Fluorodeoxyglucose metabolism associated with tau-amyloid interaction predicts memory decline.

OBJECTIVE: The aim of this article was to evaluate in normal older adults and preclinical Alzheimer's disease (AD) the impact of amyloid and regional tauopathy on cerebral glucose metabolism and subsequent memory decline. METHODS: We acquired positron emission tomography using F18 flortaucipir (tau), C11 Pittsburgh compound B (amyloid), and F18 fluorodeoxyglucose (FDG) in 90 clinically normal elderly of the Harvard Aging Brain Study. RESULTS: Posterior cingulate metabolism decreased when both amyloid and neocortical tau were high and predicted subsequent memory decline in a larger sample of normal elderly. In contrast, frontal hypometabolism related to the common age-related entorhinal tauopathy, but this dysfunction was independent of amyloid, and did not predict significant memory decline. Neocortical tauopathy was positively associated with metabolism in individuals with subthreshold amyloid, suggesting that glucose metabolism increases before decreasing in the course of preclinical AD. INTERPRETATION: Our study identified a synergistic effect of amyloid and tau deposits and demonstrated, for the first time, in normal elderly its link to AD-like hypometabolism and to AD-like memory decline. The amyloid effect was observed with tau in neocortex, but not with tau in entorhinal cortex, which is the common site of age-related tauopathy. Entorhinal tau was associated with frontal hypometabolism, but this dysfunction was not associated with memory loss. Ann Neurol 2017;81:583-596.

Microstructure of frontoparietal connections predicts individual resistance to sleep deprivation.

Sleep deprivation (SD) can degrade cognitive functioning, but growing evidence suggests that there are large individual differences in the vulnerability to this effect. Some evidence suggests that baseline differences in the responsiveness of a fronto-parietal attention system that is activated during working memory (WM) tasks may be associated with the ability to sustain vigilance during sleep deprivation. However, the neurocircuitry underlying this network remains virtually unexplored. In this study, we employed diffusion tensor imaging (DTI) to investigate the association between the microstructure of the axonal pathway connecting the frontal and parietal regions--i.e., the superior longitudinal fasciculus (SLF)--and individual resistance to SD. Thirty healthy participants (15 males) aged 20-43 years underwent functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI) at rested wakefulness prior to a 28-hour period of SD. Task-related fronto-parietal fMRI activation clusters during a Sternberg WM Task were localized and used as seed regions for probabilistic fiber tractography. DTI metrics, including fractional anisotropy, mean diffusivity, axial and radial diffusivity were measured in the SLF. The psychomotor vigilance test (PVT) was used to evaluate resistance to SD. We found that activation in the left inferior parietal lobule (IPL) and dorsolateral prefrontal cortex (DLPFC) positively correlated with resistance. Higher fractional anisotropy of the left SLF comprising the primary axons connecting IPL and DLPFC was also associated with better resistance. These findings suggest that individual differences in resistance to SD are associated with the functional responsiveness of a fronto-parietal attention system and the microstructural properties of the axonal interconnections.

Predictors of Attrition in Longitudinal Neuroimaging Research: Inhibitory Control, Head Movement, and Resting-State Functional Connectivity.

Attrition is a major problem in longitudinal neuroimaging studies, as it may lead to unreliable estimates of the stability of trait-like processes over time, of the identification of risk factors for clinical outcomes, and of the effects of treatment. Identification of characteristics associated with attrition has implications for participant recruitment and participant retention to achieve representative longitudinal samples. We investigated inhibitory control deficits, head motion, and resting-state functional connectivity within the cognitive control network (CCN) as predictors of attrition. Ninety-seven individuals with remitted major depressive disorder or healthy controls completed a functional magnetic resonance imaging scan, which included a go/no-go task and resting-state functional connectivity. Approximately 2 months later, participants were contacted and invited to return for a second scan. Seventeen individuals were lost to follow-up or declined to participate in the follow-up scan. Worse inhibitory control was correlated with greater movement within the scanner, and each predicted a greater likelihood of attrition, with movement mediating the effects of inhibitory control on attrition. Individuals who dropped out of the study exhibited greater movement than nondropouts across 9 of the 14 runs of the scan, with medium-to-large effect sizes. Finally, exploratory analyses suggested that attenuated resting-state connectivity with the CCN (particularly in bilateral dorsolateral prefrontal cortex) was associated with greater likelihood of attrition after accounting for head motion at several levels of analysis. Inhibitory control and movement within the scanner are associated with attrition, and should be considered for strategic oversampling and participant retention strategies to ensure generalizability of results in longitudinal studies.

Physical exercise and brain responses to images of high-calorie food.

Physical exercise has many health benefits, including improved cardiovascular fitness, lean muscle development, increased metabolism, and weight loss, as well as positive effects on brain functioning and cognition. Recent evidence suggests that regular physical exercise may also affect the responsiveness of reward regions of the brain to food stimuli. We examined whether the total number of minutes of self-reported weekly physical exercise was related to the responsiveness of appetite and food reward-related brain regions to visual presentations of high-calorie and low-calorie food images during functional MRI. Second, we examined whether such responses would correlate with self-reported food preferences. While undergoing scanning, 37 healthy adults (22 men) viewed images of high-calorie and low-calorie foods and provided desirability ratings for each food image. The correlation between exercise minutes per week and brain responses to the primary condition contrast (high-calorie>low-calorie) was evaluated within the amygdala, insula, and medial orbitofrontal cortex, brain regions previously implicated in responses to food images. Higher levels of exercise were significantly correlated with lower responsiveness within the medial orbitofrontal cortex and left insula to high-calorie foods. Furthermore, activation of these regions was positively correlated with preference ratings for high-calorie foods, particularly those with a savory flavor. These findings suggest that physical exercise may be associated with reduced activation in food-responsive reward regions, which are in turn associated with reduced preferences for unhealthy high-calorie foods. Physical exercise may confer secondary health benefits beyond its primary effects on cardiovascular fitness and energy expenditure.