Mitochondrial Health, Physical Functioning, and Daily Affect: Bioenergetic Mechanisms of Dementia Caregiver Well-Being.

OBJECTIVE: Chronic stress adversely affects mental and physical well-being. However, health outcomes vary among people experiencing the same stressor. Individual differences in physical and emotional well-being may depend on mitochondrial biology, as energy production is crucial for stress regulation. This study investigated whether mitochondrial respiratory capacity corresponds to individual differences in dementia spousal caregivers' mental and physical health. METHODS: Spousal caregivers of individuals with Alzheimer's disease and related dementias ( N = 102, mean age = 71, 78% female, 83% White) provided peripheral blood samples and completed self-report questionnaires on quality of life, caregiver burden, and a 7-day affect scale. Multiple and mixed linear regressions were used to test the relationship between mitochondrial biology and well-being. RESULTS: Spare respiratory capacity ( b = 12.76, confidence interval [CI] = 5.23-20.28, p = .001), maximum respiratory capacity ( b = 8.45, CI = 4.54-12.35, p < .0001), and ATP-linked respiration ( b = 10.11, CI = 5.05-15.18, p = .0001) were positively associated with physical functioning. At average ( b = -2.23, CI = -3.64 to -0.82, p = .002) and below average ( b = -4.96, CI = -7.22 to 2.70, p < .0001) levels of spare respiratory capacity, caregiver burden was negatively associated with daily positive affect. At above average levels of spare respiratory capacity, caregiver burden was not associated with positive affect ( p = .65). CONCLUSIONS: Findings suggest that higher mitochondrial respiratory capacity is associated with better psychological and physical health-a pattern consistent with related research. These findings provide some of the earliest evidence that cellular bioenergetics are related to well-being.

Optimal outbreeding is shaped during larval life-history in the splash pool copepod Tigriopus californicus.

Inbreeding and outbreeding depression are dynamic forms of selection critical to mating system evolution and the efficacy of conservation biology. Most evidence on how the relative severity and timing of these forces are shaped is confined to self-fertilization, distant outcrossing, and intermediate 'optimal outcrossing' in hermaphrodites. We tested the notion that closed population demographics may reduce and delay the costs of inbreeding relative to distant outbreeding in an intertidal copepod with separate sexes and a biphasic larval / post-metamorphic life-history (Tigriopus californicus). At three lifecycle stages (fecundity, metamorphosis, and post-metamorphosis), we quantified the effects of inbreeding and outbreeding in crosses with varying degrees of recent common ancestry. Although inbreeding and outbreeding depression have distinct genetic mechanisms, both manifested the same stage-specific consequences for fitness. Inbreeding and outbreeding depression were not apparent for fecundity, post-metamorphic survival, sex ratio, or the ability to acquire mates, but inbreeding between full siblings and outbreeding between interpopulation hybrids reduced the fraction of offspring that completed metamorphosis by 32% and 47%, respectively. On average, the effects of inbreeding on metamorphic rate were weaker and nearly twice as variable among families than those of outbreeding, suggesting genetic load was less pervasive than the incompatibilities accrued between divergent populations. Overall, our results indicate the transition from larval to juvenile life stages is markedly susceptible to both inbreeding and outbreeding depression in T. californicus. We suggest stage-specific selection acting concurrently with the timing of metamorphosis may be an instrumental factor shaping reproductive optima in species with complex life-histories.

Measures of performance validity for Hispanic/Latin American adults: A PRISMA systematic review.

Objective: Use of performance validity tests (PVTs) to assess suboptimal performance has become a recommended feature in neuropsychological evaluations. However, most of the literature has examined the utility of PVTs in primarily non-Hispanic White, monolingual English-speaking samples. Given the continual growth of culturally and linguistically diverse (CALD) populations, especially Hispanic/Latin Americans (H/Ls), it is necessary to provide an updated review on the available literature involving the use of PVTs in H/L adults. Methods: We conducted a systematic review that examined the available literature surrounding use of performance validity measures in H/L adults. This review identified evidence for the utility of PVTs in assessing invalid performance in H/Ls and compiled psychometric properties related to these measures, specifically rates of specificity and sensitivity when available. Results: We identified six standalone and four embedded performance validity measures that have been examined in H/Ls. The Test of Memory Malingering (TOMM) was identified as the PVT most studied in various H/L heritage groups. Across the studies reviewed, adjustments to cutoff scores are generally recommended for the majority of PVTs discussed. Within H/Ls, specificity rates tend to be bolstered when sociocultural factors, like education, are considered. Conclusions: Recommended cutoff scores across the different PVTs reviewed are not typically suitable for use in heritage groups of H/L adults, especially in groups that include adults with lower levels of education and literacy. Therefore, education may need to be considered when applying cutoffs to these populations.

Apathy in persons living with HIV disease: A systematic narrative review.

