MRI or 18F-FDG PET for Brain Age Gap Estimation: Links to Cognition, Pathology, and Alzheimer Disease Progression.

Deviations of brain age from chronologic age, known as the brain age gap (BAG), have been linked to neurodegenerative diseases such as Alzheimer disease (AD). Here, we compare the associations of MRI-derived (atrophy) or 18F-FDG PET-derived (brain metabolism) BAG with cognitive performance, neuropathologic burden, and disease progression in cognitively normal individuals (CNs) and individuals with subjective cognitive decline (SCD) or mild cognitive impairment (MCI). Methods: Machine learning pipelines were trained to estimate brain age from 185 matched T1-weighted MRI or 18F-FDG PET scans of CN from the Alzheimer's Disease Neuroimaging Initiative and validated in external test sets from the Open Access of Imaging and German Center for Neurodegenerative Diseases-Longitudinal Cognitive Impairment and Dementia studies. BAG was correlated with measures of cognitive performance and AD neuropathology in CNs, SCD subjects, and MCI subjects. Finally, BAG was compared between cognitively stable and declining individuals and subsequently used to predict disease progression. Results: MRI (mean absolute error, 2.49 y) and 18F-FDG PET (mean absolute error, 2.60 y) both estimated chronologic age well. At the SCD stage, MRI-based BAG correlated significantly with beta-amyloid1-42 (Aß1-42) in cerebrospinal fluid, whereas 18F-FDG PET BAG correlated with memory performance. At the MCI stage, both BAGs were associated with memory and executive function performance and cerebrospinal fluid Aß1-42, but only MRI-derived BAG correlated with phosphorylated-tau181/Aß1-42 Lastly, MRI-estimated BAG predicted MCI-to-AD progression better than 18F-FDG PET-estimated BAG (areas under the curve, 0.73 and 0.60, respectively). Conclusion: Age was reliably estimated from MRI or 18F-FDG PET. MRI BAG reflected cognitive and pathologic markers of AD in SCD and MCI, whereas 18F-FDG PET BAG was sensitive mainly to early cognitive impairment, possibly constituting an independent biomarker of brain age-related changes.

Moral Agency, Rules, and Temporality in People Who Are Diagnosed With Mild Forms of Autism: In Defense of a Sentimentalist View.

The origin of moral agency is a much-debated issue. While rationalists or Kantians have argued that moral agency is rooted in reason, sentimentalists or Humeans have ascribed its origin to empathic feelings. This debate between rationalists and sentimentalists still stands with respect to persons with mental disorders, such as individuals diagnosed with mild forms of Autism Spectrum Disorder (ASD), without intellectual impairment. Individuals with ASD are typically regarded as moral agents, however their ability for empathy remains debated. The goal of this paper is to investigate the mechanisms of moral actions in people with ASD, by finding arguments for the origin of their moral actions, supporting either the sentimentalist or the rationalist view of the dispute. We propose to revisit the debate using Interpretative Phenomenological Analysis to study the autobiographies of individuals with High-Functioning Autism (HFA) and Asperger Syndrome (AS). While conducting the systematic analysis of 10 autobiographies, we re-examined both the rationalist and the sentimentalist positions, considering the links between empathic feelings and moral agency. The investigation of the temporal dimensions of emotional experiences, an aspect overlooked by previous research, indicated that individuals with ASD empathize with others, but in different ways as compared to neurotypicals. A relationship between emotional experience and the type of moral agency exhibited by individuals with forms of ASD was established. As a consequence, our analyses support the sentimentalist stance on moral action.

Unique regional patterns of amyloid burden predict progression to prodromal and clinical stages of Alzheimer's disease.

Although beta-amyloid (Aß) positivity has shown to be associated with higher risk of progression to Alzheimer's disease (AD) in mild cognitive impairment (MCI), information on the time to conversion to manifest dementia cannot be readily deduced from this binary classification. Here, we assessed if regional patterns of Aß deposition measured with 18F-florbetapir may serve as biomarker for progression risk in Aß-positive cognitively normal (CN) and MCI patients, including clinical follow-up data and cerebrospinal fluid (CSF) biomarkers. Voxel-wise group comparisons between age and sex-matched Aß-positive groups (i.e., CN-stables [n = 38] vs. CN-to-MCI/AD progressors [n = 38], MCI-stables [n = 104] versus MCI-to-AD progressors [n = 104]) revealed higher Aß burden in precuneus, subcortical, and parietal regions in CN-to-MCI/AD progressors and cingulate, temporal, and frontal regions in MCI-to-AD progressors. Importantly, these regional patterns predicted progression to advanced stages on the AD spectrum in the short and the long-term beyond global Aß burden and CSF biomarkers. These results suggest that distinct regional patterns of Aß burden are a valuable biomarker for risk of disease progression in CN and MCI.

Features of speech in German and US-American mother-toddler dyads during toy play and book-reading.

Previous research indicates that features of speech during mother-toddler interactions are dependent on the situational context. In this study, we explored language samples of 69 mother-toddler dyads collected during standardized toy play and book-reading situations across two countries, Germany and the United States (US). The results showed that features of speech differed across situational contexts. However, situational differences were mostly found among the sample from the US but not from Germany. Few significant associations between mothers' and toddlers' language variables were found. Findings are discussed with regard to variations in language across situations and countries.