Uncomplicated general anesthesia in the elderly results in cognitive decline: does cognitive decline predict morbidity and mortality?

Elderly surgical patients constitute a unique surgical group. They require special consideration in order to preempt the long term adverse effects of anesthesia. This paper examines the proposition that general anesthesia causes harm to elderly patients with its impact being felt long after the anesthetic agents are cleared from the body. One complication, Postoperative Cognitive Decline (POCD), is associated with the administration of anesthesia and deep sedation. Its' occurrence may herald an increase in morbidity and mortality. Based on both human and animal data, this paper outlines a unitary theoretical framework to explain these phenomena. If this hypothesis proves to be correct, anesthesiologist should consider regional rather than general anesthesia for equivalent surgical procedures to reduce POCD and consequently achieving superior patient outcome.

Aging and neuro-AIDS conditions and the changing spectrum of HIV-1-associated morbidity and mortality.

Older individuals (>50 years of age) now comprise over 11% of patients with AIDS in the United States. This percentage is expected to continue to grow, due both to the improved longevity of patients prescribed highly active antiretroviral therapy (HAART) and to new infections among older individuals. This review focuses on the neuropsychiatric and neurological conditions that are most likely to be affected by advancing age-HIV-1-associated cognitive-motor disorder, peripheral neuropathy, progressive multifocal leukoencephalopathy, primary CNS lymphoma, and risk for cerebrovascular accident. Age associations with incidence of these disorders and with treatment foci are specified. Implications for future changes in management are discussed.

Caregivers' judgments of the functional abilities of the Alzheimer's disease patient: impact of caregivers' depression and perceived burden.

Research has demonstrated that caregivers of cognitively impaired patients may misjudge aspects of the patient's functional capacities. The nature and directions of these relationships are not well understood, however. Further, the effects that depression and perceived caregiver burden have on the caregivers' ability to render accurate judgments of patient's functional abilities have not been addressed. In this study, the primary caregivers of 128 patients with Alzheimer's disease (AD) were administered a questionnaire regarding the patients' functional capacities. These judgments were subsequently compared to actual functional performance of AD patients on an extended version of the Direct Assessment of Functional Status scale administered in the patients' home environment. A significant proportion of caregivers overestimated AD patients' functional performance in telling time, counting currency, making change for a purchase, brushing teeth, and using eating utensils. Further analyses revealed that self-reported depression, but not perceived burden, was related to the type of caregiver bias errors observed.

Cerebrospinal fluid 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in HIV-1 infection.

Reduced level of serotonin (5-hydroxytryptamine, 5-HT) in humans has been associated with a number of mental health and behavioral problems including depression, aggression, violence, sexual dysfunctions, sleep and eating disorders. Even though among HIV-1-infected individuals, prevalence of mental health and behavioral problems are common, their relationship with central nervous system serotonin functions is not clearly understood. This investigation was carried out to study the status of CSF 5-HT in HIV-1+ subjects (n = 21), in the early stage of infection, and HIV-1- control subjects (n = 24). Samples of CSF were obtained by lumbar puncture and were analyzed for 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA), using high-performance liquid chromatography equipped with electrochemical detector. Levels of CSF 5-HT were significantly lower in the HIV-1+ group compared to the HIV-1- group. There was no significant difference in the CSF 5-HIAA levels between the two groups. In both groups, however, there was a significant correlation between CSF 5-HT and 5-HIAA. In the HIV-1 + group, although CSF 5-HT level was significantly negatively correlated with serostatus, there was no correlation between either CSF 5-HT or 5-HIAA levels and CD4 cell number or any behavioral measures evaluated in this study, including Beck's Depression Inventory and state/trait anxiety scores. These data suggest that HIV-1 infection affects the CNS 5-HT status with no significant association with measures of depression and anxiety, at least in the early stage of infection.

Caregivers' judgments of the functional abilities of the Alzheimer's disease patient: a comparison of proxy reports and objective measures.

