Introduction:It is unknown whether vascular and metabolic diseases assessed in early adulthood are associated with Alzheimer's disease (AD) later in life.Methods: Association of AD with lipid fractions, glucose, blood pressure, body mass index (BMI), and smoking obtained prospectively from 4932 Framingham Heart Study (FHS) participants across nine quadrennial examinations was evaluated using Cox proportional hazard and Kaplan-Meier models. Age-, sex-, and education-adjusted models were tested for each factor measured at each exam and within three adult age groups (early = 35-50, middle = 51-60, and late = 61-70).Results: A 15 mg/dL increase in high density lipoprotein (HDL) cholesterol was associated with decreased AD risk during early (15.4%, P = 0.041) and middle (17.9%, P = 0.014) adulthood. A 15 mg/dL increase in glucose measured during middle adulthood was associated with 14.5% increased AD risk (P = 0.00029). These findings remained significant after adjusting for treatment. Discussion: Our findings suggest that careful management of cholesterol and glucose beginning in early adulthood can lower AD risk.

Background Suppression of behavioral and physical responses defines the anesthetized state. This is accompanied, in humans, by characteristic changes in EEG patterns. However, these measures reveal little about the neuron or circuit-level physiological action of anesthetics, nor how information is trafficked between neurons. We assess whether entropy-based metrics can differentiate between the awake and anesthetized state in C. elegans and characterize emergence from anesthesia at the level of interneuronal communication. Methods Performing volumetric fluorescence imaging, we measure neuronal activity across a large portion of the C. elegans nervous system at cellular resolution during distinct states of isoflurane anesthesia as well as during emergence from the anesthetized state. Using a generalized model of interneuronal communication, we empirically derive new entropy metrics that can distinguish the awake and anesthetized states. Results We derive three new entropy-based metrics that distinguish between stable awake and anesthetized states (4% and 8% isoflurane, n=10) while possessing plausible physiological interpretations. State Decoupling is elevated in the anesthetized state(0%: 48.8 ± 3.50%, 4%: 66.9 ± 6.08%, 8%: 65.1 ± 5.16%; 0% vs. 4%, P<0.001; 0% vs. 8%, P<0.001), while Internal Predictability (0%: 46.0 ± 2.94%, 4%: 27.7 ± 5.13%, 8%: 30.5 ± 4.56%; 0% vs. 4%, P<0.001; 0% vs. 8%, P<0.001), and System Consistency (0%: 2.64 ± 1.27%, 4%: 0.97 ± 1.38%, 8%: 1.14 ± 0.47%; 0% vs. 4%, P=0.006; 0% vs. 8%, P=0.015) are suppressed. These new metrics also resolve to baseline during gradual emergence of C. elegans from moderate levels of anesthesia to the awake state (n=8). We find that early emergence from isoflurane anesthesia in C. elegans is characterized by the rapid resolution of an elevation in high frequency activity (n=8, P=0.032). The entropy-based metrics Mutual Information and Transfer Entropy , however, did not differentiate well between awake and anesthetized states. Conclusions Novel empirically-derived entropy metrics better distinguish the awake and anesthetized states compared to extant metrics and reveal meaningful differences in information transfer characteristics between states.