Medication management error types: Associations with mild cognitive impairment subtype.

Objective: Medication management errors are suspected to be prevalent among older adults with mild cognitive impairment (MCI). This study examined types of simulated medication-taking errors in cognitively normal older adults (CN; n = 131), single domain amnestic MCI (sdMCI, n = 91), and multi-domain MCI (mdMCI, n = 44). Errors were measured using the medication management ability assessment (MMAA). Methods: 266 participants seen for neuropsychological evaluation (94.4% White, 57.9% female, average age = 72, average education = 14 years) completed the MMAA (version 4.1), a performance-based task of medication management. Group differences in MMAA total scores, accuracy, and error types were evaluated using Kruskall-Wallis H tests. This study was the first to explore a newly operationalized error, perseverations, caused by taking a specific dose ≥2 times during the simulation. Results: CN and sdMCI groups had higher MMAA total scores than individuals with mdMCI, indicating better overall performance. The mdMCI group made a higher number of omission errors (missed pills) than other groups, but no differences were found for commission errors (extra pills). The sdMCI group made more perseverative errors compared to the CN group. Conclusions: Individuals with mdMCI made more simulated medication management errors than CN and sdMCI groups, indicating that they may be most vulnerable to difficulties in medication management. In contrast, sdMCI individuals were more likely to make perseverative errors, which may reflect a tendency towards overcompensation of memory loss. Future studies should assess whether MMAA performance is associated with patterns of real-world medication-taking in more diverse samples of older adults.

Compensatory Strategy Intervention: What Older Patients Want and Why.

OBJECTIVE: Compensatory strategies can improve performance of instrumental activities of daily living in people with cognitive impairment. This study investigated patient interest in compensatory strategy interventions and preference for various intervention formats. METHODS: Semi-structured qualitative interviews with 38 older adults with cognitive impairment queried motivation to improve strategy use and interest in intervention formats/delivery methods. Two coders used thematic analysis to determine rates of interest in each intervention type and explore patient-reported barriers and facilitators to motivation and intervention models. RESULTS: Most of the samples reported motivation to enhance compensatory strategy use. Degree of motivation was driven by current experiences with strategy use, perceived benefit of potential changes, intrinsic desire to improve life and self, and current perceived need. The vast majority were interested in hour-long, multi-session, instructor-led interventions. Just over half of the sample was interested in a self-directed virtual program, and just under half was interested in involving family/friends. Facilitators and barriers to interest in intervention formats and delivery methods varied based on participants' previous experiences, preferred learning style, content, and time commitment of the intervention, and perceived current need for intervention. One-fifth of the sample expressed no interest in any intervention type, though they expressed openness to assistance in the future as needed. CONCLUSIONS: Older adults with cognitive impairment are generally motivated to enhance their compensatory strategy use. Clinicians/researchers designing compensatory strategy interventions should consider instructor-led formats, present individualized benefits of interventions, and demonstrate the benefits of both preventative and remedial intervention to optimize patient engagement.

The complementary utility of cognitive testing and the medication management ability assessment in older adults.

OBJECTIVE: Older adults are susceptible to cognitive declines that may limit independence. Though neuropsychologists opine about risk of functional decline, the degree to which cognitive testing and in-office simulations approximate everyday behavior is unclear. We assessed the complementary utility of cognitive testing and the face-valid Medication Management Ability Assessment (MMAA) to predict medication management among older adults. METHOD: This was a retrospective study of 234 older adults (age = 72 ± 7.7 years; 59% women) who completed the MMAA during outpatient neuropsychological evaluations. Based on comprehensive clinical assessment, most participants (n = 186) were independent in medication management, while 48 received assistance. Demographically adjusted composite scores were derived for attention/processing speed (A/PS), executive functioning (EF), visuospatial/constructional ability (VC), language, and memory domains. Univariate differences in cognition were examined across Assisted versus Independent groups. Logistic regression assessed which cognitive domains independently predicted group status. The incremental value of the MMAA was assessed, holding uniquely associated cognitive test scores constant. RESULTS: Those receiving assistance with medication management performed worse across all neurocognitive domains and the MMAA compared with independent counterparts. EF was the only unique cognitive predictor of medication management status. When modeled alone, EF and MMAA performance correctly classified 79.5% and 80.8% of cases, respectively. When modeled together, both were independently associated with medication management status and correctly classified 83.3% of cases. CONCLUSIONS: EF uniquely predicted medication management status beyond other cognitive domains. The MMAA provided complementary predictive utility. Concurrent interpretation of executive functioning and MMAA performance is advised when assessing older adults suspected of medication mismanagement. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

The Clinical Utility and Ecological Validity of the Medication Management Ability Assessment in Older Adults with and without Dementia.

