Ceramides and Phosphatidylcholines Associate with Cardiovascular Diseases in the Elderly.

BACKGROUND: The ceramide- and phospholipid-based cardiovascular risk score (CERT2) has been found to predict the risk for cardiovascular disease (CVD) events, especially cardiovascular mortality. In the present study, our aim was to estimate the predictive ability of CERT2 for mortality of CVD, coronary artery disease (CAD), and stroke in the elderly and to compare these results with those of conventional lipids. METHODS: We conducted a prospective study with an 18-year follow-up period that included a total of 1260 participants ages ≥64 years. Ceramides and phosphatidylcholines were analyzed using a LC-MS. Total cholesterol and triglycerides were performed by enzymatic methods and HDL cholesterol was determined by a direct enzymatic method. Concentrations of LDL-cholesterol were calculated according to the Friedewald formula. RESULTS: A higher score of CERT2 was significantly associated with higher CVD, CAD, and stroke mortality during the 18-year follow-up both in unadjusted and adjusted Cox regression models. The unadjusted hazard ratios (HRs) of CERT2 (95% CI) per SD for CVD, CAD, and stroke were 1.72 (1.52-1.96), 1.76 (1.52-2.04), and 1.63 (1.27-2.10), respectively, and the corresponding adjusted HRs (95% CI) per SD for CERT2 were 1.48 (1.29-1.69), 1.50 (1.28-1.75), and 1.41 (1.09-1.83). For conventional lipids, HRs per SD were lower than for CERT2. CONCLUSIONS: The risk score CERT2 associated strongly with CVD, CAD, and stroke mortality in the elderly, while the association between these events and conventional lipids was weak.

Body electrical loss analysis (BELA) in the assessment of visceral fat: a demonstration.

BACKGROUND: Body electrical loss analysis (BELA) is a new non-invasive way to assess visceral fat depot size through the use of electromagnetism. BELA has worked well in phantom measurements, but the technology is not yet fully validated. METHODS: Ten volunteers (5 men and 5 women, age: 22-60 y, BMI: 21-30 kg/m(2), waist circumference: 73-108 cm) were measured with the BELA instrument and with cross-sectional magnetic resonance imaging (MRI) at the navel level, navel +5 cm and navel -5 cm. The BELA signal was compared with visceral and subcutaneous fat areas calculated from the MR images. RESULTS: The BELA signal did not correlate with subcutaneous fat area at any level, but correlated significantly with visceral fat area at the navel level and navel +5 cm. The correlation was best at level of navel +5 cm (R(2) = 0.74, P < 0.005, SEE = 29.7 cm(2), LOOCV = 40.1 cm(2)), where SEE is the standard error of the estimate and LOOCV is the root mean squared error of leave-one-out style cross-validation. The average estimate of repeatability of the BELA signal observed through the study was ±9.6 %. One of the volunteers had an exceptionally large amount of visceral fat, which was underestimated by BELA. CONCLUSIONS: The correlation of the BELA signal with the visceral but not with the subcutaneous fat area as measured by MRI is promising. The lack of correlation with the subcutaneous fat suggests that subcutaneous fat has a minor influence to the BELA signal. Further research will show if it is possible to develop a reliable low-cost method for the assessment of visceral fat either using BELA only or combining it, for example, with bioelectrical impedance measurement. The combination of these measurements may help assessing visceral fat in a large scale of body composition. Before large-scale clinical testing and ROC analysis, the initial BELA instrumentation requires improvements. The accuracy of the present equipment is not sufficient for such new technology.

A feasibility study of altered spatial distribution of losses induced by eddy currents in body composition analysis.

