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Biomedical subjects

Igor Grant

Publications and source records attributed to Igor Grant.

96 records · Page 6Linked to original sources

Differential immune cell chemotaxis responses to acute psychological stress in Alzheimer caregivers compared to non-caregiver controls.

OBJECTIVE: Caregiving for a spouse with Alzheimer's disease is associated with alterations in various immune cell responses. Chemotaxis of immune cells to chemokines is an important factor involved in lymphocyte migration, which plays an essential role in inflammatory responses to infection and may also be involved in atherogenesis. However, the effects of chronic stress on chemotaxis have not been investigated. The objective of this study was to examine lymphocyte chemotaxis to chemokines, stromal cell-derived factor-1 (SDF-1), N-formyl-methionyl-leucyl-phenylalanine (FMLP), and a beta-adrenergic agonist, isoproteronol (ISO), in response to an acute stressor in Alzheimer's caregivers. Correlations between immune cell chemotaxis and epinephrine and norepinephrine levels were also examined. METHODS: Caregivers (n = 18) and noncaregiver controls (n = 9) completed a public speaking task. Blood was drawn before and immediately after the task for changes in chemotaxis to FMLP, SDF-1, and ISO, and for epinephrine and norepinephrine levels. RESULTS: Caregivers had reduced chemotaxis to FMLP, SDF-1, and ISO in response to the speech task, compared with non-caregivers. Also, the direction of the correlations between chemotaxis to FMLP, SDF-1, and ISO and epinephrine levels differed between groups. CONCLUSIONS: These findings suggest that immune cells released into circulation in response to acute stress are altered in caregivers. Group differences in immune responses may be due to sympathetically mediated alterations, which may have implications for caregivers' ability to successfully mount viable immune responses, as well as, atherogenesis.

Adaptation, Physiological↗

Depressive symptoms predict norepinephrine response to a psychological stressor task in Alzheimer's caregivers.

OBJECTIVE: Increased depressive symptoms have been associated with increased basal plasma norepinephrine (NE), and may be associated with exaggerated NE response to stress. This exaggerated response may play a role in health consequences associated with caring for a loved-one with Alzheimer's disease. The current study examined the relations between the level of depressive symptoms in spousal caregivers and the physiological response to a psychological stress task. METHODS: Fifty-five spousal caregivers (mean age 73 +/- 8 years) completed the depression subscale of the Brief Symptom Inventory (BSI). Plasma NE levels were assessed before and immediately after a speech stressor conducted at the caregiver's home. Hierarchical linear regression was used to determine whether caregiver depressive symptoms significantly improved prediction of change in NE levels beyond other factors theoretically and empirically related to NE. RESULTS: Level of depressive symptoms significantly predicted post-stressor change in NE levels (p < .01), even when controlling for age, caregiver distress, presence of caregiver hypertension, and care recipient level of cognitive function. Higher levels of depressive symptoms were associated with a greater plasma NE response to the psychological stress task. CONCLUSIONS: Depressive symptoms may act to exaggerate NE response to the stress of caregiving, potentially leading to an allostatic load that might predispose caregivers to negative health consequences, including cardiovascular morbidity.

Aged↗

Coping processes and hemostatic reactivity to acute stress in dementia caregivers.

BACKGROUND: A hypercoagulable stress response might contribute to the increased cardiovascular risk in Alzheimer's caregivers. OBJECTIVES: (1) To evaluate whether coping processes affect hemostatic reactivity to acute psychological stress and (2) whether these effects differ substantially between caregivers and noncaregivers. METHODS: Sixty elderly community-dwelling spousal caregivers of patients with Alzheimer's disease and 33 noncaregiving controls completed the revised Ways of Coping Questionnaire to assess approach/problem-solving versus avoidant coping processes. Participants were administered an acute stress test that required them to deliver a 3-minute speech challenge to the interviewer on an assigned topic. The hypercoagulability marker D-dimer was measured at three time points: baseline, immediately postspeech, and during recovery (15 minutes postspeech). RESULTS: Multivariate analysis of covariance revealed that subjects who endorsed greater levels of approach coping had decreased levels of D-dimer at all time points (p = .048). A significant three-way interaction between planful problem solving, caregiver status, and the temporal pattern of D-dimer was found (p = .004), indicating that caregivers with low levels of planful problem solving exhibited greater increases in D-dimer from baseline to speech and recovery time points relative to controls. No relationship between avoidant coping and D-dimer was found. CONCLUSIONS: These findings suggest the possibility that approach and problem-solving coping processes buffer the impact of acute psychological stressors on procoagulant activity. It remains to be seen whether interventions that increase approach/problem-solving processes might produce salutary effects among caregiving populations.