OBJECTIVE: Older adults are susceptible to medication nonadherence, which may signify functional decline. Thus, performance-based proxies of medication-taking behavior may help diagnose dementia. We assessed the Medication Management Ability Assessment's (MMAA) clinical utility and ecological validity. METHOD: This was a retrospective chart review of 180 outpatients (age = 72 ± 8 years) who completed the MMAA during clinical evaluations. Forty-seven were cognitively normal (CN), 103 had mild cognitive impairment (MCI), and 30 had dementia. Most (136) were independent in medication management, whereas 28 were assisted and 16 were dependent. Kruskal-Wallis tests assessed whether MMAA scores differed by diagnosis and independence. Receiver operating characteristic (ROC) analyses identified diagnostic cut-offs. Classification accuracy estimates were derived. RESULTS: MMAA performance differed across diagnosis as expected (p's < .001). Those who were independent in medication management outperformed assisted and dependent counterparts (p's < .001). Assisted and dependent cases were no different. At a cut-off = 23, the MMAA was good-to-strong in distinguishing dementia from CN cases (Sn = 0.96, Sp = 0.83), dementia from MCI (Sn = 0.70, Sp = 0.83), and dementia from functionally unimpaired cases (Sn = 0.78, Sp = 0.83). At a cut-off = 27, it had good sensitivity but weaker specificity when distinguishing both MCI and all cognitively impaired patients (MCI and dementia) from CN cases (Sn = 0.81, Sp = 0.66 and Sn = 0.81, Sp = 0.72, respectively). CONCLUSIONS: The MMAA has ecological validity and clinical utility in identifying dementia. Its inclusion in neuropsychological practice may be especially useful when medication mismanagement is suspected.

An fMRI investigation of the relations between Extraversion, internalizing psychopathology, and neural activation following reward receipt in the Human Connectome Project sample.

Quantitative models of psychopathology (i.e., HiTOP) propose that personality and psychopathology are intertwined, such that the various processes that characterize personality traits may be useful in describing and predicting manifestations of psychopathology. In the current study, we used data from the Human Connectome Project (N = 1050) to investigate neural activation following receipt of a reward during an fMRI task as one shared mechanism that may be related to the personality trait Extraversion (specifically its sub-component Agentic Extraversion) and internalizing psychopathology. We also conducted exploratory analyses on the links between neural activation following reward receipt and the other Five-Factor Model personality traits, as well as separate analyses by gender. No significant relations (p < .005) were observed between any personality trait or index of psychopathology and neural activation following reward receipt, and most effect sizes were null to very small in nature (i.e., r < |.05|). We conclude by discussing the appropriate interpretation of these null findings, and provide suggestions for future research that spans psychological and neurobiological levels of analysis.

Peer influence, Frontostriatal connectivity, and delay discounting in African American emerging adults.

Prior research has demonstrated the importance of delay discounting in adverse health behaviors, such as addiction, attention deficit hyperactivity disorder, risk taking, and obesity. Nevertheless, the functional connectivity of neural circuitry associated with delay discounting and the ways in which the social environment may influence frontostriatal connectivity remain largely unknown, particularly in African Americans. Building on recent literature implicating frontostriatal connectivity during active delay discounting decision making and at rest, we used functional magnetic resonance imaging to assess the association between delay discounting and frontostriatal resting state connectivity (rsFC). We also examined the capacity of social relationships with parents and peers to longitudinally predict frontostriatal rsFC. The study cohort was composed of 91 rural African American emerging adults followed over a 6-year period. Greater (i.e., more positive) frontostriatal rsFC was associated with decreased delay discounting (i.e., less impulsive decision making). In addition, peer relationships at ages 20 and 21 significantly predicted frontostriatal rsFC at age 25 above and beyond parental influence. A significant indirect effect of peer affiliation on delay discounting through frontostriatal rsFC also emerged. These results indicate a role of frontostriatal connectivity in delay discounting decision making and highlight peers' unique influence on decision making behaviors through frontostriatal rsFC during emerging adulthood.

Neurocompensatory Effects of the Default Network in Older Adults.