BACKGROUND: Tomographic imaging has revealed that the body mass index does not give a reliable state of overall fitness. However, high measurement costs make the tomographic imaging unsuitable for large scale studies or repeated individual use. This paper reports an experimental investigation of a new electromagnetic method and its feasibility for assessing body composition. The method is called body electrical loss analysis (BELA). METHODS: The BELA method uses a high-Q parallel resonant circuit to produce a time-varying magnetic field. The Q of the resonator changes when the sample is placed in its coil. This is caused by induced eddy currents in the sample. The new idea in the BELA method is the altered spatial distribution of the electrical losses generated by these currents. The distribution of losses is varied using different excitation frequencies. The feasibility of the method was tested using simplified phantoms. Two of these phantoms were rough estimations of human torso. One had fat in the middle of its volume and saline solution in the outer shell volume. The other had reversed conductivity distributions. The phantoms were placed in the resonator and the change in the losses was measured. Five different excitation frequencies from 100 kHz to 200 kHz were used. RESULTS: The rate of loss as a function of frequency was observed to be approximately three times larger for a phantom with fat in the middle of its volume than for one with fat in its outer shell volume. CONCLUSIONS: At higher frequencies the major signal contribution can be shifted toward outer shell volume. This enables probing the conductivity distribution of the subject by weighting outer structural components. The authors expect that the loss changing rate over frequency can be a potential index for body composition analysis.

A compact electroencephalogram recording device with integrated audio stimulation system.

A compact (96 x 128 x 32 mm(3), 374 g), battery-powered, eight-channel electroencephalogram recording device with an integrated audio stimulation system and a wireless interface is presented. The recording device is capable of producing high-quality data, while the operating time is also reasonable for evoked potential studies. The effective measurement resolution is about 4 nV at 200 Hz sample rate, typical noise level is below 0.7 microV(rms) at 0.16-70 Hz, and the estimated operating time is 1.5 h. An embedded audio decoder circuit reads and plays wave sound files stored on a memory card. The activities are controlled by an 8 bit main control unit which allows accurate timing of the stimuli. The interstimulus interval jitter measured is less than 1 ms. Wireless communication is made through bluetooth and the data recorded are transmitted to an external personal computer (PC) interface in real time. The PC interface is implemented with LABVIEW and in addition to data acquisition it also allows online signal processing, data storage, and control of measurement activities such as contact impedance measurement, for example. The practical application of the device is demonstrated in mismatch negativity experiment with three test subjects.

Associations of thyroid-stimulating hormone and free thyroxine concentrations with health and life satisfaction in elderly adults.

OBJECTIVE: To analyze associations between thyroid-stimulating hormone (TSH) and free thyroxine (FT4 concentrations and life satisfaction, symptoms, self-rated health, and common neuropsychiatric diseases (depression or dementia) in a community-dwelling elderly population to provide evidence whether to decrease the upper reference limit for TSH or the optimal TSH target in levothyroxine treatment in older adults. METHODS: In this cross-sectional study, we determined TSH and FT4 concentrations in a thyroid disease-free population of 502 men (median age, 71 years) and 584 women (median age, 73 years) and in a patient group of 49 women (median age, 75 years) with primary hypothyroidism who were stable users of thyroxine treatment. Life satisfaction, self-rated health, depression, and dementia were assessed with specific questions and with tools such as the Self-report Depression Scale and the Mini-Mental State Examination. Independent variables were dichotomized, and associations of these variables with TSH and FT4 levels were assessed in the thyroid disease-free population. Levels of TSH and FT4 in thyroid disease-free women and in women treated with thyroxine were also compared. RESULTS: After age adjustment, there were no associations between TSH levels and self-rated health, life satisfaction, or most symptoms in the thyroid disease-free population. No associations were found between diagnosed depression or Mini-Mental State Examination results and levels of TSH and FT4. Dementia was associated with higher FT4 concentration in men. Although women treated with thyroxine had TSH levels that were higher than thyroid disease-free women, there were no statistically significant differences in independent variables between these 2 groups. CONCLUSION: Our results do not support the need to decrease the upper reference limit for TSH or to lower the optimal TSH target in levothyroxine treatment in older adults, as recommended in recent guidelines.

Associations of sex hormone concentrations with health and life satisfaction in elderly men.

