Serum brain-derived neurotrophic factor level is reduced in antidepressant-free patients with late-life depression

Objectives. The aim of the present study is to investigate serum BDNF levels in older depressed patients as compared to healthy elderly controls. Methods. Twenty-nine elderly subjects with major depression and 42 healthy older adults were enrolled to this study. All depressed patients were antidepressant-free for at least 1 month prior clinical and laboratorial assessments. Serum BDNF levels were determined by sandwich ELISA. Results. BDNF levels were lower in elderly depressed patients as compared to controls (P = 0.034). Patients with late-onset depression had the lowest BDNF level (median 478.5, interquartile range 373.5-740.9 pg/l) when compared to early-onset depression (median 620.7, interquartile range 366.1-971.9 pg/l) and healthy controls (median 711.3, interquartile range 534.7-1181.0 pg/l) (P < 0.03). Conclusions. Reduced serum BDNF level may be a state marker of late-life depression in non-medicated elderly patients. Our findings provide further evidences that reduced neurotrophic support may have an important role in the physiopathology of late-life depression.

Profiles of functional deficits in mild cognitive impairment and dementia: benefits from objective measurement

The magnitude Of functional impairment that may indicate the threshold between MCI and incipient Alzheimer`s disease (AD) has not been clearly defined. The objective was to examine the pattern of functional impairment in the continuum MCI-AD. Eighty-nine older adults (32 cognitively unimpaired, 31 MCI, and 26 AD patients) were examined with the Brazilian version of the Direct Assessment of Functional Status (DAFS-BR) at a University-based memory clinic. MCI patients were sub-divided according to the progression to AD upon follow-up, and had baseline cognitive, functional and biological variables analyzed. MCI patients displayed mild deficits in functional abilities, with intermediate scores as compared to controls and AD. The DAFS-BR items that differentiated MCI from controls involved the ability to deal with finances and shopping skills. At baseline, scores obtained by MCI patients who converted to AD were not significantly different from scores of nonconverters. The magnitude of functional deficits was associated with AD-like pathological findings in the CSF. In conclusion, MCI patients present with early functional changes in complex, instrumental abilities that require the integrity of memory and executive functions. The objective measurement of the functional state may help identify older adults with increased risk of developing dementia in the MCI-AD continuum. (JINS, 2010, 16, 297-305.)

Social anxiety disorder: what are we losing with the current diagnostic criteria?

Objective: To assess the rate of comorbidities and the functional impairment associated with the social anxiety disorder (SAD), with an emphasis on the so-called subthreshold clinical signs and symptoms. Method: Psychiatric comorbidities and psychosocial functioning were evaluated in 355 volunteers (college students) who had been diagnosed as SAD (n = 141), Subthreshold SAD (n = 92) or Controls (n = 122). Results: The rate of comorbidities was 71.6% in the SAD group and 50% in subjects with Subthreshold SAD, both significantly greater than Controls (28.7%). Concerning psychosocial functioning, the SAD group had higher impairment than the other two groups in all domains evaluated, and subjects with Subthreshold SAD presented intermediate values. Conclusion: The rates of psychiatric comorbidities and the impairment of psychosocial functioning increase progressively along the spectrum of social anxiety. The fact that Subthreshold SAD causes considerable disability and suffering in comparison with control subjects justifies a review of the validity of the diagnostic criteria.

