Neuromarkers of fatigue and cognitive complaints following chemotherapy for breast cancer: a prospective fMRI investigation.

The aim of this study is to use functional magnetic resonance imaging (fMRI) to prospectively examine pre-treatment predictors of post-treatment fatigue and cognitive dysfunction in women treated with adjuvant chemotherapy for breast cancer. Fatigue and cognitive dysfunction often co-occur in women treated for breast cancer. We hypothesized that pre-treatment factors, unrelated to chemotherapy per se, might increase vulnerability to post-treatment fatigue and cognitive dysfunction. Patients treated with (n = 28) or without chemotherapy (n = 37) and healthy controls (n = 32) were scanned coincident with pre- and one-month post-chemotherapy during a verbal working memory task (VWMT) and assessed for fatigue, worry, and cognitive dysfunction. fMRI activity measures in the frontoparietal executive network were used in multiple linear regression to predict post-treatment fatigue and cognitive function. The chemotherapy group reported greater pre-treatment fatigue than controls and showed compromised neural response, characterized by higher spatial variance in executive network activity, than the non-chemotherapy group. Also, the chemotherapy group reported greater post-treatment fatigue than the other groups. Linear regression indicated that pre-treatment spatial variance in executive network activation predicted post-treatment fatigue severity and cognitive complaints, while treatment group, age, hemoglobin, worry, and mean executive network activity levels did not predict these outcomes. Pre-treatment neural inefficiency (indexed by high spatial variance) in the executive network, which supports attention and working memory, was a better predictor of post-treatment cognitive and fatigue complaints than exposure to chemotherapy per se. This executive network compromise could be a pre-treatment neuromarker of risk, indicating patients most likely to benefit from early intervention for fatigue and cognitive dysfunction.

Simvastatin and environmental enrichment effect on recognition and temporal order memory after mild-to-moderate traumatic brain injury.

PRIMARY OBJECTIVE: The purpose of this study was to investigate the effect of mild-to- moderate (m-mod) traumatic brain injury (TBI) on spontaneous object (SO) recognition and temporal order (TO) memory in male Wistar rats and to compare the effects of environmental enrichment (EE) and simvastatin (Sim) on SO and TO memory post-injury. RESEARCH DESIGN: A randomized repeated measure experimental design was used. METHODS AND PROCEDURE: Seven days after arrival, animals received the injury or sham surgery. Using a Y-shaped maze, SO and TO memory was assessed in the two groups of animals at 6, 24, 48, 72 hours and 7, 14, 21 and 35 days post-surgery. Total time exploring each object and discrimination ratio were calculated and analysed. Then SO and TO memory were compared between two groups that received either Sim or EE for 2 hours daily starting 24 hours post-injury and a sham group that received saline for 14 days post-injury. RESULTS: The results showed that the injury impaired SO and TO memory compared to the sham up to 35 days post-trauma. Injured animals exhibited familiarity preference, novelty aversion and impaired TO performance. EE improved the animals' SO recognition deficits 7 days post-injury after a shorter delay (1 minute) only and Sim reversed TO memory deficits 14 days post-injury after a longer delay (60 minutes). CONCLUSION: Persistent SO and TO memory deficits follow TBI in animals; Simv and EE seem to be promising therapies of TBI memory deficits.

Mild traumatic brain injury (MTBI) leads to spatial learning deficits.

PRIMARY OBJECTIVE: The aim of this study was to investigate the effect of mild and severe TBI on young male Wistar rats' spatial learning. RESEARCH DESIGN: Randomized repeated measure experimental design was used to examine spatial learning in three independent animal groups. METHODS AND PROCEDURES: Twenty-four (severe n = 9, mild n = 8, sham n = 7) male rats were included in the study. Animals received controlled mild (1.5 mm), severe (2.5 mm) cortical impact injury or sham surgery. Spatial learning was assessed daily using a modified Morris water maze test, 20 days post-trauma, for 5 consecutive days. Percentage time travelled within each quadrant and escape latency were calculated. All animals' hippocampal brain regions were examined post-injury using neuron (MAP2) and pre-synaptic protein (Synaptophysin) biomarkers. MAIN OUTCOMES AND RESULTS: It took the animals with mild injury until day 3 to reach the platform; and animals with mild and severe injury spent significantly less time in the target quadrant than the sham. The hippocampal neuron numbers differed proportionately between animals with severe and mild injury, but the percentage of synaptophysin density was significantly less in the dentate gyrus of both animals with mild and severe injury than sham group. CONCLUSION: Persistent spatial learning deficits exist after mild TBI; these deficits appear equivalent to deficits exhibited after a more severe injury.