OBJECTIVE: To analyze associations between sex hormone concentrations and self-rated health and life satisfaction, neuropsychiatric symptoms, or diagnosed depression or dementia in elderly men. METHODS: The study subjects were men from the community-based Lieto Study (N = 517). Subjects were excluded from the study if they were taking exogenous sex hormones or medication for prostate cancer or for benign prostatic hyperplasia or if data for calculating body mass index (BMI) were missing. Thus, 466 men (64 to 97 years old; mean age, 72 years; mean BMI, 26.9 kg/m(2)) remained for further analysis. RESULTS: After adjustment for age, higher levels of testosterone and free testosterone were associated with better self-rated health. After adjustment for age and BMI, no statistically significant associations were found between sex hormone levels and self-rated health or life satisfaction or most neuropsychiatric symptoms in elderly men. Diagnosed depression was associated with a lower serum testosterone concentration. Higher levels of luteinizing hormone and follicle-stimulating hormone were associated with diagnosed dementia. CONCLUSION: In this population-based study with high attendance rate, low serum testosterone concentration was associated with diagnosed depression. Subclinical hypogonadism may be associated with diagnosed dementia. Single questions on neuropsychiatric symptoms commonly associated with androgen deficiency seemed to have weak or no correlation with testosterone or free testosterone levels among this group of elderly men.

Actual practice vs guidelines in laboratory monitoring of older patients with primary hypothyroidism in primary care.

BACKGROUND AND AIMS: Clinical guidelines are produced in order to achieve an acceptable standard of care, especially for patients with common diseases in primary care. The treatment of primary hypothyroidism serves as an example of the content of clinical guidelines and actual practice. The aim of this study was to compare the follow-up of primary hypothyroidism by thyroid function tests, serum TSH and serum-free T4, in older patients managed in primary care, with recommendations in treatment guidelines and textbooks. METHODS: Participation rate 82% (n=1260), mean age 74 years, (range 64-100 yrs). Patients with primary hypothyroidism were identified by means of cross-sectional survey (Lieto Study 1998-1999) and 4-year retrospective collection of laboratory database medical records (1994-1998), performed in autumn 2003. RESULTS: In most stable (=treated for more than 14 months) thyroxine users, both serum TSH (mean 1.4 measurements/year) and serum-free T4 (mean 0.8 measurements/year) values were measured over the 4-year period of thyroxine treatment. 66.4% of serum TSH and 85.3% of serum-free T4 values were within normal range. 41.7% of serum-free T4 determinations had been performed without indication (=with TSH in normal range). CONCLUSIONS: Compared with the recommended testing frequency given in various guidelines, a considerable number of extra measurements, especially serum-free T4, were performed. However, some key issues in the recommendations were difficult to interpret, and the age or other main characteristics of the patient were not taken into consideration adequately.

Sedative drug use in the home-dwelling elderly.

BACKGROUND: The elderly use more sedatives than other populations. Reports on the sedative load of drugs and their associations with health items are scarce. OBJECTIVE: To investigate the prevalence of sedatives and drugs with sedative properties and the associations between those drugs and demographic or health items in the home-dwelling elderly in a cross-sectional community survey. METHODS: Information was obtained from 1197 persons (43% men) aged >or=64 years in the Finnish municipality of Lieto in 1998-1999. The brand names of the prescription drugs taken by each interviewee during one week prior to the interview were recorded. The classification created in a previous study, where the drugs used in Finland were divided into 4 groups by their sedative properties, was utilized to determine associations with health items. RESULTS: A total of 88% (n = 1056) of the participants used some drug. Forty percent (n = 422 persons) of the drug users took sedatives or drugs with sedative properties. The oldest individuals (>or=80 y), women, those with low education, smokers, those with poor self-perceived health, people with dementia and mobility problems, and especially those with depression had an independent association with the simultaneous use of many (>or=2) sedatives or drugs with sedative properties. CONCLUSIONS: In a population of home-dwelling elderly patients, abundant sedative drug use was common and especially associated with high age, female gender, poor basic education, poor health habits (eg, smoking), depression, dementia, or impaired mobility. Users also had poor self-perceived health. The need to further develop the classification will be a major challenge, and the classification needs to be updated every year. More studies are needed in this field.

Undiagnosed diseases in patients with dementia--a potential target group for intervention.

