Hypertension affects many older adults and is associated with impaired neural and cognitive functioning. We investigated whether a history of hypertension was associated with impairments to prospective memory, which refers to the ability to remember to perform delayed intentions such as remembering to take medication. Thirty-two cognitively-normal older adult participants with or without a history of hypertension (self-reported) performed two laboratory prospective memory tasks, one that relies more strongly on executive control (nonfocal prospective memory) and one that relies more strongly on spontaneous memory retrieval processes (focal prospective memory). We observed hypertension-related impairments for nonfocal, but not focal, prospective memory. To complement our behavioral approach, we conducted a retrospective analysis of available structural magnetic resonance imaging data. Lower white matter volume estimates in the anterior prefrontal cortex (aPFC) were associated with lower nonfocal prospective memory and with a history of hypertension. A history of hypertension may be associated with worsened executive control and lower prefrontal white matter volume. The translational implication is that individuals who must remember to take antihypertensive medications and to monitor their blood pressure at home may be impaired in the executive control process that helps to support these prospective memory behaviors.
Background: Research in adult populations has highlighted sex differences in cortisol concentrations and laboratory pain responses, with men exhibiting higher cortisol concentrations and reduced pain responses compared with women. Yet, less is known about the relationship of cortisol concentrations to pain in children.
Objective: This study examined associations between sex, cortisol, and pain responses to laboratory pain tasks in children.
Methods: Salivary cortisol samples from subjects aged 8 to 18 years were obtained at baseline after entering the laboratory (SCb), after the completion of all pain tasks (SC1), and at the end of the session (SC2), 20 minutes later. Blood cortisol samples were also taken after completion of the pain tasks (BC1) and at the end of the session (BC2), 20 minutes later. Subjects completed 3 counterbalanced laboratory pain tasks: pressure, heat, and cold pressor tasks. Pain measures included pain tolerance, and self-reported pain intensity and unpleasantness for all 3 tasks.
Results: The study included 235 healthy children and adolescents (119 boys, 116 girls; mean age, 12.7 years; range, 8–18 years; 109 [46.4%] were in early puberty; 94 [40.0%] white). Salivary and blood cortisol levels were highly correlated with each other. Salivary cortisol levels for the total sample and for boys and girls declined significantly from SCb to SC1 (P < 0.01), although there were no significant changes from SC1 to SC2. No significant sex differences in salivary or blood cortisol levels were evident at any assessment point. Separate examination of the cortisol–laboratory pain response relationships by sex (controlling for age and time of day) suggested different sex-specific patterns. Higher cortisol levels were associated with lower pain reactivity (ie, increased pressure tolerance) among boys compared with girls at SC1, SC2, and BC1 (SC1: r = 0.338, P = 0.003; SC2: r = 0.271, P = 0.020; and BC1: r = 0.261, P = 0.026). However, higher cortisol levels were related to higher pain response (ie, increased cold intensity [BC2: r = 0.229, P = 0.048] and unpleasantness [BC1: r = 0.237, P = 0.041]) in girls compared with boys.
Conclusions: These findings suggest important sex differences in cortisol–pain relationships in children and adolescents. Cortisol levels were positively associated with increased pain tolerance in boys and increased pain sensitivity in girls.
Estrogen (E2) has activational effects on sexual motivation and mitigating effects on anxiety-like behaviors that can be attenuated with chronic exposure to psychosocial stress. Some studies suggest that this attenuation can be overcome by higher doses of E2, while others show that chronic psychosocial stress may alter the mechanisms of E2 function, thus reducing any positive benefit from higher doses of E2. To determine the interaction between psychosocial stress and E2 dose on behavior, we examined the scope of attenuation across a suite of socioemotional behaviors, including reproduction, affiliation, aggression, submission, and anxiety-like behaviors on 36 ovariectomized female rhesus monkeys. Females were exposed to graded psychosocial stress, established by an intrinsic female dominance hierarchy, where subordinate animals receive high amounts of harassment. Our data show that E2 dose-dependently increased sexual motivation and male-affiliation in dominant (e.g. low-stress) females, while subordinate females showed no positive effects of E2, even at higher doses. In addition, contact aggression was attenuated in dominant females, while non-contact aggression was attenuated in both dominant and middle-ranking females. These results suggest that the stress-induced attenuation of E2's activational effects on sexual behavior and affiliation with males may not be overcome with higher doses of E2. Furthermore, the observed behavioral consequences of psychosocial stress and E2 dose may be dependent on the behaviors of all the females in the social-group, and better resolution on these effects depends on isolating treatment to individuals within the group to minimize alterations in social-group interactions.
The effects of evolutionary pressure on human immunodeficiency virus-1 (HIV) have resulted in a variety of clades and recombinants. The functional implications of HIV clades on disease onset and progression of HIV-associated neurocognitive disorders (HAND) have been suggested by clinical and basic science studies, which will be reviewed in detail. Some clinical studies suggest that patients infected with clade D show the greatest propensity for developing HIV-associated dementia (HAD) followed by clades B, C, and A respectively. However, there are conflicting reports. This review summarizes clinical studies that have assessed behavioral abnormalities and HIV clade type in HAND patients, focusing on the clades stated above. The limitations include variations in testing used to define the cohorts, patient sample size, lack of HIV clade characterization, combination antiretroviral therapy (cART) availability, and other factors, which are highlighted and compared between clinical studies performed primarily in Africa and India. Basic science studies provide substantial evidence that HIV clade differences can result in varying degrees of neuropathology and are also reviewed in some detail. These studies indicate that there are a number of clade differences, most notably in Tat, that result in different degrees of neurovirulence or neuropathological effects in vitro and in a mouse model of HAND. In order to confirm the hypothesis that HIV clade differences are important determinants of HAND pathogenesis, larger, longitudinal studies that employ standard definitions of HAND and HIV clade testing must be performed. In a larger sense, HAND continues to be highly prevalent despite the advent of cART and, therefore, further studies into HAND pathogenesis are critical to develop better therapies.