Nurse-Enhanced Memory Intervention in Heart Failure: the MEMOIR study.

BACKGROUND: Many patients with heart failure (HF) have cognitive deficits, including memory loss. OBJECTIVES: The aim of this study was to evaluate the efficacy of a cognitive training intervention on memory (primary outcome), working memory, psychomotor speed, executive function, and performance of cognitive activities and instrumental activities of daily living (IADLs). METHODS AND RESULTS: Forty patients with HF were randomly assigned to the computerized plasticity-based cognitive training intervention called Brain Fitness or to the health education active control intervention. Advanced practice nurses made weekly home visits to assess symptoms and monitor intervention adherence. Patients completed demographic and clinical data (baseline), neuropsychologic tests (baseline and 8 and 12 weeks), and measures of cognitive and IADLs performance (baseline and 12 weeks) and satisfaction (12 weeks). Linear mixed models analyses indicated a significant group by time interaction for delayed recall memory (P = .032) and a significant time effect for total (list learning) (P < .001) and delayed (P = .015) recall memory, psychomotor speed (P = .029), and performance of IADLs (P = .006). Intervention adherence and patient satisfaction were high. CONCLUSIONS: To our knowledge, this was the first test of Brain Fitness in HF. Although it was a preliminary study with limitations, results support the need for a larger randomized controlled trial to determine whether the memory loss of HF is amenable to plasticity-based interventions.

Reducing care-resistant behaviors during oral hygiene in persons with dementia.

BACKGROUND: Nursing home residents with dementia are often dependent on others for mouth care, yet will react with care-resistant behavior when receiving assistance. The oral health of these elders deteriorates in the absence of daily oral hygiene, predisposing them to harmful systemic problems such as pneumonia, hyperglycemia, cardiac disease, and cerebral vascular accidents. The purpose of this study is to determine whether care-resistant behaviors can be reduced, and oral health improved, through the application of an intervention based on the neurobiological principles of threat perception and fear response. The intervention, called Managing Oral Hygiene Using Threat Reduction, combines best mouth care practices with a constellation of behavioral techniques that reduce threat perception and thereby prevent or de-escalate care-resistant behaviors. METHODS/DESIGN: Using a randomized repeated measures design, 80 elders with dementia from 5 different nursing homes will be randomized at the individual level to the experimental group, which will receive the intervention, or to the control group, which will receive standard mouth care from research team members who receive training in the proper methods for providing mouth care but no training in resistance recognition or prevention/mediation. Oral health assessments and care-resistant behavior measurements will be obtained during a 7-day observation period and a 21-day intervention period. Individual growth models using multilevel analysis will be used to estimate the efficacy of the intervention for reducing care-resistant behaviors in persons with dementia, and to estimate the overall efficacy of the intervention using oral health outcomes. Activity-based costing methods will be used to determine the cost of the proposed intervention. DISCUSSION: At the conclusion of this study, the research team anticipates having a proven intervention that prevents and reduces care-resistant within the context of mouth care. Long-term objectives include testing the effect of the intervention on systemic illnesses among persons with dementia; examining the transferability of this intervention to other activities of daily living; and disseminating threat reduction interventions to nursing home staff, which may radically change the manner in which care is provided to persons with dementia. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01363258.

An intervention for delirium superimposed on dementia based on cognitive reserve theory.