OBJECTIVE: To study undiagnosed diseases in older people with and without dementia. DESIGN: Cross-sectional population-based study in Lieto, southwestern Finland. PARTICIPANTS: All the inhabitants aged 64 and more in Lieto. Participation rate was 82% (n = 1,260). MEASUREMENTS: Dementia and its subtypes were diagnosed according to prevailing criteria. Medical conditions were assessed in clinical examinations and from medical records. RESULTS: 112 patients with dementia were found; 66% of them had at least 1 undiagnosed disease compared to 48% of the non-demented group (p = 0.041). The demented subjects had more undiagnosed hypercholesterolaemia (p = 0.039) and undiagnosed hypothyroidism (p = 0.032) than the controls. CONCLUSION: Undiagnosing is more common among patients with dementia. Screening strategies should be developed further to find these patients.

Sleep and sleep electroencephalogram in depressed patients treated with phenelzine.

BACKGROUND: The beneficial effect of antidepressant interventions has been proposed to depend on suppression of rapid eye movement (REM) sleep or inhibition of electroencephalographic (EEG) slow-wave activity (SWA) in non-REM sleep. Use of the monoamine oxidase inhibitor phenelzine sulfate can eliminate REM sleep. We studied the relation between REM sleep suppression and antidepressant response and the effect of phenelzine therapy on sleep EEG power spectra. METHODS: Open-labeled prescriptions of 30 to 90 mg of phenelzine were given to 11 patients with major depressive disorder (6 men and 5 women; mean age, 41.4 years); all were physically healthy. Mood, dream recall, sleep, sleep EEG, and ocular and muscular activity during sleep were studied before treatment and during the third and fifth weeks of pharmacotherapy. RESULTS: Six patients remitted from depression, 2 responded partially, and 3 showed no antidepressant response. Independent from clinical response, REM sleep was dramatically suppressed. On average, only 4.9 minutes of REM sleep was observed in treatment week 5, and it was completely absent in 6 patients. This effect was compensated for by increased stage 2 sleep. In non-REM sleep, EEG power was higher than at baseline between 16.25 and 25 Hz. Slow-wave activity (power within 0.75-4.5 Hz) and the exponential decline of SWA during sleep were not affected. CONCLUSIONS: Antidepressant response to phenelzine treatment does not depend on elimination of REM sleep or inhibition of SWA in non-REM sleep. In depressed patients, REM sleep is regulated independently from non-REM sleep and can be manipulated without altering the dynamics of SWA.

A preliminary evaluation of the potential usefulness of the diagnoses of polysubstance dependence.

OBJECTIVE: The concept of polysubstance dependence (PD) has been defined several ways over the years. However, few clinicians and researchers appear to use this label in a manner consistent with any of the major diagnostic manuals. This article evaluates the prevalence and characteristics associated with PD in participants in a large collaborative study. METHOD: In DSM-IV, PD characterizes people who do not meet criteria for dependence on any one substance but, when all drugs of abuse are considered have experienced three or more of the seven dependence items across the substances. In this study, structured face-to-face interviews were administered to 8,834 men and women as part of the Collaborative Study on the Genetics of Alcoholism. The 198 subjects (2.2%) with a slightly expanded concept of the DSM-IV disorder were compared with men and women with dependence on alcohol, marijuana or stimulants, subjects with substance abuse and those with no substance use disorder. RESULTS: In this dataset, compared with subjects with a specific substance dependence, those with PD were slightly more educated and less likely to be divorced or separated, and they had fewer substance-related problems. At the same time, those with PD had more substance problems than did subjects who only met criteria for abuse. These basic conclusions were unchanged among the subset of 59 subjects who met the more restricted, classical DSM-IV PD criteria. CONCLUSIONS: The data indicate that, while relatively rare, subjects with PD might differ in potentially important ways from those with dependence or abuse on specific drugs. A large prospective study of a group with carefully defined PD is needed.

An open-label, 12-week clinical and sleep EEG study of nefazodone in chronic combat-related posttraumatic stress disorder.