Interleukin-1 beta Serum Levels is Increased in Antidepressant-Free Elderly Depressed Patients

Objective: To assess the serum levels of interleukin 1 beta (IL-1 beta) in elderly depressed patients in comparison with nondepressed healthy elderly subjects. Design: Cross-sectional study. Setting: Tertiary memory clinic. Participants: Twenty-three antidepressant-free elderly depressed patients and 44 nondepressed healthy elderly comparison group were enrolled to this study. Measurement: Serum IL-1 beta levels were determined with highly sensitive colorimetric sandwich enzyme-linked immunosorbent assay. Severity of the depressive episode was determined by scores on the Hamilton Depression Scale-21 item and cognitive performance by the scores on the Cambridge Cognition Examination, Mini Mental State Examination clock drawing test, and verbal fluency. Results: IL-1 beta serum levels were increased in elderly patients versus nondepressed elderly (t = 2.21, df = 65, p = 0.04). After categorizing elderly depressed subjects into late onset (LOD) versus early onset (EOD), patients with EOD had the highest IL-1 beta levels, when compared with nondepressed elderly patients and patients with LOD in analysis of variance (F = 4.9, df = 2, 64, p < 0.01). Conclusions: Late-life depression is associated with higher IL-1 beta levels suggesting that increased proinflammatory state may play a role in the physiopathology of depression in the elderly. The authors further show that this might be more prominent in those patients with EOD geriatric depression. (Am J Geriatr Psychiatry 2010; 18: 172-176)

Effects of topiramate or naltrexone on tobacco use among male alcohol-dependent outpatients

Background: A high smoking prevalence has been registered among alcoholics. It has been pointed out that alcoholic smokers may have a more severe course and greater severity of alcoholism. This study aims at comparing smoking and non-smoking alcoholics in terms of treatment outcomes and verifying the efficacy of topiramate and naltrexone to decrease the use of cigarettes among alcoholic smokers. Methods: The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. The sample comprised 155 male alcohol-dependent outpatients (52 nonsmokers and 103 smokers). 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, the patients randomly received placebo, naltrexone (50 mg/day) or topiramate (up to 300 mg/day). Only the alcoholic smokers who adhered to the treatment were evaluated with reference to the smoking reduction. Results: Cox regression analysis revealed that the smoking status among alcoholics increased the odds of relapse into drinking by 65%, independently of the medications prescribed, using the intention-to-treat method. Topiramate showed effectiveness to reduce the number of cigarettes smoked when compared to placebo among adherent patients (mean difference =7.91, p < 0.01). There were no significant differences between the naltrexone group and the placebo group. Conclusions: The results of this study confirm that the treatment is more challenging for smoking alcoholics than for non-smoking ones and support the efficacy of topiramate in the smoking reduction among male alcoholic smokers who adhered to the treatment. (C) 2009 Elsevier Ireland Ltd. All rights reserved.

Limitations of the Mini-Mental State Examination for screening dementia in a community with low socioeconomic status

The Mini-Mental State Examination (MMSE) is the most widely used instrument for the screening of cognitive impairment worldwide, but its ability to produce valid estimates of dementia in populations of low socioeconomic status and minimal literacy skills has not been adequately established. The authors investigated the psychometric properties of the MMSE in a community-based sample of older Brazilians. Cross-sectional one-phase population-based study of all residents of pre-defined areas of the city of Sao Paulo, aged 65 years or over. The Brazilian version of the MMSE was compared with DSM-IV diagnosis of dementia assessed with a harmonized one-phase procedure developed by the 10/66 Dementia Research Group. Analyses were performed with 1,933 participants of the SPAH study. Receiver operating characteristic analysis showed that the MMSE cut-point of 14/15 was associated with 78.7% sensitivity and 77.8% specificity for the diagnosis of dementia amongst participants with no formal education, and the cut-point 17/18 with 91.9% sensitivity and 89.5% specificity for those with at least 1 year of formal education (areas under the curves 0.87 and 0.94, respectively; P = 0.03). Even with these best fitting cut-points, the MMSE estimate of the prevalence of dementia was four times higher than determined by the DSM-IV criteria. Education, age, sex and income influenced MMSE scores, independently of dementia caseness. The MMSE is an adequate tool for screening dementia in older adults with minimum literacy skills, but misclassification is unacceptably high for older adults who are illiterate, which has serious consequences for research and clinical practice in low and middle income countries, where the proportion of illiteracy among older adults is high.