The assessment of functional capacity is essential for the diagnosis of dementia by DSM-IV criteria and has important implications for patient intervention and management. Although ratings of functional disability by family or other proxy informants are widely used by clinicians, there have been concerns and empirical evidence that potential reporter biases may result in either overestimation or underestimation of specific functional deficits. In this study, we compared family members' judgments of the functional abilities of seventy-two patients diagnosed with Alzheimer's disease (AD). These judgments were compared to actual objective functional performance on an array of real-world tasks using the Direct Assessment of Functional Status (DAFS) scale. The results indicate that caregivers were extremely accurate in predicting the functional performance of AD patients who were not impaired during objective evaluation. In contrast, caregivers significantly overestimated the ability of impaired AD patients to tell time, to identify currency, to make change for a purchase, and to utilize eating utensils. Higher patient MMSE scores were associated with caregivers' overestimation of functional capacity, while the degree of caregivers' depressive symptoms, as measured by the CES-D depression scale, was not related to either overestimation or underestimation of patients' functional performance.

A comparison of antecedents of homicide-suicide and suicide in older married men.

The authors compared characteristics of 27 older men who perpetrated a spousal homicide-suicide and 36 age-matched married men who committed suicide in west central Florida between 1988 and 1994. Data were collected as part of an ongoing retrospective study of homicide and suicide among older adults in Florida. Men who committed suicide had significantly more disease conditions than homicide-suicide perpetrators (P<0.0001). Half of the latter were in caregiving roles, vs. 17% of the suicides (chi(2)=5.40; P=0.027). Depression was a prominent premorbid feature of both groups, but none of the perpetrators tested positive for antidepressants postmortem.

Cobalamin level is related to self-reported and clinically rated mood and to syndromal depression in bereaved HIV-1(+) and HIV-1(-) homosexual men.

OBJECTIVE: An examination of the relationship of plasma cobalamin (vitamin B(12)) level to overall psychological distress, specific mood states, and major depressive disorder was conducted in 159 bereaved men (90 HIV-1(+) and 69 HIV-1(-)). METHODS: The relationship of a continuous measure of cobalamin level to psychological distress was examined, while controlling for HIV-1 serostatus, life stressors, social support, and coping styles. RESULTS: Of this sample, 23.9% were either overtly or marginally cobalamin deficient; however, the deficiency rate was not significantly different by HIV-1 serostatus. Cobalamin level was inversely related to self-reported overall distress level and specifically to depression, anxiety, and confusion subscale scores, as well as to clinically rated depressed and anxious mood. Lower plasma cobalamin levels also were associated with the presence of symptoms consistent with major depressive disorder. CONCLUSION: These findings suggest that cobalamin level may be physiologically related to depressed and anxious mood level, as well as to syndromal depression.

HIV-1 Infection, Neuroendocrine Abnormalities, and Clinical Outcomes.

Different lines of evidence suggest that human immunodeficiency virus type 1 (HIV-1) infection is complicated by a variety of adverse effects on neuroendocrine systems. Soon after the discovery of HIV-1, reports began to appear suggesting that a number of neurotransmitter and neuroendocrine activities were negatively impacted by this infection. In 1987 it was observed that fine-needle aspiration of the lung in patients with acquired immunodeficiency syndrome resulted in syncopal reactions. Subsequently, an abnormality in the autonomic nervous system was reported in these patients. However, investigations in this area have remained limited due to the assumption that HIV-1-mediated activation of various endocrine systems was related to the major life stressor of living with a fatal disease. Evidence accumulated over the years has indicated, instead, that there are various other mechanisms in addition to life stressors that also play an important role in negatively impacting the neuroendocrine systems in this infection. This article examines various developments that have taken place in this area in order to provide avenues for future research.

Music therapy increases serum melatonin levels in patients with Alzheimer's disease.

CONTEXT: Music therapy is known to have healing and relaxing effects. Although these effects appear to be mediated by release of neurotransmitters and neurohormones, the specific neurohormonal systems involved have not been fully investigated. OBJECTIVE: To assess the effects of a music therapy intervention on concentrations of melatonin, norepinephrine, epinephrine, serotonin, and prolactin in the blood of a group of patients with Alzheimer's disease. DESIGN: Blood samples were obtained before initiating the therapy, immediately at the end of 4 weeks of music therapy sessions, and at 6 weeks follow-up after cessation of the sessions. SETTING: Miami Veterans Administration Medical Center, Miami, Fla. PATIENTS: 20 male inpatients with Alzheimer's disease. INTERVENTION: 30- to 40-minute morning sessions of music therapy 5 times per week for 4 weeks. MAIN OUTCOME MEASURES: Changes in melatonin, norepinephrine, epinephrine, serotonin, and prolactin following music therapy. RESULTS: Melatonin concentration in serum increased significantly after music therapy and was found to increase further at 6 weeks follow-up. A significant increase was found between baseline values and data recorded after the music therapy sessions as well as at 6 weeks follow-up. Norepinephrine and epinephrine levels increased significantly after 4 weeks of music therapy, but returned to pretherapy levels at 6 weeks follow-up. Serum concentration of prolactin and platelet serotonin levels remained unchanged after 4 weeks of music therapy and at 6 weeks follow-up. CONCLUSION: Increased levels of melatonin following music therapy may have contributed to patients' relaxed and calm mood.