Delirium superimposed on dementia (DSD) accelerates the trajectory of functional decline and results in prolonged hospitalization, re-hospitalization, premature nursing home placement, and death. In this article we propose a theory-based intervention for DSD that is derived from the literature on cognitive reserve and neuroplasticity. We begin by defining cognitive reserve, the guiding framework for our hypothesis. We review the pathophysiology and neuropsychology of delirium noting the similarities with dementia-these two conditions reflecting acute and chronic reductions in cognitive reserve, respectively. We then review the evidence for activity-dependent plasticity as a possible mechanism for sparing cognitive reserve in dementia and its potential for addressing DSD. Cognitive training (CT) in the form of stimulating activities has been shown to evoke cognitive processing and facilitate plasticity in dementia. Because of the similarities between dementia and delirium, the use of recreational activities as a vehicle for supporting attentional capacity, and delivering cognitive stimulation, may hold promise for the resolution of DSD. Based on integrated evidence from the literature, we hypothesize that engagement in cognitively stimulating recreational activities will help reduce delirium severity and duration in persons with dementia while providing improved quality of life and reduced costs of care.

Spatial Learning Responses to Lipopolysaccharide in Adult and Aged Rats.

Sickness behaviors, adaptive responses to infections, include lethargy, depression, reduced eating and grooming, and concentration problems resulting from interactions between the immune and neuroendocrine systems. Detecting these responses is especially critical in the elderly, as the infections that cause them can lead to cognitive impairment. While deficits in spatial learning, a hippocampal-dependent form of learning, are part of the sickness response, directional heading errors (DHEs; an indicator of spatial-learning deficits) and their time trajectories need further examination. Therefore, we simultaneously investigated the time trajectory of age-dependent sickness responses and spatial learning over 5 days in adult (5-6 months) and aged (22 months) male Brown-Norway rats injected with 250 µg/kg lipopolysaccharide (LPS; experimental group) or 0.9% sodium chloride (control group). LPS administration resulted in pronounced, age-dependent weight loss and decreased food intake that persisted in the aged group. Animals were tested for 5 days (trial) in the Morris water maze. After 7 days of rest, animals were retested for 2 days (retention). Adult and aged LPS-treated animals displayed greater differences in mean DHE than the control groups, indicating that they exhibited more DHE over the trial days. Experimental groups did not show consistent DHE improvement until Day 4 (adult) or 5 (aged). LPS had no effect on probe or retention trials. We conclude that LPS activation of the immune system results in a selective, age-dependent impairment in spatial learning, decreased food intake, and weight loss. All of these results are prolonged in aged animals.

Different Sickness Responses in Adult and Aged Rats Following Lipopolysaccharide Administration.

OBJECTIVE: Immune challenges result in sickness responses such as decreased activity, fever, and spatial learning deficits. While these responses occur simultaneously, they are not usually evaluated concurrently or for an extended time. The purpose of this study was to examine how an immune challenge affected activity and temperature responses in animals tested concurrently in the Morris water maze (MWM) over 5 days and how aging interacts with such responses. METHOD: An accepted model of aging, adult ( n = 10; 5-6 months) and aged ( n = 7; 22 months) male Brown-Norway rats were implanted with a telemetry device (Mini Mitter, Oakmont, PA) to continuously monitor temperature and activity following an immune challenge. These animals were injected with either 250 µg/kg lipopolysaccharide (LPS) or 0.9% sodium chloride and then assessed in the MWM for 5 days. RESULTS: Temperature responses varied by age. Initial temperatures decreased in both experimental groups followed by an increase (fever) in the adult group, while the temperatures of the aged animals remained decreased. Although both age groups were sedentary at baseline, activity decreased after LPS only in the adult group. CONCLUSION: An LPS immune challenge resulted in age-dependent temperature and activity changes. There was an absence of fever and no effect on activity in aged LPS-treated animals. These results may suggest the need to assess a broader spectrum of sickness responses when monitoring elderly individuals for infection and not rely on the presence of fever. Activity may not be a sensitive indicator of sickness in some aging models.

Effect of antipsychotic medication use on memory in patients with Alzheimer's disease: Assessing the potential risk for accelerated recent autobiographical memory loss.