BACKGROUND: Apathy was identified as a feature of HIV early in the epidemic; however, there are no systematic reviews of the diverse literature on the sociodemographic and clinical correlates of apathy in HIV disease. METHODS: The current study adopted a hybrid systematic-narrative review methodology in which we used PRISMA guidelines to identify, summarize, and critique peer-reviewed, empirical studies of apathy in HIV disease in the era of combination antiretroviral therapy. RESULTS: A total of 34 studies of apathy in persons living with HIV (PLWH) were identified. Findings across these studies showed that apathy was reliably related to the structure of grey and white matter pathways commonly implicated in apathy, poorer everyday functioning, education, and other neuropsychiatric symptoms (e.g., depression). Apathy was not reliably associated with age, sex, race/ethnicity, cognition, and clinical markers of HIV disease. LIMITATIONS: The current review does not provide rigorous quantitative estimates of clinical correlates of apathy, and the exclusion criteria of non-English and non-peer reviewed publications introduces risk of bias and Type I error. CONCLUSIONS: Apathy occurs at higher rates in PLWH and is linked to neuroanatomical differences, as well as negative outcomes for everyday functions, aspects of neurocognition, and neuropsychiatric symptoms. As such, apathy is an important component to consider in the clinical assessment, diagnosis, and management of neurocognitive disorders in PLWH. Future work is needed to replicate existing findings with larger sample sizes and longitudinal designs, examine apathy as a multi-dimensional construct, and develop evidence-based treatments for apathy in PLWH.

Health literacy mediates the association between cognition and healthcare provider interactions among gay and bisexual men with HIV disease.

Introduction: Gay and bisexual men (GBM) account for the highest rates of incident infection with HIV in the U.S., and experience social, systemic barriers to accessing and engaging in healthcare services. Interacting with healthcare providers can be a complex process for some GBM with HIV disease. The current study examined the contributions of cognition and health literacy to perceived interactions with healthcare providers among GBM with HIV disease. Methods: The sample included 100 adults with HIV disease (ages 24-75) who identified as GBM. All participants completed the Dealing with Health Professionals subscale of the Beliefs Related to Medication Adherence survey, as well as the Cogstate neuropsychological battery, self-report measures of cognitive symptoms, and well-validated measures of health literacy. Results: Worse performance-based cognition and subjective cognitive symptoms were both associated with perceived difficulties dealing with healthcare providers, but these associations were fully mediated by lower health literacy. Conclusion: Health literacy may play a role in the association between poorer cognitive functioning and difficulties navigating healthcare interactions among GBM with HIV disease. Further studies are needed to determine whether cognitive approaches to enhancing the access, understanding, and use of health information in GBM with HIV disease improves healthcare interactions and outcomes.

Development of the Telephone-based Daily Instrumental Activities of Living (T-DIAL) to assess financial management remotely in older adults.

The current study evaluated the reliability and validity of a novel, performance-based banking task in 60 younger (18-34 years) and 60 older (50-85 years) adults. All participants completed the Telephone-based Daily Instrumental Activities of Living (T-DIAL) using interactive voice response technology to complete a series of mock actions with a financial institution via telephone. The T-DIAL showed strong inter-rater reliability and internal consistency. T-DIAL accuracy was significantly and independently related to better self-reported instrumental activities of daily living and executive functions at a large effect size. Findings from this study provided preliminary supportive evidence for the reliability and validity of the T-DIAL, which had robust associations with manifest everyday functioning and higher-order cognitive ability. Future work is needed on the psychometrics (e.g. test-retest reliability, normative standards), and construct validity (e.g. diagnostic accuracy) of the T-DIAL in neurocognitive disorders and under-served communities for whom remote evaluations might be particularly relevant.

LPS-induced whole-blood cytokine production and depressive symptoms in dementia spousal caregivers: The moderating effect of childhood trauma.

Dementia spousal caregivers are at risk for adverse mental and physical health outcomes. Caregiver burden, anticipatory grief, and proinflammatory cytokine production may contribute to depressive symptoms among caregivers. People who report childhood trauma are more likely to have exaggerated stress responses that may also contribute to depressive symptoms in adulthood. This study aimed to test whether the relationship between whole-blood cytokine production and depressive symptoms is strongest in caregivers who report high levels of childhood trauma. METHODS: A sample of 103 dementia spousal caregivers provided self-report data on demographics, health information, caregiver burden, anticipatory grief, and depressive symptoms. We also determined lipopolysaccharide-induced whole-blood cytokine production as the primary measure of immune cell reactivity. We measured interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and interleukin-10 (IL-10) and converted z-scores of each cytokine into a composite panel. We regressed depressive symptoms on proinflammatory cytokine production, caregiver burden, and anticipatory grief, adjusting for demographic and health-related covariates. RESULTS: Whole-blood cytokine production and childhood trauma were associated with depressive symptoms. Childhood trauma moderated the relationship between whole-blood cytokine production and depressive symptoms. Whole-blood cytokine production was only associated with depressive symptoms at mean and high levels of childhood trauma, but not at low levels of childhood trauma. The main effects of burden and anticipatory grief on depressive symptoms were strongest for caregivers reporting high levels of childhood trauma. DISCUSSION: Childhood trauma has lasting impacts on psychosocial experiences later in life and has effects that may confer susceptibility to inflammation-related depression. Our findings contribute to ongoing efforts to identify risk factors for adverse mental health in dementia spousal caregivers.