Independent evolution of HIV type 1 in different brain regions.

HIV-1-associated brain pathology exhibits regional variability and we therefore studied the genetic differences in the V1-V5 domains of the HIV env gene in up to four regions of brain (frontal lobe, basal ganglia, medial temporal lobe, and nonmedial temporal lobe) from three patients. We found that in each separate brain region HIV-1 forms different quasispecies and that there is little gene flow among these regions. In further support of brain region-specific evolution of HIV-1, we analyzed amino acid signatures in these clones. In addition to known amino acid signatures associated with macrophage tropism and the lack of syncytium formation, we found 15 majority amino acid signature patterns from the V1-V5 env sequences associated with the neuroanatomical regions analyzed from the three individuals. Furthermore, on average, intrabrain genetic distances for the HIV-1 env were estimated to be much smaller than genetic distances between brain regions. Specific strains of HIV-1 may be neurotropic or neuroinvasive (replication preference in brain tissue) and may contribute to pathology, cognitive loss, and neuropsychiatric disease.

Peripheral serotonin levels in women: role of aging and ethnicity.

Serotonin has been implicated to play an important role in regulating emotions and behavior, and it is well accepted that the platelet serotonergic system mirrors the presynaptic central serotonergic system. Since prevalence of psychiatric problems increases with age and women are known to be more vulnerable than men, the present investigation was carried out to study the relationship between serotonin activity and age in women. Levels of serotonin (5-hydroxytryptamine, 5-HT) and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were measured in platelets and plasma in women (n = 49) aged 40-84 years (30 women aged 40-60 years and 19 women aged 61-84 years). There was a significant age difference between the two groups (mean: 47.6 +/- 5.91 years in the younger and 73.0 +/- 6.83 years in the older women, respectively, p < 0.00001). Platelet 5-HT as well as 5-HIAA levels were significantly higher in older women as compared to those in the younger women (89.41 +/- 21.95 ng/10(8) platelets in younger vs. 112.9 +/- 36.07 in older women, p < 0.02, and 1.20 +/- 1.10 in younger vs. 2.19 +/- 1.88 ng/10(8) platelets in older women, p < 0.05, respectively). Pearson correlation coefficients determined in the combined group (n = 49) showed a significant positive correlation between platelet 5-HT and age (r = 0.31, p < 0.03). Plasma 5-HT levels on the other hand were lower in older women compared to those in the younger women (4.50 +/- 3.20 in younger vs. 1.04 +/- 1.28 ng/ml plasma in older women, p < 0.0001) and a significant negative correlation was observed between plasma 5-HT and age (r = -0.44, p < 0.002). Plasma 5-HIAA concentration did not differ between the two groups. Platelet 5-HT levels in the younger group were independent of ethnicity. Since high serotonin activity has also been associated with psychiatric problems, our results of increased concentration of platelet 5-HT as well as 5-HIAA with age may have implications in predisposing aging women to behavioral/psychiatric problems.

Mild cognitive impairment and risk of mortality in HIV-1 infection.

HIV-1-associated cognitive impairment has only been preliminarily investigated for associations with mortality. The authors examined 119 HIV-1-positive homosexual men (asymptomatic: n = 96; early symptomatic: n = 23). At follow-up (to 3.5 years), there were 105 survivors and 14 nonsurvivors. Those at the 25th percentile in response speeds and in long-term memory retrieval accuracy were at 6.4 (P < 0.02) and 3.5 (P < 0.05) times increased mortality risk, respectively, of those at the 75th percentile--independent of baseline CDC clinical stage, CD4 cell count, hemoglobin level, antiretroviral and prophylactic medication use, and sociodemographics. Cognitive impairment should be identified early--for maximization of both functional status and survival time.

Homicide-suicide in older persons.

