*3.8. Mental Health and Cardiovascular Function Correlates*

Behavioral correlates with cardiovascular function and HPA axis activation were analyzed. The most statistically significant correlations found when considering the whole sample of animals are illustrated in Figure 9. Amygdala CBF was positively correlated with body weight (Figure 9A, *p* = 0.001), and corticosterone levels with the number of intact marbles (Figure 9B, *p* = 0.002) and errors in the T-maze (Figure 9C, *p* < 0.001). Systolic blood pressure was positively correlated with the number of half-buried marbles (Figure 9D, *p* = 0.009) and negatively correlated with latency to arrive to T-intersection with four paws in the TMSA test (Figure 9E, *p* = 0.007) and TM test (Figure 9F, *p* = 0.005). Sodium nitroprusside relaxations (area under the curve), a measure of endothelium-independent relaxations, were negatively correlated with the total horizontal activity in the first open-field test (Figure 9G) and vertical activity in the two open-fields (Figure 9H, *p* = 0.007, and 9I, *p* = 0.006). Asymmetry of several brain regions was also correlated with behavior. Cortical areas were positively correlated with risk assessment behavior (Figure 9J, *p* = 0.003), neophobia in the corner test (Figure 9K, *p* = 0.004), and errors in the T-maze (Figure 9L, *p* = 0.008). Hippocampal's asymmetry index (AI), defined as (right-left)/(right + left) \* 100 was negatively correlated with neophobia in the corner test (Figure 9M, *p* = 0.009), while amygdala's asymmetry index was positively correlated with neophobia in the second open-field test (Figure 9N, *p* = 0.005).

The functional correlates of the behavioral signatures were also analyzed for the corresponding group and are presented as supplementary data (supplementary material). Briefly, the increased and persistent neophobia in female 3xTg-AD mice, confirmed also in the open-field test, was correlated with Phe %KCL- pEC50 (r > −0.983, *p* < 0.003), area under the curve (AUC) (r = −0.983, *p* = 0.001), PEC50 (r = -0.983, *p* = 0.007), and KCL (r > −0.965, *p* < 0.008). The hyperactive pattern of male 3xTg-AD mice in the open-field test was correlated with the striatum (Bregma -1.5 mm) asymmetry index (AI) (r = 0.790, *p* = 0.006), systolic blood pressure (r = −0.910, *p* = 0.002), PEC50 Acetylcholine (% Phe) (r = −0.842, *p* = 0.002), and amygdala (Bregma −1.5 mm) AI (r> 0.776, *p* < 0.009). The disinhibitory behavior in male and female 3xTg-AD mice in the dark–light box was correlated with acetylcholine (% Phe)- area under curve (r= 0.707, +, *p* = 0.003); cortex (Bregma -2.5 mm) AI (r= 0.612, +, *p* = 0.009), acetylcholine (% Phe)- maximum effect (r = -0.679, +, *p* = 0.005); the frailty index FI (r= 0.616, +, *p* = 0.009) and global cerebral blood flow in the selected slices (r= 0.660, +, p = 0.004), striatum (r = 0.709, +, *p* = 0.001), caudate putamen (r = 0.671, +, *p* = 0.003), amygdala (r = 0.622, +, p = 0.009); striatum (Bregma −2.5 mm) AI (r = −0.766, *p* < 0.001). The slower speed of female 3xTg-AD mice in the water maze was correlated with the cerebral blood flow of whole brain (r = -0.878, *p* = 0.009), striatum (r = −0.893, +, *p* = 0.007), caudate putamen (r = -0.916, +, *p* = 0.004), and hippocampus (r = −0.906, *p* = 0.005). Finally, paradoxal performances in male 3xg-AD mice probably related to their emotional and physical comorbid conditions to cognitive function were found correlated with acetylcholine (% Phe)- PEC50 (r = 0.774, +, *p* = 0.009), sodium nitroprusside (% Phe)- PEC50 (r = 0.784, +, *p* = 0.007), cerebral blood flow of whole brain (r= 0.778, +, p = 0.008), striatum (r = 0.795, +, *p* = 0.006), caudate putamen (r = 0.807, +, *p* =0.005), and cortex (Bregma −1.5 mm) AI (r = 0.844, +, *p* = 0.002).

**Figure 9.** Mental health—cardiovascular function correlation analysis. Meaningful significant Pearson r correlations between behavior and cardiovascular function and HPA axis. (**A**) Amygdala CBF with body weight (**B**) corticosterone levels with the number of intact marbles, and (**C**) errors in the T-maze. (**D**) Systolic blood pressure with the number of half-buried marbles and (**E**) with the latency to arrive to T-intersection with 4 paws in TMSA test and (**F**) TM test. (**G**) Vascular function, as measured by the area under the curve (AUC) of sodium nitroprusside and the total horizontal activity in the first open-field test and (**H**,**I**) vertical activity in the two open fields. (**J**) Cortical asymmetry index (AI) and risk assessment behavior, (**K**) neophobia in the corner test, and (**L**) errors in the T-maze. (**M**) Hippocampal's asymmetry index and neophobia in the corner test, (**N**) amygdala's asymmetry index and neophobia in the second open-field test.