Autobiographical memory loss is a common and disturbing problem for individuals with Alzheimer's disease (AD). Patients with AD who are taking antipsychotic medications may be at further risk for loss of recent autobiographical memory because of the potential anticholinergic side effects of antipsychotics. The purpose of this post hoc, descriptive study was to compare the recent autobiographical memory scores of patients with AD taking antipsychotics to those who were not taking antipsychotics. The study population was composed of 35 patients with moderate-stage AD. Patients who were taking antipsychotics scored significantly worse on a recent autobiographical memory measure compared with patients who were not taking antipsychotics. This study provides further evidence for judicious use of antipsychotic medications with AD patients.

Effects of low-dose lipopolysaccharide and age on spatial learning in different Morris water maze protocols.

OBJECTIVES: Animals administered lipopolysaccharide exhibit dose-related sickness behaviors (decreased food intake, weight loss, and cognitive changes). While research has demonstrated that spatial learning is impaired following a lipopolysaccharide immune challenge, the results differ depending on the methodology used to evaluate spatial learning. Additionally, few studies have evaluated the effects of low-dose lipopolysaccharide on spatial learning. Therefore, we assessed spatial learning, food intake, and weight changes in adult and aged rats after a low-dose lipopolysaccharide immune challenge in the Morris water maze using two water temperatures. METHODS: Adult (5-6 months) and aged (22 months) male Brown-Norway rats were administered either 50 or 100 µg/kg lipopolysaccharide or saline, and then tested in the Morris water maze for 5 days, rested for 7 days, and later underwent 2 days of retention tests. Probe trials were conducted at the end of initial and retention testing. RESULTS: Low-dose lipopolysaccharide administration did not result in food intake or weight changes. While the aged experimental group took longest to improve directional heading error in both cold and warm water, heading error was greater in cold water. Behavioral testing revealed an apparent age and water temperature effect on swim time. Retention and probe trial results showed that aged experimental animals had the worst performance in cold water. CONCLUSION: We conclude that while low-dose lipopolysaccharide did not result in typical sickness behaviors (decreased food intake or weight), spatial learning and memory were impaired in the aged experimental group. These results have important implications for the care of elderly individuals experiencing mild to moderate infections.

Cognitive dysfunction and symptom burden in women treated for breast cancer: a prospective behavioral and fMRI analysis.

Neural dysfunction and cognitive complaints are associated with chemotherapy for breast cancer although trajectory and contributory factors remain unclear. We prospectively examined neurocognition using fMRI and self-reported cognitive, physical and psychological symptoms in women treated with adjuvant chemotherapy over one year. Patients treated with (n = 28) or without (n = 34) chemotherapy for localized breast cancer and healthy controls (n = 30) performed a Verbal Working Memory Task (VWMT) during fMRI and provided self-reports at baseline (pre-adjuvant treatment), five- (M5) and 12-months (M12). Repeated measures ANOVA and multivariable regression determined change over time and possible predictors (e.g., hemoglobin, physical symptoms, worry) of VWMT performance, fMRI activity in the frontoparietal executive network, and cognitive complaints at M12. Trajectories of change in VWMT performance for chemotherapy and healthy control groups differed significantly with the chemotherapy group performing worse at M12. Chemotherapy patients had persistently higher spatial variance (neural inefficiency) in executive network fMRI-activation than both other groups from baseline to M12. Cognitive complaints were similar among groups over time. At M12, VWMT performance and executive network spatial variance were each independently predicted by chemotherapy treatment and their respective baseline values, while cognitive complaints were predicted by baseline level, physical symptoms and worry. Executive network inefficiency and neurocognitive performance deficits pre-adjuvant treatment predict cognitive dysfunction one-year post-baseline, particularly in chemotherapy-treated patients. Persistent cognitive complaints are linked with physical symptom severity and worry regardless of treatment. Pre-chemotherapy interventions should target both neurocognitive deficits and symptom burden to improve cognitive outcomes for breast cancer survivors.

Alzheimer's disease behaviors from past self-identities: an exploration of the memory and cognitive features.

Alzheimer's disease (AD) patients have been reported by caregivers to display "behaviors from past self-identities " (BPSI); however, there is little known about these distinct behaviors. This study, the first to explore BPSI, hypothesized that BPSI were associated with self-memory and cognitive impairments. Its purpose was to determine if AD subjects with and without BPSI differed on measures of autobiographical memory, selective attention, and fluency. The cross-sectional design compared 35 moderate-stage AD subjects from an AD research center. Subjects demonstrating BPSI (37 percent) recalled significantly fewer recent autobiographical memories than AD subjects without BPSI. The results establish BPSI as a common behavior among moderate-stage AD patients and suggest that paucity of recent self-memories contributes to BPSI.