OBJECTIVE: The objective of this study was to determine the annual incidence of homicide-suicide and to compare patterns and antecedents in old and young spousal/consortial cases. METHODS: Homicide-suicide cases were ascertained in four medical examiner districts covering seven entire Florida counties from 1988 to 1994. The districts were chosen to determine rates in two regions of Florida, comparable in size of the total population and proportion of older persons. Annual homicide-suicide incidence rates per 100,000 population and homicide-suicides as a percentage of total homicides and total suicides separately were calculated by age group and Florida region. Complete medical examiner files were obtained, and 160 variables were coded from medical examiner reports to compare features and clinical characteristics by age and region. RESULTS: Annual incidence rates ranged from 0.3 to 0.7 per 100,000 for persons under age 55 and from 0.4 to 0.9 per 100,000 for persons age 55 and older, with higher rates in the older group every year but two. Cases of spousal/consortial homicide-suicide were the most common in both age groups. The younger couples in both regions were comparable, except for racial composition, but the older couples differed. West central Florida couples were in their seventies, Caucasian, usually married, and both in poor health; and there were indications of depression or alcohol abuse in half the perpetrators. Two-thirds of the southeastern Florida couples were Hispanic; there was a mean age difference of 18 years between perpetrators and victims; and verbal discord, physical violence, and separation were prominent antecedents. CONCLUSIONS: The base rate for homicide-suicide in both age groups was higher than that reported in previous studies. Spousal/consortial homicide-suicides were the dominant form, and although psychopathology was strongly implicated, homicide-suicides are violent lethal acts resulting from additive or multiplicative effects of diathesis, including culture, and stressful experiences.

Psychological distress in HIV-1 disease in relationship to hypocholesterolemia.

OBJECTIVE: Altered levels of serum cholesterol, which are prevalent in early HIV-1 infection, have been associated with disturbances in mood state and behavior. The objective of this study was to evaluate the relationship of serum cholesterol status and psychological distress in HIV-1 seropositive and seronegative men. METHOD: The association between serum cholesterol level and psychological distress, measured with the Profile of Mood States (POMS), was examined in 169 individuals (117 HIV-1 seropositive and 52 seronegative homosexual men), controlling for negative life events, social support, coping style, and HIV-1 serostatus. RESULTS: Individuals with hypocholesterolemia (serum cholesterol levels < 150 mg/dL), exhibited significantly higher levels of distress, relative to individuals with values of cholesterol > 150 mg/dL (p = 0.01). HIV-1 seropositive men had significantly lower cholesterol levels (p = 0.0001) and higher levels of distress than the seronegative men (p = 0.03). A significant interaction between negative life events and cholesterol status was demonstrated as well (p = 0.04). CONCLUSIONS: Hypocholesterolemia appears to be associated with increased psychological distress. Whereas the causal direction of the cholesterol-distress association cannot be specified, our results suggest that HIV-1 infected men with low cholesterol levels may benefit from being monitored for changes in distress level, so that appropriate psychosocial intervention can be instituted, as necessary.

Serotonin uptake and its kinetics in platelets of women with Alzheimer's disease.

The uptake of serotonin (14C-5-hydroxytryptamine, 5HT) in platelets and its kinetic characteristics were investigated in a group of women (n = 20) with probable Alzheimer's Disease (mean age = 76.0, years, SD = 8.27, range = 63-88) and in healthy normal women (n = 18, mean age = 72.6 years, SD = 7.24, range = 61-84). Both the apparent affinity of binding of 5HT to the platelet membrane (Km) and the maximum velocity (Vmax) of the rate of transport of 14C-5HT into platelets were significantly higher in the Alzheimer's Disease group than in the normal comparison group. Initial velocity of 14C-5HT uptake not passive diffusion (nonspecific uptake of 14C-5HT at 4 degrees C) differed significantly in the two groups. Our findings suggest abnormalities in the kinetic mechanisms involved in the uptake of 14C-5HT by platelets in women with Alzheimer's Disease.

Micronutrients and HIV-1 disease progression.

