Ericksen Borba

Brain-derived neurotrophic factor serum levels and hippocampal volume in mild cognitive impairment and dementia due to Alzheimer disease

Background/Aims: Hippocampal atrophy is a recognized biomarker of Alzheimer disease (AD) pathology. Serum brain-derived neurotrophic factor (BDNF) reduction has been associated with neurodegeneration. We aimed to evaluate BDNF serum levels and hippocampal volume in clinical AD (dementia and mild cognitive impairment [MCI]). Methods: Participants were 10 patients with MCI and 13 with dementia due to AD as well as 10 healthy controls. BDNF serum levels were determined by ELISA and volumetric measures with NeuroQuant®. Results: MCI and dementia patients presented lower BDNF serum levels than healthy participants; dementia patients presented a smaller hippocampal volume than MCI patients and healthy participants. Discussion: The findings support that the decrease in BDNF might start before the establishment of neuronal injury expressed by the hippocampal reduction.

DNA methyltransferase haplotype is associated with Alzheimer's disease.

Epigenetic mechanisms have been implicated in syndromes associated with neuropsychiatric disorders, but little is known about the role of epigenetics in Alzheimers disease (AD). DNA methylation, one of the main epigenetic mechanisms, is a complex process carried out by specific enzymes, such as DNMT1 and DNMT3B. This study aimed to investigate the association between DNMT1 and DNMT3B polymorphisms and AD. Two hundred and ten elderly subjects (108 healthy controls and 102 with AD-NINCDS/ARDA, DSM-IV-TR criteria) were assessed. DNA was obtained from whole blood, and genotypes were detected by an allelic discrimination assay using TaqMan(®) MGB probes on a real-time PCR system. The polymorphisms studied were rs2162560, rs759920 (DNMT1) and rs998382, rs2424913, rs2424932 (DNMT3B). For both genes, the polymorphisms were in strong linkage disequilibrium. Carriers of the DNMT3B TGG haplotype were associated with AD (OR=3.03, 95% CI 1.63 to 5.63, P<0.001). No significant difference between AD and the control group were observed for DNMT1 polymorphisms. This study is one of the first describing a significant association between DNMT3B polymorphisms and AD. This enzyme, which is responsible for methylation in a general way, may be involved in AD.

Neuropsychiatric symptoms as the main determinant of caregiver burden in Alzheimer's disease

Caregiver burden is common in Alzheimer’s disease (AD), decreasing the quality of life among caregivers and patients. Projections of aging and aging-related diseases such as AD in developing countries justify additional data about this issue because people living in these countries have shown similarly high levels of caregiver strain as in the developed world. Objective The aim of this study was to analyze the association of AD caregivers’ burden with patients’ neuropsychiatric symptoms (NPS), cognitive status, severity of dementia, functional capacity, caregiver sociodemographic characteristics, and the characteristics of care provided by caregivers. Methods A cross-sectional study was conducted in a sample of 39 consecutive AD patients and their primary caregivers. NPS were evaluated using the Neuropsychiatric Inventory (NPI). Severity of dementia was assessed with the Clinical Dementia Rating (CDR) scale. Functional capacity was assessed using the Katz and Lawton scales. The burden level was rated using the Burden Interview (BI). Sociodemographic characteristics of caregivers and the characteristics of care provided by them were evaluated. The Mann-Whitney U-test, Kruskal-Wallis test and Spearman’s rho coefficient were performed. Results The BI had a moderate correlation with NPI intensity (rho=0.563), p<001. Female caregivers reported a greater level of burden (p=0.031) than male caregivers. The other variables were not significantly associated to caregiver burden. Conclusion NPS were the main determinant of burden in primary caregivers of AD patients. This result underscores the need for prevention and treatment of these symptoms. Sex also had an effect on caregiver burden, but the small male sample in this study precludes the generalization of this finding.

Association of serum brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-alpha (TNF-α) with diagnosis of delirium in oncology inpatients.