Adaptation, Psychological↗

Exaggerated plasma fibrin formation (D-dimer) in elderly Alzheimer caregivers as compared to noncaregiving controls.

BACKGROUND: The chronic stress of providing care for a spouse suffering from Alzheimer's disease has been associated with an increased risk for coronary artery disease and overall mortality. Procoagulant changes are kindled by mental stress, and they are prospectively associated with atherothrombotic events. OBJECTIVE: To examine whether dementia caregivers would show greater coagulation activity and less fibrinolytic capacity than noncaregiving controls. METHODS: Subjects were 48 (30 female and 18 male) elderly (mean age +/- SD, 72 +/- 9 years) community-dwelling spousal Alzheimer caregivers and 20 noncaregiving age- and gender-matched controls. Plasma levels of thrombin-antithrombin III, fibrin D-dimer, von Willebrand factor, tissue-type plasminogen activator, and plasminogen activator inhibitor 1 were measured. RESULTS: D-dimer, a marker of fibrin formation and degradation, was significantly higher in caregivers than in controls (688 +/- 575 vs. 406 +/- 157 ng/ml, p = 0.021). Plasma levels of the four other hemostasis variables were not significantly different between the two groups. Controlling for the classic cardiovascular risk factors body mass index, hypertension status, smoking status, hypercholesterolemia, type II diabetes, and medication potentially affecting hemostasis did not change results. CONCLUSION: The findings suggest that Alzheimer caregivers have an increased fibrin turnover as compared to noncaregiving controls independent of common confounders of hemostasis. Such an elevated clotting diathesis might contribute to increased cardiovascular risk and overall mortality with dementia caregiving strain.

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In-home respite intervention reduces plasma epinephrine in stressed Alzheimer caregivers.

OBJECTIVE: Some excess morbidity and mortality in Alzheimer caregivers (CGs) may be related to chronic activation of the sympatho-adrenal-medullary (SAM) system. Authors tested the efficacy of an in-home respite intervention to reduce peripheral markers of SAM activation and psychological distress in spousal caregivers of patients with Alzheimer disease. METHODS: Caregivers were classified as Vulnerable (n = 27) or Non-Vulnerable (n = 28). Vulnerable CGs were those with a severe mismatch between caregiving demand and help received in the preceding 6 months. CGs had plasma catecholamine levels sampled at rest and in response to a stressor (speech task) before and 1 month after a 2-week in-home respite intervention. Self-reported symptoms of anxiety and depression were also obtained. RESULTS: ANOVA revealed a group x treatment interaction: At the 1-month follow-up, plasma epinephrine declined significantly in the vulnerable caregivers who received respite, but rose in those who were wait-listed. No effect was found for norepinephrine, heart rate, blood pressure, or psychological symptoms. CONCLUSION: Findings suggest that an in-home respite program may reduce SAM activation independent of psychological symptoms. To the extent that sympathetic activation mediates pathophysiological events, these results suggest an approach that may reduce morbidity and mortality in certain caregivers.

Aged↗

Vulnerable caregivers of Alzheimer disease patients have a deficit in beta 2-adrenergic receptor sensitivity and density.

OBJECTIVE: The chronic stress of caregiving may lead to sympathetic nervous system activation and immune suppression. beta(2)-adrenergic receptors are expressed on all immune cells and contribute to the stress-induced loss of immune-cell function. The authors examined the effects of being a spousal caregiver of a patient with Alzheimer disease (AD) on the lymphocyte beta(2)-adrenergic receptor. METHODS: One hundred and six women and men, spousal caregivers and non-caregivers, participated (mean age: 71.5 years). Caregivers were classified as either vulnerable or non-vulnerable on the basis of the amount of care required by the patient relative to the amount of respite the caregiver received during the previous 6 months. beta(2)-adrenergic receptor sensitivity (cyclic-AMP response to isoproterenol stimulation) and density (radioligand binding) were determined by use of whole lymphocytes. RESULTS: Vulnerable caregivers had reduced beta(2)-adrenergic receptor sensitivity and density when compared with their non-vulnerable counterparts or with non-caregivers. CONCLUSION: The findings indicate that for more vulnerable caregivers, the stress of caregiving leads to a loss of lymphocyte beta(2)-adrenergic receptors. This finding may be relevant to previous observations of clinically-relevant reduced immunity in highly stressed caregivers of AD patients.

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