Comparing topiramate with naltrexone in the treatment of alcohol dependence

To compare the efficacy of topiramate with naltrexone in the treatment of alcohol dependence. The investigation was a double-blind, placebo-controlled, 12-week study carried out at the University of Sao Paulo, Brazil. A total of 155 patients, 18-60 years of age, with an International Classification of Diseases (ICD-10) diagnosis of alcohol dependence. After a 1-week detoxification period, patients were assigned randomly to receive topiramate (induction to 300 mg/day), naltrexone (50 mg/day) or placebo. Time to first relapse (consumption of > 60 g ethyl alcohol), cumulative abstinence duration and weeks of heavy drinking. In intention-to-treat analyses, topiramate was statistically superior to placebo on a number of measures including time to first relapse (7.8 versus 5.0 weeks), cumulative abstinence duration (8.2 versus 5.6 weeks), weeks of heavy drinking (3.4 versus 5.9) and percentage of subjects abstinent at 4 weeks (67.3 versus 42.6) and 8 weeks (61.5 versus 31.5), but not 12 weeks (46.2 versus 27.8). Results remained significant after controlling for Alcoholics Anonymous attendance, which was higher in topiramate than in other groups. There were no significant differences between naltrexone versus placebo or naltrexone versus topiramate groups, but naltrexone showed trends toward inferior outcomes when compared to topiramate. The results of this study support the efficacy of topiramate in the relapse prevention of alcoholism. Suggestive evidence was also obtained for superiority of topiramate versus naltrexone, but this needs to be verified in future research with larger sample sizes.

Presence of tropical spastic paraparesis/human T-cell lymphotropic virus type 1-associated myelopathy (TSP/HAM)-like among HIV-1-infected patients

Human immunodeficiency virus type 1 (HIV-1) and human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and -2) are retroviruses that share similar routes of transmission and some individuals may have a dual infection. These co-infected subjects may be at increased risk for tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)-like. To study the prevalence of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) among coinfected HIV-1/HTLV-1 subjects. Since July 1997, our group has been following a cohort to study the interaction of HTLV with HIV and/or hepatitis C virus (HCV), as well as HTLV-1-only infected asymptomatic carriers or those already presenting with TSP/HAM. During these 9 years, 296 HTLV-1-infected individuals were identified from a total of 538 patients who were referred to our clinic at the Institute of Infectious Diseases ""Emilio Ribas,"" in Sao Paulo, Brazil. All subjects were evaluated by two neurologists, blinded to the HTLV status. TSP/HAM diagnosis was based on Kagoshima diagnostic criteria. Results: A total of 38 HIV-1/HTLV-1 co-infected subjects were identified in this cohort: Twenty-six had already been diagnosed with AIDS and 12 remained asymptomatic. Six of 38 co-infected subjects (18%) were diagnosed as having TSP/HAM and also AIDS, and for 5 of them TSP/HAM was their first illness. One additional incident case was diagnosed after 2 years of follow-up. No modifications on HIV-1 viral load was seen. In contrast, the co-infected with TSP/HAM-like group showed higher HTLV-1 proviral load (505 +/- 380 vs. 97 +/- 149 copies/10(4) PBMC, P= 0.012) than asymptomatic co-infected subjects, respectively. The incidence of myelopathy among HIV-1/HTLV-1 co-infected subjects is probably higher than among patients infected only with HTLV-1, and related to a higher HTLV-1 proviral load. Thus, HTLV-1/2 screening should be done for all HIV-1-infected patients in areas where HTLV-1 infection is endemic.