OBJECTIVE To evaluate brain-derived neurotrophic factor (BDNF) and tumor necrosis factor-α (TNF-α) blood levels as disease biomarkers of delirium in oncology inpatients. METHODS Seventeen oncology inpatients with delirium, 28 oncology inpatients without delirium, and 25 non-oncology controls (caregivers) were consecutively recruited from a Brazilian cancer center. This sample was matched by age, sex, and education level. The Confusion Assessment Method, the Mini-Mental State Examination, and the Digit Span Test were administered to ascertain delirium diagnosis. BDNF and TNF-α levels were measured by the Sandwich-ELISA method and flow cytometry, respectively. Blood samples were collected immediately after clinical evaluation. RESULTS Oncology inpatients (with and without delirium) showed significantly lower BDNF levels compared with non-oncology controls (F = 13.830; p = 0.001). TNF-α levels did not differ between the three groups. CONCLUSION A cross-sectional relationship of BDNF and TNF-α blood levels with delirium in oncology inpatients was not demonstrated. The association between cancer and reduced serum BDNF levels may be mediated by confounding factors.

Correlation between serum brain-derived neurotrophic factor and verbal fluency

ering “probable AD” alone as well as “probable” plus “ possible” AD. The neuropathological diagnosis of AD was defined using multiple combinations of CERAD neuritic plaque density scores and Braak neurofibrillary tangle stages.Results:The sensitivity of the clinical diagnosis of AD ranged from 65% to 87% while specificity ranged from 64% to 78%. Sensitivity was increased with more permissive clinical criteria and specificity was increased with more restrictive criteria while the opposite was true for neuropathological criteria. The highest combined diagnostic performance (sensitivity of 79% and specificity of 71%) was achieved when the clinical diagnosis was defined as including both probable and possible AD and the neuropathological diagnosis was defined as being inclusive of the following two situations: 1) frequent neuritic plaque density with Braak stage III-VI 2) moderate neuritic plaque density with Braak stage V or VI. Conclusions: Agreement between the clinical and neuropathological definitions of AD, based on data from NIA ADC’s, varies depending on the levels of clinical and neuropathological confidence, with sensitivities and specificities ranging between 64% and 87%. The rate of misdiagnosis is critical for many types of research, including the calculation of sample size for clinical trials.

Patient and caregiver's characteristics related with neuropsychiatric symptoms in Alzheimer's disease

was associated with support service need, worse psychologial well-being, and patient’s neuropsychiatric symptoms. Time spent caring was related to patient’s functional status. There was no relationship between the patient’s cognitive functioning/depression and burden. Conclusions: Caregivers of individuals with MCI report greater burden in caring for their loved ones and this level of burden appears to be related to the patient’s neurobehavioral and functional status. Early identification of MCI patients with psychiatric issues may be particularly important for predicting caregiver burden.

Were elderly patients, who were escorted by family members for medical appointments, more likely to present cognitive dysfunction?

the strongest associations. The estimated relative risks with 95% confidence intervals were 0.94 (0.89 to 0.99) per 10 year increase in age, 0.33 (0.23 to 0.49) comparing blacks to non-blacks, and 1.61 (1.37 to 1.89) for individuals with a college education or more compared to those with less than college education. These estimates are all adjusted for family and clinical characteristics. Conclusions: Performance of autopsy does not occur randomly, in fact, many factors appear to play a role. This study was among the first attempts to approach the problem using multivariate statistical methods. Our results suggest that autopsy was much more likely to be performed on younger subjects, Caucasians, and subjects with higher education. These results show that neuropathological data are available on a rather select sample, which influences generalizability. We also illustrate how such results can be used to help correct for selective sampling in neuropathology studies.

Did patient's cognitive status correlate with functional impairment assessment?

daytime sleepiness were measured using the SCOPA-SLEEP scale during the 6-week treatment period (Baseline and Days 8, 15, 29 and 42). Results: Mean baseline (pretreatment) SCOPA Part B (nighttime sleep) scores were 10.5 for the placebo and 40 mg dose groups (N 1⁄4 97 and 92, respectively). Statistically significant improvement in nighttime sleep scores were observed in the 40 mg pimavanserin group vs. placebo as early as Day 8 (-1.0 vs. no change, p 1⁄4 0.003) and continued through Day 29. At the end of treatment (Day 42), a trend toward significance remained (-1.7 40-mg vs. -1.2 placebo; p 1⁄4 0.066). The 10 mg pimavanserin group was not significantly different from placebo at any timepoint. Daytime sleepiness scores were unaffected by pimavanserin treatment indicating no sedative effects of the drug. Conclusions: Pimavanserin appears to improve nighttime sleep without negative effects on daytime sleepiness in patients with PDP. Studies of pimavanserin in Alzheimer’s psychosis, where sleep impairment is also a common comorbidity, are planned. Evaluation of sleep in these studies may be of interest.

