Amyloid-dependent and amyloid-independent effects of Tau in individuals without dementia.

OBJECTIVE: To investigate the relationship between the topography of amyloid-ß plaques, tau neurofibrillary tangles, and the overlap between the two, with cognitive dysfunction in individuals without dementia. METHODS: We evaluated 154 individuals who were assessed with amyloid-ß PET with [18 F]AZD4694, tau-PET with [18 F]MK6240, structural MRI, and neuropsychological testing. We also evaluated an independent cohort of 240 individuals who were assessed with amyloid-ß PET with [18 F]Florbetapir, tau-PET with [18 F]Flortaucipir, structural MRI, and neuropsychological testing. Using the VoxelStats toolbox, we conducted voxel-wise linear regressions between amyloid-PET, tau-PET, and their interaction with cognitive function, correcting for age, sex, and years of education. RESULTS: In both cohorts, we observed that tau-PET standardized uptake value ratio in medial temporal lobes was associated with clinical dementia rating Sum of Boxes (CDR-SoB) scores independently of local amyloid-PET uptake (FWE corrected at p < 0.001). We also observed in both cohorts that in regions of the neocortex, associations between neocortical tau-PET and clinical function were dependent on local amyloid-PET (FWE corrected at p < 0.001). INTERPRETATION: In medial temporal brain regions, characterized by the accumulation of tau pathology in the absence of amyloid-ß, tau had direct associations with cognitive dysfunction. In brain regions characterized by the accumulation of both amyloid-ß and tau pathologies such as the posterior cingulate and medial frontal cortices, tau's relationship with cognitive dysfunction was dependent on local amyloid-ß concentrations. Our results provide evidence that amyloid-ß in Alzheimer's disease influences cognition by potentiating the deleterious effects of tau pathology.

Does effort-cost decision-making relate to real-world motivation in people living with HIV?

INTRODUCTION: Low motivation is frequent in older people with HIV, yet poorly understood. Effort-cost decision-making (ECDM) tasks inspired by behavioral economics have shown promise as indicators of motivation or apathy. These tasks assess the willingness to exert effort to earn a monetary reward, providing an estimate of the subjective "cost" of effort for each participant. Here we sought evidence for a relationship between ECDM task performance and self-reported motivation in a cross-sectional study involving 80 middle-aged and older people with well-controlled HIV infection, a chronic health condition with a high burden of mental and cognitive health challenges. METHODS: Participants attending a regular follow-up visit for a Canadian longitudinal study of brain health in HIV completed a computerized ECDM task and a self-report measure of motivation. Other brain health measures were available, collected for the parent study (cognition, depression, anxiety, and vitality, as well as self-reported time spent on real-world leisure activities). RESULTS: Contrary to our hypothesis, we found no relationship between ECDM performance and self-reported motivation. However, those willing to accept higher effort in the ECDM task also reported more time engaged in real-world activities. This association had a small-to-moderate effect size. CONCLUSIONS: The behavioral economics construct of subjective cost of effort, measured with a laboratory ECDM task, does not relate to motivation in people living with chronic HIV. However, the task shows some relationship with real-world goal-directed behavior, suggesting this construct has potential clinical relevance. More work is needed to understand how the subjective cost of effort plays out in clinical symptoms and everyday activities.

Ventromedial Frontal Lobe Damage Alters how Specific Attributes are Weighed in Subjective Valuation.

The concept of subjective value is central to current neurobiological views of economic decision-making. Much of this work has focused on signals in the ventromedial frontal lobe (VMF) that correlate with the subjective value of a variety of stimuli (e.g., food, monetary gambles), and are thought to support decision-making. However, the neural processes involved in assessing and integrating value information from the attributes of such complex options remain to be defined. Here, we tested the necessary role of VMF in weighting attributes of naturalistic stimuli during value judgments. We asked how distinct attributes of visual artworks influenced the subjective value ratings of subjects with VMF damage, compared to healthy participants and a frontal lobe damaged control group. Subjects with VMF damage were less influenced by the energy (emotion, complexity) and color radiance (warmth, saturation) of the artwork, while they were similar to control groups in considering saliency, balance and concreteness. These dissociations argue that VMF is critical for allowing certain affective content to influence subjective value, while sparing the influence of perceptual or representational information. These distinctions are important for better defining the often-underspecified concept of subjective value and developing more detailed models of the brain mechanisms underlying decision behavior.