OBJECTIVE: To determine whether nutritional status affects immunological markers of HIV-1 disease progression. DESIGN: A longitudinal study, to evaluate the relationship between plasma levels of nutrients and CD4 cell counts, along and in combination with beta 2-microglobulin (beta 2M; AIDS index) over an 18-month follow-up. METHODS: Biochemical measurements of nutritional status including plasma proteins, zinc, iron and vitamins B1, B2, B6, B12 (cobalamin), A, E, C and folate and immunological markers [lymphocyte subpopulations (CD4) and beta 2M] were obtained in 108 HIV-1-seropositive homosexual men at baseline and over three 6-month time periods. Changes in nutrient status (e.g., normal to deficient, deficient to normal), were compared with immunological parameters in the same time periods using an autoregressive model. RESULTS: Development of deficiency of vitamin A or vitamin B12 was associated with a decline in CD4 cell count (P = 0.0255 and 0.0377, respectively), while normalization of vitamin A, vitamin B12 and zinc was associated with higher CD4 cell counts (P = 0.0492, 0.0061 and 0.0112, respectively). These findings were largely unaffected by zidovudine use. For vitamin B12, low baseline status significantly predicted accelerated HIV-1 disease progression determined by CD4 cell count (P = 0.041) and the AIDS index (P = 0.005). CONCLUSIONS: These data suggest that micronutrient deficiencies are associated with HIV-1 disease progression and raise the possibility that normalization might increase symptom-free survival.

Psychotropic drug use in relation to psychiatric symptoms in community-living persons with Alzheimer's disease.

We attempted to determine the relationship between psychiatric symptoms and psychotropic drug use in persons with Alzheimer's disease based on a multicenter patient registry of 671 community-living persons diagnosed with the disease by published criteria. Logistic regression was performed to determine which symptoms were associated psychotropic use after controlling for age, sex, and Mini-Mental Status Examination (MMSE) score. At least one psychotropic drug was reported by 31% of patients, and 66% had at least one psychiatric symptom. Antipsychotics were associated with a lower MMSE score (odds ratio = 0.92, 95% confidence interval 0.88-0.97), emotional lability (OR = 4.52, 95% CI 1.69-11.94), and hallucinations (OR = 6.54, 95% CI 2.99-14.26). Antidepressants were associated with depressive symptoms (OR = 5.8, 95% CI 2.61-13.46), and benzodiazepines with a lower MMSE score (OR = 0.93, 95% CI 0.90-0.97). Community-living persons with Alzheimer's disease are frequently prescribed psychotropic drugs; however, more than 50% of patients with a psychiatric symptom did not report taking one of these agents. This suggests that alternative therapies and no treatment are also prevalent.

Plasma cobalamin levels affect information processing speed in a longitudinal study of HIV-1 disease.

OBJECTIVE: To determine whether information processing speed is influenced by change in plasma cobalamin status in human immunodeficiency virus type 1 disease. DESIGN: A longitudinal study, using autoregression, to evaluate the relationship between plasma cobalamin status and change in information processing speed assessed by Posner Letter Matching, Sternberg Short-Term Memory Search, Figure Visual Scanning and Discrimination of Pictures, and continuous paired associates learning tasks. SETTING: University of Miami (Fla) School of Medicine from fall 1987 through summer 1991. PARTICIPANTS: Eighty-four human immunodeficiency virus type 1-infected homosexual men aged 20 to 55 years. None of the subjects displayed acquired immunodeficiency syndrome-defining symptoms at baseline; over the course of the study, 9.5% progressed to acquired immunodeficiency syndrome. MAIN OUTCOME MEASURES: Biochemical measurement of plasma cobalamin; performance on information processing speed tasks. RESULTS: Significant improvement in the Posner Letter Matching NI-PI (Name Identity minus Physical Identity) differential was associated with becoming cobalamin adequate or remaining adequate. Becoming cobalamin deficient, in contrast, was associated with a significant decline in the speed of accessing overlearned name codes. CONCLUSION: Normalization of plasma cobalamin inadequacy in human immunodeficiency virus type 1 disease may provide significant improvement in the speed of retrieving overlearned information from long-term memory.

Peripheral serotonin in Alzheimer's disease.

The platelet has been suggested to be a peripheral model of the central serotonergic neuron. This investigation was carried out in order to test the hypothesis that levels of serotonin (5-HT) in the platelet will be decreased in Alzheimer's disease (AD) since neurochemical studies suggest that levels of 5-HT are decreased in the brain of AD patients. We investigated platelet and plasma 5-HT in a group of AD patients (n = 22) as well as in age-matched normal control subjects (n = 20). The results show that the platelet level of 5-HT was significantly reduced in AD (65.7 +/- 28.41 ng/10(8) platelets in AD vs. 112.9 +/- 35.11 ng/10(8) platelets in controls; p = 0.0001). There was no effect on the levels of its metabolite 5-hydroxyindoleacetic acid. These findings suggest that the peripheral serotonergic system in AD is adversely affected.