What it takes: perspectives from developing nurse scientists.

The need for nurse scientists has never been greater, given the complexity of health problems facing our world and the rising cost of providing care to prevent and treat them. The development of nurse researchers is critical to preserve and advance the scientific foundation of the discipline. In this article, two successful doctoral students present their personal views about the cognitive and behavioral transformation they experienced during their program of study, highlighting what they believe to be important resources that enhance doctoral education and sharing how they overcame the challenges encountered. The framework of transformational leadership is used to highlight important aspects of their development as nurse scientists. Action steps for attracting a greater number of nurses to a career in science are recommended.

Pretreatment worry and neurocognitive responses in women with breast cancer.

UNLABELLED: [Correction Notice: An Erratum for this article was reported in Vol 33(3) of Health Psychology (see record 2014-07787-001). The name of author Misook Jung was misspelled as Mi Sook Jung. All versions of this article have been corrected.] OBJECTIVE: Altered cognitive function has been associated with breast cancer treatment, particularly adjuvant chemotherapy, but the underlying neuropsychological mechanisms are not yet understood. Recent research indicates that compromised attention and working memory can exist before adjuvant treatment, implicating psychological distress, such as worry, as a possible contributor to observed alterations in cognitive function. We hypothesized that worry associated with breast cancer diagnosis might influence neurocognitive responses before any adjuvant therapy. DESIGN: Fifty women, 25 due to receive chemotherapy and 25 due to receive radiation therapy, participated in the study. Women performed a verbal working memory task during functional magnetic resonance imaging scanning to assess neurocognitive responses before any adjuvant treatment and to test the relationship of such responses with self-reports of worry. RESULTS: Although prechemotherapy participants showed significantly higher levels of worry compared with preradiation participants, higher worry, across both groups, was related to altered brain function. Specifically, increased worry was associated with reduced demand-related deactivation in default-mode regions, such as the precuneus/posterior cingulate. Reduced demand-related deactivation was critically related to worse behavioral performance, which was partially mediated by worry. CONCLUSION: Worry appears to be a significant contributor to neurocognitive dysfunction independent of adjuvant treatment for breast cancer. These results suggest that alterations in cognitive function may develop before any chemotherapy treatment and that worry about cancer diagnosis may contribute to reports of "chemo brain" during treatment. Psychological interventions aimed at mitigating worry may help to alleviate cognitive dysfunction associated with life-threatening illness such as breast cancer.

Cue color and familiarity in place learning for older adults.

Older adults often have problems finding their way (place learning) in unfamiliar environments. We examined how colorful familiar cues-versus black-and-white abstract cues-affected place learning in 133 community-dwelling older adults using a computerized virtual environment. Participants were required to learn the location of the hidden platform using only environmental cues repeatedly over 3 days in four cue conditions that varied with respect to the color and familiarity of cues. Place learning was measured by the distance traveled to the platform. Participants found the hidden target with the shortest distance traveled when cues were colorful and familiar. Older participants showed poorer performance than the younger groups. Study results showed that place learning was assisted by using colorful familiar cues and that the older participants and those with lower cognition scores were most impaired in place learning.

No more fighting and biting during mouth care: applying the theoretical constructs of threat perception to clinical practice.

The purpose of this article is to describe how the neurobiological principles of threat perception and fear response can support clinical approaches to prevent and reduce care-resistant behaviors during mouth care. Nursing home residents who exhibit care-resistant behavior are at risk for poor oral health because daily oral hygiene may not be consistently provided. Poor oral health predisposes these older people to systemic problems such as pneumonia, cerebral vascular accidents, and hyperglycemia. Care-resistant behavior is a fear-evoked response to nurses' unintentionally threatening behavior during mouth care. Nurses can safely and effectively provide mouth care to persons with dementia who resist care by using personalized combinations of 15 threat reduction strategies.