Clinical usefulness of B-type natriuretic peptide in the diagnosis of pleural effusions due to heart failure

Background and objective: Light`s criteria are frequently used to evaluate the exudative or transudative nature of pleural effusions. However, misclassification resulting from the use of Light`s criteria has been reported, especially in the setting of diuretic use in patients with heart failure (HF). The objective of this study was to evaluate the utility of B-type natriuretic peptide (BNP) measurements as a diagnostic tool for determining the cardiac aetiology of pleural effusions. Methods: Patients with pleural effusions attributable to HF (n = 34), hepatic hydrothorax (n = 10), pleural effusions due to cancer (n = 21) and pleural effusions due to tuberculosis (n = 12) were studied. Diagnostic thoracentesis was performed for all 77 patients. Receiver operating characteristic (ROC) curves were constructed to determine the diagnostic accuracy of plasma BNP and pleural fluid BNP for the prediction of HF. Results: The areas under the ROC curves were 0.987 (95% CI 0.93-0.998) for plasma BNP and 0.949 (95% CI 0.874-0.986) for pleural fluid BNP, for distinguishing between patients with pleural effusions caused by HF (n = 34) and those with pleural effusions attributable to other causes (n = 43). The cut-off concentrations with the highest diagnostic accuracy for the diagnosis of HF as the cause of pleural effusion were 132 pg/mL for plasma BNP (sensitivity 97.1%, specificity 97.4%) and 127 pg/mL for pleural fluid BNP (sensitivity 97.1%, specificity 87.8%). Conclusions: In patients with pleural effusions of suspected cardiac origin, measurements of BNP in plasma and pleural fluid may be useful for the diagnosis of HF as the underlying cause.

Comparison of language impairment in late-onset depression and Alzheimer`s disease

Objectives: Depression and dementia are highly prevalent in the elderly. Language impairment is an inherent component of Alzheimer`s disease (AD), which can also be encountered in depressed patients. The aim of this study wasto compare the profiles of language abilities in late-onset depression and mild AD groups. Methods: We studied 25 patients with late-onset depression (mean age 73.6 +/- 6.6 years; schooling 9.1 +/- 5.7 years) and 30 patients with mild AD (77.6 +/- 5.4 years; 7.5 +/- 7.1 years) using the Arizona Battery for Communication Disorders of Dementia (ABCD), compared to a group of 30 controls (73.8 +/- 5.8 years; 9.1 +/- 5.4 years). Cut-off scores to discriminate between Controls x Depression and Depression x AD were determined. Results: Depressed patients` scores were similar to AD in confrontation naming, concept definition, following commands, repetition and reading comprehension (sentence). Episodic memory and mental status subtests were useful in differentiating depressed patients from AD, a result that was reproduced when using analysis of covariance to control for the effect of age in the same subtests (p = 0.01 and 0.04, respectively). Conclusion: Language impairment resembling AD was found in the aforementioned language subtests of the ABCD in elderly depressed patients; the mental status and episodic memory subtests were useful to discriminate between AD and depression. The ABCD has proven to be a suitable tool for language evaluation in this population and should aid in the differentiation of AD and pseudodementia (as that of depression).

Increased platelet GSK3B activity in patients with mild cognitive impairment and Alzheimer`s disease

The disruption of glycogen synthase kinase 3-beta (GSK3B) homeostasis has implications in the pathophysiology of neuropsychiatric disorders, namely Alzheimer`s disease (AD). GSK3B activity is increased within the AD brain, favoring the hyperphosphorylation of microtubule-associated protein Tau and the formation of neurofibrillary tangles. Such abnormality has also been detected in leukocytes of patients with cognitive disorders. The aim of the present study was to determine the expression of total and phosphorylated GSK3B at protein level in platelets of older adults with varying degrees of cognitive impairment, and to compare GSK3B activity in patients with AD, mild cognitive impairment (MCI) and healthy controls. Sixty-nine older adults were included (24 patients with mild to moderate AD, 22 patients with amnestic MCI and 23 elderly controls). The expression of platelet GSK3B (total- and Ser-9 phosphorylated GSK3B) was determined by Western blot. GSK3B activity was indirectly assessed by means of the proportion between phospho-GSK3B to total GSK3B (GSK3B ratio), the former representing the inactive form of the enzyme. Ser-9 phosphorylated GSK3B was significantly reduced in patients with MCI and AD as compared to controls (p = 0.04). Platelet GSK3B ratio was significantly decreased in patients with MCI and AD (p = 0.04), and positively correlated with scores on memory tests (r = 0.298, p = 0.01). In conclusion, we corroborate previous evidence of increased GSK activity in peripheral tissues of patients with MCI and AD, and further propose that platelet GSK may be an alternative peripheral biomarker of this abnormality, provided samples are adequately handled in order to preclude platelet activation. (C) 2010 Elsevier Ltd. All rights reserved.