BACKGROUND: We examined the effects of nefazodone on polysomnographic sleep measures and subjective reports of sleep quality and nightmares. as well as other symptoms, in patients with chronic combat-related posttraumatic stress disorder (PTSD) during a 12-week, open-label clinical trial. To our knowledge, this is the first polysomnographic study of treatment in patients with PTSD. METHOD: The subjects were 12 male veterans (mean age = 54 years) who met DSM-IV diagnostic criteria for PTSD (mean duration = 30 years). All but I patient also met DSM-IV criteria for major depressive disorder. Patients were evaluated weekly with clinical ratings in an open-label clinical trial. Polysomnographic recordings for 2 consecutive nights were obtained before treatment and at 2, 4, 8, and 12 weeks. The dose of nefazodone was adjusted according to individual clinical needs. Final mean daily dose was 441 mg. RESULTS: The patients reported significantly fewer nightmares and sleep problems during treatment. Nevertheless, contrary to studies in depressed patients, nefazodone did not significantly affect polysomnographic sleep measures compared with baseline. In addition, the patients showed significant improvement in the Clinical Global Impressions of PTSD symptoms (global score, hyperarousals and intrusions subscales), the Clinician-Administered PTSD Scale (global, hyperarousal, and intrusions subscales), the Hamilton Rating Scale for Depression (HAM-D). and the Beck Depression Inventory (BDI). CONCLUSION: These patients with chronic, treatment-resistant, combat-related PTSD showed significant improvement of subjective symptoms of nightmares and sleep disturbance, as well as depression and PTSD symptoms. in this 12-week open-label clinical trial. Nevertheless, objective polysomnographic sleep measures did not change. Further studies, including double-blind. placebo-controlled trials, are needed to extend these findings and to understand the relationships between the physiology of sleep and symptoms of poor sleep and nightmares.

Clinical characteristics and family histories of alcoholics with stimulant dependence.

OBJECTIVE: While much is known about the clinical patterns and family histories of individuals with alcoholism or stimulant (cocaine and amphetamine) dependence, there are few data that describe men and women with concomitant alcohol and stimulant dependence. METHOD: As part of the Collaborative Study on the Genetics of Alcoholism, structured interviews were administered to 3,882 (2,432 male) DSM-III-R defined alcohol and/or stimulant dependent subjects. The characteristics and family histories of four groups were compared: Group 1 (26%), with the onset of alcohol before stimulant dependence; Group 2 (10%), with alcohol dependence simultaneously with or after stimulant dependence; Group 3 (58%), with alcohol dependence only; Group 4 (6%), with stimulant dependence only. RESULTS: Individuals with concomitant alcohol and stimulant dependence (Groups 1 and 2) reported more general life problems (e.g., marital instability), a higher rate of antisocial personality disorder and more substance-induced mood disorders, additional drug dependencies and substance-related difficulties than those with dependence on one substance only. People with alcohol dependence before stimulant dependence had the most severe clinical patterns. In addition, alcohol dependence and stimulant dependence were found to breed true in families of subjects with these concomitant disorders. The major findings were confirmed with logistic regression analyses, and were independent of ASPD and gender. CONCLUSIONS: It is important for clinicians to be aware of the severe clinical characteristics of patients with concomitant alcohol and stimulant dependence. In addition, the data consistent with drug-specific heritability in this heterogeneous population may be useful to researchers.

Clinical correlates of cigarette smoking and nicotine dependence in alcohol-dependent men and women. The Collaborative Study Group on the Genetics of Alcoholism.

This paper examines the clinical characteristics associated with tobacco use and nicotine dependence in a large sample of alcohol-dependent subjects. The goal was to determine if the characteristics of the alcohol use history were associated with the smoking status, even after controlling for additional characteristics, such as the antisocial personality disorder, other drug dependence and gender. As part of the Collaborative Study on the Genetics of Alcoholism, a semi-structured interview, including a detailed history of alcohol and tobacco use, was administered to 1005 alcohol-dependent men and women, made up of 658 (65.5%) current smokers, 167 (16.6%) former smokers, and 180 (17.9%) non-smokers. Among former smokers, 50.3%, and among current smokers, 72.8% had ever been nicotine-dependent (DSM-III-R). Current smokers and nicotine-dependent subjects had a greater severity of alcohol dependence, even as evaluated through logistic regression analyses in which gender and associated diagnoses were considered. The data also enabled us to study the relationships among depression, nicotine dependence, and alcohol dependence, with most of the correlation occurring for substance-induced, not independent, mood disorders.

