. It may be possible that the cognitive uncertainty and repeated behavioral checking evident in Obsessive Compulsive Disorder (OCD) is due to the existence of abnormalities in basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional-laden stimuli. The objective of the present study was to test if patients with OCD show evidence of altered basic survival circuits, particularly those associated with the visual processing of the physical characteristics of emotional stimuli. Fifteen patients with OCD and 12 healthy controls underwent functional magnetic resonance imaging acquisition while being exposed to emotional pictures, with different levels of arousal, intended to trigger the defensive and appetitive basic survival circuits. Overall, the present results seem to indicate dissociation in the activity of the defense and appetitive survival systems in OCD. Results suggest that the clinical group reacts to basic threat with a strong activation of the defensive system mobilizing widespread brain networks (i.e., frontal, temporal, occipital-parietal, and subcortical nucleus) and blocking the activation of the appetitive system when facing positive emotional triggers from the initial stages of visual processing (i.e., superior occipital gyrus).