Burden interview versus neuropsychiatric inventory: Evaluation of burden in caregivers of Alzheimer's disease patients

This study aims to evaluate patient and caregiver’s characteristics related with neuropsychiatric symptoms. Methods: A cross-sectional study was conducted in a sample of 58 probable Alzheimer’s disease (AD) patients (NINCDS-ADRDA criteria). The neuropsychiatric symptoms were evaluated by the Brazilian version of the Neuropsychiatric Inventory (NPI). The dementia severity was assessed with the Clinical Dementia Rating (CDR), Brazilian version. The analyzed patient’s variables were sex, age, age of onset of AD symptoms and education. The analyzed caregiver’s variables were sex, type of relationship, age, education, time as caregiver, weekly time of care, residing with patient and type of job. Student’s t test and one-way Anova were performed for parametric variables. Spearman’s rho was used for correlations. Results: NPI intensity and distress were similar in both patient’s sex (p 1⁄4 0.742 and p 1⁄4 0.902, respectively) and in the three stages of severity of dementia (F1⁄4 1.951, p1⁄4 0.152; F1⁄4 0.763, p1⁄4 0.471, respectively). Patient’s education was inversely correlated with NPI frequency, intensity and distress (rho1⁄4 -0.283, rho1⁄4 -0.276, rho1⁄4 -0.262, p1⁄4 0.05). NPI intensity and distress were similar in both caregiver’s sex (p1⁄4 0.809 and p1⁄4 0.743, respectively), relationship type (p> 0.5) and caregiver’s type of job (p > 0.5). However, a tendency for statistical difference was observed between caregivers who resided and those who not resided with patients (p 1⁄4 0.05), caregivers who resided with patients showed higher NPI intensity and NPI distress. Caregiver’s education was inversely correlated with NPI frequency, intensity and distress (rho1⁄4 -0.302, rho1⁄4 -0. 272, rho1⁄4 -0. 300, p1⁄4 0.05). Caregiver’s age was inversely correlated with NPI severity (rho 1⁄4 -0.270, p 1⁄4 0.05). Weekly time of care was correlated with NPI frequency (rho 1⁄4 0. 291, p1⁄4 0.05). Conclusions: Some variables may interfere on neuropsychiatric symptoms evaluation by caregivers of AD patients, as age, education, weekly time of care and residing with patients. Some of them can be modified through different approaches improving quality of care.

Factorial analysis of the symptoms in the neuropsychiatric inventory

was unable to follow letters of Karaoke although his visual acuity was good. He memorized songs. At 68-year-old, he was unable to climb mountains. He showed difficulty climbing stairs. When he drove his car backward, he crashed his car (he had never done such a thing). He became easy to fall. At 69-year-old, he showed mild walking difficulty and used wheelchair. At 71-year-old, he admitted to the nursing home. Because of the chance of walking was less, he became unable to walk. He gradually became less lively. At 74-year-old, he was absent-minded, slept daytime and he showed appetite loss. Neurological examaination showed dementia, supranuclear gaze palsy, pseudobulbar palsy, neck dorsiflexion, plastic rigidity and akinesia. MRI showed midbrain atrophy like hummingbird. MIBG myocardial scintigraphy showed normal findings: early H/M ratio1⁄42.90. L-DOPA did not improve his clinical symptoms. Neuropathological examination: brain weight 1,040g. Macroscopic findings: frontotemporal atrophy of cerebrum, depigmentations of substantia nigra and locus ceruleus. Microscopic findings: 1) AD pathology plaque: Braak C, tangle: Braak VI, granulovacuolar degenerations and a Hirano body. 2) Lewy body pathology: DLB limbic form, pigmented neurons in substantia nigra were relatively preserved. Lewy bodies were in substantiae nigrae. 3) Mild PSP pathology: grumose degeneration of dentate nucleus, neurofibrillary tangles at midbrain tegmentum and loci cerulei. Conclusions: We think it important that there is parkinsonism variant of AD with DLB, who may show midbrain atrophy, negative result MIBG cardiac scintigraphy and PSP like clinical features: dementia, supranuclear gaze palsy, neck dorsiflexion and l-DOPA nonresponsive parkinsonism.