Can the CAMCOG be a good cognitive test for patients with Alzheimer`s disease with low levels of education?

Background: The Cambridge Cognitive Examination (CAMCOG) is a useful test in screening for Alzheimer`s disease (AD). However, the interpretation of CAMCOG cut-off scores is problematic and reference values are needed for different educational strata. Given the importance of earlier diagnoses of mild dementia, new cut-off values are required which take into account patients with low levels of education. This study aims to evaluate whether the CAMCOG can be used as an accurate screening test among AD patients and normal controls with different educational levels. Methods: Cross-sectional assessment was undertaken of 113 AD and 208 elderly controls with heterogeneous educational levels (group 1: 1-4 years; group 2: 5-8 years; and group 3: >= 9 years) from a geriatric clinic. submitted to a thorough diagnostic evaluation for AD including the Cambridge Examination for Mental Disorders of the Elderly (CAMDEX). Controls had no cognitive or mood complaints. Sensitivity (SE) and specificity (SP) for the CAMCOG in each educational group was assessed with receiver-operator-characteristic (ROC) curves. Results: CAMCOG mean values were lower when education was reduced in both diagnostic groups (controls - group 1: 87; group 2: 91; group 3: 96; AD - group 1: 63; group 2: 62; group 3: 77). Cutoff scores for the three education groups were 79, 80 and 90, respectively. SE and SP varied among the groups (group 1: 88.1% and 83.5%; group 2: 84.6% and 96%; group 3: 70.8% and 90%). Conclusion: The CAMCOG can be used as a cognitive test for patients with low educational level with good accuracy. Patients with higher education showed lower scores than previously reported.

Comparison of Different Spectral Domain Optical Coherence Tomography Scanning Areas for Glaucoma Diagnosis

Purpose: To evaluate retinal nerve fiber layer (RNFL), optic nerve head (ONH), and macular thickness measurements for glaucoma detection using the RTVue spectral domain optical coherence tomograph. Design: Diagnostic, case-control study. Participants: One hundred forty eyes of 106 glaucoma patients and 74 eyes of 40 healthy subjects from the Diagnostic Innovations in Glaucoma Study (DIGS). Methods: All patients underwent ocular imaging with the commercially available RTVue. Optic nerve head, RNFL thickness, and macular thickness scans were obtained during the same visit. Receiver operating characteristic (ROC) curves and sensitivities at fixed specificities (80% and 95%) were calculated for each parameter. Main Outcome Measures: Areas under the ROC curves (AUC) and sensitivities at fixed specificities of 80% and 95%. Results: The AUC for the RNFL parameter with best performance, inferior quadrant thickness, was significantly higher than that of the best-performing ONH parameter, inferior rim area (0.884 vs 0.812, respectively; P = 0.04). There was no difference between ROC curve areas of the best RNFL thickness parameters and the best inner macular thickness measurement, ganglion cell complex root mean square (ROC curve area = 0.870). Conclusions: The RTVue RNFL and inner retinal macular thickness measurements had good ability to detect eyes with glaucomatous visual field loss and performed significantly better than ONH parameters.