The hemispheric asymmetry reduction in older adults (HAROLD) is a neurocompensatory process that has been observed across several cognitive functions but has not yet been examined in relation to task-induced relative deactivations of the default mode network. The present study investigated the presence of HAROLD effects specific to neural activations and deactivations using a functional magnetic resonance imaging (fMRI) n-back paradigm. It was hypothesized that HAROLD effects would be identified in relative activations and deactivations during the paradigm, and that they would be associated with better 2-back performance. Forty-five older adults (M age = 63.8; range = 53-83) were administered a verbal n-back paradigm during fMRI. For each participant, the volume of brain response was summarized by left and right frontal regions of interest, and laterality indices (LI; i.e., left/right) were calculated to assess HAROLD effects. Group level results indicated that age was significantly and negatively correlated with LI (i.e., reduced left lateralization) for deactivations, but positively correlated with LI (i.e., increased left lateralization) for activations. The relationship between age and LI for deactivation was significantly moderated by performance level, revealing a stronger relationship between age and LI at higher levels of 2-back performance. Findings suggest that older adults may employ neurocompensatory processes specific to deactivations, and task-independent processes may be particularly sensitive to age-related neurocompensation.

Higher Peripheral Inflammatory Signaling Associated With Lower Resting-State Functional Brain Connectivity in Emotion Regulation and Central Executive Networks.

BACKGROUND: Researchers document bidirectional pathways linking peripheral inflammation and neural circuitries subserving emotion processing and regulation. To extend this work, we present results from two independent studies examining the relationship between inflammation and resting-state functional connectivity (rsFC), as measured by functional magnetic resonance imaging. METHODS: Study 1 involved 90 rural African American young adults, 25 years of age (52% female), and study 2 involved 82 urban African American youths, 13 to 14 years of age (66% female). Both studies measured circulating inflammatory biomarkers (C-reactive protein, interleukin 6, interleukin 10, tumor necrosis factor alpha), and the measures were averaged to form a composite. Study 2 also enumerated classical monocytes, a key leukocyte subpopulation involved in immune-to-brain signaling. All participants completed a resting-state functional magnetic resonance imaging scan. RESULTS: Consistent with our prediction, higher scores on the inflammatory composite were associated with lower rsFC within an emotion regulation network in study 1, controlling for sex. Study 2 replicated study 1, showing that higher scores on the inflammatory composite were associated with lower rsFC within the emotion regulation network, controlling for sex, age, and pubertal status, and found a similar pattern for rsFC within a central executive network. Study 2 also found that higher numbers of classical monocytes were associated with lower rsFC within both the emotion regulation and central executive networks. There was no relationship between rsFC in the anterior salience or default mode networks with inflammation in either study. CONCLUSIONS: With these findings, we document relationships between peripheral inflammation and rsFC within an emotion regulation and central executive network and replicate these associations with the emotion regulation network across two independent samples.

Socioeconomic hardship and delayed reward discounting: Associations with working memory and emotional reactivity.

Prolonged exposure to socioeconomic hardship (SH) is associated with greater delayed reward discounting (DRD), a form of impulsive decision-making that reflects a reduced capacity to delay gratification and a significant correlate of diverse risk behaviors, but the neurobehavioral mechanisms linking SH and DRD are unknown. An emerging hypothesis suggests that cognitive and affective stress associated with poverty may tax neurocognitive functions, such as working memory (WM), and lead to impulsive DRD. Furthermore, research suggests that emotional reactivity (ER) is an important dispositional factor to consider in the link between executive functions and DRD. Thus, we longitudinally examined the indirect effect of SH on impulsive DRD via a network of brain regions associated with WM function in a sample of young adults, and whether that link was moderated by ER. Participants were 119 rural African Americans (aged 19-24 years) assessed behaviorally on four occasions, with fMRI at the last time point. Results showed that, among emerging adults with higher ER, SH severity was predictive of increased DRD via reduced response in brain regions activated during an n-back WM task. These findings reveal both the cognitive and affective mechanisms that underlie the relationship between SH and DRD.

The Mediating Role of Neural Activity on the Relationship Between Childhood Maltreatment and Impulsivity.

Child maltreatment is associated with a variety of risk behaviors in young adulthood; however, the underlying cognitive and neural mechanisms of this relation are not well understood. The primary aim of the present study was to examine the direct and indirect effects between maltreatment in childhood and downstream impulsivity via neural activity during a cognitive task. In a sample of emerging adult women from the rural southeastern United States, childhood abuse and neglect were assessed using the childhood trauma questionnaire. Outcome measures of neural activity during a functional magnetic resonance imaging N-back verbal working memory (WM) task and trait impulsivity on the Impulsive Behavior Scale were assessed approximately 1 year later. Results indicate that adults with higher levels of reported childhood maltreatment demonstrate worse behavioral performance and lower neural response during a difficult verbal WM task. Furthermore, neural activity significantly mediated the relation between abuse and neglect in childhood and trait impulsivity. These new findings demonstrate an association between neurocognitive functioning and reported childhood abuse and neglect, and indicate that such changes may underlie the relation between maltreatment and trait-level impulsivity.