An intervention to reduce care-resistant behavior in persons with dementia during oral hygiene: a pilot study.

The primary purpose of this pilot study was to test the feasibility of an intervention designed to reduce care-resistant behaviors (CRBs) in persons with moderate-to-severe dementia during oral hygiene activities. The intervention, Managing Oral Hygiene Using Threat Reduction (MOUTh), combined best oral hygiene practices with CRB reduction techniques. Oral health was operationalized as the total score obtained from the Oral Health Assessment Tool (OHAT). CRB was measured using a refinement of the Resistiveness to Care Scale. Seven nursing home residents with dementia received twice daily mouth care for 14 days. The baseline OHAT mean score of 7.29 (SD = 1.25) improved to 1.00 (SD = 1.26, p < .001); CRB improved from 2.43 CRBs/minute (SD = 4.26) to 1.09 CRBs/minute (SD = 1.56, t = 1.97, df 41, p= .06). The findings from this pilot study suggest that the MOUTh intervention is feasible and reduced CRBs, thus allowing more effective oral care.

Death concerns among individuals newly diagnosed with lung cancer.

Confronting the reality of death is an important challenge for individuals facing life-threatening illness such as lung cancer, the leading cause of cancer death. Few studies, however, document the nature of death-related concerns in individuals newly diagnosed with lung cancer. The aims of this exploratory study were to examine unsolicited death-related concerns among newly diagnosed individuals, and to determine if age, gender, marital status, stage of disease, type of treatment, presence of comorbid conditions, and veteran status were related to extent of death concerns. A mixed-method approach was used to examine death concerns in 73 individuals newly diagnosed with non-small cell lung cancer. Seven categories related to death were identified: psychological preparation, time left, impact, behavioral preparation, acceptance, cancer death experiences, and post-death. Stage of disease and veteran status were factors that were related to increased numbers of death-related content. Findings demonstrate that death concerns are varied, primarily negative, and are relevant to the person facing a new lung cancer diagnosis, thus highlighting the importance for health care providers to assess, discuss, and listen for death concerns in the acute care setting.

Cognitive performance associated with self-care activities in Mexican adults with type 2 diabetes.

PURPOSE: The purpose of this study was to determine the effect of memory-learning on self-care activities in adults with type 2 diabetes moderated by previous education/understanding in diabetes and to explore the explicative capacity of age, gender, schooling, diabetes duration, and glycemic control in memory-learning. METHODS: A descriptive correlational study was conducted in a randomized sample of 105 Mexican adult patients with type 2 diabetes at a community-based outpatient clinic. Evaluation measures included the Wechsler Memory Scale for memory-learning; 2 questionnaires for self-care activities and previous education/understanding in diabetes, respectively; and glycosylated hemoglobin for glycemic control. Multiple linear regression analysis was used to examine the effect of memory-learning on self-care activities and the moderator capacity of previous education/understanding on diabetes. Multivariate analysis was used to identify the capacity of age, schooling, diabetes duration, and glycemic control in memory-learning types. RESULTS: A significant positive effect of memory-learning on self-care activities was found. Education/understanding in diabetes moderated the relationship between immediate and delayed memory-learning and self-care in glucose monitoring and diet. Gender, schooling, and the gender-glycemic control interaction explained memory-learning performance. CONCLUSIONS: Immediate and delayed verbal and visual memory-learning were important for the patient to carry out self-care activities, and this relationship can be moderated by previous education/understanding in diabetes. These findings suggest potential benefits in emphasizing cognitive strategies to promote relearning of self-care behaviors in persons who live with diabetes.

Prechemotherapy alterations in brain function in women with breast cancer.

Despite clinical reports of cognitive deficits associated with cancer chemotherapy, the underlying brain mechanisms are not clear. This research examined selective attention and working memory using functional magnetic resonance imaging (fMRI) in women before chemotherapy for localized breast cancer. Patients were tested with an established selective attention and working memory task during fMRI. Compared with healthy controls, patients showed (a) bilateral brain activation in high-demand task conditions with recruitment of additional components of attention/working memory circuitry, and (b) less accurate and slower task performance. Results indicate compromised cognitive functioning before any chemotherapy and raise key questions for further research.