Clinical characteristics of alcoholism in alcohol-dependent subjects with and without a history of alcohol treatment.

BACKGROUND: Most clinical alcohol research is carried out on alcoholics who are in treatment, usually inpatients. However, most alcohol-dependent men and women never enter treatment, and even fewer ever receive inpatient care. Thus, some generally accepted data on the clinical course of alcoholism, derived from treatment samples, might not generalize to the entire population of alcohol-dependent individuals. This article characterizes the clinical characteristics of alcohol dependence in three groups of alcoholics, based on their histories of treatment for alcohol problems: those without prior rehabilitation; those with only outpatient approaches or Alcoholics Anonymous (AA); and subjects with an inpatient experience. METHODS: Semistructured interviews were administered to 3572 DSM-III-R-defined alcohol-dependent subjects from the Collaborative Study on the Genetics of Alcoholism. The clinical patterns were compared across the three groups of alcoholics: Group 1, never-treated (n = 1582; 44%); Group 2, histories of outpatient or AA only (n = 399; 11%); and Group 3, at least one inpatient experience (n = 1591; 45%). RESULTS: A progression was shown from Groups 1 to 3 for more general life problems (e.g., unemployment, marital instability); higher rates of additional drug dependencies and psychiatric disorders; and more alcohol-related adverse events. Logistic regression analyses revealed that those with no prior treatment were more likely to be women, Caucasian, and employed, and to report a lower rate of divorce/separation, lower levels of alcohol intake, and fewer alcohol problems. Among those who received help, inpatient care was predicted by an opposite profile. CONCLUSIONS: These results indicate that studies using data from inpatient populations may give a skewed picture of the clinical characteristics of alcohol dependence.

Alcohol-induced depersonalization.

BACKGROUND: A case of alcohol-induced depersonalization disorder is presented. The subject had experienced several depersonalization states following the consumption of alcohol rather than from a psychogenic etiology, and the episodes were transient, not chronic. METHODS: Three quantitative EEG (QEEG) studies were performed on the subject, one during the index depersonalization episode and two subsequent studies when the subject was clinically asymptomatic. RESULTS: Slow wave activity (relative theta power) was significantly increased when symptomatic. This slowing was still present over the occiput 3 days after the symptoms had remitted but was absent 17 days after symptoms had ameliorated. CONCLUSIONS: The time course of EEG slowing suggests a metabolic encephalopathy, a condition which likely contributes to the manifestations of depersonalization syndrome.

Alcohol dependence and mood disorders.

This article explores the complex relationships between alcohol dependence and mood disorders. Although many alcoholics present with substance-induced depressions, once appropriate methodological controls are used, there does not appear to be a significant relationship between independent unipolar depression and alcohol dependence. However, the data support a small, but significant, relationship between bipolar manic-depressive disease and alcoholism. The literature does not support the relevance of self-medication as a course of alcoholism, unless one includes the use of alcohol to alleviate alcohol-induced psychological and neurochemical perturbations. The clinical importance of distinguishing between substance-induced and independent mood disorders is reviewed.

The expression of bipolar affective disorders in brain injured patients.

OBJECTIVE: A prospective study was designed to investigate the varied presentations of major affective disorders in patients with organic brain disease. METHOD: Patients admitted to our neuropsychiatry service, with affective and behavioral disturbances, and known neurological disorders, were classified, on phenomenological grounds, into the following groups: 1) elated mania; 2) irritable mania; 3) affective lability with periods of irritability, but without other symptoms pathognomonic for mania; and 4) intermittent psychosis with absent or ambiguous mood changes. RESULTS: A majority of patients in all four groups responded to pharmacotherapy with anti-cycling agents. CONCLUSIONS: It is proposed that these groups represent different expressions of mania in brain injured persons, and that these expressions range through a spectrum of phenomenology, included elated mania, irritable mania, episodic psychosis and explosive organic personality disorder. The DSM-III-R classification of these disorders, and approaches to their clinical management, are discussed.