Insula thickness asymmetry relates to risk of major depressive disorder in middle-aged to older adults.

A growing body of research implicates the insula as a critical brain structure in major depressive disorder (MDD), emotional salience, and interoception. Despite a high prevalence of depressive symptoms among middle-aged to older adults and the elevated risks that they confer towards poor outcomes like deteriorating health and suicidality, only limited research has examined the role of the insula in this population. The present study investigates associations between insula thickness and risk of developing MDD in middle-aged to older adults. A composite measure of MDD risk was quantified based upon current Beck Depression Inventory-II scores, current antidepressant medication use, and self-reported history of depression. Linear regressions were performed to analyze the relationships between insula thickness and MDD risk. Linear regression established that left-right insula thickness difference and left insula thickness significantly predicted MDD risk; however, right insula thickness did not. These findings provide evidence of the importance of insula thickness in middle-aged to older adults at elevated risk for MDD, while highlighting the left insula as an area of particular interest.

A Family Focused Intervention Influences Hippocampal-Prefrontal Connectivity Through Gains in Self-Regulation.

The stressors associated with poverty increase the risks for externalizing psychopathology; however, specific patterns of neurobiology and higher self-regulation may buffer against these effects. This study leveraged a randomized control trial, aimed at increasing self-regulation at ~11 years of age. As adults, these same individuals completed functional MRI scanning (Mage  = 24.88 years; intervention n = 44; control n = 49). Functional connectivity between the hippocampus and ventromedial prefrontal cortex was examined in relation to the intervention, gains in self-regulation, and present-day externalizing symptoms. Increased connectivity between these brain areas was noted in the intervention group compared to controls. Furthermore, individual gains in self-regulation, instilled by the intervention, statistically explained this brain difference. These results begin to connect neurobiological and psychosocial markers of risk and resiliency.

Cognitive processing speed mediates the effects of cardiovascular disease on executive functioning.

OBJECTIVE: The goal of this study was to examine the hypothesized mediating role of cognitive processing speed (CPS) in the relationship between cardiovascular disease (CVD) and executive functioning (EF). We investigated whether the processing-speed hypothesis in aging also explains the unique contribution that CPS may have to EF deficits in CVD patients. METHOD: A neuropsychological assessment, including multiple measures of CPS and EF, was administered to 21 older adults with a history of CVD and 73 older adults with no history of CVD. Structural equation models were used to measure the indirect associations between CVD and 6 EF task outcomes through a CPS factor. Competing indirect links were assessed using the product-of-coefficients (α*ß) approach with bias-corrected bootstrap confidence intervals. RESULTS: CVD was significantly, negatively related to CPS (ß = -.239, 95% CI [-.457, -.021]). CPS was significantly, positively related to an EF composite score (ß = .566, 95% CI [.368, .688]). CVD was significantly, negatively related to the EF composite score (ß = -.137, 95% CI [-.084, -.211]). The indirect links from CVD to the individual measures of the EF composite score via CPS were all significant. CVD most adversely affected tasks of cognitive flexibility and inhibition indirectly through CPS. CONCLUSION: With the present study, we have demonstrated that the processing-speed hypothesis in aging extends to older adult patients with CVD. Reduced CPS significantly underlies the link between CVD status and poorer EF. Individuals with CVD demonstrated poorer CPS and EF than those without CVD, and CPS was specifically implicated as a CVD-related mechanism leading to worse EF. (PsycINFO Database Record

Flavor Identification and Intensity: Effects of Stimulus Context.

Two experiments presented oral mixtures containing different proportions of the gustatory flavorant sucrose and an olfactory flavorant, either citral (Experiment 1) or lemon (Experiment 2). In 4 different sessions of each experiment, subjects identified each mixture as "mostly sugar" or "mostly citrus/lemon" or rated the perceived intensities of the sweet and citrus components. Different sessions also presented the mixtures in different contexts, with mixtures containing relatively high concentrations of sucrose or citral/lemon presented more often (skew sucrose or skew citral/lemon). As expected, in both experiments, varying stimulus context affected both identification and perceived intensity: Skewing to sucrose versus citral/lemon decreased the probability of identifying the stimuli as "mostly sugar" and reduced the ratings of sweet intensity relative to citrus intensity. Across both contextual conditions of both experiments, flavor identification associated closely with the ratio of the perceived sweet and citrus intensities. The results accord with a model, extrapolated from signal-detection theory, in which sensory events are represented as multisensory-multidimensional distributions in perceptual space. Changing stimulus context can shift the locations of the distributions relative to response criteria, Decision rules guide judgments based on both sensory events and criteria, these rules not necessarily being identical in tasks of identification and intensity rating.