Effect of brain-derived neurotrophic factor Val66Met polymorphism and serum levels on the progression of mild cognitive impairment

Objectives. Abnormalities in neurotrophic systems have been reported in Alzheimer`s disease (AD), as shown by decreased serum brain-derived neurotrophic factor (BDNF) levels and association with BDNF genetic polymorphisms. In this study, we investigate whether these findings can be detected in patients with mild cognitive impairment (MCI), which is recognized as a high risk condition for AD. We also address the impact of these variables on the progression of cognitive deficits within the MCI-AD continuum. Methods. One hundred and sixty older adults with varying degrees of cognitive impairment (30 patients with AD, 71 with MCI, and 59 healthy controls) were longitudinally assessed for up to 60 months. Baseline serum BDNF levels were determined by sandwich ELISA, and the presence of polymorphisms of BDNF and apolipoprotein E (Val66Met and APOE*E4, respectively) was determined by allelic discrimination analysis on real time PCR. Modifications of cognitive state were ascertained for non-demented subjects. Results. Mean serum BDNF levels were reduced in patients with MCI and AD, as compared to controls (509.2 +/- 210.5; 581.9 +/- 379.4; and 777.5 +/- 467.8 pg/l respectively; P < 0.001). Baseline serum BDNF levels were not associated with the progression of cognitive impairment upon follow-up in patients with MCI (progressive MCI, 750.8 +/- 463.0; stable MCI, 724.0 +/- 343.4; P = 0.8), nor with the conversion to AD. Although Val66Met polymorphisms were not associated with the cross-sectional diagnoses of MCI or AD, the presence of Met-BDNF allele was associated with a higher risk of disease-progression in patients with MCI (OR = 3.0 CI(95%) [1.2-7.8], P = 0.02). We also found a significant interaction between the APOE*E4 and Met-BDNF allele increasing the risk of progression of cognitive impairment in MCI patients (OR = 4.4 CI(95%) [1.6-12.1], P = 0.004). Conclusion. Decreased neurotrophic support, as indicated by a reduced systemic availability of BDNF, may play role in the neurodegenerative processes that underlie the continuum from MCI to AD. The presence of Met-BDNF allele, particularly in association with APOE*E4, may predict a worse cognitive outcome in patients with MCI.

Effect of Disease Severity on the Performance of Cirrus Spectral-Domain OCT for Glaucoma Diagnosis

PURPOSE. To evaluate the effect of disease severity on the diagnostic accuracy of the Cirrus Optical Coherence Tomograph (Cirrus HD-OCT; Carl Zeiss Meditec, Inc., Dublin, CA) for glaucoma detection. METHODS. One hundred thirty-five glaucomatous eyes of 99 patients and 79 normal eyes of 47 control subjects were recruited from the longitudinal Diagnostic Innovations in Glaucoma Study (DIGS). The severity of the disease was graded based on the visual field index (VFI) from standard automated perimetry. Imaging of the retinal nerve fiber layer (RNFL) was obtained using the optic disc cube protocol available on the Cirrus HD-OCT. Pooled receiver operating characteristic (ROC) curves were initially obtained for each parameter of the Cirrus HD-OCT. The effect of disease severity on diagnostic performance was evaluated by fitting an ROC regression model, with VFI used as a covariate, and calculating the area under the ROC curve (AUCs) for different levels of disease severity. RESULTS. The largest pooled AUCs were for average thickness (0.892), inferior quadrant thickness (0.881), and superior quadrant thickness (0.874). Disease severity had a significant influence on the detection of glaucoma. For the average RNFL thickness parameter, AUCs were 0.962, 0.932, 0.886, and 0.822 for VFIs of 70%, 80%, 90%, and 100%, respectively. CONCLUSIONS. Disease severity had a significant effect on the diagnostic performance of the Cirrus HD-OCT and thus should be considered when interpreting results from this device and when considering the potential applications of this instrument for diagnosing glaucoma in the various clinical settings. (Invest Ophthalmol Vis Sci. 2010;51:4104-4109) DOI:10.1167/iovs.094716